Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children Susan V. Lynch, PhD, Robert A. Wood, MD, Homer.

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Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children Susan V. Lynch, PhD, Robert A. Wood, MD, Homer Boushey, MD, Leonard B. Bacharier, MD, Gordon R. Bloomberg, MD, Meyer Kattan, MD, George T. O’Connor, MD, Megan T. Sandel, MD, Agustin Calatroni, MS, Elizabeth Matsui, MD, Christine C. Johnson, PhD, Henry Lynn, PhD, Cynthia M. Visness, PhD, Katy F. Jaffee, MS, Peter J. Gergen, MD, Diane R. Gold, MD, MPH, Rosalind J. Wright, MD, MPH, Kei Fujimura, PhD, Marcus Rauch, PhD, William W. Busse, MD, James E. Gern, MD Journal of Allergy and Clinical Immunology Volume 134, Issue 3, Pages 593-601.e12 (September 2014) DOI: 10.1016/j.jaci.2014.04.018 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Relationships between specific allergen exposures and recurrent wheezing. A, Probability of recurrent wheeze (95% CIs) according to the number of allergen exposures (cockroach, mouse, and/or cat). B-E, Probability of recurrent wheeze (95% CI) determined by using logistic regression. Fig 1, C is shown stratified by aeroallergen sensitivity (pink = sensitive, blue = not sensitive). Fig 1, D and E, show the probability of recurrent wheeze for allergen exposures during years 2 and 3. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 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, and greater intersample 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 was compared with those of the Atopy (Fig 2, D), Both (Fig 2, E), and Wheeze (Fig 2, F) groups to identify specific bacterial taxa associated with clinical outcomes. Taxa in the left lower quadrant are underrepresented in the Atopy (Fig 2, D) and Both (Fig 2, E) groups compared with the Neither group. Colors indicate phylum-level classification of individual taxa, and the horizontal lines indicate P values of less than .05 after correction for false discovery rates. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 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 with the distribution in the Neither group. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Relationship of recurrent wheeze, aeroallergen sensitization, and eczema at age 3 years. The Venn diagram illustrates overall rates and interrelationships between recurrent wheeze, sensitization to at least 1 aeroallergen, and eczema. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Distribution of first-year bedroom allergen levels by site. The box plots represent 25th and 50th percentiles, medians are represented by horizontal lines, and whisker bars represent the 10th and 90th percentiles. BA, Baltimore; BO, Boston; NY, New York; SL, St Louis. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Median bacterial taxa richness by study group in the nested case-control study. P values represent pairwise comparisons with the Neither group, and the horizontal line illustrates the overall median value for bacterial richness for all groups combined. Overall P = .02. Journal of Allergy and Clinical Immunology 2014 134, 593-601.e12DOI: (10.1016/j.jaci.2014.04.018) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions