Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children

Abstract

Background: Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma.

Objective: We sought to examine environmental factors associated with recurrent wheezing in inner-city environments.

Methods: The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years.

Results: Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P ≤ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze.

Conclusions: In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.

Keywords: Asthma; allergen exposure; atopy; inner city; microbial exposure.

Figure 1

Relationships between specific allergen exposures and recurrent wheezing. (A) Probability of recurrent wheeze (95% confidence intervals [CI]) according to the number of allergen exposures (cockroach, mouse and/or cat). (B–E) Probability of recurrent wheeze (95% CI) determined by logistic regression; (C) is stratified by aeroallergen sensitivity (pink=sensitive, blue=not sensitive), (D) and (E) show the probability of recurrent wheeze for allergen exposures during years 2 and 3.

Figure 2

House dust microbiome composition is associated with clinical outcomes. (A–C) Similarity or dissimilarity of house dust microbiota composition is indicated by the distance between samples (colored dots); samples plotted close together are compositionally similar, greater inter-sample distance indicates compositionally distinct bacterial communities. Ellipses represent 95% CIs for each group. (D–F) Mean taxon relative abundance across house dust samples from the Neither group were compared to those of the Atopy (D), Both (E) and Wheeze (F) groups to identify specific bacterial taxon associated with clinical outcomes. Taxa in the left lower quadrant are underrepresented in the Atopy (D) and Both (E) groups compared to the Neither group. Colors indicate phylum-level classification of individual taxa, and the horizontal lines indicate p<0.05 after correction for false discovery rates.

Figure 2

House dust microbiome composition is associated with clinical outcomes. (A–C) Similarity or dissimilarity of house dust microbiota composition is indicated by the distance between samples (colored dots); samples plotted close together are compositionally similar, greater inter-sample distance indicates compositionally distinct bacterial communities. Ellipses represent 95% CIs for each group. (D–F) Mean taxon relative abundance across house dust samples from the Neither group were compared to those of the Atopy (D), Both (E) and Wheeze (F) groups to identify specific bacterial taxon associated with clinical outcomes. Taxa in the left lower quadrant are underrepresented in the Atopy (D) and Both (E) groups compared to the Neither group. Colors indicate phylum-level classification of individual taxa, and the horizontal lines indicate p<0.05 after correction for false discovery rates.

Figure 3

Distribution of allergen and bacterial exposure among children with atopy, recurrent wheeze, atopy with wheeze and neither outcome. Exposure to allergen is classified as high or low with respect to the median of the allergen exposure index, and richness of exposure to all microbes (A) or taxa of interest (B). The distribution of exposure in each outcome group is compared to the distribution in the "Neither" group.