Early Childhood Infectious Diseases and the Development of Asthma up to School Age: A Birth Cohort Study

Abstract

Purpose of the Study. To investigate the association between early childhood infections and subsequent development of asthma.Study Population. A total of 1314 children born in 1990 followed from birth to the age of 7 years.Methods. A total of 499 newborn infants were recruited with risk factors for atopy (elevated cord blood immunoglobulin E (IgE) or at least 2 atopic family members) and 815 newborn infants without these risk factors. The cohort of children were followed at the ages of 1, 3, 6, 12, and 18 months, and from then on at yearly intervals up to the age of 7 years. At each follow-up, parents were interviewed on respiratory symptoms, the child’s development, and assessment of childhood illnesses, including the frequency and number of antibiotic courses used. IgE to milk, egg, soy, wheat, dust mite, cat, dog, grass, and birch were determined by radioallergo-sorbent testing at age 1, 2, 3, 4, 5, 6, and 7 years. At age 7, bronchial histamine challenge was performed to assess bronchial hyperreactivity. Main outcome measures included asthma symptoms, atopic sensitization, and bronchial hyperreactivity.Results. The number of lower respiratory tract infections in the first 3 years of life showed a positive dose-response with doctor-diagnosed asthma and bronchial hyperreactivity at age 7, with the strongest effect for >4 lower respiratory infections (odds ratio [OR]: 3.37; 95% confidence interval [CI]: 1.92–4.92). The total number of infectious diseases other than lower respiratory tract infections in first 3 years of life was inversely related to a diagnosis of asthma by age 7 years (OR: 0.31; 95% CI: 0.11–0.85) to current wheeze at age 7 (OR: 0.55; 95% CI: 0.20–1.48), and to bronchial hyperreactivity at age 7 (OR: 0.40; 95% CI: 0.16–1.01). Children with <1 episode of rhinorrhea before age 1 compared with those with >2 episodes were less likely to have a doctor’s diagnosis of asthma at 7 years (OR: 0.52; 95% CI: 0.29–0.92) or to have wheeze at 7 years (OR: 0.60; 95% CI: 0.38–0.94) and were less likely to be atopic before the age of 5 years. Similarly, having >1 viral infection of the herpes type in the first 3 years of life was inversely associated with asthma at age 7 (OR: 0.48; 95% CI: 0.26–0.89).Conclusion. Repeated viral infections other than lower respiratory tract infections early in life may reduce the risk of developing asthma up to school age.Reviewer’s Comments. The “hygiene hypothesis” has been a recent hot topic in attempts to understand the role of infections in early childhood and suggestion has been made that infections may stimulate the immature immune system towards the Th1 phenotype and therefore reduce the risk of asthma and atopy. This study found that although lower respiratory infections may increase the risk of developing asthma, upper respiratory infections may actually reduce the risk and may further support this “hygiene hypothesis.” Additional long-term studies such as this would be useful in our understanding of the complicated mix of environmental and genetic factors that play important roles in the development of atopy and asthma.