Relevance of the Hygiene Hypothesis to Early vs. Late Onset Allergic Rhinitis

Abstract

Matheson MC, Walters EH, Simpson JA, et al. Clin Exp Allergy. 2009;39(3):370–378PURPOSE OF THE STUDY. To compare the effects of siblings, infections, and rural environment on the development of allergic rhinitis before and after 7 years of age.STUDY POPULATION. The population-based cohort of participants in the Tasmanian Longitudinal Health Study (TAHS) was studied. Initial data were collected on 8583 children 7 years of age, comprising 99% of the schoolchildren in Tasmania born in 1961. The most recent follow-up evaluation occurred in 2004 and captured 5729 of the original participants at the age of 44 years, with the balance either lost to follow-up monitoring or deceased.METHODS. Subjects were categorized according to outcome, as those with early-onset allergic rhinitis (developed before the age of 7 years), those with late-onset allergic rhinitis (developed after the age of 7 years), and a reference group of those who did not report allergic rhinitis. The exposures considered were siblings, infections, tonsillectomy, and farm residence during childhood. Potential confounders considered were gender, maternal and paternal atopy, mother's age at participant's birth, paternal socioeconomic status in 1968, and personal socioeconomic status in 2004. Univariate associations were evaluated by using χ2 tests. Multinomial logistic regression was used to examine independent effects of different exposures on outcome with adjustment for confounders. The main analysis included 3429 subjects.RESULTS. Subjects with sibling exposure before the age of 2 had less early-onset allergic rhinitis than did those with no siblings (<1-year sibling exposure, odds ratio [OR]: 0.6 [95% confidence interval [CI]: 0.3–1.0]; 1- to 3-year sibling exposure, OR: 0.6 [95% CI: 0.4–0.9]; >3-year sibling exposure, OR: 0.4 [95% CI: 0.3–0.8]). This effect was dose dependent, with a P value of .0001 for trend. It was stronger than the effect of sibling exposure before 6 months or before 4 years. The trend for the effect of sibling exposure before the age of 2 was apparent (P = .001), although weaker, in late-onset allergic rhinitis. Early- but not later-onset allergic rhinitis decreased with viral infections during childhood (OR: 0.7 [95% CI: 0.5–0.9]). Tonsillectomy before the age of 7 increased the rate of early- but not later-onset allergic rhinitis (OR: 1.7 [95% CI: 1.2–2.5]).CONCLUSIONS. Exposures related to the hygiene hypothesis are more strongly related to early- than late-onset allergic rhinitis. The immunologic mechanisms for these risk factors are poorly understood. Additional research should focus on early-onset allergic rhinitis when exploring causal relationships for the effects demonstrated in this study.REVIEWERS COMMENTS. This large study is one of the few longitudinal studies to have examined the relationship between sibling exposure and allergic rhinitis; most other studies have been cross-sectional. The method of evaluation of sibling exposure quantifies both timing and dose and helps to pinpoint a potentially fruitful area for further research (before 2 years). One limitation is that the specific viral infections recorded for this study did not include viruses that primarily cause airway damage, such as respiratory syncytial virus and influenza. The mechanism for the effect of tonsillectomy is open to speculation. Possibilities include its significance as a marker of antibiotic use or, alternatively, a marker of severe, repeated, upper respiratory infection resulting in inflammation and, therefore, increased risk of sensitization via increased mucosal permeability.