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Background: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important., Objective: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma., Methods: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment., Results: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years., Conclusion: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Aim: Uncontrolled asthma is a global health challenge with substantial impact on quality of life (QoL) and overall healthcare costs. Unrecognised and/or unmanaged comorbidities often contribute to presence of uncontrolled asthma. Abnormalities in breathing pattern are termed dysfunctional breathing and are not only common in asthma but also lead to asthma-like symptoms and reduced QoL, and, in keeping with this, improvement with breathing normalisation. Evidence-based guidelines recommend breathing retraining interventions as an adjuvant treatment in uncontrolled asthma. Physiotherapy-based breathing pattern modification interventions incorporating relaxation have been shown to improve asthma-related QoL in primary care patients with impaired asthma control. Despite anecdotal reports, effectiveness of breathing retraining in patients referred to secondary care with incomplete asthma control has not been formally assessed in a randomised controlled trial (RCT). We aim to investigate the effect of breathing exercises on asthma-related QoL in patients with incomplete asthma control despite specialist care., Methods and Analysis: This two-armed assessor-blinded multicentre RCT will investigate the effect of physiotherapist-delivered breathing retraining on asthma QoL questionnaire (MiniAQLQ) in addition to usual specialist care, recruiting from seven outpatient departments and one specialised clinic representing all regions of Denmark during 2017-2019. We will include 190 consenting adults with incomplete asthma control, defined as Asthma Control Questionnaire 6-item score ≥0.8. Participants will randomly be allocated to either breathing exercise programme in addition to usual care (BrEX +UC) or UC alone. BrEX compiles three physiotherapy sessions and encouragement to perform home exercise daily. Both groups continue usual secondary care management. Primary outcome is between-group difference in MiniAQLQ at 6 months. Secondary outcomes include patient-reported outcome measures, spirometry and accelerometer., Ethics and Dissemination: Ethics Committee, Region Zealand (SJ-552) and Danish Data Protection Agency (REG-55-2016) approved the trial. Results will be reported in peer-reviewed scientific journals., Trial Registration Number: NCT03127059; Pre-results., Competing Interests: Competing interests: STS is an associate editor of the Journal of Orthopaedic & Sports Physical Therapy, has received grants from The Lundbeck Foundation, personal fees from Munksgaard, all of which are outside the submitted work. He is co-founder of GLA:D®, a not-for profit initiative hosted at University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Viral infection and allergy have been identified as major risk factors for exacerbation in asthma, especially in the presence of both. However, whether patients with allergic asthma are more susceptible to respiratory infections requiring antibiotics remains unknown., Objective: To investigate allergy as a risk factor for respiratory infections requiring antibiotics based on register data from a nationwide population of patients with asthma., Methods: A register-based prospective follow-up study was performed using the Danish prescription database. In the inclusion period from 2010 through 2011, we identified patients with allergic asthma 18 to 44 years old. Patients were investigated during the follow-up period from 2012 through 2013, depending on their prescription drug use of antiallergic medication and antibiotics. Odds ratios were adjusted for age, sex, asthma severity, education, and urban vs rural residence., Results: In a nationwide population we identified 60,415 patients with asthma. Based on prescriptions fillings for antiallergic medication, patients were subdivided into (1) nonallergic asthma (n = 35,334, 51.5%) and (2) allergic asthma (n = 25,081, 48.5%). Allergic asthma was associated with an increased risk of filling at least 2 antibiotic prescriptions per year compared with nonallergic asthma (odds ratio 1.28, 95% confidence interval 1.24-1.33, P < .0001). Interestingly, a subgroup analysis showed a protective effect of immunotherapy against the risk of requiring antibiotics (odds ratio 0.76, 95% confidence interval 0.66-0.87, P = .0001)., Conclusion: Patients with allergic asthma have an increased risk of being prescribed antibiotics for respiratory infections compared with those with nonallergic asthma. Treatment with allergen immunotherapy appears to have a protective effect against this risk., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.

Background: Asthma-onset in older individuals has been associated with an accelerated decline in lung function, but direct comparisons with younger adults have not been reported., Methods: In a random population sample comprising 4983 individuals from the Copenhagen City Heart Study without asthma at baseline, we compared young (<35 years), middle-aged (35-64 years) and older (>64 years) adults with newly diagnosed asthma during a 10-year follow-up., Results: The proportion of cases with newly diagnosed asthma during follow-up was similar across age groups (Older adults: 7% (84/1168), middle-aged adults: 7% (223/3147), and young adults: 6% (42/668) (p = ns)). In all three age groups, lung function was reduced at baseline in subjects who were subsequently diagnosed with asthma, but most pronounced in those >35 years. (Mean FEV1%: Young 90.2% (±13.9), middle-aged 80.8% (±20.8), and older adults 80.8% (±24.2), p < 0.001). Furthermore, incident asthma was associated with an accelerated decline in lung function in older adults (young adults 11.0 mL/year, middle-aged adults 18.2 mL/year, and older adults 30.8 mL/year). These differences were independent of FEV1 at baseline and smoking status, and were not explained by undiagnosed asthma in older adults, as the frequency of respiratory symptoms, including wheeze, was similar in all three age groups at baseline., Conclusions: Asthma was diagnosed as frequently in older as in younger adults. Preexisting symptoms were equally common, but lung function was more reduced pre-diagnosis, and declined more rapidly in older adults. This emphasizes the need for a high level of therapeutic attention in patients with asthma diagnosed late in life., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry., Methods: To accomplish this, two unselected populations of Inuit were recruited, one living in Greenland (n = 618) and the other in Denmark (n = 739). Subjects were genotyped for CD14 C-159T, SCGB1A1 A38G, ADRB2 Arg16Gly and Gln27Glu. The resulting genetic data were analysed for relationships with asthma-related parameters including lung function, ever asthma, atopy, rhinitis and dermatitis., Results: The results showed contrasting magnitude and direction of genetic associations between the two geographically separate Inuit populations. In Greenland, the ADRB2 16Arg allele was associated with male-specific lower lung function, but in Denmark the same allele was associated with male-specific higher lung function. This allele was also associated with higher incidence of ever asthma in Denmark but not in Greenland. The SCGB1A1 38A allele was associated with lower rhinitis prevalence in Greenland but not in Denmark., Conclusions: These associations suggest that environment interacts with candidate asthma genes to modulate asthma pathogenesis in the Inuit.

Background: Early prevention of COPD and immediate consultation about tobacco cessation is a major issue in respiratory medicine., Aim: To evaluate if a community-based walk-in lung function service, either in a clinic or a shopping mall, could result in early detection of COPD. Early detection would facilitate prevention., Materials and Methods: In an area with 1.5 mill inhabitants, a walk-in lung function service opened in 2005/06 once a month for 3 hours at a clinic and on two full days in a mall. The staff consisted of two respiratory nurses and one chest physician. The nurses informed all participants about their lung function level and all received a preventive talk about tobacco consumption. Those with signs of COPD spoke with the doctor immediately., Results: A total of 1169 subjects, 59% women, with a mean (SD) age of 60 years (15), visited the walk-in services, 602 (52%) of whom visited the walk-in service at the clinic. Among the participants, 826 (71%) were smokers (n=452) or former smokers (n=374). The mean tobacco consumption was 32 (18) packs a year. We found that more current smokers visited the walk-in service at the clinic (45% versus 33%), whereas more ex-smokers visited the lung function service at the mall (38% versus 25%) (p < 0.01). The mean tobacco consumption was 32 (18) packs a year, with a difference between those visiting the mall and the clinic (32 (20) versus 23 (16), p<0.05). Among smokers, 54% had normal lung function, 15% had signs of airway obstruction, whereas 31% had developed moderate to severe COPD., Conclusion: Despite free medical access, more that one thirds had signs of airway obstruction. As all were informed about tobacco cessation, a walk-in service in a clinic and not a supermarket is most cost effective.

In recent decades, there has been a worldwide increase in the prevalence of atopic diseases. The aim of this study was to investigate whether there has been a change in the prevalence of rhinitis among children in Denmark from 1986 to 2001. We compared data from two random population-based samples of Danish children, aged 7-17 yr, who were examined in 1986 (n = 527) and 2001 (n = 480) using similar designs. Symptoms of rhinitis, skin test reactivity, and bronchial responsiveness to inhaled histamine were assessed. The prevalence of rhinitis increased from 11.8% in 1986 to 23.3% in 2001 (p < 0.001). The increase was most pronounced among subjects who suffered from non-allergic rhinitis (p < 0.001), and among subjects with severe symptoms (p < 0.001). The prevalence of asymptomatic positive skin prick test (SPT) decreased substantially (p < 0.001). A history of asthma and parental atopic disease were strong predictors of non-allergic rhinitis, whereas a history of asthma, parental atopic disease, bronchial hyperresponsiveness, eczema, and age at examination were statistically significant predictors of allergic rhinitis. The prevalence of non-allergic rhinitis among Danish children has increased substantially from 1986 to 2001. Furthermore, in general more severe symptoms of rhinitis were observed in 2001 compared with 1986. These results underline the importance of using objective measurements such as skin test reactivity when estimating time trends in the prevalence of allergic airways disease, as clinical interviews alone can be misleading.

Background: A novel IL4RA polymorphism, Ala57Thr, was identified in Greenlander Inuit., Objective: We sought to determine whether the novel Thr57 allele is population specific and to assess the associations of Ala57Thr and Ile50Val with atopy in 2 Inuit populations., Methods: Ala57Thr and Ile50Val were genotyped in 651 Inuit living in Denmark, 1295 Inuit living in Greenland, and 1329 individuals from 7 populations from widely differing global locations. In Inuit the polymorphisms were evaluated for associations with atopy, rhinitis, asthma, and pulmonary function., Results: Thr57 was in linkage disequilibrium with Ile50 (D' = 1, r(2) = 0.13) and was common (33%) in the Inuit but rare (<0.6%) in all other populations. In Inuit living in Denmark, the Thr57 allele (in a dose-dependent manner) and the Ile50/Thr57 haplotype were associated with lower risk of atopy (P(linear) = .003 and P = .034, respectively), with similar trends observed for atopic rhinitis and atopic asthma. In Inuit living in Greenland, Thr57 was not associated with atopy or atopic diseases, but Ile50 was weakly associated with lower risk of atopy., Conclusion: The novel IL4RA Ala57Thr was common in and population specific to Greenlander Inuit, with Thr57 associated with a lower risk of atopy in those living in Denmark. Hence a full investigation of genotype-phenotype relationships in a given population can only be achieved if each gene is screened for novel polymorphisms in that population., Clinical Implications: Clinical risk attributable to variations in a gene in an ethnic group requires that all variations of the gene are known for that group.

A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin test reactivity to 10 common aeroallergens was measured using standard techniques. Atopic disease was defined as a history of hayfever and/or asthma concomitantly with a positive skin-prick test. Logistic regression showed that parental atopy (odds ratio [OR] = 1.98; 95% confidence interval [CI], 1.12, 3.49; p = 0.019) and wheezy bronchitis before the age of 2 years (OR = 3.13; 95% CI, 1.63, 6.01; p < 0.001) were predictors of atopic disease, the latter especially when predisposition to atopy was present (OR = 8.63; 95% CI, 3.64, 20.44; p < 0.001). Duration of breast-feeding was longer in subjects with atopic heredity (p = 0.017), whereas smoking exposure during pregnancy (p = 0.019) and in the 1st year of life (p = 0.018) was less prevalent. Wheezy bronchitis was equally frequent among subjects with and without atopic predisposition (p = 0.893). Wheezy bronchitis before the age of 2 years seems to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits.

Background: Knowledge of secular trends in the prevalence of allergy among children stems in large part from questionnaire surveys, whereas repeated cross-sectional studies using objective markers of atopic sensitization are sparse., Objectives: To investigate whether the prevalence of skin prick test (SPT) positivity in Danish children has changed from 1986 to 2001., Methods: Serial cross-sectional studies of two different random population samples of children aged 7 to 17 years of age, living in urban Copenhagen, Denmark, were performed 15 years apart. The first cohort was investigated in 1986 (n = 527) and the second in 2001 (n = 480). Skin test reactivity to nine common aeroallergens was measured at both occasions., Results: The prevalence of positive SPT to at least one allergen decreased from 24.1% in 1986 to 18.9% in 2001, (p = 0.05). We found a declining prevalence of sensitization to most allergens tested, statistically significant; however, only for mugwort and Alternaria iridis. Among subjects, who were sensitized to only one allergen, we found significantly fewer individuals with reactions to D. pteronyssinus and mugwort., Conclusions: The prevalence of atopic sensitization as judged by SPT positivity has decreased or remained unchanged among Danish children during the 15-year period from 1986 to 2001. The increase in prevalence of allergic disease often reported in comparable studies using questionnaires as sole diagnostic criterion could not be reproduced in this study where objective markers of allergic sensitization were included in the design.

Background: Studies of the clinical outcome in adulthood of asymptomatic airway hyperresponsiveness (AHR) to histamine or exercise-induced bronchospasm (EIB) detected in childhood in general population samples are sparse and have produced conflicting results., Objective: To describe the outcome of asymptomatic AHR to histamine and EIB., Methods: Data from a 12-year follow-up study of a random population sample of individuals aged 7 to 17 years at enrollment were analyzed; only individuals without asthma at enrollment were included in the analysis. AHR to inhaled histamine, EIB, lung function, and sensitization to aeroallergens were measured., Results: Among the 281 nonasthmatic participants studied, 58 (22%) had AHR to histamine, 33 (12%) had EIB, and 82 (29%) had AHR to histamine and/or EIB. At follow-up, 37.9% of individuals with AHR to histamine and 30% of individuals with EIB had developed current asthma, compared with only 5% of individuals in whom these test results were negative. In patients with AHR to histamine, parental asthma (odds ratio [OR], 12.6; 95% confidence interval [CI], 1.5-108.5), furred pets ownership (OR, 6.0; 95% CI, 1.2-19.6), and dermatitis and/or rhinitis in childhood (OR, 2.2; 95% CI, 1.1-5.1) predicted the subsequent development of asthma, whereas no risk factors for the development of asthma could be identified in individuals with EIB CONCLUSION: Asymptomatic AHR to histamine and EIB in childhood predict the subsequent development of asthma in adulthood. A genetic disposition to asthma, furred pets ownership, and concomitant rhinitis or dermatitis increase the risk of asthma development in individuals with AHR to histamine.

The gene for Clara cell 16-kDa (CC16) protein is a promising candidate for asthma susceptibility. The CC16 38A allele has been associated with decreased CC16 plasma levels and increased incidence of asthma in Australian children. To date these results have not been replicated in adults. Therefore, potential links between CC16 A38G, asthma and atopy were investigated in an unselected population of young adult Danes. Four hundred sixty-four Danes, aged 19-29 years, from Copenhagen participated in an asthma and allergy phenotype-genotype study. Genotyping was done by Sau96I restriction digestion of PCR products spanning the A38G polymorphism. Potential A38G genotype and asthma-related phenotype associations were investigated using regression analysis, adjusting for potential confounders where appropriate. Adults with the 38AA genotype had higher odds of current asthma (OR 3.2, P=0.013) and ever asthma (OR 2.2, P=0.045) compared with those with the 38GG genotype. Adjusting for atopy had minimal effect on this relationship. A positive linear trend was evident between the 38A allele and atopic dermatitis (OR 1.67, P=0.02). No associations were found between the A38G polymorphism and rhinitis, atopy, forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), airway responsiveness (AR) to histamine or peripheral blood eosinophil level (PBEL). An atopy-independent association between CC16 38AA and asthma prevalence was identified, suggesting the CC16 38A allele predisposes to adult asthma independent of Th1/Th2 processes. This finding is consistent with previous studies in children, but is the first reported association between CC16 A38G and asthma in adults. CC16 38A also displayed a positive linear trend with atopic dermatitis.

Background: Knowledge of respiratory diseases in an arctic population with increasingly westernized lifestyles provides the opportunity to obtain new information in this field., Objective: To investigate the influence of environment and lifestyle on the presence of respiratory symptoms in a genetically homogenous population sample living under widely differing conditions., Methods: Greenland is a part of Denmark, but its climate is mainly arctic, as opposed to the temperate climate of southern Denmark. A random sample of Inuits who had immigrated to Denmark and Inuits from 3 towns and 4 remote settlements in Greenland were studied. Of the 6,695 invited Inuits, 4,162 (62%) completed a questionnaire concerning respiratory symptoms and risk factors., Results: Of the 4,162 Inuits, 847 (20%) had respiratory symptoms. Bronchitis was more frequent in the areas of Greenland than in Denmark (26% and 20% vs 13%; P < .001), whereas the pattern of asthma was contradictory (6% and 9% vs 10%; P = .057). Bronchitis was associated with living area (P = .01), tobacco consumption (P < .001), and asthma (P = .001), whereas asthma was related to living area (P = .03), hay fever (P < .001), low intake of whale (P = .04), years in Denmark (P = .09), and bronchitis (P < .001)., Conclusions: Inuits' prevalence of bronchitis and asthma differed, with a higher frequency of bronchitis and a lower frequency of asthma in Inuits living in Greenland compared with Denmark. Living conditions or areas, diet, tobacco use, climate, and atopy are important for the presence of symptoms.

The aim of this study was to estimate the prevalence of allergic sensitization and possible risk factors in a genetically homogenous Inuit population living under widely differing climatic and cultural conditions. A written questionnaire and skin prick test for 10 aeroallergens were obtained from 1119 adult Greenlanders residing in Denmark, Nuuk (main city in Southern Greenland) and Uummannaq (rural settlement in Northern Greenland). Allergen exposure was assessed by pollen counts, questions on pet keeping and counts of house dust mites in dust samples. The overall prevalence of at least one positive skin prick test was 22.8% in Denmark, 10.6% in Nuuk, and 6.4% in Uummannaq. In Denmark, the total birch pollen counts were 40-1000 times higher compared to Nuuk, whereas the grass pollen count was 13-30 times higher in Denmark compared to Nuuk. Dogs were held indoor with a similar frequency in Denmark and Nuuk, but much less frequently in Uummannaq. In Denmark, house dust mites were found in 72% of house holds (>10/0.1 g dust). Less than 15% of households in Greenland had measurable levels of house dust mites. The prevalence of sensitization to aeroallergens in Inuit Greenlanders differed significantly between Denmark, Nuuk and Uummannaq. These findings correlated with the observed differences in population allergen exposure in the three regions. Furthermore, differences in lifestyle factors such as educational level, stress and ethnic self-identification seemed to be associated with the risk of allergic sensitization in Greenland.

Background: The prevalence of asthma appears to be increasing, but our knowledge about factors associated with asthma in young adults is limited. Factors associated with asthma were studied in 624 (66% of those invited) young Danish adults (aged 19 to 29 years)., Objective: The purpose of this study was to investigate the prevalence and predictors of asthma in young Danish adults., Methods: Case history, including respiratory symptoms, smoking habits, education, and employment, was obtained by interview, and a questionnaire and was used to evaluate the presence or absence of asthma. Pulmonary function, beta2-reversibility, airway responsiveness to histamine, and blood eosinophil count were measured using standard techniques., Results: The lifetime prevalence of asthma in these young Danish adults was 17%, and the prevalence of current asthma was 9%. The proportion of current smokers was disturbingly high, 41%, and, further, the proportion of current smokers was significantly higher among those with asthma than among those without asthma (52% and 38%, respectively; P < 0.01). Asthma was significantly associated with current smoking, with lower than predicted forced expiratory volume in 1 second, with lower than predicted ratio of forced expiratory volume in 1 second/forced vital capacity, atopy, higher eosinophil count, and higher degree of airway responsiveness to histamine. The proportion of subjects with no education after junior high school was higher among those with asthma than among those without asthma (P < 0.05). Further, 16 of the 103 (16%) people with asthma had work-related worsening of their respiratory symptoms., Conclusions: The presence of current asthma was predicted by current smoking, lower level of lung function, less education, higher blood eosinophil count, and more pronounced airway responsiveness. Further, the proportion of current smokers was higher among asthmatic subjects than among nonasthmatic subjects. Greater efforts must be made to encourage young people with asthma not to smoke.

Background: The prevalence of atopic diseases is increasing in western countries, and environmental exposures in childhood may influence development of atopic sensitization., Objective: To investigate the prevalence and predictors of atopy among young Danish adults., Methods: Of 940 invited subjects, aged 19-29 years, complete data were obtained from 525 (56%) subjects. All completed a questionnaire concerning asthma, rhinitis, preschool nursery care, smoking habits, family size, education and employment. A skin prick test was performed, and pulmonary function was measured using standard techniques. Atopy was defined as a positive skin prick test., Results: The frequency of atopy was 32% (males 43% vs. females 23%, P < 0.001). We found a positive association between atopy and atopic dermatitis (P < 0.05), rhinitis (P < 0.001), itching when eating nuts (P < 0.001) and current asthma (P < 0.001). There was an inverse relation between atopy and having furred pets in childhood (P < 0.05), passive smoking in childhood (P < 0.01) and current passive smoking (P < 0.05). An increasing number of siblings was inversely related to atopy to grass (P < 0.05); however, only an increasing number of older siblings seemed to protect from atopy to grass (P < 0.05). Subjects who had never attended a day-care centre had significantly more atopy to grass (P < 0.05). No significant association was found between atopy and airway infections requiring hospitalization before the age of 5 years, or between atopy and bedroom sharing in childhood., Conclusion: Atopy is common among young Danish adults, especially in males. Participants were less likely to be atopic, especially to grass allergen, if they came from large families, had kept furred pets as children, and had been exposed to tobacco smoke.