Long-term effects of asthma medication on asthma symptoms: an application of the targeted maximum likelihood estimation.

BACKGROUND: Long-term effectiveness of asthma control medication has been shown in clinical trials but results from observational studies with children and adolescents are lacking. Marginal structural models estimated using targeted maximum likelihood methods are a novel statistiscal approach for such studies as it allows to account for time-varying confounders and time-varying treatment. Therefore, we aimed to calculate the long-term risk of reporting asthma symptoms in relation to control medication use in a real-life setting from childhood to adulthood applying targeted maximum likelihood estimation. METHODS: In the prospective cohort study SOLAR (Study on Occupational Allergy Risks) we followed a German subsample of 121 asthmatic children (9-11 years old) of the ISAAC II cohort (International Study of Asthma and Allergies in Childhood) until the age of 19 to 24. We obtained self-reported questionnaire data on asthma control medication use at baseline (1995-1996) and first follow-up (2002-2003) as well as self-reported asthma symptoms at baseline, first and second follow-up (2007-2009). Three hypothetical treatment scenarios were defined: early sustained intervention, early unsustained intervention and no treatment at all. We performed longitudinal targeted maximum likelihood estimation combined with Super Learner algorithm to estimate the relative risk (RR) to report asthma symptoms at SOLAR I and SOLAR II in relation to the different hypothetical scenarios. RESULTS: A hypothetical intervention of early sustained treatment was associated with a statistically significant risk increment of asthma symptoms at second follow-up when compared to no treatment at all (RR: 1.51, 95% CI: 1.19-1.83) or early unsustained intervention (RR:1.38, 95% CI: 1.11-1.65). CONCLUSIONS: While we could confirm the tagerted maximum likelihood estimation to be a usable and robust statistical tool, we did not observe a beneficial effect of asthma control medication on asthma symptoms. Because of potential due to the small sample size, lack of data on disease severity and reverse causation our results should, however, be interpreted with caution.

Work-related stress and incident asthma and rhinitis: results from the SOLAR study.

OBJECTIVES: This study analyzes the association of work-related stress with incident asthma and rhinitis in young adults with a special focus on gender-specific differences. METHODS: Incident asthma, wheezing and rhinitis were measured in a cohort of 2051 young German adults (aged 16-18 years at baseline) recruited by the prospective population-based SOLAR study (Study of Occupational Allergy Risks). Work-related stress was measured by the Trier Inventory for the Assessment of Chronic Stress (TICS). Two TICS scales, work overload and work discontent, were analysed. Logistic regression was conducted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In females, the odds for incident asthma were found to be 17% higher for each increase of the work discontent score by one point (OR 1.17, 95% CI 1.04-1.31). In males, no association was statistically significant. Incident rhinitis showed no association with any exposure variable. CONCLUSION: This study shows a link between work-related stress and incident asthma which seems to be confined to women. This study adds evidence about the association of work-related stress and asthma in young adults and can contribute to prevention for that particular age group.

Do young adults with atopic dermatitis avoid harmful workplace exposure at their first job? A prospective cohort study.

PURPOSE: Patients with atopic dermatitis (AD) are at high risk of chronic hand eczema. In this prospective cohort study, we assessed the influence of pre-hire-onset AD on the first job choice. We also analysed the potential association between AD and usage of preventive measures in high-risk occupations. METHODS: Subjects (aged 19-24 years) who were followed from childhood until the second Study on Occupational Allergy Risks and indicated a job were included (n = 1566). We defined AD as doctor-diagnosed AD and symptoms of an itchy rash during the past 12 months before the study. Pre-hire-onset AD was having AD prior to the first job. Preventive measure usage was self-reported gloves use or use of ointment or moisturizer. We performed multiple imputations to deal with missing values and analysed associations using logistic regression models adjusted for several potential confounders. RESULTS: Risk categories of the first job did not differ between participants with pre-hire-onset AD and those without (odds ratio 1.05, 95 % confidence interval 0.59-1.87). AD status was not statistically significantly associated with usage of preventive measures (1.22, 0.56-2.64). Conversely, having received job counselling (2.76, 1.15-6.63) and a family history of AD (2.09, 1.01-4.31) were associated with a higher use of such measures. CONCLUSION: We could not confirm a healthy hire effect in this cohort of young adults. Although subjects with AD in high-risk occupations do not seem to use more preventive measures than their non-affected peers, job counselling seems to be an effective approach to encourage secondary prevention.

Body mass index change and atopic diseases are not always associated in children and adolescents.

BACKGROUND: Several studies have suggested an association between the increasing prevalence of allergic diseases and dietary factors. OBJECTIVE: To prospectively explore the association between changes in body mass index (BMI) and symptoms of asthma, rhinitis, rhinoconjunctivitis, and atopic dermatitis to find out whether an increase in BMI increases the risk of developing atopic diseases in adolescence. METHODS: Comprehensive questionnaires and anthropometric measurements were applied in a random subsample of the International Study of Asthma and Allergies in Childhood phase II (1995-1996, 9 to 11 years of age) in Germany. Of these participants, 1,794 could be followed up in 2002 to 2003 in the Study on Occupational Allergy Risks (16 to 18 years of age). The associations between changes of BMI from baseline to follow-up and incident and persistent respiratory diseases and atopic dermatitis were assessed. RESULTS: In logistic regression analyses, weight change in either direction was not statistically significantly associated with the incidence or persistence of any of the diseases of interest except for rhinitis. An increase in BMI was linked to an increased risk of incident rhinitis (odds ratio 1.9, 95% confidence interval 1.2-2.9). CONCLUSION: These results indicate a nonsignificant trend between increased body weight and risk of atopic diseases. Aside from limitations owing to a small subgroup of obese participants and questionnaire-based asthma diagnosis, reasons might be related to an interaction between BMI and hormonal influences, age, and duration and severity of overweight. The results underline that BMI does not necessarily play a decisive role in the course of atopic diseases in all populations.

Prediction of the incidence and persistence of allergic rhinitis in adolescence: a prospective cohort study.

BACKGROUND: Predictive models have rarely been used in allergy research and practice. However, they might support physicians in advising patients. OBJECTIVE: The aim of this study was to create predictive models for the incidence and persistence of allergic rhinitis (AR) during adolescence. METHODS: A prospective population-based cohort study was conducted starting at age 9 to 11 years. Potential risk factors for atopic diseases obtained at baseline in 2810 subjects were used to create predictive logistic regression models for the incidence and persistence of physician-diagnosed AR with current symptoms at age 15 to 18 years. RESULTS: Positive skin prick test responses to outdoor allergens at baseline were the most important determinant for both the incidence and persistence of AR until follow-up. For the incidence of AR, positive skin prick test responses to indoor allergens, parental history of asthma, female sex, and not having been breast-fed exclusively for 2 or more months were additional statistically significant independent risk factors. Depending on the number of risk factors present, the probability of the incidence of AR increased from 2% (no risk factors present) to 72% (full model; 95% CI, 58% to 85%). The probability of persistence of AR ranged from 33% (no risk factors present) to 83% (full model; 95% CI, 70% to 97%). CONCLUSION: The course of AR over puberty can be predicted using risk factors that are easy to determine in childhood. Sensitization to outdoor allergens seems to play a much greater role for disease development than sensitization to indoor allergens. This might help pediatricians in advising patients.

Prediction of the incidence, recurrence, and persistence of atopic dermatitis in adolescence: a prospective cohort study.

BACKGROUND: Although it is known that atopic dermatitis (AD) can develop during adolescence, research on its course and predictors in this age group is thus far limited. OBJECTIVE: We aimed to describe the course of AD over puberty and prospectively determine risk factors for the incidence, recurrence, and persistence of AD until adolescence in a population-based cohort study. METHODS: German participants of the International Study of Asthma and Allergies in Childhood Phase II were followed prospectively. The final dataset comprised 2857 adolescents, of whom 2433 were unaffected by AD at baseline. Bivariate and multivariate prediction models for the incidence, recurrence, and persistence of AD using early-life factors, family history of atopic diseases, and job history as predictors were developed. RESULTS: The incidence of AD between ages 9 to 11 and 16 to 20 years was 1.7%, and recurrence was 2.4%. AD persisted in 47.6% of adolescents with AD symptoms at baseline (n = 424). High socioeconomic status, female sex, asthma symptoms and a positive skin prick test response at baseline, parental history of rhinitis/AD, and having worked in a high-risk job were significant predictors for the course of disease. With all the factors present, the probability of the incidence of AD was 21.4% (95% CI, 1.8% to 80.2%) and increased up to 81.7% (95% CI, 47.0% to 95.8%) for recurrence of AD and 87.6% (95% CI, 63.4% to 96.6%) for persistence of AD among those affected by AD. Early-life exposures did not predict the course of AD over puberty. CONCLUSION: Genetic factors, early allergen sensitization, and having worked in a high-risk job seem to be more important for disease development in late adolescence than other early-life exposures.

Exposure to animals and risk of oligoarticular juvenile idiopathic arthritis: a multicenter case-control study.

BACKGROUND: An inverse association between early contact with microbial compounds and respiratory allergies is well established. The protective effect of infant contact with animals was also shown for inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). We aimed to test the association between animal contact in infancy and oligoarticular juvenile idiopathic arthritis (OA JIA). METHODS: Parents of children with OA JIA registered at the Hospital for Pediatric Rheumatology in Garmisch-Partenkirchen were asked to complete a questionnaire. Children who underwent strabismus surgery at six referral centers for ophthalmology served as controls. Children age 6 to 18 years born in Germany without malformations were included (238 cases; response 89% and 832 controls; response 86%). Data were analyzed using logistic regression models after adjusting for potential confounders. RESULTS: Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were clearly related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95). CONCLUSIONS: Contact with farm environments in infancy might not be associated with OA JIA. This finding is consistent with previous findings for diabetes mellitus type 1 but contradicts results for IBD and SLE.

Nickel allergy is associated with wheezing and asthma in a cohort of young German adults: results from the SOLAR study.

BACKGROUND: Nickel allergy is the most prevalent contact allergy. It belongs to a different hypersensitivity type to asthma and rhinoconjunctivitis. The aim of this analysis was to assess whether self-reported nickel allergy is associated with incident wheezing, asthma and rhinoconjunctivitis in young German adults, taking into account potential effect modification by sex. METHODS: In total, 2051 (70.6%) participants aged 19-24 years took part in the second phase of SOLAR (Study on Occupational Allergy Risks), a follow-up study of ISAAC II (the second phase of the International Study of Asthma and Allergies in Childhood) in Germany. Self-reported nickel allergy, as well as having pierced ears, and the three outcomes incident wheezing, asthma and rhinoconjunctivitis, were analysed stratified for sex. Logistic regression adjusted for potential confounders was performed. RESULTS: An association between self-reported nickel allergy and incident wheezing was observed for men and women, while only in males did pierced ears show a significant association with the outcome (adjusted OR 2.26, 95% CI 1.10-4.62). Also only in males, self-reported nickel allergy was associated with elevated odds for incident asthma (adjusted OR 4.34, 95% CI 1.22-15.41). Neither in men nor in women was a significant association observed for incident rhinoconjunctivitis. CONCLUSION: Our results suggest that self-reported nickel allergy is associated with incident wheezing. Whether this association is due to environmental or genetic predisposition, or due to an overlap of the mechanisms of type I and type IV hypersensitivity, needs to be elucidated.

Association Between Occupational Exposure to Disinfectants and Asthma in Young Adults Working in Cleaning or Health Services: Results From a Cross-Sectional Analysis in Germany.

OBJECTIVE: To analyze the association of occupational disinfectants use with asthma and wheezing in young professionals. METHODS: Three hundred sixty-five participants from the German Study on Occupational Allergy Risks II aged 20 to 24 years and working in cleaning or health services answered a questionnaire on respiratory health, occupational exposure to disinfectants, and potential confounders. By logistic regression, we calculated the association between duration of occupational disinfectants exposure and doctor-diagnosed asthma, current asthma, and current wheezing. RESULTS: Individuals exposed to disinfectants for more than 12 months had almost three times the odds of doctor-diagnosed asthma compared with those not exposed (odds ratio [OR]: 2.99, 95% confidence interval [CI]: 1.36-6.55). CONCLUSIONS: Our findings provide some further evidence for an association between occupational exposure to disinfectants and asthma, indicating that this association can be seen already after the first year of exposure.

Greenness and job-related chronic stress in young adults: a prospective cohort study in Germany.

OBJECTIVES: We aimed to prospectively study the association between normalised difference vegetation index (NDVI) as a measure of greenness around homes and occupational stress. SETTING: A population-based cohort in Munich and Dresden cities was followed from age 16-18 years to age 20-23 years (n=1632). PARTICIPANTS: At baseline, all participants attended high-school while at follow-up some had started working and others studying at university. At baseline and in each follow-up, we assigned NDVI based on participants' residential geocoded addresses and categorised it by quartiles. OUTCOME MEASURES: School-related, university-related or job-related self-reported chronic stress was assessed at the two follow-ups by the Trier Scale for Assessment of Chronic Stress using work discontent and work overload as outcomes. We modelled the association employing ordinal generalised estimating equations model accounting for changes in sociodemographics, non-job-related stress, job history and environmental covariates. Stratified analysis by each city was performed. RESULTS: NVDI at baseline was higher for participants from Dresden (median=0.36; IQR 0.31-0.41) than Munich (0.31; 0.26-0.34). At follow-up, it decreased only for participants in Dresden (0.34; 0.30-0.40). Higher greenness (quartile 4 vs quartile 1) was associated with less work discontent (OR 0.89; 95% CI 0.80 to 0.99) and less work overload (OR 0.87; 95% CI 0.78 to 0.96). In stratified analyses, results were more consistent for Munich than for Dresden. CONCLUSIONS: Our results suggest that residential green spaces, using the vegetation index as a proxy for exposure, are inversely associated with two types of job-related chronic stress in German young adults transitioning from school to university or working life.

Chronic Stress in Young German Adults: Who Is Affected? A Prospective Cohort Study.

We aimed to prospectively assess changes in chronic stress among young adults transitioning from high school to university or working life. A population-based cohort in Munich and Dresden (Germany) was followed from age 16-18 (2002-2003) to age 20-23 (2007-2009) (n = 1688). Using the Trier Inventory for the Assessment of Chronic Stress, two dimensions of stress at university or work were assessed: work overload and work discontent. In the multiple ordinal generalized estimating equations, socio-demographics, stress outside the workplace, and job history were additionally considered. At follow-up, 52% of the population were university students. Work overload increased statistically significantly from first to second follow-up, while work discontent remained constant at the population level. Students, compared to employees, reported a larger increase in work overload (adjusted odds ratio (OR): 1.33; 95% confidence interval (95% CI): 1.07, 1.67), while work discontent did not differ between the groups. In conclusion, work overload increases when young adults transition from school to university/job life, with university students experiencing the largest increase.

Exposure to farming environments in early life and type 1 diabetes: a case-control study.

It has been hypothesized that a stimulation of regulatory cytokines by microbial compounds reduces autoimmune as well as atopic diseases. Farm-related contact to microbial compounds protects from allergies, but no data on the association between farm contact and type 1 diabetes is available. The aim of this study was to test this association. A case-control study was conducted in five children's hospitals. Regular contact to farm animals and potential confounders were assessed using a postal questionnaire. Eligible subjects were all prevalent cases with type 1 diabetes registered in the hospitals and hospital-based control subjects (response rate 91%). Included were children aged 6-16 years living in rural areas with German nationality (242 case and 224 control subjects). Regular contact to stables (adjusted odds ratio 1.2 [95% CI 0.5-2.7]) was not associated with type 1 diabetes. In addition, regular contact to specific farm animals was not associated with case status. There was a tendency for an inverse relationship between allergic rhinitis and type 1 diabetes (0.6 [0.3-1.1]; P = 0.11). There was no evidence that early exposure to farm animals largely decreases the risk in children for developing type 1 diabetes.

Adolescents' jobs and the course of dermatitis symptoms throughout puberty.

OBJECTIVES: This study evaluated the course of dermatitis symptoms throughout puberty taking into account occupational exposures in a population-based study. METHODS: Participants enrolled in the ISAAC-II (International Study of Asthma and Allergies in Childhood) study in Munich and Dresden in 1995 and 1996 were sent a postal questionnaire in 2002 (age at follow-up 16 to 18 years). The questionnaire included items on atopic diseases, jobs, including holiday jobs and vocational training, and potential confounders. The most recent of the adolescents' jobs held for at least 8 hours a week, and for at least 1 month, were coded according to the ISCO-88 system. RESULTS: Overall, data of 3785 adolescents were included in the analyses. The incidence of dermatitis symptoms during puberty among those without such symptoms at baseline was 7%. Altogether 31% of the participants reported an employment history. Those already employed were more likely to report a new onset of dermatitis symptoms. Jobs associated with a new onset of symptoms were work in the health care sector, vocational training in bakeries, and cleaning. The first 9 months of exposure were particularly relevant for new cases of dermatitis symptoms (odds ratio 3.7, 95% confidence interval 1.5-9.6). CONCLUSIONS: Early occupational exposure is associated with the development of symptoms of dermatitis. The types of skin alterations need to be assessed in the next stage of the study.

Contact with farm animals in early life and juvenile inflammatory bowel disease: a case-control study.

OBJECTIVE: The aim of this study was to test the association between farm animal contact in infancy and the development of juvenile Crohn disease and ulcerative colitis. METHODS: A case-control study was conducted in 13 children's hospitals by using a mailed questionnaire. Case subjects with Crohn disease or ulcerative colitis who were registered in these hospitals were eligible (response rate: 90%). Children who underwent strabismus surgery at 11 of the 13 centers served as control subjects (response rate: 85%). All children 6 to 18 years of age who were born in Germany without malformations were included (444 case subjects with Crohn disease, 304 case subjects with ulcerative colitis, and 1481 control subjects). RESULTS: Regular contact with farm animals during the first year of life was associated inversely with Crohn disease and ulcerative colitis. In addition, regular contact with cats in infancy was linked inversely with case status. Allergic rhinitis was correlated significantly with Crohn disease but not with ulcerative colitis. CONCLUSION: Contact with farm environments in infancy might decrease the risk of juvenile Crohn disease and ulcerative colitis.