Abstract Rationale Lipopolysaccharide (LPS) is a ubiquitous bacterial product that strongly stimulates the immune response. Past studies examining the association of early-life household exposure to LPS with asthma have yielded conflicting results, with some showing a protective effect and others a detrimental effect. We hypothesized that the effect of early-life household exposure to LPS on asthma would differ based on sociodemographic or environmental factors. To test this hypothesis, we capitalized on data from U.S. birth cohorts participating in the Children’s Allergy and Asthma Data Repository (CADRE). Our aims were to 1) test the association between early-life household exposure to LPS and asthma, and 2) determine whether this association is modified by sex, race and ethnicity, socioeconomic status, maternal asthma, or cohort asthma risk status (a surrogate marker for parental history of atopy). Methods This multicenter study included eight CADRE cohorts: four enrolled children at high risk of asthma, and four enrolled children from the general population. LPS concentrations were measured in household dust samples obtained in the first year of life. Our primary outcome was asthma at age 5-10 years, defined as parent report of physician diagnosis of asthma plus ≥1 wheezing episode in the past year. We used logistic regression to assess the association between LPS and childhood asthma, adjusting for potential confounders. In addition, we tested for effect modification by sex, race and ethnicity, socioeconomic status, maternal asthma, and cohort risk status. Results Our study population included 3,999 children. The LPS median concentration was 47.5 EU/mg of dust (interquartile range=17.1-101.8). The proportion of children with asthma was 349/2186 (16%). In adjusted analyses in the combined population, there was an effect modification of the association of early-life household LPS exposure with asthma by cohort asthma risk status (interaction p = 0.02). Early-life household LPS exposure was protective against the development of asthma in high-risk cohorts (aOR=0.80 95%CI=0.67-0.96, p = 0.01), whereas there was no association for general-risk cohorts (aOR=1.04 95%CI=0.77-1.41, p = 0.78) (Figure). There were no other significant effect modifications (p 0.05 for other interaction terms). Conclusions In this large multicenter study, early-life household exposure to higher levels of LPS was protective against the development of asthma in cohorts that enrolled children at high risk of asthma, but not in those that enrolled children from the general population. Cohort asthma risk status may be a marker for environmental or genetic risk factors that were not fully captured in this study and that we are now exploring. This abstract is funded by: NIH/NIAID, NIH/NHLBI, NIH/OD
Saxena et al. (2026) studied this question.