IgE sensitization to inhalant allergens and the risk of airway infection and disease: A population-based study.

BACKGROUND: Immunoglobulin E (IgE) sensitization, which is the propensity to develop IgE antibodies against common environmental allergens, is associated with a lymphocyte T-helper type 2 (Th2) skewed immune response and a high risk of allergic respiratory disease. Little is known about whether IgE sensitization confers an increased risk of respiratory infections in adults. We investigated the association between IgE sensitization and the incidence of acute airway infections, other infections and chronic lower airway disease events as recorded in nation-wide registries. METHODS: We included 14,849 persons from five population-based studies with measurements of serum specific IgE positivity against inhalant allergens. Participants were followed by linkage to Danish national registries (median follow-up time 11.3 years). The study-specific relative risks were estimated by Cox regression analysis, meta-analysed, and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: The relative risks for IgE sensitized vs. non-sensitized were: for pneumonia (HR = 1.20, 95% CI: 1.01, 1.41), other acute airway infection (HR = 0.86, 95% CI: 0.60, 1.22), infection (HR = 1.06, 95% CI: 0.90, 1.24), asthma (HR = 2.26, 95% CI: 1.79, 2.86), and other chronic lower airway disease (HR = 1.31, 95% CI: 1.08, 1.58). In never smokers, the higher risk of pneumonia (HR = 1.73, 95% CI: 1.23, 2.44) and asthma (HR = 3.17, 95% CI: 2.10, 4.76) among IgE sensitized was more pronounced. CONCLUSIONS: IgE sensitization was associated with a higher risk of asthma, other chronic lower airway diseases, and pneumonia. However, the association between IgE sensitization and pneumonia may be explained by undiagnosed asthma causing the pneumonia. Further studies are needed for confirmation.

Specific IgE positivity against inhalant allergens and development of autoimmune disease.

BACKGROUND: Allergic and autoimmune diseases have been suggested to be inversely associated. We investigated the association between atopy and development of any and specific types of autoimmune disease. METHODS: We included a total of 14,849 individuals from five population-based studies with measurements of atopy defined as specific IgE positivity against inhalant allergens. We followed the participants by linkage to the Danish National Patient Register (median follow-up time 11.2 years). Hazard ratio (HR) and 95% confidence interval (CI) of autoimmune disease were estimated by Cox regression. RESULTS: The risk for atopics versus non-atopics was: for any autoimmune disease (HR = 0.99, 95% CI: 0.83, 1.18), thyrotoxicosis (HR = 0.69, 95% CI: 0.34, 1.37), type 1 diabetes (HR = 1.16, 95% CI: 0.84, 1.60), multiple sclerosis (HR = 1.97, 95% CI: 0.95, 4.11), iridocyclitis (HR = 0.82, 95% CI: 0.38, 1.74), Crohn's disease (HR = 1.03, 95% CI: 0.47, 2.25), ulcerative colitis (HR = 0.93, 95% CI: 0.52, 1.69), psoriasis vulgaris (HR = 1.50, 95% CI: 0.86, 2.62), seropositive rheumatoid arthritis (HR = 0.74, 95% CI: 0.48, 1.14) and polymyalgia rheumatica (HR = 0.79, 95% CI: 0.44, 1.44). CONCLUSIONS: We found no statistically significant associations between atopy and autoimmune disease, but we cannot exclude relatively small to moderate effects - protective or promotive - of atopy on autoimmune disease.

Vitamin D status and chronic obstructive pulmonary disease: a prospective general population study.

OBJECTIVES: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population. METHODS: We included a total of 12,041 individuals from three general population studies conducted in 1993-94, 1999-2001, and 2006-2008, respectively, with vitamin D measurements. Information on COPD was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death. RESULTS: There were 85 prevalent and 463 incident cases of COPD (median follow-up 9.7 years). We found a statistically significant inverse association between vitamin D status and prevalent COPD with odds ratio = 0.89 (95% confidence interval, CI: 0.79, 1.0), but no statistically significant association with incident COPD with a hazard ratio = 0.98 (95% CI: 0.94, 1.0), respectively, per 10 nmol/l higher vitamin D status, when adjusted for possible confounders. CONCLUSIONS: We found a statistically significant inverse cross-sectional association between vitamin D status and COPD, but no association between vitamin D status and incident COPD.

Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach.

BACKGROUND: Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. METHODS: Three population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. RESULTS: Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. CONCLUSION: Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Immunoglobulin E sensitization to cross-reactive carbohydrate determinants: epidemiological study of clinical relevance and role of alcohol consumption.

BACKGROUND: The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal. OBJECTIVE: To investigate the relationship of alcohol consumption with CCD sensitization, the role of alcohol dehydrogenase gene polymorphisms, and the clinical consequences of CCD sensitization. METHODS: Serum-specific IgE sensitization (> or =0.1 kU/l) to a CCD (the N-glycan from bromelain) was assessed in 1,197 adults participating in a population-based study in Copenhagen, Denmark. Alcohol consumption and atopic symptoms (rhinitis, asthma and oral allergy syndrome) were assessed by questionnaire. Examinations included skin prick tests (SPTs), qualitative multiallergen IgE test (Phadiatop), methacholine bronchial hyperreactivity, eosinophil cationic protein and alcohol dehydrogenase (ADH) gene polymorphisms. RESULTS: Alcohol consumption was significantly associated with CCD sensitization and this was particularly evident in SPT-negative individuals. The fast-metabolizing allele of the ADH1b polymorphism was significantly associated with CCD sensitization in alcohol drinkers. CCD sensitization was associated with atopic symptoms, but associations attenuated markedly when adjusting for SPT reactivity. CONCLUSIONS: Our results suggest that the positive association between alcohol consumption and CCD sensitization is universal and not specific to certain populations. The observed association between the ADH1b polymorphism and CCD sensitization may support that alcohol is causally related to the risk of CCD sensitization. The observed association between CCD sensitization and atopic phenotypes did not appear to be independent of SPT reactivity indicating limited significance of CCD sensitization per se.