Key Risk Factors of Asthma-Like Symptoms Are Mediated Through Infection Burden in Early Childhood

The infection burden of young children is high, as are asthma-like symptoms, defined in this study as wheezing, cough, and shortness of breath. This study used previously identified risk factors for developing asthma-like symptoms to determine if an increased propensity for infection might act as a mediator between the risk factors and development of asthma-like symptoms. The previously identified risk factors that were associated with more asthma-like symptoms in the cohort were atopic dermatitis within the first 3 years of life, male sex, and lower birth weight. Previously identified parental asthma risk factors include maternal asthma (across years 0–3) and paternal asthma (more episodes in second year of life). Antibiotic use during pregnancy, Caesarean section delivery, and low vitamin D at 6 months of age also were shown to be risk factors.Utilizing the 2010 Copenhagen Prospective Studies on Asthma in Childhood, a prospective mother-child cohort study collected data from birth to 3 years of age. Infections were registered in daily diaries. Subjects whose diary was >90% compliant were included for analysis (662 of the original 700).Daily diary cards were used to log symptom tracking for the children that were suggestive of a cold, acute otitis media, gastroenteritis, acute tonsillitis, fever, and physician-diagnosed pneumonia. Asthma-like symptoms were also logged and defined when symptoms lasted for at least 3 consecutive days.There was a median of 16 (interquartile range 12–23) infectious episodes for children included in the study between ages 0 and 3. The study used mediation analyses and showed that infection burden significantly mediated the association of asthma-like episodes with the following factors: maternal asthma, siblings at birth, bacterial airway immune score, antibiotics during pregnancy, and asthma exacerbation polygenic risk score (all P average causal mediation effect < .05). Colds, pneumonia, gastroenteritis, and fever were statistically significant drivers, whereas otitis media and acute tonsillitis were not.Shared risk factors for the development of asthma-like symptoms and infections within the first 3 years of life were noted: siblings at birth, maternal asthma, receiving antibiotics during pregnancy, and 2 risk scores. The cohort also demonstrated that maternal asthma was associated with increased infection risk (for colds, pneumonias, and gastroenteritis).This study highlights the importance of preventing and managing infections during early childhood to reduce the number of asthma-like episodes in an at-risk population. The study also sheds light on the complex relationship between certain risk factors and the development of asthma, especially for those who do not seem to mediate the association through infection burden.