INTRODUCTION:Tests for dog and cat allergen molecules might be useful to characterize individuals with clinical symptoms in unselected population samples. The aim of this study was to present prevalence data and to investigate airway symptoms to cats and dogs in relation to sensitization to cat and dog allergen molecules. METHODS:In a random sample from a population-based cohort aged 19 years, 595 subjects were tested for sensitization to airborne allergens. Sera from subjects with IgE levels of >0.10 kU/L to cat, dog, or horse were further analyzed by microarray (ImmunoCAP™ ISAC 112) for dog molecules Can f 1-6 and cat molecules Fel d 1, 2, and 4. Fel d 7 was analyzed with ImmunoCAP™. Information about symptoms of asthma and rhinoconjunctivitis upon cat and dog exposure was obtained by a structured interview. RESULTS:The most prevalent (51.6%) sensitizing dog allergen molecule was Can f 5. The prevalence of asthma upon dog contact increased from 0.9% in individuals negative to all tested dog molecules to 40% in individuals sensitized to 6 dog molecules. The prevalence of asthma upon dog contact was related to the number of dog lipocalin sensitizations independent of sensitization to Can f 5, whereas for rhinoconjunctivitis Can f 5 co-sensitization played a role. The most prevalent (91.2%) sensitizing cat molecule was Fel d 1 and co-sensitization to up to three molecules increased the prevalence of asthma when exposed to cat. CONCLUSION:In individuals sensitized to cat as in individuals sensitized to dog, the prevalence of allergic symptoms increased with the number of sensitizing allergen molecules. Individuals sensitized to dog had more complex sensitization patterns to allergen molecules compared to those sensitized to cat. Asthma upon dog exposure was mostly associated with dog lipocalin sensitization, whereas Can f 5 sensitization increased the risk of rhinoconjunctivitis.

Objective To determine whether the genetic disorder severe α1-antitrypsin deficiency, which has a known association with increased risk for development of lung and liver diseases, is also associated with increased risk for development of gastrointestinal diseases. Patients and Methods We conducted a national, longitudinal, registry-based study of individuals with severe α1-antitrypsin deficiency (phenotype PiZZ; n=1561) and controls (n=5964) who were part of Swedish population-based cohorts between January 1,1991, through January 1, 2015. Data on gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), hospitalizations, and mortality were obtained by cross-linkage with national registries. Risk factors for development of gastrointestinal diseases were analyzed using Cox proportional hazards models and Fine-Gray regression models, adjusted for baseline age, sex, smoking status, the presence of chronic obstructive pulmonary disease, and liver diseases. Results During a median follow-up of 10 years (IQR, 11 years) for the whole study population, the incidence rate of any gastrointestinal disease per 1000 person-years was 10.6 (95% CI, 9.0 to 12.4) for the individuals with the PiZZ phenotype and 3.6 (95% CI, 3.2 to 4.1) for the controls, with an adjusted hazard ratio (aHR) of 2.7 (95% CI, 2.1 to 3.4). Individuals with PiZZ had an increased risk of Crohn disease (aHR, 4.1; 95% CI, 2.0 to 8.4), ulcerative colitis (aHR, 4.6; 95% CI, 2.4 to 8.6), noninfectious gastroenteritis (aHR, 2.6; 95% CI, 1.3 to 5.2), and diverticular disease (aHR, 2.1; 95% CI, 1.5 to 2.9). Conclusion Individuals with PiZZ have an increased risk for development of gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), as compared with the general population.

BACKGROUND:COPD is largely underdiagnosed. Active identification of cases is crucial to establish preventive measures before manifestation of clinical disease. The significance of different spirometric patterns preceding COPD, especially preserved ratio impaired spirometry (PRISm), has been highlighted but remains unclear. RESEARCH QUESTION:Which clinical characteristics, smoking habits, and spirometric patterns, with primary focus on PRISm findings, precede the development of airway obstruction (AO)? STUDY DESIGN AND METHODS:The OLIN COPD Study was established from 2002 through 2004. After re-examination of population-based cohorts, individuals with AO (n = 993; FEV1 to VC ratio < 0.70) were identified together with control participants without AO (n = 993; FEV1 to VC ratio ≥ 0.70). Most of these people had participated in examinations during the 1980s or 1990s, and in total, 902 cases and 819 control participants had previous clinical data. Logistic regression was performed with case status as outcome and spirometric patterns, age, sex, smoking habits, and BMI at first examination as covariates. RESULTS:The mean (SD) person-years between first examination and inclusion in the OLIN COPD Study was 10.5 (4.0) years. At first examination, the prevalence of PRISm was higher in cases (18.6%) vs control participants (13.4%). Current smoking was more common in cases (45.1% vs 18.2%), whereas former smoking was similar (31.8% vs 34.9%). Cases reported more respiratory symptoms (78.0% vs 44.3%) than control participants. At first examination, PRISm, current smoking, and former smoking were strongly associated with becoming a case when adjusted for confounders, with adjusted OR (aOR) of 3.5, 4.1, and 1.5, respectively. When stratifying for smoking habits, aORs for PRISm in those with current smoking, former smoking, and nonsmoking status were 2.9, 3.8 and 3.7, respectively. INTERPRETATION:In this study, PRISm was associated with transition into AO corresponding to COPD within 1 decade, independent of smoking habits and with similar strength of association among those who have never smoked, who formerly smoked, and who currently smoke.

Exposure to high levels of vehicle traffic during childhood seems to have a negative effect on lung function. Less is known about the effects of exposure to relatively low levels during childhood. We aimed to study how exposure to vehicle traffic in childhood is associated with lung function and asthma in young adulthood in a 10-year follow-up of a population-based cohort in a municipality with relatively low levels of vehicle traffic. The Obstructive Lung Disease in Northern Sweden (OLIN) pediatric cohort II was recruited in 2006 at age 8 years. Exposure to vehicle traffic at baseline was studied in relation to lung function at follow-up at age 19 years (n = 1056 participants). Lung function measures included FEV1, FVC and FEV1/FVC. Different exposure thresholds were defined based on proximity (within a 200 m radius from the home address) to a road with a minimum daily count of heavy vehicles (≥ 250 and ≥ 500) or any type of vehicle (≥ 4000 and ≥ 8000). The association between exposure to vehicle traffic at baseline and lung function at follow-up was analyzed by linear regression adjusting for potential confounders. In general, those above the exposure thresholds had lower lung function than those below, but not significantly so in all comparisons. Those exposed to ≥ 250 heavy vehicles/day had lower mean FEV1 z-score at follow-up (-0.38) compared with those exposed to < 250 heavy vehicles/day (-0.21), p = 0.033, and this association remained after adjustment for confounders (p = 0.036). Also, those exposed to ≥ 8000 vehicles/day had lower mean FVC z-score (-0.19) than those exposed to < 8000 vehicles/day (-0.02), p = 0.047, with p = 0.032 after adjustment. Exposure to vehicle traffic in childhood, in a relatively low traffic-flow environment, may be associated with a slightly lower lung function in young adulthood.

Nickel allergy is common among children. The present study investigated prevalence trends of self-reported nickel allergy, risk factors, and atopic comorbidity among children. Eight-year-old children from Norrbotten County, Sweden, were recruited in 1996 (n = 3,430), 2006 (n = 2,585), and 2017 (n = 2,785). Self-reported nickel allergy decreased from 7.7% (2006) to 6.1% (2017; p = 0.024) and was significantly more common among girls. In 1996, only children with atopic dermatitis answered questions on nickel allergy. Among children with atopic dermatitis, no significant decrease was seen over the years 1996 to 2017. Ear piercing (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.39–2.68 and OR 5.57, 95% CI 3.71–8.38) and female sex (OR 4.05, 95% CI 2.68–6.13 and OR 1.73, 95% CI 1.09–2.74) were risk factors for self-reported nickel allergy in 2006 and 2017, respectively. Self-reported nickel allergy was significantly more prevalent among children with atopic dermatitis than without in 2006 (12.3% vs 6.4%; p < 0.001) and 2017 (11.5% vs 5.1%; p < 0.001), and among children with allergic rhinitis in 2017 (8.6% vs 4.7%; p = 0.015). In conclusion, we found a decreasing prevalence of self-reported nickel allergy, but not among children with atopic dermatitis. Ear piercing and female sex were strongly associated with nickel allergy. Our findings also suggest that nickel allergy is associated with atopic dermatitis and allergic rhinitis.

Chronic Obstructive Pulmonary disease (COPD) is largely underdiagnosed. Active case finding is crucial to establish preventive measures before manifestation of clinical disease. The significance of different spirometric patterns preceding COPD, especially Preserved Ratio Impaired Spirometry (PRISm), has been highlighted but is still unclear. Which clinical characteristics, smoking habits and spirometric patterns, with primary focus on PRISm, precede the development of airway obstruction? The OLIN COPD COPD Study was established in 2002-04. After re-examinations of population-based cohorts, individuals with airway obstruction (AO) (n=993 cases, FEV1/VC<0.70) were identified together with non-obstructive controls (n=993, FEV1/VC≥0.70). The majority of these had participated in examinations during the 1980s or 1990s and in total 902 cases and 819 controls had previous clinical data. Logistic regression was performed with case as outcome and spirometric patterns, age, sex, smoking habits and body mass index (BMI) at first examination as covariates. The mean person-years between first examination and inclusion in the OLIN COPD COPD study was 10.5±4.0y. At first examination, the prevalence of PRISm was higher in cases (18.6%) vs controls (13.4%). Current smoking was more common in cases (45.1% vs 18.2%), while former smoking was similar (31.8 vs. 34.9%). Cases reported more respiratory symptoms (78.0 vs. 44.3%) than controls. At first examination, PRISm, current smoking and former smoking were strongly associated with becoming a case when adjusted for confounders, with adjusted OR (aOR) of 3.5, 4.1 and 1.5, respectively. When stratifying for smoking habits, aORs for PRISm in current smokers, former smokers and non-smokers were 2.9, 3.8 and 3.7, respectively. PRISm associated with transition into airway obstruction corresponding to COPD within a decade, independent of smoking habits and with similar strength of association among non-, former and current smokers.

BACKGROUND:Longitudinal studies on allergic rhinitis (AR) incidence and remission from childhood to adulthood are limited. This study aimed to estimate AR incidence and remission from age 8 to 19 years and to identify related risk factors. METHODS:In 2006, all children in grades 1 and 2 (median age 8 years) in three municipalities in Northern Sweden were invited to participate in a questionnaire survey. The children in two of the municipalities underwent a skin prick test (SPT) for airborne allergens. The protocol was repeated at age 19 years. In total, 2250 participants (91% participation rate) completed the questionnaire, and 1338 underwent SPTs at 8 and 19 years of age. RESULTS:From age 8 to 19 years, the cumulative incidence of AR was 33.6%, significantly higher among girls than boys (37.4% vs. 29.8%, p < .001). Factors that independently increased the risk of developing AR were sensitisation by age 8 (adjusted odds ratio [aOR] 3.75, 95% confidence interval [CI] 2.68-5.23), sensitisation between 8 and 19 years (aOR 2.57, 95% CI 1.82-3.63), and female sex (aOR 1.71, 95% CI 1.30-2.26). The remission rate was 40.0%, with boys experiencing significantly higher remission than girls (45.4% vs. 32.2%, p = .015). The probability of remission was decreased by sensitisation before (aOR 0.26, 95% CI 0.13-0.53) and after age 8 years (aOR 0.20, 95% CI 0.05-0.77). CONCLUSION:This study found a high incidence of AR between age 8 and 19 years, especially among girls, while boys had a higher remission rate. Sensitisation increased the risk of developing AR and decreased the remission rate.

BACKGROUND:Aeroallergen sensitization is a major factor in asthma, and asthma is associated with impaired lung function. The independent association between sensitization and lung function is unclear. OBJECTIVES:To examine factors associated with lung function in adolescence, with special interests in sensitization and asthma. METHODS:All schoolchildren in grade one and two (median age 8) in two municipalities in Northern Sweden were invited to a questionnaire survey of allergic diseases and skin prick tests to aeroallergens. This was repeated at ages 12 and, at 19 years also including spirometry and n = 1495 participated at all three occasions. Associations between risk factors and FEV1, FVC and FEV1/FVC were analysed by linear regression. RESULTS:Aeroallergen sensitization was not associated with lung function, irrespective of age at onset, type or degree of sensitization. Early-onset asthma, both persistent (B -0.35, 95% CI -0.60 to -0.09) and in remission (B -0.43, 95% CI -0.74 to -0.12) was associated with lower FEV1. Persistent asthma was associated with lower FEV1/FVC (B -0.81, 95% CI -1.07 to -0.55), and remission with lower FVC (B -0.37, 95% CI -0.67 to -0.70). No interaction between asthma and sensitization was found. Maternal smoking in pregnancy was associated with lower FEV1/FVC. Underweight at age 19 years was associated with lower FEV1 and FVC and overweight was associated with higher FEV1 and FVC, but lower FEV1/FVC. CONCLUSIONS:Aeroallergen sensitization was not independently associated with lung function. Early onset asthma was strongly associated with lung function impairments in young adulthood and in sensitized and non-sensitized individuals alike.

Background:The extent to which airflow obstruction, a key feature of COPD, can be already present in early adulthood is unclear. We investigated the prevalence of airflow obstruction in young adults across European populations. Methods:We identified 48 612 individuals aged 20-40 years across eight population-based European cohorts in the Chronic Airway Diseases Early Stratification (CADSET) collaboration and applied two commonly used definitions of airflow obstruction: pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70 and below the lower limit of normal (LLN). We explored how the prevalence of airflow obstruction according to both criteria was related to age, sex and smoking. Results:Airflow obstruction prevalence increased with increasing age from 2.3% in those aged 20-24.9 years to 6.3% in those aged 35-39.9 years according to FEV1/FVC <0.70, and from 7.3% to 8.3% according to FEV1/FVC <LLN. The corresponding increase in airflow obstruction prevalence was up to 8.8% in males versus 7.5% in females, and up to 9.0% in ever-smokers versus 6.9% in never-smokers. Difference in prevalence of airflow obstruction between FEV1/FVC <0.70 and <LLN was highest for females and ever-smokers. Active smoking ranged from 19% to 28% and ever-smoking from 37% to 51%. The prevalence of airflow obstruction increased with pack-years, plateauing at ∼5 pack-years. Conclusion:Up to 8% of young adults across Europe have airflow obstruction; its cause and its role in prior, concurrent and future airway disease merit further investigation.

Respiratory symptoms are common in the general adult population. Increased burden of respiratory symptoms may increase the risk of mortality. We assessed the association between respiratory symptom clusters and mortality. Participants were derived from two population-based Swedish adult cohorts (N = 63,060). Cluster analysis was performed with Locality Sensitive Hashing (LSH)-k-prototypes in subjects with ≥ 1 self-reported respiratory symptom. Linked mortality register data (up to 21 years of follow-up, > 600,000 person-years) were used. Associations between clusters and all-cause/cause-specific mortality were assessed using asymptomatic subjects as reference. Over 60

INTRODUCTION How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. METHODS A prospective, population-based study of random samples of the population (age 16-69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006-2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. RESULTS In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p<0.001). Among current smokers at baseline, tobacco smoking cessation was less common in e-cigarette users than e-cigarette non-users (14.2% vs 47.6%, p<0.001) and there was no association with a reduction in the number of tobacco cigarettes smoked per day. Those who were persistent smokers reported increasing respiratory symptoms. In contrast, the symptoms decreased among those who quit tobacco smoking, but there was no significant difference in respiratory symptoms between quitters with and without e-cigarette use. CONCLUSIONS E-cigarette use was associated with persistent tobacco smoking and reporting respiratory symptoms. We found no association between e-cigarette use and tobacco smoking cessation, reduction of number of tobacco cigarettes smoked per day or reduction of respiratory symptoms.