Tari Haahtela

We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Rapidly declining biodiversity may be a contributing factor to another global megatrend--the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the "biodiversity hypothesis," reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects' homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.

The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy. We compared the effect of an inhaled corticosteroid, budesonide, with that of an inhaled beta 2-agonist, terbutaline, in the long-term treatment of newly detected asthma.We studied 103 patients (29 male and 74 female patients 15 to 64 years old) in whom asthma had appeared within the previous year. The patients were randomly assigned in blinded fashion to two treatment groups: one to receive 600 micrograms of inhaled budesonide twice a day, and the other to receive 375 micrograms of inhaled terbutaline twice a day. The study period was two years.After six weeks of treatment, the patients treated with budesonide tolerated inhaled histamine better than the patients treated with terbutaline (a difference of one doubling dose step, P less than 0.001), and the difference was sustained. Patients' diaries kept during the first three months of the study and during the last month of the first and second years showed budesonide to be more effective than terbutaline in improving peak expiratory flow in the morning (average increase from the pretreatment value, 32.8 liters per minute for budesonide vs. 4.8 liters per minute for terbutaline; P less than 0.001) and in the evening (P less than 0.01). Budesonide was also more effective in reducing the symptoms of asthma (P less than 0.01) and the use of supplemental beta 2-agonist medication (P less than 0.01). Ten patients were withdrawn from the terbutaline group because treatment was insufficiently effective, whereas only one dropped out of the budesonide group. The adverse reactions to both treatments were few and mild.Antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected, mild asthma, and it is superior to the use of terbutaline in such patients.

The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system. Probiotics, live health-promoting microbes, might offer such stimulation.We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases.We randomized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery. Their infants received the same probiotics plus galacto-oligosaccharides (n = 461) or a placebo (n = 464) for 6 months. At 2 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, and allergic rhinitis) and IgE sensitization (positive skin prick test response or serum antigen-specific IgE level >0.7 kU/L). Fecal bacteria were analyzed during treatment and at age 2 years.Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated (atopic) diseases (odds ratio [OR], 0.71; 95% CI, 0.50-1.00; P = .052). Probiotic treatment reduced eczema (OR, 0.74; 95% CI, 0.55-0.98; P = .035) and atopic eczema (OR, 0.66; 95% CI, 0.46-0.95; P = .025). Lactobacilli and bifidobacteria more frequently (P < .001) colonized the guts of supplemented infants.Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema. The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics.The prevention of atopic eczema in high-risk infants is possible by modulating the infant's gut microbiota with probiotics and prebiotics.

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.

Skin prick testing is an essential test procedure to confirm sensitization in IgE-mediated allergic disease in subjects with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and food and drug allergy. This manuscript reviews the available evidence including Medline and Embase searches, abstracts of international allergy meetings and position papers from the world allergy literature. The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, interpretation of the tests after 15 - 20 minutes of application, with a positive result defined as a wheal ≥3 mm diameter. A standard prick test panel for Europe for inhalants is proposed and includes hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (Poa pratensis, Dactilis glomerata, Lolium perenne, Phleum pratense, Festuca pratensis, Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Standardization of the skin test procedures and standard panels for different geographic locations are encouraged worldwide to permit better comparisons for diagnostic, clinical and research purposes.

<h2>Abstract</h2> Sulphidopeptide leukotrienes are potent bronchoconstrictors and increase bronchial hyperreactivity, one of the hallmarks of asthma. We have demonstrated that leukotriene LTE₄, the most stable of the sulphidopeptide leukotrienes, elicited an increase in the numbers of eosinophils and neutrophils in the lamina propria of the airway mucosa 4 h after inhalation in 4 asthmatic subjects. The numbers of eosinophils were, on average, 10-fold greater than those of neutrophils. There was no significant change in numbers of lymphocytes, plasma cells, mast cells, or macrophages. Since LTE₄ recruits granulocytes, the potential of antisulphidopeptide leukotriene drugs as antiinflammatory and "steroid-sparing" agents should be tested.

We have studied bronchial biopsies from 14 patients with newly diagnosed asthma (four men and 10 women), who had had asthma symptoms, on average, 7.4 months (range, 2 to 12 months) and from four control subjects. The patients had not received corticosteroids, disodium cromoglycate, or theophylline before the study. The bronchial biopsies were taken, using a rigid-tube bronchoscope under local anaesthesia, from two different airway levels: (1) inside the right upper lobe bronchus, and (2) at the opening of the right middle lobe. The specimens were prepared for both light and electron microscopy. The use of Slot grids 1 x 2 mm enabled a large area of the thin sections to be photographed and analyzed by applying a graphic Autocad program. There was an increase in the numbers of mast cells (p < 0.001), eosinophils (p < 0.05), lymphocytes (p < 0.05), and macrophages (p < 0.05) in the epithelium of patients with newly diagnosed asthma as compared with those in control subjects. In the lamina propria, these asthmatic patients had more eosinophils (p < 0.001), lymphocytes (p < 0.001), macrophages (p < 0.001), and plasma cells (p < 0.001) than did the control subjects. We conclude that, in asthma, an airway inflammatory process is present even at a clinically early stage of the disease. In the asthmatic airways, there are signs of a general inflammatory response caused by more than one cell type.

To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi‐Maesano I, Baena‐Cagnani CE, Bergmann KC, Bindslev‐Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth‐van‐Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova‐Baranova L, O’Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid‐Grendelmeier P, Todo‐Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012; 67 : 18–24. Abstract This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA 2 LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis–conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including ‘practicing allergists’, general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in‐depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA 2 LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.

<h3>Background</h3> Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. <h3>Objective</h3> We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. <h3>Methods</h3> In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. <h3>Results</h3> Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; <i>P</i> = .035). <h3>Conclusions</h3> No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

<h2>Abstract</h2> The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO₂), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Rationale: We hypothesized that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction. Methods: RBM thickness and numbers of inflammatory cells were determined in ultrathin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A: 16 infants with a median age of 12 months (range 3.4–26 months), with decreased specific airway conductance (sGaw) and bronchodilator reversibility; Group B: 22 infants with a median age of 12.4 months (5.1–25.9 months), with decreased sGaw but without bronchodilator reversibility; and Group C: 15 infants with a median age of 11.5 months (3.4–24.3 months) with normal sGaw. Additional comparisons were made with the following groups. Group D: 17 children, median age 10.3 years (6–16 years), with difficult asthma; Group E: 10 pediatric control subjects without asthma, median age 10 years (6–16 years); and Group F: nine adult normal, healthy control subjects, median age 27 years (21–42 years). Main Results: There were no significant differences in RBM thickness or inflammatory cell number between the infant groups. RBM thickness was similar in the infants and Groups E and F. However, the RBM in all infant groups (Group A: median 4.3 μm [range 2.8–9.2 μm]; Group B: median 4.15 μm [range 2.7–5.8 μm]; Group C: median 3.8 μm [range 2.7–5.5 μm]) was significantly less thick than that in the older children with asthma (Group D: median 8.3 μm [range 5.3–12.7 μm]; p < 0.001). Conclusion: RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.

To compare the efficacy of self management of asthma with traditional treatment.12 month prospective randomised trial.Outpatient clinics in Finland.115 patients with mild to moderately severe asthma.Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements.Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life.The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare.Self management reduces incidents caused by asthma and improves quality of life.

Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe.The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel.The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres.The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe.The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis.The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation.The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete.The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease.Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis.While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated.This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.

Background. In clinical practice, patients whose airway disease shares features of both asthma and chronic obstructive pulmonary disease (COPD) remain poorly recognized. Material and methods. The study population consisted of 1546 patients with a diagnosis of asthma or COPD or both. Based on patient-reported outcomes and retrospective medical record data, the study population was divided into three groups: () asthma only, () COPD only, and () both asthma and COPD (overlap syndrome group). We evaluated patient characteristics associated with health-related quality of life (HRQoL). Results. In many respects, the overlap group fell between the asthma and COPD groups. In the overlap group, however, HRQoL was the poorest of all. In the logistic regression model, with the asthma group as the reference, both the overlap and the COPD group showed higher risk for low HRQoL [odd ratio (OR): 1.9; 95% confidence interval (CI): 1.2–3.2; and OR: 1.8, 95% CI: 1.0–3.2; respectively]. In addition, female gender, obesity, duration of disease, disability pension, and coexisting cardiovascular disease were associated with low HRQoL across the study population. Conclusions. Patients with overlapping asthma and COPD differed from those patients with asthma or COPD only. Overlap syndrome was associated with low HRQoL.

Abstract Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008‐2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well‐being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.

Background Western lifestyle is associated with high prevalence of allergy, asthma and other chronic inflammatory disorders. To explain this association, we tested the ‘biodiversity hypothesis’, which posits that reduced contact of children with environmental biodiversity, including environmental microbiota in natural habitats, has adverse consequences on the assembly of human commensal microbiota and its contribution to immune tolerance. Methods We analysed four study cohorts from Finland and Estonia (n = 1044) comprising children and adolescents aged 0.5–20 years. The prevalence of atopic sensitization was assessed by measuring serum IgE specific to inhalant allergens. We calculated the proportion of five land-use types – forest, agricultural land, built areas, wetlands and water bodies – in the landscape around the homes using the CORINE2006 classification. Results The cover of forest and agricultural land within 2–5 km from the home was inversely and significantly associated with atopic sensitization. This relationship was observed for children 6 years of age and older. Land-use pattern explained 20% of the variation in the relative abundance of Proteobacteria on the skin of healthy individuals, supporting the hypothesis of a strong environmental effect on the commensal microbiota. Conclusions The amount of green environment (forest and agricultural land) around homes was inversely associated with the risk of atopic sensitization in children. The results indicate that early-life exposure to green environments is especially important. The environmental effect may be mediated via the effect of environmental microbiota on the commensal microbiota influencing immunotolerance.

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Background Allergic rhinitis (AR) is increasingly acknowledged as having a substantial socioeconomic impact associated with impaired work productivity, although available information remains fragmented. Objective This systematic review summarizes recently available information to provide a quantitative estimate of the burden of AR on work productivity including lost work time (ie, absenteeism) and reduced performance while working (ie, presenteeism). Methods A Medline search retrieved original studies from 2005 to 2015 pertaining to the impact of AR on work productivity. A pooled analysis of results was carried out with studies reporting data collected through the validated Work Productivity and Activity Impairment (WPAI) questionnaire. Results The search identified 19 observational surveys and 9 interventional studies. Six studies reported economic evaluations. Pooled analysis of WPAI-based studies found an estimated 3.6% (95% confidence interval [CI], 2.4; 4.8%) missed work time and 35.9% (95% CI, 29.7; 42.1%) had impairment in at-work performance due to AR. Economic evaluations indicated that indirect costs associated with lost work productivity are the principal contributor to the total AR costs and result mainly from impaired presenteeism. The severity of AR symptoms was the most consistent disease-related factor associated with a greater impact of AR on work productivity, although ocular symptoms and sleep disturbances may independently affect work productivity. Overall, the pharmacologic treatment of AR showed a beneficial effect on work productivity. Conclusions This systematic review provides summary estimates of the magnitude of work productivity impairment due to AR and identifies its main determinant factors. This information may help guide both clinicians and health policy makers. Allergic rhinitis (AR) is increasingly acknowledged as having a substantial socioeconomic impact associated with impaired work productivity, although available information remains fragmented. This systematic review summarizes recently available information to provide a quantitative estimate of the burden of AR on work productivity including lost work time (ie, absenteeism) and reduced performance while working (ie, presenteeism). A Medline search retrieved original studies from 2005 to 2015 pertaining to the impact of AR on work productivity. A pooled analysis of results was carried out with studies reporting data collected through the validated Work Productivity and Activity Impairment (WPAI) questionnaire. The search identified 19 observational surveys and 9 interventional studies. Six studies reported economic evaluations. Pooled analysis of WPAI-based studies found an estimated 3.6% (95% confidence interval [CI], 2.4; 4.8%) missed work time and 35.9% (95% CI, 29.7; 42.1%) had impairment in at-work performance due to AR. Economic evaluations indicated that indirect costs associated with lost work productivity are the principal contributor to the total AR costs and result mainly from impaired presenteeism. The severity of AR symptoms was the most consistent disease-related factor associated with a greater impact of AR on work productivity, although ocular symptoms and sleep disturbances may independently affect work productivity. Overall, the pharmacologic treatment of AR showed a beneficial effect on work productivity. This systematic review provides summary estimates of the magnitude of work productivity impairment due to AR and identifies its main determinant factors. This information may help guide both clinicians and health policy makers.

Abstract Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence‐based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good‐quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow‐up of patients.

AllergyVolume 75, Issue 10 p. 2440-2444 EAACI Position Paper Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement Jean Bousquet, Corresponding Author Jean Bousquet [email protected] Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany University Hospital Montpellier, Montpelllier, France MACVIA-France, Montpellier, France Correspondence Jean Bousquet, CHU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Email: [email protected]Search for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorMarek Jutel, Marek Jutel Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland ALL-MED Medical Research Institute, Wroclaw, PolandSearch for more papers by this authorClaus Bachert, Claus Bachert orcid.org/0000-0003-4742-1665 Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium Sun Yat-sen University, International Airway Research Center, Ghent University Hospital, First Affiliated Hospital, Guangzhou, China Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorLudger Klimek, Ludger Klimek Center for Rhinology and Allergology, Wiesbaden, GermanySearch for more papers by this authorIoana Agache, Ioana Agache orcid.org/0000-0001-7994-364X Transylvania University Brasov, Brasov, RomaniaSearch for more papers by this authorIgnacio J. Ansotegui, Ignacio J. Ansotegui Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, SpainSearch for more papers by this authorAnna Bedbrook, Anna Bedbrook MACVIA-France, Montpellier, FranceSearch for more papers by this authorSinthia Bosnic-Anticevich, Sinthia Bosnic-Anticevich Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, AustraliaSearch for more papers by this authorG. Walter Canonica, G. Walter Canonica Personalized Medicine, Asthma and Allergy - Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy Department of Biomedical Sciences - Humanitas University -, Pieve Emanuele, Milan,, ItalySearch for more papers by this authorTomas Chivato, Tomas Chivato School of Medicine, University CEU San Pablo, Madrid, SpainSearch for more papers by this authorAlvaro A. Cruz, Alvaro A. Cruz orcid.org/0000-0002-7403-3871 ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Salvador, Brasil WHO GARD Planning Group, Montpellier, BrazilSearch for more papers by this authorWienczyslawa Czarlewski, Wienczyslawa Czarlewski Medical Consulting Czarlewski, Levallois, and MASK-air, Montpellier, FranceSearch for more papers by this authorStefano Del Giacco, Stefano Del Giacco Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Cagliari, ItalySearch for more papers by this authorHui Du, Hui Du Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, Hubei, ChinaSearch for more papers by this authorJoao A. Fonseca, Joao A. Fonseca Center for Research in Health Technologies and Information Systems- CINTESIS, Universidade do Porto, Porto, Portugal Allergy Unit, Instituto CUF Porto e Hospital CUF Porto, Porto, Portugal Health Information and Decision Sciences Department - CIDES, Faculdade de Medicina, Universidade do Porto, Porto, Portugal Faculdade de Medicina da Universidade do Porto, Porto, PortugalSearch for more papers by this authorYadong Gao, Yadong Gao Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaSearch for more papers by this authorTari Haahtela, Tari Haahtela orcid.org/0000-0003-4757-2156 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorKarin Hoffmann-Sommergruber, Karin Hoffmann-Sommergruber Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorJuan-Carlos Ivancevich, Juan-Carlos Ivancevich Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, ArgentinaSearch for more papers by this authorNikolaï Khaltaev, Nikolaï Khaltaev GARD Chairman, Geneva, SwitzerlandSearch for more papers by this authorEdward F. Knol, Edward F. Knol Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this authorPiotr Kuna, Piotr Kuna Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorDesiree Larenas-Linnemann, Desiree Larenas-Linnemann Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, MexicoSearch for more papers by this authorJoaquim Mullol, Joaquim Mullol Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, SpainSearch for more papers by this authorRobert Naclerio, Robert Naclerio Johns Hopkins School of Medicine, Baltimore, MD, USASearch for more papers by this authorKen Ohta, Ken Ohta orcid.org/0000-0001-9734-4579 National Hospital Organization, Tokyo National Hospital, Tokyo, JapanSearch for more papers by this authorYoshitaka Okamoto, Yoshitaka Okamoto Department of Otorhinolaryngology, Chiba University Hospital, Chiba, JapanSearch for more papers by this authorLiam O'Mahony, Liam O'Mahony orcid.org/0000-0003-4705-3583 Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, IrelandSearch for more papers by this authorGabrielle L. Onorato, Gabrielle L. Onorato MACVIA-France, Montpellier, FranceSearch for more papers by this authorNikos G. Papadopoulos, Nikos G. Papadopoulos orcid.org/0000-0002-4448-3468 Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK Allergy Dpt, 2nd Pediatric Clinic, University of Athens, Athens, GreeceSearch for more papers by this authorOliver Pfaar, Oliver Pfaar orcid.org/0000-0003-4374-9639 Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, GermanySearch for more papers by this authorBoleslaw Samolinski, Boleslaw Samolinski Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Warsaw, PolandSearch for more papers by this authorJürgen Schwarze, Jürgen Schwarze Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UKSearch for more papers by this authorSanna Toppila-Salmi, Sanna Toppila-Salmi Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorMaria-Teresa Ventura, Maria-Teresa Ventura Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, ItalySearch for more papers by this authorArunas Valiulis, Arunas Valiulis Vilnius University Faculty of Medicine, Institute of Clinical Medicine & Institute of Health Sciences, Vilnius, Lithuania European Academy of Paediatrics (EAP/UEMS-SP), Brussels, BelgiumSearch for more papers by this authorArzu Yorgancioglu, Arzu Yorgancioglu Celal Bayar University Department of Pulmonology, Manisa, TurkeySearch for more papers by this authorTorsten Zuberbier, Torsten Zuberbier orcid.org/0000-0002-1466-8875 Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin, Berlin, Germany Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Member of GA2LEN, Berlin, GermanySearch for more papers by this authorRuby Pawankar, Ruby Pawankar Department of Pediatrics, Nippon Medical School, Tokyo, JapanSearch for more papers by this authorthe ARIA-MASK Study Group, the ARIA-MASK Study GroupThe ARIA-MASK Study Group members are shown in Appendix 1.Search for more papers by this author Jean Bousquet, Corresponding Author Jean Bousquet [email protected] Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany University Hospital Montpellier, Montpelllier, France MACVIA-France, Montpellier, France Correspondence Jean Bousquet, CHU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Email: [email protected]Search for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorMarek Jutel, Marek Jutel Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland ALL-MED Medical Research Institute, Wroclaw, PolandSearch for more papers by this authorClaus Bachert, Claus Bachert orcid.org/0000-0003-4742-1665 Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium Sun Yat-sen University, International Airway Research Center, Ghent University Hospital, First Affiliated Hospital, Guangzhou, China Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorLudger Klimek, Ludger Klimek Center for Rhinology and Allergology, Wiesbaden, GermanySearch for more papers by this authorIoana Agache, Ioana Agache orcid.org/0000-0001-7994-364X Transylvania University Brasov, Brasov, RomaniaSearch for more papers by this authorIgnacio J. Ansotegui, Ignacio J. Ansotegui Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, SpainSearch for more papers by this authorAnna Bedbrook, Anna Bedbrook MACVIA-France, Montpellier, FranceSearch for more papers by this authorSinthia Bosnic-Anticevich, Sinthia Bosnic-Anticevich Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, AustraliaSearch for more papers by this authorG. Walter Canonica, G. Walter Canonica Personalized Medicine, Asthma and Allergy - Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy Department of Biomedical Sciences - Humanitas University -, Pieve Emanuele, Milan,, ItalySearch for more papers by this authorTomas Chivato, Tomas Chivato School of Medicine, University CEU San Pablo, Madrid, SpainSearch for more papers by this authorAlvaro A. Cruz, Alvaro A. Cruz orcid.org/0000-0002-7403-3871 ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Salvador, Brasil WHO GARD Planning Group, Montpellier, BrazilSearch for more papers by this authorWienczyslawa Czarlewski, Wienczyslawa Czarlewski Medical Consulting Czarlewski, Levallois, and MASK-air, Montpellier, FranceSearch for more papers by this authorStefano Del Giacco, Stefano Del Giacco Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Cagliari, ItalySearch for more papers by this authorHui Du, Hui Du Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, Hubei, ChinaSearch for more papers by this authorJoao A. Fonseca, Joao A. Fonseca Center for Research in Health Technologies and Information Systems- CINTESIS, Universidade do Porto, Porto, Portugal Allergy Unit, Instituto CUF Porto e Hospital CUF Porto, Porto, Portugal Health Information and Decision Sciences Department - CIDES, Faculdade de Medicina, Universidade do Porto, Porto, Portugal Faculdade de Medicina da Universidade do Porto, Porto, PortugalSearch for more papers by this authorYadong Gao, Yadong Gao Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaSearch for more papers by this authorTari Haahtela, Tari Haahtela orcid.org/0000-0003-4757-2156 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorKarin Hoffmann-Sommergruber, Karin Hoffmann-Sommergruber Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorJuan-Carlos Ivancevich, Juan-Carlos Ivancevich Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, ArgentinaSearch for more papers by this authorNikolaï Khaltaev, Nikolaï Khaltaev GARD Chairman, Geneva, SwitzerlandSearch for more papers by this authorEdward F. Knol, Edward F. Knol Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this authorPiotr Kuna, Piotr Kuna Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorDesiree Larenas-Linnemann, Desiree Larenas-Linnemann Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, MexicoSearch for more papers by this authorJoaquim Mullol, Joaquim Mullol Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, SpainSearch for more papers by this authorRobert Naclerio, Robert Naclerio Johns Hopkins School of Medicine, Baltimore, MD, USASearch for more papers by this authorKen Ohta, Ken Ohta orcid.org/0000-0001-9734-4579 National Hospital Organization, Tokyo National Hospital, Tokyo, JapanSearch for more papers by this authorYoshitaka Okamoto, Yoshitaka Okamoto Department of Otorhinolaryngology, Chiba University Hospital, Chiba, JapanSearch for more papers by this authorLiam O'Mahony, Liam O'Mahony orcid.org/0000-0003-4705-3583 Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, IrelandSearch for more papers by this authorGabrielle L. Onorato, Gabrielle L. Onorato MACVIA-France, Montpellier, FranceSearch for more papers by this authorNikos G. Papadopoulos, Nikos G. Papadopoulos orcid.org/0000-0002-4448-3468 Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK Allergy Dpt, 2nd Pediatric Clinic, University of Athens, Athens, GreeceSearch for more papers by this authorOliver Pfaar, Oliver Pfaar orcid.org/0000-0003-4374-9639 Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, GermanySearch for more papers by this authorBoleslaw Samolinski, Boleslaw Samolinski Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Warsaw, PolandSearch for more papers by this authorJürgen Schwarze, Jürgen Schwarze Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UKSearch for more papers by this authorSanna Toppila-Salmi, Sanna Toppila-Salmi Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorMaria-Teresa Ventura, Maria-Teresa Ventura Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, ItalySearch for more papers by this authorArunas Valiulis, Arunas Valiulis Vilnius University Faculty of Medicine, Institute of Clinical Medicine & Institute of Health Sciences, Vilnius, Lithuania European Academy of Paediatrics (EAP/UEMS-SP), Brussels, BelgiumSearch for more papers by this authorArzu Yorgancioglu, Arzu Yorgancioglu Celal Bayar University Department of Pulmonology, Manisa, TurkeySearch for more papers by this authorTorsten Zuberbier, Torsten Zuberbier orcid.org/0000-0002-1466-8875 Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin, Berlin, Germany Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Member of GA2LEN, Berlin, GermanySearch for more papers by this authorRuby Pawankar, Ruby Pawankar Department of Pediatrics, Nippon Medical School, Tokyo, JapanSearch for more papers by this authorthe ARIA-MASK Study Group, the ARIA-MASK Study GroupThe ARIA-MASK Study Group members are shown in Appendix 1.Search for more papers by this author First published: 31 March 2020 https://doi.org/10.1111/all.14302Citations: 93 Bousquet, Akdis and Jutel participated equally to the paper. Bousquet, Bachert, Bedbrook, Bosnic-Anticevich, Canonica, Cruz, Czarlewski, Fonseca, Haahtela, Ivancevich, Kuna, Larenas-Linnemann, Mullol, Naclerio, Ohta, Okamoto, Papadopoulos, Pawankar, Pfaar, Samolinski, Toppila-Salmi, Valiulis, Yorgancioglu and Zuberbier are members of the ARIA and MASK boards. Jutel, Klimek, Agache, Chivato, Sommergruber, Knol, O'Mahony and Schwarze are members of the EAACI board of officers. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Google Scholar Citing Literature Volume75, Issue10October 2020Pages 2440-2444 This article also appears in:COVID-19 Articles in Allergy ReferencesRelatedInformation

The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet.Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.

Abstract The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano‐technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in‐depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody‐ (I‐III), cell‐mediated (IVa‐c), tissue‐driven mechanisms (V‐VI) and direct response to chemicals (VII). Types I‐III are linked to classical and newly described clinical conditions. Type IVa‐c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V‐VI involve epithelial barrier defects and metabolic‐induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

To determine the prevalence of asthma in cohorts of Finnish young men in the period 1926-89.A retrospective analysis using reports and statistics of Finnish defence forces.Call up examinations of candidates for military conscription and examination of conscripts discharged because of poor health.Roughly 900,000 men--that is, 98% of men of conscription age--examined in 1966-89 and a proportional but unknown number examined in 1926-61.Asthma recognised at call up examination, exemption from military service, and discharge from military service because of asthma.During 1926-61 the prevalence of asthma recorded at call up examinations remained steady at between 0.02% and 0.08%. Between 1961 and 1966, however, a continuous, linear rise began, the prevalence increasing from 0.29% in 1966 to 1.79% in 1989--that is, representing a sixfold increase. Compared with 1961 the rise was 20-fold. From 1966 to 1989 the sum of exemptions and discharges from military service due to asthma increased analogously sixfold.If the apparent increase in asthma detected in Finnish young men was due entirely to improved diagnostic methods and other confounding effects then some 95% of cases must have gone undiagnosed in the years before 1966. This seems inconceivable, which suggests that much of the increase was real. This conclusion is strengthened by the observed rise in exemptions and discharges due to asthma.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA 2 LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal &gt;3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus : 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA 2 LEN Pan‐European core SPT panel.

Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy. We studied the effects of similar therapy in teenagers and young adults, who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and/or mild asthma.We conducted a double-blind, placebo-controlled study, in which respiratory and eye symptoms and use of medications in two groups were compared. Open oral challenge tests with a slice of apple were performed trice: before, during and after the birch-pollen season. There were 18 patients in each group. They used Lactobacillus rhamnosus for 5.5 months; 2.5 months before the pollen season, 1 month during the season (May), and 2 months after.The results were negative. The treatment did not alleviate the symptoms of the patients or reduce their use of medication during the birch-pollen season or the subsequent 2 months. The treatment did not significantly affect the symptoms caused by apple in the oral challenge tests.We found no indication of a beneficial treatment effect in our patients. As the number of patients was relatively small, conclusions should be drawn with caution.

Exercise may increase ventilation up to 200 L/min for short periods of time in speed and power athletes, and for longer periods in endurance athletes, such as long-distance runners and swimmers. Therefore highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many pollen allergens in spring and summer. Competitive swimmers inhale and microaspirate large amounts of air that floats above the water surface, which means exposure to chlorine derivatives from swimming pool disinfectants. In the summer Olympic Games, 4% to 15% of the athletes showed evidence of asthma or used antiasthmatic medication. Asthma is most commonly found in endurance events, such as cycling, swimming, or long-distance running. The risk of asthma is especially increased among competitive swimmers, of which 36% to 79% show bronchial hyperresponsiveness to methacholine or histamine. The risk of asthma is closely associated with atopy and its severity among athletes. A few studies have investigated occurrence of exercise-induced bronchospasm among highly trained athletes. The occurrences of exercise-induced bronchospasm vary from 3% to 35% and depend on testing environment, type of exercise used, and athlete population tested. Mild eosinophilic airway inflammation has been shown to affect elite swimmers and cross-country skiers. This eosinophilic inflammation correlates with clinical parameters (ie, exercise-induced bronchial symptoms and bronchial hyperresponsiveness). Athletes commonly use antiasthmatic medication to treat their exercise-induced bronchial symptoms. However, controlled studies on their long-term effects on bronchial hyperresponsiveness and airway inflammation in the athletes are lacking. Follow-up studies on asthma in athletes are also lacking. What will happen to bronchial hyperresponsiveness and airway inflammation after discontinuation of competitional career is unclear. In the future, follow-up studies on bronchial responsiveness and airway inflammation, as well as controlled studies on both short- and long-term effects of antiasthmatic drugs in the athletes are needed.

Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants.Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point.Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections).Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

To investigate respiratory symptoms, increased bronchial responsiveness, and signs of airway inflammation in elite swimmers, we examined 29 swimmers from the Finnish national team and 19 healthy control subjects (nonasthmatic, symptom-free). They answered a questionnaire and were interviewed for respiratory symptoms. Lung volumes were measured and bronchial responsiveness assessed by a histamine challenge test. Induced sputum samples were also collected. Fourteen (48%) of the swimmers and three (16%) of the control subjects showed increased bronchial responsiveness (P<0.05). The sputum cell differential counts of eosinophils (mean 2.7% vs 0.2%) and neutrophils (54.7% vs 29.9%) from swimmers were significantly higher than those from controls (P<0.01). Eosinophilia (sputum differential eosinophil count of >4%) was observed in six (21%) of the swimmers and in none of the controls (P<0.05). Symptomatic swimmers had significantly more sputum eosinophils than did the symptom-free. The concentrations of sputum eosinophil peroxidase (EPO) and human neutrophil lipocalin (HNL) were significantly higher in swimmers than control subjects (P<0.001 and P=0.05). We conclude that elite swimmers had significantly more often increased bronchial responsiveness than control subjects. Sputum from swimmers contained a higher percentage of eosinophils and neutrophils, and higher concentrations of EPO and HNL than sputum from controls. Long-term and repeated exposure to chlorine compounds in swimming pools during training and competition may contribute to the increased occurrence of bronchial hyperresponsiveness and airway inflammation in swimmers.

Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known.Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants.In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years.Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use.The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

BackgroundThe human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject.ObjectivePrevious studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo.MethodsThe skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.ResultsIn healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin.ConclusionThese results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens. The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters. In healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin. These results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens.

Background: The prevalence of allergic diseases has grown in Finland, similarly to many other western countries. Although the origin of allergy remains unresolved, increasing body of evidence indicates that the modern man living in urban built environment is deprived from environmental protective factors (e.g. soil microorganisms) that are fundamental for normal tolerance development. The current dogma of allergen avoidance has not proved effective in halting the ‘epidemic’, and it is the Finnish consensus that restoring and strengthening tolerance should more be in focus. Aim: The national 10‐year programme is aimed to reduce burden of allergies. The main goals are to (i) prevent the development of allergic symptoms; (ii) increase tolerance against allergens; (iii) improve the diagnostics; (iv) decrease work‐related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies and (vi) decrease costs caused by allergic diseases. Methods: For each goal, specific tasks, tools and evaluation methods are defined. Nationwide implementation acts through the network of local co‐ordinators (primary care physicians, nurses, pharmacists). In addition, three nongovernmental organizations (NGOs) take care of the programme implementation. The 21 central hospital districts carry out a three step educational process: (i) healthcare personnel; (ii) representatives and educators of NGOs and (iii) patients and the general population. For outcome evaluation, repeated surveys are performed and healthcare registers employed at the beginning, at 5 years, and at the end of the programme. The process will be evaluated by an independent external body. Conclusion: The Finnish initiative is a comprehensive plan to reduce burden of allergies. The aim is to increase immunological tolerance and change attitudes to support health instead of medicalizing common and mild allergy symptoms. It is time to act, when allergic individuals are becoming a majority of western populations and their numbers are in rapid increase worldwide. The Programme is associated with the Global Alliance of Chronic Respiratory Diseases (GARD), WHO.

Several recent reports have provided evidence that the burden of asthma may have levelled off, after increasing for decades. Implementation of the national and global asthma prevention and management guidelines that have led to earlier detection and improved treatment of asthmatics, is considered to be involved in this apparent change for the better. In addition, environmental influences associated with the modern life may have reached the maximum in inducing symptoms and disease in genetically susceptible individuals in some areas. Available data obtained from Canada and non‐English‐speaking countries in Europe show that the peak in asthma prevalence has been reached at the level of 8–12%. This review outlines the most recent literature on time trends in asthma prevalence and considers the possible causes of the current trends. Problems and pitfalls in appraising studies on time trends are also discussed.

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Heavy exercise is associated with an increased risk of upper respiratory tract infections. Strenuous exercise also causes gastrointestinal (GI) symptoms. In previous studies probiotics have reduced respiratory tract infections and GI symptoms in general populations including children, adults, and the elderly. These questions have not been studied in athletes before. The purpose of this study was to investigate the effect of probiotics on the number of healthy days, respiratory infections, and GI-symptom episodes in marathon runners in the summer. Marathon runners (N = 141) were recruited for a randomized, double-blind intervention study during which they received Lactobacillus rhamnosus GG (LGG) or placebo for a 3-mo training period. At the end of the training period the subjects took part in a marathon race, after which they were followed up for 2 wk. The mean number of healthy days was 79.0 in the LGG group and 73.4 in the placebo group (P = 0.82). There were no differences in the number of respiratory infections or GI-symptom episodes. The duration of GI-symptom episodes in the LGG group was 2.9 vs. 4.3 d in the placebo group during the training period (P = 0.35) and 1.0 vs. 2.3 d, respectively, during the 2 wk after the marathon (P = 0.046). LGG had no effect on the incidence of respiratory infections or GI-symptom episodes in marathon runners, but it seemed to shorten the duration of GI-symptom episodes.

Abstract Exhaled nitric oxide (FE NO ) was proposed as a marker of airway inflammation, but data about FE NO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FE NO in healthy children, we investigated a population‐based sample of school‐age children (n = 276) with a questionnaire, skin‐prick tests, spirometry, and the measurement of FE NO . The FE NO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FE NO , which on average showed an increase in the height range of 120–180 cm from 7 to 14 ppb. In the random sample of children, increased FE NO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9–21.1; P &lt; 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom‐free children with skin‐prick test positivity had significantly higher FE NO than healthy nonatopic subjects. We conclude that height is the best determinant of FE NO in healthy children. Due to the strong effect of atopy, FE NO data should not be interpreted without knowing the atopic status of the child. The present reference values of FE NO may serve in clinical assessments for measuring airway inflammation in children. Pediatr Pulmonol. 2006; 41: 635–642. © 2006 Wiley‐Liss, Inc.

Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case-control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, alpha1-antitrypsin (alpha1-AT), tumour necrosis factor-alpha (TNF-alpha), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (alpha1-AT, TNF-alpha, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal alpha1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases.

Allergies are caused by the immune reaction to commonly harmless proteins, allergens. This reaction is typified by immunoglobulin E (IgE) antibodies. We report the crystal structure of an IgE Fab fragment in complex with beta-lactoglobulin (BLG), one of the major allergens of bovine milk. The solved structure shows how two IgE/Fab molecules bind the dimeric BLG. The epitope of BLG consists of six different short fragments of the polypeptide chain, which are located especially in the beta strands, covering a flat area on the allergen surface. All six CDR (complementary-determining region) loops of the IgE Fab participate in the binding of BLG. The light chain CDR loops are responsible for the binding of the flat beta sheet region of BLG. The IgE epitope is different from common IgG epitopes that are normally located in the exposed loop regions of antigens and observed also in the two recently determined allergen-IgG complexes.

The traditional Mediterranean diet is claimed to possess antioxidant and immune-regulatory properties in several chronic diseases. Typical Mediterranean foods have recently been associated with improvement of symptoms of asthma and rhinitis in children. However the effect of adherence to Mediterranean diet on adult asthma outcomes is unknown. We aimed to investigate the association between adherence to Mediterranean diet and asthma control.Cross sectional study of 174 asthmatics, mean (SD) age of 40 (15) years. The patients were defined as controlled, in contrast to noncontrolled, if they showed FEV1 >or= 80% of predicted, exhaled nitric oxide (NO) <or=35 ppb, and Asthma Control Questionnaire score <1. Dietary intake was obtained by a food frequency questionnaire, and Mediterranean diet was assessed by alternate Mediterranean Diet (aMED) Score. Logistic regression models adjusting for confounders were performed to estimate the association between Mediterranean diet and asthma control.Controlled asthmatics (23%) had significantly higher aMED Score, intake of fresh fruit, and lower intake of ethanol compared to noncontrolled (77%). High adherence to Mediterranean diet reduced 78% the risk of noncontrolled asthma after adjusting for gender, age, education, inhaled corticosteroids and energy intake (OR = 0.22; 95% CI = 0.05-0.85; P-trend = 0.028). The higher intake of fresh fruit decreased the probability of having noncontrolled asthma (OR = 0.29; 95% CI = 0.10-0.83; P-trend = 0.015), while the higher intake of ethanol had the opposite effect (OR = 3.16; 95% CI = 1.10-9.11; P-trend = 0.035).High adherence to traditional Mediterranean diet increased the likelihood of asthma to be under control in adults. The study introduces a novel link between diet and asthma control, as measured by symptoms, lung function and exhaled NO.

The Finnish and Russian Karelia are adjacent areas in northern Europe, socio-economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non-existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti-inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10-year National Allergy Programme was started in 2008 to combat the epidemic in Finland.

Heavy exercise induces marked immunodepression, which is multifactorial in origin. Evidence showing clinical significance of this immunodepression is scarce.We assessed in a systematic manner whether physical activity or intensity of exercise increase susceptibility to upper respiratory tract infections (URTI). A literature search was performed using the keywords 'upper respiratory tract infections', 'athletes', 'exercise' and 'physical activity'. We considered all studies reporting of the effect of exercise, physical activity, sport and training on susceptibility to URTI. A total of 162 publications were identified and 30 studies were eligible (4 descriptive, 18 observational and 8 interventional). The 30 studies included 8595 athletes (5471 runners, 2803 swimmers) and 1798 non-athletes.Moderate activity may enhance immune function, whereas prolonged, high-intensity exercise temporarily impairs the immune competence. Athletes, when compared with lesser active individuals, experience higher rate of URTI after training and competitions. In non-athletes, increasing physical activity is associated with a decreased risk of URTI.The relationship between exercise and URTI is affected by poorly known individual determinants such as genetic factors, fitness, nutritional status or atopy. Elite athletes may have a decreased susceptibility to URTI.The dose-response relationship between immunodepression and risk for URTI during the weeks following heavy exercise. What are the clinically relevant methods to assess exercise-induced immunodepression? Is down-regulation of immunity after intense exercise a protective response to limit inflammation? Is there a role for nutritional or pharmaceutical interventions to reduce risk of URTI?

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.

Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

In 1995, the Global Initiative for Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that recommendations remain current. Although the report has been widely disseminated and influenced clinical practice and research, its major objective, of forming the basis for local and national initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes have been published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic settings.

Atopic allergy has been more common among schoolchildren in Finland, as compared to Russian Karelia. These adjacent regions show one of the most contrasting socio-economical differences in the world.We explored changes in allergy from school age to young adulthood from 2003 to 2010/2012 in these two areas. The skin and nasal microbiota were also compared.Randomly selected children from Finnish (n = 98) and Russian Karelia (n = 82) were examined in 2003, when the children were 7-11 years of age, and again in 2010 (Finnish Karelia) and 2012 (Russian Karelia). We analysed self-reported allergy symptoms and sensitization to common allergens by serum sIgE values. The skin (volar forearm) and nasal mucosa microbiota, collected in 2012 (aged 15-20 years), identified from DNA samples, were compared with multivariate methods.Asthma, hay fever, atopic eczema, self-reported rhinitis, as well as atopic sensitization, were threefold to 10-fold more common in Finland, as compared to Russian Karelia. Hay fever and peanut sensitization were almost non-existent in Russia. These patterns remained throughout the 10-year follow-up. Skin microbiota, as well as bacterial and fungal communities in nasal mucosa, was contrastingly different between the populations, best characterized by the diversity and abundance of genus Acinetobacter; more abundant and diverse in Russia. Overall, diversity was significantly higher among Russian subjects (Pskin < 0.0001, Pnasal-bacteria < 0.0001 and Pnasal-fungi < 0.01). Allergic diseases were not associated with microbial diversity in Finnish subjects.Differences in allergic phenotype, developed in early life, remain between populations. A parallel difference in the composition of skin and nasal microbiota suggests a potential underlying mechanism. Our results also suggest that high abundance and diversity of Acinetobacter might contribute to the low allergy prevalence in Russia. Implications of early-life exposure to Acinetobacter should be further investigated.

Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control.A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR.A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H1-antihistamines were studied.Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H1-antihistamines were found.This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.

Urban living in built environments, combined with the use of processed water and food, may not provide the microbial stimulation necessary for a balanced development of immune function. Many chronic inflammatory disorders, including allergic, autoimmune, metabolic, and even some behavioural disorders, are linked to alteration in the human commensal microbiota. Sedentary lifestyle is associated with reduced exposure to a broad spectrum of environmental micro-organisms and surplus energy balance, both risk factors of chronic inflammatory disorders. According to the Biodiversity Hypothesis, an environment with diverse macrobiota and microbiota modifies and enriches the human microbiota, which in turn is crucial in the development and maintenance of appropriate immune function. These issues were discussed in the symposium 'Chronic Inflammation, Lifestyle and Environment', held in Helsinki, 20-22 August 2014, under the sponsorship of the Yrjö Jahnsson Foundation. This paper briefly outlines the recent findings in the context of the environment, lifestyle, and health; discusses the forces that undermine immune tolerance in urban environments; and highlights the possibilities to restore broken immune tolerance among urban dwellers, summarizing the main messages in four statements and calling for actions to combat major public health threats.

Abstract Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen‐specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono‐ and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE‐mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re‐occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE‐mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe.

The composition of human microbiota is affected by a multitude of factors. Understanding the dynamics of our microbial communities is important for promoting human health because microbiota has a crucial role in the development of inflammatory diseases, such as allergies. We have studied the skin microbiota of both arms in 275 Finnish children of few months old to teenagers living in contrasting environments. We show that while age is a major factor affecting skin microbial composition, the living environment also discriminates the skin microbiota of rural and urban children. The effect of environment is age-specific; it is most prominent in toddlers but weaker for newborns and non-existent for teenagers. Within-individual variation is also related to age and environment. Surprisingly, variation between arms is smaller in rural subjects in all age groups, except in teenagers. We also collected serum samples from children for characterization of allergic sensitization and found a weak, but significant association between allergic sensitization and microbial composition. We suggest that physiological and behavioral changes, related to age and the amount of contact with environmental microbiota, jointly influence the dynamics of the skin microbiota, and explain why the association between the living environment skin microbiota is lost in teenager.

Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology.A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries.A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control).This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Abstract Background The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK ‐rhinitis ( MACVIA ‐ ARIA Sentinel NetworK for allergic rhinitis) App ( Allergy Diary ) assesses allergic rhinitis symptoms, disease control and impact on patients’ lives. It is freely available in 20 countries ( iOS and Android platforms). Aims To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. Methods The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1–2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. Results By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. Conclusions This is the first App ( iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

Abstract Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ ‐5D (EuroQuol) and WPAI ‐ AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality‐of‐life data ( EQ ‐5D visual analogue scale and WPA ‐ IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0‐2). Users with a score of 3 or 4 had a significant impairment in quality‐of‐life questionnaires.

AllergyVolume 71, Issue 11 p. 1513-1525 Review ArticleOpen Access Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010–2015 J. Bousquet, Corresponding Author J. Bousquet jean.bousquet@orange.fr University Hospital, Montpellier, France MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, France INSERM, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, UVSQ, Université Versailles St-Quentin-en-Yvelines, Paris, FranceThe first two authors contributed equally to the paper. Correspondence J Bousquet, CHRU Montpellier, 34295 Montpellier Cedex 5, France. Tel.: 33 4 67 41 67 00 E-mail: jean.bousquet@orange.frSearch for more papers by this authorJ. M. Anto, J. M. Anto Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainThe first two authors contributed equally to the paper.Search for more papers by this authorM. Akdis, M. Akdis Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorC. Auffray, C. Auffray European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorT. Keil, T. Keil Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin Berlin, Berlin, Germany Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, GermanySearch for more papers by this authorI. Momas, I. Momas Department of Public Health and Health Products, Paris Descartes University-Sorbonne Paris Cité, Paris, France Paris Municipal Department of Social Action, Childhood, and Health, Paris, FranceSearch for more papers by this authorD.S. Postma, D.S. Postma Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorR. Valenta, R. Valenta Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Wickman, M. Wickman Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorA. Cambon-Thomsen, A. Cambon-Thomsen UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorT. Haahtela, T. Haahtela Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorB. N. Lambrecht, B. N. Lambrecht VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorK. C. Lodrup Carlsen, K. C. Lodrup Carlsen Department of Paediatrics, Faculty of Medicine, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorG. H. Koppelman, G. H. Koppelman Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorJ. Sunyer, J. Sunyer Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorT. Zuberbier, T. Zuberbier Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Allergy-Centre-Charité at the Department of Dermatology, Charité–Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorI. Annesi-Maesano, I. Annesi-Maesano EPAR U707 INSERM, EPAR UMR-S UPMC, Paris VI, Paris, FranceSearch for more papers by this authorA. Arno, A. Arno Onmedic Networks, Barcelona, SpainSearch for more papers by this authorC. Bindslev-Jensen, C. Bindslev-Jensen Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorG. De Carlo, G. De Carlo EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, BelgiumSearch for more papers by this authorF. Forastiere, F. Forastiere Department of Epidemiology, Regional Health Service Lazio Region, Rome, ItalySearch for more papers by this authorJ. Heinrich, J. Heinrich Institute of Epidemiology I, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, GermanySearch for more papers by this authorM. L. Kowalski, M. L. Kowalski Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorD. Maier, D. Maier Biomax Informatics AG, Munich, GermanySearch for more papers by this authorE. Melén, E. Melén Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Stockholm County Council, Centre for Occupational and Environmental Medicine, Stockholm, SwedenSearch for more papers by this authorS. Palkonen, S. Palkonen EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, BelgiumSearch for more papers by this authorH. A. Smit, H. A. Smit Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the NetherlandsSearch for more papers by this authorM. Standl, M. Standl Institute of Epidemiology I, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, GermanySearch for more papers by this authorJ. Wright, J. Wright Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UKSearch for more papers by this authorA. Asarnoj, A. Asarnoj Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Astrid Lindgren Children's Hospital, Department of Pediatric Pulmonology and Allergy, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorM. Benet, M. Benet Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorN. Ballardini, N. Ballardini Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden St John's Institute of Dermatology, King's College London, London, UKSearch for more papers by this authorJ. Garcia-Aymerich, J. Garcia-Aymerich Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorU. Gehring, U. Gehring Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the NetherlandsSearch for more papers by this authorS. Guerra, S. Guerra Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorC. Hohman, C. Hohman Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin, Berlin, GermanySearch for more papers by this authorI. Kull, I. Kull Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorC. Lupinek, C. Lupinek Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Pinart, M. Pinart Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorI. Skrindo, I. Skrindo Department of Paediatrics, Faculty of Medicine, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorM. Westman, M. Westman Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorD. Smagghe, D. Smagghe Inserm Transfert, Paris, FranceSearch for more papers by this authorC. Akdis, C. Akdis Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorR. Albang, R. Albang Biomax Informatics AG, Munich, GermanySearch for more papers by this authorV. Anastasova, V. Anastasova UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorN. Anderson, N. Anderson Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorC. Bachert, C. Bachert ENT Department, Ghent University Hospital, Gent, BelgiumSearch for more papers by this authorS. Ballereau, S. Ballereau European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorF. Ballester, F. Ballester Environment and Health Area, Centre for Public Health Research (CSISP), CIBERESP, Department of Nursing, University of Valencia, Valencia, SpainSearch for more papers by this authorX. Basagana, X. Basagana Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorA. Bedbrook, A. Bedbrook MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, FranceSearch for more papers by this authorA. Bergstrom, A. Bergstrom Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorA. von Berg, A. von Berg Research Institute, Department of Pediatrics, Marien-Hospital, Wesel, GermanySearch for more papers by this authorB. Brunekreef, B. Brunekreef Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the NetherlandsSearch for more papers by this authorE. Burte, E. Burte INSERM, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, UVSQ, Université Versailles St-Quentin-en-Yvelines, Paris, FranceSearch for more papers by this authorK. H. Carlsen, K. H. Carlsen Department of Paediatrics, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorL. Chatzi, L. Chatzi Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, GreeceSearch for more papers by this authorJ. M. Coquet, J. M. Coquet VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorM. Curin, M. Curin Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorP. Demoly, P. Demoly Department of Respiratory Diseases, Montpellier University Hospital, FranceSearch for more papers by this authorE. Eller, E. Eller Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorM. P. Fantini, M. P. Fantini Department of Medicine and Public Health, Alma Mater Studiorum–University of Bologna, Bologna, ItalySearch for more papers by this authorB. Gerhard, B. Gerhard Biomax Informatics AG, Munich, GermanySearch for more papers by this authorH. Hammad, H. Hammad VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorL. von Hertzen, L. von Hertzen Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorV. Hovland, V. Hovland Department of Paediatrics, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorB. Jacquemin, B. Jacquemin Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorJ. Just, J. Just Allergology Department, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP), Sorbonne Universités, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, FranceSearch for more papers by this authorT. Keller, T. Keller Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin, Berlin, GermanySearch for more papers by this authorM. Kerkhof, M. Kerkhof Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorR. Kiss, R. Kiss Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Kogevinas, M. Kogevinas Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorS. Koletzko, S. Koletzko Division of Paediatric Gastroenterology and Hepatology, Ludwig Maximilians University of Munich, Munich, GermanySearch for more papers by this authorS. Lau, S. Lau Department for Pediatric Pneumology and Immunology, Charité Medical University, Berlin, GermanySearch for more papers by this authorI. Lehmann, I. Lehmann Department of Environmental Immunology/Core Facility Studies, Helmholtz Centre for Environmental Research, UFZ, Leipzig, GermanySearch for more papers by this authorN. Lemonnier, N. Lemonnier European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorR. McEachan, R. McEachan Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UKSearch for more papers by this authorM. Mäkelä, M. Mäkelä Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorJ. Mestres, J. Mestres Chemotargets SL and Chemogenomics Laboratory, GRIB Unit, IMIM-Hospital del Mar and University Pompeu Fabra, Barcelona, Catalonia, SpainSearch for more papers by this authorE. Minina, E. Minina Biomax Informatics AG, Munich, GermanySearch for more papers by this authorP. Mowinckel, P. Mowinckel Department of Paediatrics, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorR. Nadif, R. Nadif INSERM, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, UVSQ, Université Versailles St-Quentin-en-Yvelines, Paris, FranceSearch for more papers by this authorM. Nawijn, M. Nawijn Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorS. Oddie, S. Oddie Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UKSearch for more papers by this authorJ. Pellet, J. Pellet European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorI. Pin, I. Pin Département de Pédiatrie, CHU de Grenoble, Grenoble Cedex 9, FranceSearch for more papers by this authorD. Porta, D. Porta Department of Epidemiology, Regional Health Service Lazio Region, Rome, ItalySearch for more papers by this authorF. Rancière, F. Rancière Department of Public Health and Health Products, Paris Descartes University-Sorbonne Paris Cité, Paris, FranceSearch for more papers by this authorA. Rial-Sebbag, A. Rial-Sebbag UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorY. Saeys, Y. Saeys VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorM. J. Schuijs, M. J. Schuijs VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorV. Siroux, V. Siroux Inserm, U823, Grenoble, FranceSearch for more papers by this authorC. G. Tischer, C. G. Tischer Institute of Epidemiology I, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, GermanySearch for more papers by this authorM. Torrent, M. Torrent Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain ib-salut, Area de Salut de Menorca, SpainSearch for more papers by this authorR. Varraso, R. Varraso INSERM, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, UVSQ, Université Versailles St-Quentin-en-Yvelines, Paris, FranceSearch for more papers by this authorJ. De Vocht, J. De Vocht EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, BelgiumSearch for more papers by this authorK. Wenger, K. Wenger Biomax Informatics AG, Munich, GermanySearch for more papers by this authorS. Wieser, S. Wieser Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorC. Xu, C. Xu Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this author J. Bousquet, Corresponding Author J. Bousquet jean.bousquet@orange.fr University Hospital, Montpellier, France MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, France INSERM, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, UVSQ, Université Versailles St-Quentin-en-Yvelines, Paris, FranceThe first two authors contributed equally to the paper. Correspondence J Bousquet, CHRU Montpellier, 34295 Montpellier Cedex 5, France. Tel.: 33 4 67 41 67 00 E-mail: jean.bousquet@orange.frSearch for more papers by this authorJ. M. Anto, J. M. Anto Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainThe first two authors contributed equally to the paper.Search for more papers by this authorM. Akdis, M. Akdis Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorC. Auffray, C. Auffray European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorT. Keil, T. Keil Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin Berlin, Berlin, Germany Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, GermanySearch for more papers by this authorI. Momas, I. Momas Department of Public Health and Health Products, Paris Descartes University-Sorbonne Paris Cité, Paris, France Paris Municipal Department of Social Action, Childhood, and Health, Paris, FranceSearch for more papers by this authorD.S. Postma, D.S. Postma Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorR. Valenta, R. Valenta Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Wickman, M. Wickman Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorA. Cambon-Thomsen, A. Cambon-Thomsen UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorT. Haahtela, T. Haahtela Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorB. N. Lambrecht, B. N. Lambrecht VIB Inflammation Research Center, Ghent University, Ghent, BelgiumSearch for more papers by this authorK. C. Lodrup Carlsen, K. C. Lodrup Carlsen Department of Paediatrics, Faculty of Medicine, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorG. H. Koppelman, G. H. Koppelman Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsSearch for more papers by this authorJ. Sunyer, J. Sunyer Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorT. Zuberbier, T. Zuberbier Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Allergy-Centre-Charité at the Department of Dermatology, Charité–Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorI. Annesi-Maesano, I. Annesi-Maesano EPAR U707 INSERM, EPAR UMR-S UPMC, Paris VI, Paris, FranceSearch for more papers by this authorA. Arno, A. Arno Onmedic Networks, Barcelona, SpainSearch for more papers by this authorC. Bindslev-Jensen, C. Bindslev-Jensen Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorG. De Carlo, G. De Carlo EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, BelgiumSearch for more papers by this authorF. Forastiere, F. Forastiere Department of Epidemiology, Regional Health Service Lazio Region, Rome, ItalySearch for more papers by this authorJ. Heinrich, J. Heinrich Institute of Epidemiology I, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, GermanySearch for more papers by this authorM. L. Kowalski, M. L. Kowalski Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorD. Maier, D. Maier Biomax Informatics AG, Munich, GermanySearch for more papers by this authorE. Melén, E. Melén Department of Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Stockholm County Council, Centre for Occupational and Environmental Medicine, Stockholm, SwedenSearch for more papers by this authorS. Palkonen, S. Palkonen EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, BelgiumSearch for more papers by this authorH. A. Smit, H. A. Smit Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the NetherlandsSearch for more papers by this authorM. Standl, M. Standl Institute of Epidemiology I, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, GermanySearch for more papers by this authorJ. Wright, J. Wright Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UKSearch for more papers by this authorA. Asarnoj, A. Asarnoj Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Astrid Lindgren Children's Hospital, Department of Pediatric Pulmonology and Allergy, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorM. Benet, M. Benet Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorN. Ballardini, N. Ballardini Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden St John's Institute of Dermatology, King's College London, London, UKSearch for more papers by this authorJ. Garcia-Aymerich, J. Garcia-Aymerich Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorU. Gehring, U. Gehring Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the NetherlandsSearch for more papers by this authorS. Guerra, S. Guerra Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorC. Hohman, C. Hohman Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin, Berlin, GermanySearch for more papers by this authorI. Kull, I. Kull Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorC. Lupinek, C. Lupinek Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Pinart, M. Pinart Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorI. Skrindo, I. Skrindo Department of Paediatrics, Faculty of Medicine, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwaySearch for more papers by this authorM. Westman, M. Westman Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorD. Smagghe, D. Smagghe Inserm Transfert, Paris, FranceSearch for more papers by this authorC. Akdis, C. Akdis Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorR. Albang, R. Albang Biomax Informatics AG, Munich, GermanySearch for more papers by this authorV. Anastasova, V. Anastasova UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorN. Anderson, N. Anderson Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorC. Bachert, C. Bachert ENT Department, Ghent University Hospital, Gent, BelgiumSearch for more papers by this authorS. Ballereau, S. Ballereau European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, FranceSearch for more papers by this authorF. Ballester, F. Ballester Environment and Health Area, Centre for Public Health Research (CSISP), CIBERESP, Department of Nursing, University of Valencia, Valencia, SpainSearch for more papers by this authorX. Basagana, X. Basagana Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, SpainSearch for more papers by this authorA. Bedbrook, A. Bedbrook MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, FranceSearch for more papers by this authorA. Bergstrom, A. 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Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients.The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control.Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS.Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours.The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.

Summary Background Mobile technology may help to better understand the adherence to treatment. MASK ‐rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient‐centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods An observational cross‐sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio ( MPR ) and the Proportion of days covered ( PDC ) approach. Results A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty‐six (11.28%) users were adherent ( MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent ( MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non‐adherent to medications ( MPR &lt;70%). Of those, the largest group was non‐adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance Adherence to treatment is low. The relative efficacy of continuous vs on‐demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication‐taking behaviour in a real‐world setting.

Abstract Background Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary . Methods We undertook a 1‐year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels &lt;20/100 were categorized as “Low” burden and VAS levels ≥50/100 as “High” burden. Results Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis‐driven patterns were defined based on “Low” and “High” VAS levels. There were &lt;0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High—Asthma Low pattern. There were 1.7% days with a Rhinitis High—Asthma High—Conjunctivitis Low pattern. A novel Rhinitis High—Asthma High—Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. Conclusions In a novel approach examining daily symptoms with mobile technology, we found considerable intra‐individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

AllergyVolume 76, Issue 3 p. 689-697 EAACI POSITION PAPEROpen Access ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020) Jean Bousquet, Corresponding Author Jean Bousquet [email protected] Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany University Hospital Montpellier, Montpellier, France MACVIA-France, Montpellier, France Correspondence Jean Bousquet, CHU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Email: [email protected]Search for more papers by this authorMarek Jutel, Marek Jutel Department of Clinical Immunology, Wrocław Medical University and ALL-MED Medical Research Institute, Wroclaw, PolandSearch for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Akdis M. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorLudger Klimek, Ludger Klimek Center for Rhinology and Allergology, Wiesbaden, GermanySearch for more papers by this authorOliver Pfaar, Oliver Pfaar orcid.org/0000-0003-4374-9639 Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, Marburg, GermanySearch for more papers by this authorKari C. Nadeau, Kari C. Nadeau orcid.org/0000-0002-2146-2955 Stanford University School of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USASearch for more papers by this authorThomas Eiwegger, Thomas Eiwegger orcid.org/0000-0002-2914-7829 The Hospital for Sick Children, Department of Paediatrics, Division of Clinical Immunology and Allergy, Food allergy and Anaphylaxis Program, The University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorAnna Bedbrook, Anna Bedbrook MACVIA-France, Montpellier, FranceSearch for more papers by this authorIgnacio J. Ansotegui, Ignacio J. Ansotegui Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Erandio, SpainSearch for more papers by this authorJosep M. Anto, Josep M. Anto Centre for Research in Environmental Epidemiology (CREAL), ISGlobAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainSearch for more papers by this authorClaus Bachert, Claus Bachert orcid.org/0000-0003-4742-1665 Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorEric D. Bateman, Eric D. Bateman Department of Medicine, University of Cape Town, Cape Town, South AfricaSearch for more papers by this authorKazi S. Bennoor, Kazi S. Bennoor Department of Respiratory Medicine, National Institute of Diseases of the Chest and Hospital, Dhaka, BangladeshSearch for more papers by this authorElena Camelia Berghea, Elena Camelia Berghea Allergology and Clinical Immunology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Clinical Emergency Hospital for Children MS Curie, Bucharest, RomaniaSearch for more papers by this authorKarl-Christian Bergmann, Karl-Christian Bergmann orcid.org/0000-0002-0306-9922 Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorHubert Blain, Hubert Blain Department of Geriatrics, Montpellier University Hospital, Montpellier, France EA:2991, Euromov, University Montpellier, Montpellier, FranceSearch for more papers by this authorMateo Bonini, Mateo Bonini orcid.org/0000-0002-3042-0765 Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy National Heart and Lung Institute, Royal Brompton Hospital and Imperial College London, London, UKSearch for more papers by this authorSinthia Bosnic-Anticevich, Sinthia Bosnic-Anticevich Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, AustraliaSearch for more papers by this authorLouis-Philippe Boulet, Louis-Philippe Boulet orcid.org/0000-0003-3485-9393 Quebec Heart and Lung Institute, Laval University, Québec City, QC, CanadaSearch for more papers by this authorLuisa Brussino, Luisa Brussino Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino and Mauriziano Hospital, Torino, ItalySearch for more papers by this authorRoland Buhl, Roland Buhl Department of Pulmonary Medicine, Mainz University Hospital, Mainz, GermanySearch for more papers by this authorPaulo Camargos, Paulo Camargos Department of Pediatrics, Medical School, Federal University of Minas Gerais, Belo Horizonte, BrazilSearch for more papers by this authorGiorgio Walter Canonica, Giorgio Walter Canonica Personalized Medicine Asthma and Allergy Clinic-Humanitas University and Research Hospital, IRCCS-Milano, Milano, ItalySearch for more papers by this authorVictoria Cardona, Victoria Cardona orcid.org/0000-0003-2197-9767 Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron and ARADyAL research network, Barcelona, SpainSearch for more papers by this authorThomas Casale, Thomas Casale orcid.org/0000-0002-3149-7377 Division of Allergy/immunology, University of South Florida, Tampa, FL, USASearch for more papers by this authorSharon Chinthrajah, Sharon Chinthrajah Stanford University School of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USASearch for more papers by this authorMübeccel Akdis, Mübeccel Akdis orcid.org/0000-0003-0554-9943 Akdis M. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorTomas Chivato, Tomas Chivato School of Medicine, University CEU San Pablo, Madrid, SpainSearch for more papers by this authorGeorge Christoff, George Christoff Faculty of Public Health, Medical University - Sofia, Sofia, BulgariaSearch for more papers by this authorAlvaro A. Cruz, Alvaro A. Cruz orcid.org/0000-0002-7403-3871 Fundação ProAR, Federal University of Bahia and GARD/WHO Planning Group, Salvador, BrazilSearch for more papers by this authorWienczyslawa Czarlewski, Wienczyslawa Czarlewski Medical Consulting Czarlewski, Levallois, FranceSearch for more papers by this authorStefano Del Giacco, Stefano Del Giacco Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Cagliari, ItalySearch for more papers by this authorHui Du, Hui Du Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, Hubei, ChinaSearch for more papers by this authorYehia El-Gamal, Yehia El-Gamal Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University, Cairo, EgyptSearch for more papers by this authorWytske J. Fokkens, Wytske J. Fokkens orcid.org/0000-0003-4852-229X Department of Otorhinolaryngology, Academic Medical Centers, AMC, Amsterdam, The Netherlands EUFOREA, Brussels, BelgiumSearch for more papers by this authorJoao A. Fonseca, Joao A. Fonseca Center for Research in Health Technologies and Information Systems, CINTESIS, Universidade do Porto, Porto, Portugal Allergy Unit, Instituto CUF Porto e Hospital CUF Porto, Porto, Portugal Health Information and Decision Sciences Department - CIDES, Faculdade de Medicina, Universidade do Porto, Porto, Portugal Faculdade de Medicina da Universidade do Porto, Porto, PortugalSearch for more papers by this authorYadong Gao, Yadong Gao Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaSearch for more papers by this authorMina Gaga, Mina Gaga 7th Respiratory Medicine Department and Asthma Center, Athens Chest Hospital, Athens, GreeceSearch for more papers by this authorBilun Gemicioglu, Bilun Gemicioglu Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, TurkeySearch for more papers by this authorMaia Gotua, Maia Gotua orcid.org/0000-0003-2497-4128 Center of Allergy and Immunology, Georgian Association of Allergology and Clinical Immunology, Tbilisi, GeorgiaSearch for more papers by this authorTari Haahtela, Tari Haahtela orcid.org/0000-0003-4757-2156 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorDavid Halpin, David Halpin College of Medicine and Health, University of Exeter Medical School, University of Exeter, Exeter, UKSearch for more papers by this authorEckard Hamelmann, Eckard Hamelmann orcid.org/0000-0002-2996-8248 Klinik für Kinder- und Jugendmedizin, Kinderzentrum Bethel, Evangelisches Klinikum Bethel EvKB, University Bielefeld, Bielefeld, GermanySearch for more papers by this authorKarin Hoffmann-Sommergruber, Karin Hoffmann-Sommergruber Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorMarc Humbert, Marc Humbert Service de Pneumologie, Hôpital Bicêtrem, Inserm UMR_S999, Université Paris-Sud, Le Kremlin Bicêtre, FranceSearch for more papers by this authorNataliya Ilina, Nataliya Ilina National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, RussiaSearch for more papers by this authorJuan-Carlos Ivancevich, Juan-Carlos Ivancevich IServicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, ArgentinaSearch for more papers by this authorGuy Joos, Guy Joos Department of Respiratory Medicine, Ghent University Hospital, Ghent, BelgiumSearch for more papers by this authorMusa Khaitov, Musa Khaitov National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, RussiaSearch for more papers by this authorBruce Kirenga, Bruce Kirenga Makerere University Lung Institute, Kampala, UgandaSearch for more papers by this authorEdward F. Knol, Edward F. Knol Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this authorFanny W. Ko, Fanny W. Ko Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong KongSearch for more papers by this authorSeppo Koskinen, Seppo Koskinen Finnish Institute for Health and Welfare, Helsinki, FinlandSearch for more papers by this authorMarek L. Kowalski, Marek L. Kowalski Department of Immunology and Allergy, Healthy Ageing Research Center, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorHelga Kraxner, Helga Kraxner Department of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, Budapest, HungarySearch for more papers by this authorDmitry Kudlay, Dmitry Kudlay orcid.org/0000-0003-1878-4467 National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, RussiaSearch for more papers by this authorPiotr Kuna, Piotr Kuna Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorMaciej Kupczyk, Maciej Kupczyk Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorVioleta Kvedariene, Violeta Kvedariene Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania Clinic of Chest diseases and Allergology, Faculty of Medicine, Institute of Clinical medicine, Vilnius University, Vilnius, LithuaniaSearch for more papers by this authorAmir H. Abdul Latiff, Amir H. Abdul Latiff Allergy and Immunology Centre, Pantai Hospital, Kuala Lumpur, MalaysiaSearch for more papers by this authorLan T. Le, Lan T. Le University of Medicine and Pharmacy, Hochiminh City, VietnamSearch for more papers by this authorMichael Levin, Michael Levin orcid.org/0000-0003-2439-7981 Division Paediatric Allergology, University of Cape Town, Cape Town, South AfricaSearch for more papers by this authorDesiree Larenas-Linnemann, Desiree Larenas-Linnemann orcid.org/0000-0002-5713-5331 Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, MexicoSearch for more papers by this authorRenaud Louis, Renaud Louis Department of Pulmonary Medicine, CHU Sart-Tilman, and GIGA I3 Research Group, Liege, BelgiumSearch for more papers by this authorMohammad R. Masjedi, Mohammad R. Masjedi Tobacco Control Research Centre, Iranian Anti Tobacco Association, Tehran, IranSearch for more papers by this authorErik Melén, Erik Melén Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorFlorin Mihaltan, Florin Mihaltan National Institute of Pneumology M Nasta, Bucharest, RomaniaSearch for more papers by this authorBranislava Milenkovic, Branislava Milenkovic Clinic for Pulmonary Diseases, Clinical Center of Serbia, Faculty of Medicine, Serbian Association for Asthma and COPD, University of Belgrade, Belgrade, SerbiaSearch for more papers by this authorYousser Mohammad, Yousser Mohammad National Center for Research in Chronic Respiratory Diseases, Tishreen University School of Medicine, Latakia, Syria Syrian Private University-Damascus, Damas, SyriaSearch for more papers by this authorMario Morais-Almeida, Mario Morais-Almeida orcid.org/0000-0003-1837-2980 Allergy Center, CUF Descobertas Hospital, Lisbon, PortugalSearch for more papers by this authorJoaquim Mullol, Joaquim Mullol Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, SpainSearch for more papers by this authorLeyla Namazova, Leyla Namazova Scientific Centre of Children's Health Under the MoH, Moscow, Russia Russian National Research Medical University Named Pirogov, Moscow, RussiaSearch for more papers by this authorHugo Neffen, Hugo Neffen Director of Center of Allergy, Immunology and Respiratory Diseases, Santa Fe, Argentina Argentina Center for Allergy and Immunology, Santa Fe, ArgentinaSearch for more papers by this authorElisabete Nunes, Elisabete Nunes Serviço de Pneumologia Hospital Central and Faculdade de Medicina Dr Eduardo Mondelane, Maputo, MozambiqueSearch for more papers by this authorPaul O'Byrne, Paul O'Byrne Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, ON, CanadaSearch for more papers by this authorRobyn O'Hehir, Robyn O'Hehir Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, and Alfred Health, Melbourne, Vic., AustraliaSearch for more papers by this authorLiam O'Mahony, Liam O'Mahony Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, IrelandSearch for more papers by this authorKen Ohta, Ken Ohta orcid.org/0000-0001-9734-4579 National Hospital Organization, Tokyo National Hospital, Tokyo, JapanSearch for more papers by this authorYoshitaka Okamoto, Yoshitaka Okamoto Department of Otorhinolaryngology, Chiba University Hospital, Chiba, JapanSearch for more papers by this authorGabrielle L. Onorato, Gabrielle L. Onorato MACVIA-France, Montpellier, FranceSearch for more papers by this authorPetr Panzner, Petr Panzner Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech RepublicSearch for more papers by this authorNikos G. Papadopoulos, Nikos G. Papadopoulos orcid.org/0000-0002-4448-3468 Division of Infection, Immunity and Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UKSearch for more papers by this authorGianni Passalacqua, Gianni Passalacqua orcid.org/0000-0002-5139-3604 Allergy and Respiratory Diseases, Ospedale Policlino San Martino -University of Genoa, Genoa, ItalySearch for more papers by this authorVincenzo Patella, Vincenzo Patella orcid.org/0000-0001-5640-6446 Division of Allergy and Clinical Immunology, Department of Medicine, Agency of Health ASL Salerno, "Santa Maria della Speranza" Hospital, Salerno, ItalySearch for more papers by this authorRuby Pawankar, Ruby Pawankar Department of Pediatrics, Nippon Medical School, Tokyo, JapanSearch for more papers by this authorNhân Pham-Thi, Nhân Pham-Thi Ecole Polytechnique Palaiseau, IRBA (Institut de Recherche bio-Médicale des Armées),, Bretigny, FranceSearch for more papers by this authorBernard Pigearias, Bernard Pigearias Société de Pneumologie de Langue Française, Espace Francophone de Pneumologie, Paris, FranceSearch for more papers by this authorTodor A. Popov, Todor A. Popov University Hospital 'Sv Ivan Rilski'", Sofia, BulgariaSearch for more papers by this authorFrancesca Puggioni, Francesca Puggioni Personalized Medicine Asthma and Allergy Clinic-Humanitas University and Research Hospital, IRCCS-Milano, Milano, ItalySearch for more papers by this authorFrederico S. Regateiro, Frederico S. Regateiro Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal Faculty of Medicine, Institute of Immunology, University of Coimbra, Coimbra, Portugal Faculty of Medicine, ICBR - Coimbra Institute for Clinical and Biomedical Research, CIBB, University of Coimbra, Coimbra, PortugalSearch for more papers by this authorGiovanni Rolla, Giovanni Rolla Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino and Mauriziano Hospital, Torino, ItalySearch for more papers by this authorMenachem Rottem, Menachem Rottem Division of Allergy Asthma and Clinical Immunology, Emek Medical Center, Afula, Israel Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, IsraelSearch for more papers by this authorBoleslaw Samolinski, Boleslaw Samolinski Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Warsaw, PolandSearch for more papers by this authorJoaquin Sastre, Joaquin Sastre orcid.org/0000-0003-4689-6837 Faculty of Medicine, Fundacion Jimenez Diaz, CIBERES, Autonoma University of Madrid, Madrid, SpainSearch for more papers by this authorJurgen Schwarze, Jurgen Schwarze Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UKSearch for more papers by this authorAziz Sheikh, Aziz Sheikh The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UKSearch for more papers by this authorNicola Scichilone, Nicola Scichilone PROMISE Department, University of Palermo, Palermo, ItalySearch for more papers by this authorManuel Soto-Quiros, Manuel Soto-Quiros Department of Pediatrics, Hospital Nacional de Niños, San José, Costa RicaSearch for more papers by this authorManuel Soto-Martinez, Manuel Soto-Martinez Department of Pediatrics, Hospital Nacional de Niños, San José, Costa RicaSearch for more papers by this authorMilan Sova, Milan Sova Department of Respiratory Medicine, University Hospital Olomouc, Olomouc, Czech RepublicSearch for more papers by this authorStefania Nicola, Stefania Nicola Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino and Mauriziano Hospital, Torino, ItalySearch for more papers by this authorRafael Stelmach, Rafael Stelmach Pulmonary Division, Heart Institute (InCor), Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, BrazilSearch for more papers by this authorCharlotte Suppli-Ulrik, Charlotte Suppli-Ulrik Department of Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkSearch for more papers by this authorLuis Taborda-Barata, Luis Taborda-Barata Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal Department of Immunoallergology, Cova da Beira University Hospital Centre, Covilhã, PortugalSearch for more papers by this authorTeresa To, Teresa To The Hospital for Sick Children, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorPeter-Valentin Tomazic, Peter-Valentin Tomazic orcid.org/0000-0001-6445-4800 Department of General ORL, H&NS, Medical University of Graz, ENT-University Hospital Graz, Graz, AustriaSearch for more papers by this authorSanna Toppila-Salmi, Sanna Toppila-Salmi orcid.org/0000-0003-0890-6686 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorIoanna Tsiligianni, Ioanna Tsiligianni Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece International Primary Care Respiratory Group International Primary Care Respiratory Group, (IPCRG), Aberdeen, ScotlandSearch for more papers by this authorOmar Usmani, Omar Usmani Airways Disease Section, National Heart and Lung Institute (NHLI), Imperial College London and Royal Brompton Hospital, London, UKSearch for more papers by this authorArunas Valiulis, Arunas Valiulis Faculty of Medicine, Institute of Clinical Medicine and Institute of Health Sciences, Vilnius University, Vilnius, Lithuania European Academy of Paediatrics (EAP/UEMS-SP), Brussels, BelgiumSearch for more papers by this authorMaria Teresa Ventura, Maria Teresa Ventura Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, ItalySearch for more papers by this authorGiovanni Viegi, Giovanni Viegi Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Pisa, Italy CNR Institute for Biomedical Research and Innovation, Palermo, ItalySearch for more papers by this authorTheodor Vontetsianos, Theodor Vontetsianos Sotiria Hospital, Athens, GreeceSearch for more papers by this authorDe Yun Wang, De Yun Wang Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSearch for more papers by this authorSian Williams, Sian Williams International Primary Care Respiratory Group IPCRG, Aberdeen, ScotlandSearch for more papers by this authorGary W. K. Wong, Gary W. K. Wong orcid.org/0000-0001-5939-812X Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong KongSearch for more papers by this authorArzu Yorgancioglu, Arzu Yorgancioglu Department of Pulmonology, Celal Bayar University, Manisa, TurkeySearch for more papers by this authorMario Zernotti, Mario Zernotti Universidad Nacional de Villa Maria, Universidad Católica de Córdoba, Córdoba, ArgentinaSearch for more papers by this authorMihaela Zidarn, Mihaela Zidarn University Clinic of Respiratory and Allergic Diseases, Golnik, SloveniaSearch for more papers by this authorTorsten Zuberbier, Torsten Zuberbier orcid.org/0000-0002-1466-8875 Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorIoana Agache, Ioana Agache orcid.org/0000-0001-7994-364X Transylvania University Brasov, Brasov, RomaniaSearch for more papers by this author Jean Bousquet, Corresponding Author Jean Bousquet [email protected] Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany University Hospital Montpellier, Montpellier, France MACVIA-France, Montpellier, France Correspondence Jean Bousquet, CHU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Email: [email protected]Search for more papers by this authorMarek Jutel, Marek Jutel Department of Clinical Immunology, Wrocław Medical University and ALL-MED Medical Research Institute, Wroclaw, PolandSearch for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Akdis M. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandSearch for more papers by this authorLudger Klimek, Ludger Klimek Center for Rhinology and Allergology, Wiesbaden, GermanySearch for more papers by this authorOliver Pfaar, Oliver Pfaar orcid.org/0000-0003-4374-9639 Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, Marburg, GermanySearch for more papers by this authorKari C. Nadeau, Kari C. Nadeau orcid.org/0000-0002-2146-2955 Stanford University School of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USASearch for more papers by this authorThomas Eiwegger, Thomas Eiwegger orcid.org/0000-0002-2914-7829 The Hospital for Sick Children, Department of Paediatrics, Division of Clinical Immunology and Allergy, Food allergy and Anaphylaxis Program, The University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorAnna Bedbrook, Anna Bedbrook MACVIA-France, Montpellier, FranceSearch for more papers by this authorIgnacio J. Ansotegui, Ignacio J. Ansotegui Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Erandio, SpainSearch for more papers by this authorJosep M. Anto, Josep M. Anto Centre for Research in Environmental Epidemiology (CREAL), ISGlobAL, Barcelona, Spain IMIM (Hospital del Mar Research Institute), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainSearch for more papers by this authorClaus Bachert, Claus Bachert orcid.org/0000-0003-4742-1665 Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden Department of ENT Diseases, Karolinska University Hospital, Stockholm, SwedenSearch for more papers by this authorEric D. Bateman, Eric D. Bateman Department of Medicine, University of Cape Town, Cape Town, South AfricaSearch for more papers by this authorKazi S. Bennoor, Kazi S. Bennoor Department of Respiratory Medicine, National Institute of Diseases of the Chest and Hospital, Dhaka, BangladeshSearch for more papers by this authorElena Camelia Berghea, Elena Camelia Berghea Allergology and Clinical Immunology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Clinical Emergency Hospital for Children MS Curie, Bucharest, RomaniaSearch for more papers by this authorKarl-Christian Bergmann, Karl-Christian Bergmann orcid.org/0000-0002-0306-9922 Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorHubert Blain, Hubert Blain Department of Geriatrics, Montpellier University Hospital, Montpellier, France EA:2991, Euromov, University Montpellier, Montpellier, FranceSearch for more papers by this authorMateo Bonini, Mateo Bonini orcid.org/0000-0002-3042-0765 Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy National Heart and Lung Institute, Royal Brompton Hospital and Imperial College London, London, UKSearch for more papers by this authorSinthia Bosnic-Anticevich, Sinthia Bosnic-Anticevich Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, AustraliaSearch for more papers by this authorLouis-Philippe Boulet, Louis-Philippe Boulet orcid.org/0000-0003-3485-9393 Quebec Heart and Lung Institute, Laval University, Québec City, QC, CanadaSearch for more papers by this authorLuisa Brussino, Luisa Brussino Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino and Mauriziano Hospital, Torino, ItalySearch for more papers by this authorRoland Buhl, Roland Buhl Department of Pulmonary Medicine, Mainz University Hospital, Mainz, GermanySearch for more papers by this authorPaulo Camargos, Paulo Camargos Department of Pediatrics, Medical School, Federal University of Minas Gerais, Belo Horizonte, BrazilSearch for more papers by this authorGiorgio Walter Canonica, Giorgio Walter Canonica Personalized Medicine Asthma and Allergy Clinic-Humanitas University and Research Hospital, IRCCS-Milano, Milano, ItalySearch for more papers by this authorVictoria Cardona, Victoria Cardona orcid.org/0000-0003-2197-9767 Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron and ARADyAL research network, Barcelona, SpainSearch for more papers by this

Abstract Background Validated combined symptom‐medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real‐life data from the MASK‐air ® app to generate and validate hypothesis‐ and data‐driven CSMSs. Methods We used MASK‐air ® data to assess the concurrent validity, test‐retest reliability and responsiveness of one hypothesis‐driven CSMS (modified CSMS: mCSMS), one mixed hypothesis‐ and data‐driven score (mixed score), and several data‐driven CSMSs. The latter were generated with MASK‐air ® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK‐air ® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI‐AS]), (ii) quality‐of‐life (EQ‐5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). Results We assessed 317,176 days of MASK‐air ® use from 17,780 users aged 16‐90 years, in 25 countries. The mCSMS and the factor analyses‐based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate‐to‐strong correlations with the tested comparators, high test‐retest reliability and moderate‐to‐large responsiveness. Among data‐driven CSMSs, a better performance was observed for cluster analyses‐based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC‐ROC = 0.904) and for the mixed CSMS (AUC‐ROC = 0.820). Conclusion The mixed CSMS and the cluster‐based CSMSs presented medium‐high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

Planetary health provides a perspective of ecological interdependence that connects the health and vitality of individuals, communities, and Earth's natural systems. It includes the social, political, and economic ecosystems that influence both individuals and whole societies. In an era of interconnected grand challenges threatening health of all systems at all scales, planetary health provides a framework for cross-sectoral collaboration and unified systems approaches to solutions. The field of allergy is at the forefront of these efforts. Allergic conditions are a sentinel measure of environmental impact on human health in early life-illuminating how ecological changes affect immune development and predispose to a wider range of inflammatory noncommunicable diseases (NCDs). This shows how adverse macroscale ecology in the Anthropocene penetrates to the molecular level of personal and microscale ecology, including the microbial systems at the foundations of all ecosystems. It provides the basis for more integrated efforts to address widespread environmental degradation and adverse effects of maladaptive urbanization, food systems, lifestyle behaviors, and socioeconomic disadvantage. Nature-based solutions and efforts to improve nature-relatedness are crucial for restoring symbiosis, balance, and mutualism in every sense, recognizing that both personal lifestyle choices and collective structural actions are needed in tandem. Ultimately, meaningful ecological approaches will depend on placing greater emphasis on psychological and cultural dimensions such as mindfulness, values, and moral wisdom to ensure a sustainable and resilient future.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Plant species vary under different climatic conditions and the distribution of pollen in the air. Trends in pollen distribution can be used to assess the impact of climate change on public health. In 2015, the Mobile Airways Sentinel networK for rhinitis and asthma (MASK-air®) was launched as a project of the European Innovation Partnership on Active and Healthy Ageing (EIP-on-AHA, DG Santé and DG CONNECT). This project aimed to develop a warning system to inform patients about the onset of the pollen season, namely, the System for Integrated modeLling of Atmospheric coMposition (SILAM). A global-to-meso-scale dispersion model was developed by the Finnish Meteorological Institute (FMI). It provides quantitative information on atmospheric pollution of anthropogenic and natural origins, particularly on allergenic pollens. Impact of Air Pollution on Asthma and Rhinitis (POLLAR, EIT Health) has combined MASK-air clinical data with SILAM forecasts. A new Horizon Europe grant (Climate Action to Advance HeaLthY Societies in Europe [CATALYSE]; grant agreement number 101057131), which came into force in September 2022, aims to improve our understanding of climate change and help us find ways to counteractit. One objective of this project is to develop early warning systems and predictive models to improve the effectiveness of strategies for adapting to climate change. One of the warning systems is focused on allergic rhinitis (CATALYSE Task 3.2), with a collaboration between the FMI (Finland), Porto University (Portugal), MASK-air SAS (France), ISGlobal (Spain), Hertie School (Germany), and the University of Zurich (Switzerland). It is to be implemented with the support of the European Academy of Allergy and Clinical Immunology. This paper reports the planning of CATALYSE Task 3.2.

Climate change is not just jeopardizing the health of our planet but is also increasingly affecting our immune health. There is an expanding body of evidence that climate-related exposures such as air pollution, heat, wildfires, extreme weather events, and biodiversity loss significantly disrupt the functioning of the human immune system. These exposures manifest in a broad range of stimuli, including antigens, allergens, heat stress, pollutants, microbiota changes, and other toxic substances. Such exposures pose a direct and indirect threat to our body's primary line of defense, the epithelial barrier, affecting its physical integrity and functional efficacy. Furthermore, these climate-related environmental stressors can hyperstimulate the innate immune system and influence adaptive immunity-notably, in terms of developing and preserving immune tolerance. The loss or failure of immune tolerance can instigate a wide spectrum of noncommunicable diseases such as autoimmune conditions, allergy, respiratory illnesses, metabolic diseases, obesity, and others. As new evidence unfolds, there is a need for additional research in climate change and immunology that covers diverse environments in different global settings and uses modern biologic and epidemiologic tools.

Global warming and climate change have increased the pollen burden and the frequency and intensity of wildfires, sand and dust storms, thunderstorms, and heatwaves—with concomitant increases in air pollution, heat stress, and flooding. These environmental stressors alter the human exposome and trigger complex immune responses. In parallel, pollutants, allergens, and other environmental factors increase the risks of skin and mucosal barrier disruption and microbial dysbiosis, while a loss of biodiversity and reduced exposure to microbial diversity impairs tolerogenic immune development. The resulting immune dysregulation is contributing to an increase in immune-mediated diseases such as asthma and other allergic diseases, autoimmune diseases, and cancer. It is now abundantly clear that multisectoral, multidisciplinary, and transborder efforts based on Planetary Health and One Health approaches (which consider the dependence of human health on the environment and natural ecosystems) are urgently needed to adapt to and mitigate the effects of climate change. Key actions include reducing emissions and improving air quality (through reduced fossil fuel use), providing safe housing (e.g., improving weatherization), improving diets (i.e., quality and diversity) and agricultural practices, and increasing environmental biodiversity and green spaces. There is also a pressing need for collaborative, multidisciplinary research to better understand the pathophysiology of immune diseases in the context of climate change. New data science techniques, biomarkers, and economic models should be used to measure the impact of climate change on immune health and disease, to inform mitigation and adaptation efforts, and to evaluate their effectiveness. Justice, equity, diversity, and inclusion (JEDI) considerations should be integral to these efforts to address disparities in the impact of climate change.

New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen-specific immunotherapy (IT). However little is known about the kinetics of the changes in antibody reactivities.Twenty-four allergic children and adults were treated with birch pollen rush IT (RIT). Fifteen matched patients served as allergic controls. Sera were obtained at regular intervals for up to three years and analyzed with immunoblotting and Pharmacia CAP System with recombinant (r) birch pollen allergens (rBet v 1, rBet v 2, and rBet v 4).All birch-allergic patients had specific IgE to the major birch pollen allergen Bet v 1, but only three had IgE to rBet v 2 and/or rBet v 4 at the beginning of the study. New IgE sensitizations developed in 65% of the birch RIT-treated patients when studied by immunoblotting. Twenty-nine percent of the patients developed new sensitizations to rBet v 2 and/or rBet v 4 during RIT as measured by Pharmacia CAP System. Generally, new specific IgE reactivities occurred after at least one year of RIT, and only at low levels (< 1 kUA/l).Sensitization to additional allergenic pollen components frequently occurs during prolonged birch RIT. However, the IgE levels are low and the clinical relevance is not known.

Sensitivity to birch pollen allergens is a common feature among European patients with seasonal pollen allergy. In this in vitro study, we examined the specific serum IgE binding profiles to individual birch pollen allergens in birch-sensitive patients from six European populations.The study included 242 patients from Finland, Sweden, Austria, France, Switzerland and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their sera were analyzed for specific IgE reactivity to individual birch pollen allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen extract using Pharmacia CAP System and immunoblotting.Almost all Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%). Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65 and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were positive (27%). The immunoblot results supported the specific IgE profiles obtained with Pharmacia CAP System showing a broader IgE reactivity profile in patients from central and southern Europe as compared to northern Europe.Component-resolved allergy diagnosis with recombinant allergens reveals that the IgE reactivity profiles to individual birch pollen allergens vary between European populations. This observation may be explained by sensitization to different allergen sources and will have an impact on allergen-specific prevention and therapy strategies.

There is growing evidence to show that atopic diseases are more common in Western Europe than in the former socialist countries of Eastern Europe.The aim of this study was to assess whether a similar difference exists between the most eastern province of Finland and a neighboring western district of Russia.A random sample of 25- to 54-year-old subjects was taken from the population registers in the North Karelia Province in eastern Finland and from the Pitkäranta district across the border in the western part of Russia. Participants filled out a questionnaire on atopic and allergic symptoms and participated in a clinical study, which included skin prick tests with 11 airborne allergens and IgE measurements.Self-reported hay fever, allergic eye symptoms, atopic eczema, and asthma were much more common in Finland than in Russia. In Finland 34.2% and in Russia 21.8% had at least one positive skin prick test reaction. In Finland 21.5% but in Russia only 15.8% had at least one elevated allergen-specific IgE value of the 5 values measured. From 6% to 47% of the differences in self-reported symptoms between the countries were explained by atopy, as measured by means of skin prick testing or specific IgE values.A major difference in clinical allergic diseases and signs of symptoms was observed between the 2 geographically adjacent areas. This suggests that the difference in clinical allergy and atopic disposition is related to the differences in lifestyle and environmental factors.

In order to study the determinants of respiratory system impedance and bronchodilator response in preschool children, a sample (n = 109) of healthy children (age 2.1-7.0 years) attending kindergarten was measured by using the impulse oscillometry. Their selection was based on a standardized questionnaire, negative skin prick test results and clinical examination, and sufficient cooperation. Triple measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance frequency (Fr) and the frequency dependence of resistance (dRrs/df) were performed, to determine individual mean values. Measurements were repeated after inhalation of 300 microg salbutamol (n = 89) or placebo (n = 19). At the baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive correlations with age, height and weight. However, logarithmic transformed height was the best independent variable for the regression equations of all the oscillometric variables. After inhalation of placebo, none of the oscillometric variables changed significantly. In the salbutamol group, the mean (SD) change in Rrs5 was -0.187 (0.124) kPa l(-1) s(-1) and -19.2 (10.2)%, corresponding to a lower reference limit of -36.9%. Both the within-test and between-test repeatabilities for the measurement of respiratory resistance were acceptable, for Rrs5 the coefficients of variation being 6.2 and 6.1%, respectively. As the overall success rate in our sample was high (89%), the forced oscillation technique seems to be a useful method in assessing respiratory function and bronchial lability in preschool children.

To evaluate the 5-year prognosis of patients with stage I and stage II newly detected (< 3 months) pulmonary sarcoidosis treated immediately after diagnosis with prednisolone for 3 months followed by inhaled budesonide for 15 months.Randomized, double-blind, placebo-controlled, parallel-group study for 18 months. Thereafter, open follow-up without treatment.Twenty pulmonary medicine departments in Finland.One hundred eighty-nine adult patients, most of them with normal lung function, were randomized to treatment. One hundred forty-nine patients were followed up for 5 years: 79 patients with initial stage I disease and 70 patients with stage II disease.Oral prednisolone for 3 months followed by inhaled budesonide for 15 months (800 microg bid), or placebo tablets followed by placebo inhaler therapy. Thereafter, treatment only on an individual basis in the case of clinical deterioration.Yearly follow-up visits with chest radiographs, lung function tests (FEV(1), FVC), diffusion capacity of the lung for carbon monoxide (DLCO), serum angiotensin-converting enzyme (SACE), and serum and urinary calcium measurements.No initial differences were observed in chest radiographic findings between the active-treatment and placebo-treatment groups, either in patients with initial stage I or stage II(-III) disease. However, after the 5-year follow-up, 18 steroid-treated patients (26%) and 30 placebo-treated patients (38%) still had remaining chest radiographic changes. Placebo-treated patients more frequently required treatment with corticosteroids during the 5-year follow-up (p < 0.05). Steroid-treated patients with initial stage II(-III) disease improved more in FVC and DLCO (p < 0.05). No differences in reported adverse events or in SACE, serum calcium, or urinary calcium values were seen.Immediate treatment of pulmonary stage II(-III) sarcoidosis-but not stage I disease-improved the 5-year prognosis with regard to lung function variables.

Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed.The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma.Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers).Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P =.025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P =.023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P =.025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P =.0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P =.033 and P =.0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period (P =.17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P =.019).In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career.

Recent reports on time trends in atopic disease suggest that the prevalence of asthma and allergic rhinitis has levelled off in some European countries after several decades of increasing.1 2 We reported earlier that the prevalence of asthma in young Finnish men remained stable from 1926 to 1961 but started to rise steeply during the 1960s; a sixfold, virtually linear increase in asthma prevalence was found between 1966 and 1989, in parallel with increases in indicators of disabling asthma (on the basis of the percentage of men exempted from military service at call-up owing to asthma and of men discharged during service as a result of asthma).3 We examined whether similar trends have continued during the subsequent 13 years (1990-2003). As data on current trends in prevalence of allergic conditions are scarce, we also examined the trends in prevalence of allergic rhinitis and eczema from 1966 to 2003 among these young men. In Finland, about 98% of all men aged 18-19 are examined to establish their fitness for …

We have compared the inflammatory changes in the bronchial mucosa and the increase in the airway hyperresponsiveness in an asthmatic patient during the deterioration of symptoms. A striking increase in the number of bronchial epithelial eosinophils was associated with an increase in both airway hyperresponsiveness and asthma symptoms. During 16 wk of treatment with the inhaled corticosteroid, budesonide, the patient's clinical status and airway hyperresponsiveness improved. This was accompanied by an improvement in the ultrastructure of bronchial mucosa and a decrease in the number of epithelial eosinophils.

Summary Simple living conditions and farming environment have been associated with reduced risk for allergic diseases such as atopy and asthma but the factors responsible for this effect remain unresolved. We examined the bacterial composition of house dusts obtained from Finnish and Russian Karelia, two adjacent areas with high and low occurrence of atopic diseases respectively. Two dust mixes, both composed of 10 randomly selected dust samples from 349 Finnish and 417 Russian Karelian households were studied for bacterial biomarkers (DNA, Limulus‐active endotoxin, 3‐OH fatty acids, muramic acid) and for 16S rRNA gene sequences. Overall, the DNA cloning revealed more taxons (94 different genera) of dustborne bacteria than seen in any previous study on residential environments. Majority (67%) of the bacterial DNA clones in house dust from the low‐allergy Russian Kareliarepresented Gram‐positive bacteria ( Firmicutes and Actinobacteria ), predominantly Staphylococcaceae and Corynebacteriaceae. Russian Karelian dust showed up to 20‐fold higher contents of muramic acid (marker of Gram‐positive bacteria) and a sevenfold higher number of clones of animal‐associated species, whereas in Finnish Karelian dust Gram‐negatives (mainly Proteobacteria ) predominated. Clones of plant‐associated bacterial species and of chloroplast, indicating plant biomass, were more numerous in Finnish than in Russian Karelian dust. In conclusion, this study revealed major disparities between Finnish and Russian house dusts. The higher bacterial content and the predominance of Gram‐positive bacteria in Russian dust may have implications for occurrence of atopy.

BACKGROUND: Intensive endurance training has been associated with a high prevalence of symptoms compatible with asthma in elite athletes. It is not known, however, whether there is an association between the type of training for competitive events and the risk of asthma in highly trained athletes. METHODS: Two hundred and thirteen track and field athletes, mostly from Finnish national teams, and 124 controls of the same age completed a respiratory symptom questionnaire. Positive answers to physician diagnosed asthma were confirmed by personal interviews. The athletes were divided into two groups depending on whether they were speed and power athletes (n = 106) or long distance runners (n = 107). RESULTS: According to a logistic regression model the prevalence of physician diagnosed asthma was not associated with age, sex, or a family history of asthma. Long distance runners (OR 6.7; 95% CI 2.1 to 22.1) and speed and power athletes (OR 3.2; 95% CI 0.90 to 11.4) had a higher prevalence of physician diagnosed asthma than control subjects. Physician diagnosed asthma was found in 18 of 107 long distance runners (17%), in nine of 106 speed and power athletes (8%; p = 0.07 (chi 2 test)), and in four of 124 controls (3%; p &lt; 0.0004 (chi 2 test for trend)). CONCLUSIONS: The prevalence of physician diagnosed asthma is high in elite athletes and an association with the competitive event is suggested with long distance runners having a greater risk of developing asthma than speed and power athletes. This may be due to prolonged hyperventilation and increased exposure to inhalant allergens and irritants during endurance training and competition.

Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease. Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease. The current asthma and atopy epidemic in Western societies has raised a common concern and questions of factors involved. Although in some countries prevalence rates in atopic diseases appear to have leveled off,1Braun-Fahrländer C. Gassner M. Grize L. Takken-Sahli K. Neu U. Sticker T. et al.No further increase in asthma, hay fever and atopic sensitisaton in adolescents living in Switzerland.Eur Respir J. 2004; 23: 407-413Crossref PubMed Scopus (185) Google Scholar, 2Ronchetti R. Villa M.P. Barreto M. Rota R. Pagani J. Martella S. et al.Is the increase in childhood asthma coming to an end? Findings from three surveys of schoolchildren in Rome, Italy.Eur Respir J. 2001; 17: 881-886Crossref PubMed Scopus (164) Google Scholar, 3Verlato G. Corsico A. Villani S. Cerveri I. Migliore E. Accordini S. et al.Is the prevalence of adult asthma and allergic rhinitis still increasing? Results of an Italian study.J Allergy Clin Immunol. 2003; 111: 1232-1238Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 4Yura A. Shimizu T. Trends in the prevalence of atopic dermatitis in school children: longitudinal study in Osaka Prefecture, Japan, from 1985 to 1997.Br J Dermatol. 2001; 145: 966-973Crossref Scopus (65) Google Scholar trends are still on the increase in many other countries.5Bråbäck L. Hjern A. Rasmussen F. Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from farming and non-farming environments. A nationwide study over three decades.Clin Exp Allergy. 2004; 34: 38-43Crossref Scopus (133) Google Scholar, 6Latvala J. von Hertzen L. Lindholm H. Haahtela T. Trends in prevalence of asthma and allergy in Finnish young men: a nationwide study from 1966 to 2003.BMJ. 2005; 330: 1186-1187Crossref PubMed Scopus (93) Google Scholar Numerous studies have consistently shown that high asthma and atopy rates are associated with urbanization and Western lifestyle.7von Mutius E. The environmental predictors of allergic disease.J Allergy Clin Immunol. 2000; 105: 9-19Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar, 8von Hertzen L. Haahtela T. Asthma and atopy—the price of affluence?.Allergy. 2004; 59: 124-137Crossref PubMed Scopus (127) Google Scholar Accumulating data suggest that something that is necessary for the normal maturation of the immune system might be lacking in our affluence.9Ring J. Krämer U. Schäfer T. Behrendt H. Why are allergies increasing?.Curr Opin Immunol. 2001; 13: 701-708Crossref PubMed Scopus (204) Google Scholar Conversely, farm environment and a more traditional lifestyle in nonaffluent countries appear to confer protection against atopic disease.8von Hertzen L. Haahtela T. Asthma and atopy—the price of affluence?.Allergy. 2004; 59: 124-137Crossref PubMed Scopus (127) Google Scholar, 10von Mutius E. Influences in allergy: epidemiology and the environment.J Allergy Clin Immunol. 2004; 113: 373-379Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 11Björksten B. Dumitrascu D. Foucard T. Khetsuriani N. Khaitov R. Leja M. et al.Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe.Eur Respir J. 1998; 12: 432-437Crossref PubMed Scopus (176) Google Scholar Although the ultimate factors responsible for the asthma and atopy epidemic have remained unidentified, a common denominator for both living on a farm and in a nonaffluent environment is the heavy exposure to microorganisms in soil and vegetation. Most of the microorganisms we encounter do not cause any overt infection but are still recognized by the innate immune system. Microbes in this respect need not be alive because even nonviable microbial components interact with the innate immune system. Persistent and moderate environmental exposure to microbial components might play a decisive role in the normal maturation of the immune system in childhood.12Kabesch M. Lauener R.P. Why Old McDonald had a farm but no allergies: genes, environment, and the hygiene hypothesis.J Leukoc Biol. 2004; 75: 383-387Crossref PubMed Scopus (34) Google Scholar It has been proposed that certain microorganisms that have been present throughout the mammalian evolutionary history are recognized by the innate immune system as “no danger” signals and thus do not trigger inflammatory responses but instead have the ability to induce tolerance through rapid regulatory T (Treg) cell responses.13Rook G.A.W. Adams V. Hunt J. Palmer R. Martinelli R. Brunet L.R. Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.Springer Semin Immunopathol. 2004; 25: 237-255Crossref PubMed Scopus (160) Google Scholar These organisms include saprophytic mycobacteria, lactobacilli, and some intestinal parasites that are able to elicit Treg cell responses in vivo14Zuany-Amorim C. Manlius C. Trifilieff A. Brunet L.R. Rook G. Bowen G. et al.Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation.J Immunol. 2002; 169: 1492-1499PubMed Google Scholar, 15Adams V.C. Hunt J.R. Martinelli R. Palmer R. Rook G.A. Brunet L.R. Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice.Eur J Immunol. 2004; 34: 631-638Crossref Scopus (60) Google Scholar, 16van den Biggelaar A.H. van Ree R. Rodrigues L.C. Lell B. Deelder A.M. Kremsner P.G. et al.Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10.Lancet. 2000; 356: 1723-1727Abstract Full Text Full Text PDF PubMed Scopus (580) Google Scholar, 17Yazdanbakhsh M. Kremsner P. van Ree R. Allergy, parasites and the hygiene hypothesis.Science. 2002; 296: 490-494Crossref PubMed Scopus (1173) Google Scholar and in vitro.18Smits H. Engering A. van der Kleij D. de Jong E. Schipper K. van Capel T. et al.Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin.J Allergy Clin Immunol. 2005; 115: 1260-1267Abstract Full Text Full Text PDF PubMed Scopus (579) Google Scholar The list of such microbes will certainly grow in the next few years. The focus of the research in the context of the hygiene hypothesis has largely shifted from overt infections and the TH1/TH2 paradigm to noninfectious organisms, Treg cells, and Toll-like receptors (TLRs), as new data have been accumulated and the paradigm was found to be unable to unambiguously explain some important epidemiologic findings.19Smit J.J. Folkerts G. Nijkamp F.P. Mycobacteria, genes and the ‘hygiene hypothesis’.Curr Opin Allergy Clin Immunol. 2004; 4: 57-62Crossref PubMed Scopus (27) Google Scholar, 20Horner A.A. Redecke V. Raz E. Toll-like receptor ligands: hygiene, atopy and therapeutic implications.Curr Opin Allergy Clin Immunol. 2004; 4: 555-561Crossref Scopus (31) Google Scholar Indeed, diseases of immune dysregulation, including atopic diseases, are now considered to develop, more or less, as a result of failure in Treg cell function.13Rook G.A.W. Adams V. Hunt J. Palmer R. Martinelli R. Brunet L.R. Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.Springer Semin Immunopathol. 2004; 25: 237-255Crossref PubMed Scopus (160) Google Scholar Immune defense mechanisms that evolved during the long history of humankind in a hostile environment appear now to be less appropriate when living in a clean environment.21LeSouëf P. Goldblatt J. Lynch N. Evolutionary adaptation of inflammatory immune responses in human beings.Lancet. 2000; 356: 242-244Abstract Full Text Full Text PDF Google Scholar In this review we propose a hypothesis that one major factor in the current asthma and atopy epidemic might be the disconnection of man and the soil. There is abundant literature on adverse respiratory health effects attributable to exposure to environmental bioparticles (eg, bacteria, molds, and fugal spores).22Hauswirth D.W. Sundy J.S. Bioaerosols and innate immune responses in airway diseases.Curr Opin Allergy Clin Immunol. 2004; 4: 361-366Crossref Scopus (11) Google Scholar Paradoxically, data are now accumulating to suggest that exposure to microbes in soil and vegetation might be beneficial, even necessary, for the normal maturation of the immune system. Several lines of evidence indicate that settings associated with high-level exposure to microorganisms in soil are associated with reduced risk for asthma and atopy. Such settings include farm environments, environments in nonaffluent Eastern countries, and rural areas, particularly in developing countries. More than 30 studies from the last 6 years have consistently shown that children who have lived or are living on a farm are less likely to have atopic disease than their counterparts not living on a farm. The issue of farming and atopic disease has been thoroughly reviewed elsewhere and is not reiterated here.8von Hertzen L. Haahtela T. Asthma and atopy—the price of affluence?.Allergy. 2004; 59: 124-137Crossref PubMed Scopus (127) Google Scholar, 10von Mutius E. Influences in allergy: epidemiology and the environment.J Allergy Clin Immunol. 2004; 113: 373-379Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 23Braun-Fahrländer C. Environmental exposure to endotoxin and other microbial products and the decreased risk of childhood atopy: evaluating developments since April 2002.Curr Opin Allergy Clin Immunol. 2003; 3: 325-329Crossref PubMed Scopus (97) Google Scholar In many of these studies, the effect of parental farming on the development of atopic disease in the child has been found to be dose dependent,24Braun-Fahrländer C. Gassner M. Grize L. Neu U. Sennhauser F.H. Varonier H.S. et al.Prevalence of hay fever and allergic sensitization in farmers' children and their peers living in the same rural community.Clin Exp Allergy. 1999; 29: 28-34Crossref PubMed Scopus (579) Google Scholar, 25von Ehrenstein O. von Mutius E. Illi S. Bauman L. Böhm O. von Kries R. Reduced risk of hay fever and asthma among children of farmers.Clin Exp Allergy. 2000; 30: 187-193Crossref PubMed Scopus (584) Google Scholar, 26Riedler J. Braun-Fahrländer C. Eder W. Schreuer M. Waser M. Maisch S. et al.Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey.Lancet. 2001; 358: 1129-1133Abstract Full Text Full Text PDF PubMed Scopus (1181) Google Scholar and many of these studies have also revealed “frequent contacts with farm animals” as one of the major factors responsible for this effect.25von Ehrenstein O. von Mutius E. Illi S. Bauman L. Böhm O. von Kries R. Reduced risk of hay fever and asthma among children of farmers.Clin Exp Allergy. 2000; 30: 187-193Crossref PubMed Scopus (584) Google Scholar, 27Waser M. von Mutius E. Riedler J. Nowak D. Maisch S. Carr D. et al.Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children.Allergy. 2005; 60: 177-184Crossref PubMed Scopus (85) Google Scholar, 28Remes S. Iivanainen K. Koskela H. Pekkanen J. Which factors explain the lower prevalence of atopy amongst farmers' children?.Clin Exp Allergy. 2003; 33: 427-434Crossref PubMed Scopus (90) Google Scholar However, frequent contacts with farm animals can also be a surrogate marker for exposure to microorganisms in soil and vegetation because farm animals (and pets) are likely to serve as a secondary source of exposure to such microorganisms. In addition, frequent contacts with farm animals could also reflect general activity of the child on the farm. The effect of farming on conferring protection against asthma and atopy might not be restricted to early life only because current parental farming has been found to be an even stronger protective factor than that in early life.28Remes S. Iivanainen K. Koskela H. Pekkanen J. Which factors explain the lower prevalence of atopy amongst farmers' children?.Clin Exp Allergy. 2003; 33: 427-434Crossref PubMed Scopus (90) Google Scholar Frequent compost and waste handling, wood handling, and animal excreta and manure handling are examples of high-level microbial exposure22Hauswirth D.W. Sundy J.S. Bioaerosols and innate immune responses in airway diseases.Curr Opin Allergy Clin Immunol. 2004; 4: 361-366Crossref Scopus (11) Google Scholar associated with a traditional lifestyle. Unchlorinated surface water from lakes and rivers might be used as domestic water, untreated waste water might be used for irrigation, and animal excreta might be used as manure. Traditional lifestyle might also be associated with a microbe-rich diet (eg, frequent use of fermented vegetables).20Horner A.A. Redecke V. Raz E. Toll-like receptor ligands: hygiene, atopy and therapeutic implications.Curr Opin Allergy Clin Immunol. 2004; 4: 555-561Crossref Scopus (31) Google Scholar We found recently that occurrences of atopy (determined by means of skin prick tests) and atopic diseases were substantially lower among schoolchildren and their mothers in Russian Karelia compared with that seen in their counterparts in North Karelia, Finland, irrespective of the geographic proximity of the areas and similar geoclimatic and vegetative conditions (see Fig E1 in the Online Repository at www.jacionline.org). Analysis of generational differences revealed that in Finland children had higher atopy rates than their mothers, whereas in Russia the opposite trend, children having lower atopy rates than their mothers, emerged. No signs of westernization, with atopy prevalence as a proxy, were yet discernible in Russian Karelia, which was part of the Soviet Union until 1991.29von Hertzen L. Mäkelä M.J. Petäys T. Jousilahti P. Kosunen T.U. Laatikainen T. et al.Growing disparities in atopy between the Finns and the Russians—a comparison of two generations.J Allergy Clin Immunol. 2006; 117: 151-157Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar The results are in line with those reported earlier from other Eastern countries in transition crisis.11Björksten B. Dumitrascu D. Foucard T. Khetsuriani N. Khaitov R. Leja M. et al.Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe.Eur Respir J. 1998; 12: 432-437Crossref PubMed Scopus (176) Google Scholar The East-West gradient in light of the occurrence of atopic diseases has been thoroughly reviewed.8von Hertzen L. Haahtela T. Asthma and atopy—the price of affluence?.Allergy. 2004; 59: 124-137Crossref PubMed Scopus (127) Google Scholar Data both from Western and particularly from developing countries, in which great differences in lifestyle still exist between urban and rural areas, have shown that living in rural areas might confer protection against atopic disease, even in a dose-dependent manner.30Viinanen A. Munhbayarlah S. Zevgee T. Narantsetseg L. Naidansuren T. Koskenvuo M. et al.Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitisation in Mongolia.Allergy. 2005; 60: 1370-1377Crossref Scopus (64) Google Scholar, 31Yemaneberahn H. Bekele Z. Venn A. Lewis S. Parry E. Britton J. Prevalence of wheeze and asthma and relation to atopy in urban and rural Ethiopia.Lancet. 1997; 350: 85-90Abstract Full Text Full Text PDF Scopus (314) Google Scholar, 32Perzanowski M. Ng'ang'a L. Carter M. Odhiambo J. Ngari P. 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Allergic disease in teenagers in relation to urban or rural residence at various stages of childhood.Allergy. 1999; 54: 716-721Crossref PubMed Scopus (53) Google Scholar A recent study in Mongolia that compared the occurrence of atopy and allergic disorders in 3 different environments of various degree of urbanization—a city area, rural towns, and villages—found significant increasing trends in the prevalence of allergic rhinitis and atopy, as determined by using skin prick tests, with increasing degree of urbanization.30Viinanen A. Munhbayarlah S. Zevgee T. Narantsetseg L. Naidansuren T. Koskenvuo M. et al.Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitisation in Mongolia.Allergy. 2005; 60: 1370-1377Crossref Scopus (64) Google Scholar Analysis of the effect of relocation revealed that continuous living in a village since birth was most protective against atopy and allergic rhinitis, whereas those who relocated from villages to towns in adolescence or adulthood acquired allergic conditions at rates approaching those found in subjects who had always lived in towns.35Viinanen A. Occurrence and risk factors of asthma, allergic rhinoconjunctivitis and allergic sensitisation in rural and urban Mongolia [thesis]. Turku (Finland): University of Turku; 2004. Annales Universitatis Turkuensis D/604.Google Scholar The results are in line with those of other migrant studies showing that sensitizaton rates and profiles among immigrants shift along with time, resembling finally those in natives,36Kalyoncu A.F. Stålenheim G. Serum IgE levels and allergic spectra in immigrants to Sweden.Allergy. 1992; 47: 277-280Crossref PubMed Scopus (48) Google Scholar, 37Grüber C. Illi S. Plieth A. Sommerfeld C. Wahn U. Cultural adaptation is associated with atopy and wheezing among children of Turkish origin living in Germany.Clin Exp Allergy. 2002; 32: 526-531Crossref Scopus (50) Google Scholar thus supporting the view that there might not be any strictly limited window period in early life during which the individual is susceptible to immunomodulatory effects of the environment; rather, susceptibility to immunomodulation probably continues to adolescence, even to adulthood.38Matricardi P.M. Yazdanbakhsh M. Mycobacteria and atopy, 6 years later: a fascinating, still unfinished, business.Clin Exp Allergy. 2003; 33: 717-720Crossref Scopus (27) Google Scholar, 39Kemp A. Björksten B. Immune deviation and the hygiene hypothesis: a review of the epidemiological evidence.Pediatr Allergy Immunol. 2003; 14: 74-80Crossref Scopus (85) Google Scholar, 40Linneberg A. Hypothesis: urbanization and the allergy epidemic—a reverse case of immuno-therapy.Allergy. 2005; 60: 538-539Crossref Scopus (10) Google Scholar However, it must be borne in mind that disparities between asthma and atopic conditions in this respect might exist.10von Mutius E. Influences in allergy: epidemiology and the environment.J Allergy Clin Immunol. 2004; 113: 373-379Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar Before urbanization, humans have lived in close contact with soil, either directly or indirectly through food, water, and air,41Santamaria J. Toranzos G.A. Enteric pathogens and soil: a short review.Int Microbiol. 2003; 6: 5-9Google Scholar and heavy exposure to environmental microorganisms has occurred through inhalation, ingestion, and skin contact.20Horner A.A. Redecke V. Raz E. Toll-like receptor ligands: hygiene, atopy and therapeutic implications.Curr Opin Allergy Clin Immunol. 2004; 4: 555-561Crossref Scopus (31) Google Scholar Inhalation of bioaerosols (composed of microbes and their components, such as products of plants and fecal material from animals) has been considered to represent the major route of exposure.22Hauswirth D.W. Sundy J.S. Bioaerosols and innate immune responses in airway diseases.Curr Opin Allergy Clin Immunol. 2004; 4: 361-366Crossref Scopus (11) Google Scholar This natural exposure to microbes, particularly in soil, has been dramatically reduced along with urbanization characterized by living in environments covered with asphalt and concrete. There are no unambiguous and commonly accepted criteria for urbanization. Many of the suggested criteria are based on population density and are not relevant for sparsely populated countries, such as Finland. We performed time-series analyses of occurrence of atopic diseases and urbanization using the asphalt index (use of asphalt, tons per inhabitant per year, years 1960-1990; The Road Administration, the Ministry of Traffic and Communication, and The Finnish Asphalt Association. Census statistics; Statistics Finland; http://statfin.stat.fi) and the decreasing proportion of farmers among the population (years 1966-2000, Statistics Finland; http://statfin.stat.fi) as indicators of urbanization here because both are closely related to reduced contacts with soil. Prevalences of asthma and allergic rhinitis were based on our recent data on occurrence of atopic disease among military conscripts.6Latvala J. von Hertzen L. Lindholm H. Haahtela T. Trends in prevalence of asthma and allergy in Finnish young men: a nationwide study from 1966 to 2003.BMJ. 2005; 330: 1186-1187Crossref PubMed Scopus (93) Google Scholar The database here covered the years 1966 through 2000 and comprised more than 1 million military conscripts aged 18 to 19 years. The men had been examined to establish their fitness for service at the call up. Similar diagnostic codes for asthma and allergic rhinitis have been used throughout the study period on the basis of ICD-8 and ICD-9 in 1966 through 1996 and ICD-10 in 1997 through 2000. We found that the use of asphalt, which in Finland started at the end of the 1950s and was very modest still in the early 1960s (The Road Administration and The Finnish Asphalt Association, unpublished data), increased 10-fold in 3 decades. A nearly similar increase was also found in asthma prevalence among military conscripts, from 0.3% in 1966 to 2.6% in 1995 during a 30-year period, and the trend was upward for the whole study period (Fig 1, A).6Latvala J. von Hertzen L. Lindholm H. Haahtela T. Trends in prevalence of asthma and allergy in Finnish young men: a nationwide study from 1966 to 2003.BMJ. 2005; 330: 1186-1187Crossref PubMed Scopus (93) Google Scholar Along with urbanization, heavy structural changes have occurred in agriculture and forestry. In Finland, the proportion of farmers among the population has decreased from 17.3% in 1970 to 4.9% in 2000. During the same time, the occurrence of allergic rhinitis, as assessed among young Finnish men, increased almost exponentially, from 0.1% in 1966 to 8.9% in 2000 (Fig 1, B).6Latvala J. von Hertzen L. Lindholm H. Haahtela T. Trends in prevalence of asthma and allergy in Finnish young men: a nationwide study from 1966 to 2003.BMJ. 2005; 330: 1186-1187Crossref PubMed Scopus (93) Google Scholar The proportion of population that is continuously in natural connection with soil has thus diminished since the 1960s and will evidently still diminish, whereas the opposite has occurred for the prevalence of allergic rhinitis. Urbanization can also be characterized by living in apartment houses, which is, similarly to the use of asphalt and decrease in farming occupation, likely to reduce contact with soil. Dwelling type has indeed been shown to affect the magnitude of exposure to microorganisms in the environment. A study among 81 randomly selected teachers showed that both personal exposure to microorganisms (assessed with transportable inhalable aerosol samplers) and microbial concentrations in their homes were higher among persons living in family (single) houses compared with those in apartment houses, and this was considered partly to be due to increased outdoor activities among those living in family houses.42Toivola M. Personal exposure to microbial aerosols [thesis]. Kuopio (Finland): University of Kuopio; 2004. Publications of the National Public Health Institute A13/2004.Google Scholar A sedentary lifestyle with little outdoor activity might not only be involved in the association between asthma and obesity43Brisbon N. Plumb J. Brawer R. Paxman D. The asthma and obesity epidemics: the role played by the built environment—a public health perspective.J Allergy Clin Immunol. 2005; 115: 1024-1028Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar but can also increase the risk of atopy through reduced exposure to saprophytes in the environment. Although exposure to pathogens has been found to be inversely associated with atopic diseases44Bach J.F. The effect of infections on susceptibility to autoimmune and allergic diseases.N Engl J Med. 2002; 347: 911-920Crossref PubMed Scopus (2003) Google Scholar and undoubtedly is able to exert immunomodulatory effects in early life, infectious agents might represent only a minimal part of our total exposure to microorganisms. The largely neglected group of saprophytes in the environment might play a decisive role, in addition to gut microbiota,45Rakoff-Nahoum S. Paglino J. Eslami-Varzaneh F. Edberg S. Medzhitov R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis.Cell. 2004; 118: 229-241Abstract Full Text Full Text PDF PubMed Scopus (3193) Google Scholar in the development and maintenance of immunologic homeostasis. An important issue closely related to soil is the runoff of soil microorganisms into natural waters46Lindström E.S. Bergström A.K. Community composition of bacterioplankton and cell transport in lakes in two different drainage areas.Aquat Sci. 2005; 67: 210-219Crossref Scopus (38) Google Scholar and the use of such waters as drinking water. We found that in Russian Karelia, where atopy and atopic diseases are uncommon,29von Hertzen L. Mäkelä M.J. Petäys T. Jousilahti P. Kosunen T.U. Laatikainen T. et al.Growing disparities in atopy between the Finns and the Russians—a comparison of two generations.J Allergy Clin Immunol. 2006; 117: 151-157Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar surface water bodies, lakes and rivers, are used as domestic water, frequently without any chemical or other treatment. Previous data have shown that consumption of unpasteurized milk in early life is associated with reduced risk of asthma and atopy in later life independently from other determinants.26Riedler J. Braun-Fahrländer C. Eder W. Schreuer M. Waser M. Maisch S. et al.Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey.Lancet. 2001; 358: 1129-1133Abstract Full Text Full Text PDF PubMed Scopus (1181) Google Scholar It is reasonable to assume that consumption of untreated surface water could have similar effects and could be involved in the low atopy prevalence in Russian Karelia. Indeed, this view is supported by recent data from Ethiopia showing that consumption of river water in rural areas, as contrasted with consumption of pipe water in urban areas, conferred protection against atopic eczema.47Haileamlak A. Dagoye D. Williams H. Venn A.J. Hubbard R. Britton J. Early life risk factors for atopic dermatitis in Ethiopian children.J Allergy Clin Immunol. 2005; 115: 370-376Abstract Full Text Full Text PDF Scopus (61) Google Scholar In another study among schoolchildren in a rural area of Latin America, consumption of river water was found to be weakly protective against atopy.48Cooper P.J. Chico M.E. Rodriguest L.C. Strachan D.P. Anderson H.R. Rodrigues E.A. et al.Risk factors for atopy among school children in a rural area of Latin America.Clin Exp Allergy. 2004; 34: 845-852Crossref PubMed Scopus (59) Google Scholar Soil is considered the most complicated biomaterial and at the same time the most diverse and important ecosystem on the planet.49Young I.M. 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The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma.Subjects with persistent allergic asthma (aged 12.7¡3.4yrs; n534) were randomly allocated into training and control groups.Exercise consisted of twice-weekly 50-min sessions for 12 weeks.Inflammation was assessed by levels of exhaled nitric oxide, blood eosinophils, eosinophil cationic protein, C-reactive protein, and total and mite-specific immunoglobulin (Ig)E.Lung volumes and bronchial responsiveness to methacholine were determined.The Paediatric Asthma Quality of Life Questionnaire and Paediatric Asthma Caregiver's Quality of Life Questionnaire were used to evaluate activity restrictions, symptoms and emotional stress.The efficacy of the training was assessed by accelerometry.Following the programme, the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities.No differences in changes were seen between groups for asthma outcomes.However, total IgE decreased more in the exercise group, as did mite-specific IgE.Training did not increase inflammation in children with persistent asthma, and may have decreased both total and allergen-specific immunoglobulin E levels.It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise.

Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.

We aimed to assess the prevalence of allergic sensitization and multiple sensitization, risk factors, and the clinical impact of being sensitized in the adult population of Helsinki, Finland.As a part of the FinEsS study, a population-based random sample of 498 adults aged 26-60 years were tested for 15 common aeroallergens with skin prick tests (SPTs) and interviewed on respiratory symptoms and diseases, including respiratory irritants and childhood environment.The prevalence of at least one positive prick test was 46.9%. A large difference by age was found: 56.8% were sensitized among those aged 26-39 years, 49.2% in the age group 40-49 years, and 35.6% in the age group 50-60 years (P<0.001). Sensitization to multiple allergens was common among young subjects with 42% of the sensitized responding to at least four allergens, while this proportion was only 16% of the sensitized among those aged 50-60 years. The prevalence of physician-diagnosed asthma, allergic rhinitis (AR) or conjunctivitis, and wheeze increased significantly with increasing number of positive responses to SPTs. Having a family history of AR or conjunctivitis was a significant risk factor for allergic sensitization and for sensitization to any of the pollens. Further, urban living in childhood yielded an increased risk for pollen sensitization.The prevalence of allergic sensitization was high in the urban adult population of Helsinki. More than half of those aged 26-39 years was sensitized and 24% was sensitized to at least four allergens. Sensitization to multiple allergens was associated with a high prevalence of asthma, AR or conjunctivitis, and wheeze.

The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment.The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria.Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+).Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta2-agonists.

The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample (n = 360) of children (age 2.1-11.1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90-160 cm) are presented.

We studied the prevalence of allergic disorders in an unselected group of 708 adolescents aged 15–17 years. All subjects were physically examined and interviewed by the authors. The prevalence of past or present asthma was 5.7% in boys and 3.1% in girls. The figures for hay fever were H% and 8%, and for atopic dermatitis (including allergic urticaria) 25% and 30%, respectively. In 24% of all symptomatic subjects, the condition had not been active during the year preceding the study. The sex difference in the prevalence of hay fever was significant. It is associated with higher immediate skin test reactivity in boys. A progressive increase in the frequency of allergic disorders was observed with increasing number of positive skin reactions in both boys and girls. Respiratory allergy was closely related to a positive skin test: 87% of the asthmatics and 83% of all those with allergic rhinitis exhibited at least one positive skin reaction. For atopic dermatitis the association was less pronounced. Nineteen per cent of the population studied had a positive symptom history and a positive skin test to pollens, animal epithelia or dusts indicating a clinically significant relationship. However, 39% of the 346 subjects with a positive skin test, including some with a large number of positive reactions, were completely asymptomatic.

Asthma is a highly prevalent condition across Europe and numerous guidelines have been developed to optimise management. However, asthma can be neither cured nor prevented, treatment choices are limited and many patients have poorly controlled or uncontrolled asthma. The Brussels Declaration on Asthma, sponsored by The Asthma, Allergy and Inflammation Research Charity, was developed to call attention to the shortfalls in asthma management and to urge European policy makers to recognise that asthma is a public health problem that should be a political priority. The Declaration urges recognition and action on the following points: the systemic inflammatory component of asthma should be better understood and considered in assessments of treatment efficacy; current research must be communicated and responded to quickly; the European Medicines Agency guidance note on asthma should be updated; "real world" studies should be funded and results used to inform guidelines; variations in care across Europe should be addressed; people with asthma should participate in their own care; the impact of environmental factors should be understood; and targets should be set for improvement. The present paper reviews the evidence supporting the need for change in asthma management and summarises the ten key points contained in the Brussels Declaration.

This consensus document is aimed at reviewing evidence that the rhinits‐asthma links have peculiar features in athletes. Beside a review of epidemological data on the high prevalence of rhinitis and asthma in athletes, the effects on intense physical exercise on the immune system and repiratory functions are discussed, with special reference to the role of allergens and pollutants. In extending the Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations to athletes, the issue is addressed of adapting diagnosis and management to criteria set by the International Olympic Committee (IOC) and regulations adopted by the World Anti‐Doping Agency (WADA).

Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA 2 LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle Allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan‐European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA 2 LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project‐related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA 2 LEN are reported in this paper.