TY - JOUR
T1 - Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations
AU - National Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma Consortium
AU - McCauley, Kathryn E.
AU - Flynn, Kaitlin
AU - Calatroni, Agustin
AU - DiMassa, Vincent
AU - LaMere, Brandon
AU - Fadrosh, Douglas W.
AU - Lynch, Kole V.
AU - Gill, Michelle A.
AU - Pongracic, Jacqueline A.
AU - Khurana Hershey, Gurjit K.
AU - Kercsmar, Carolyn M.
AU - Liu, Andrew H.
AU - Johnson, Christine C.
AU - Kim, Haejin
AU - Kattan, Meyer
AU - O'Connor, George T.
AU - Bacharier, Leonard B.
AU - Teach, Stephen J.
AU - Gergen, Peter J.
AU - Wheatley, Lisa M.
AU - Togias, Alkis
AU - LeBeau, Petra
AU - Presnell, Scott
AU - Boushey, Homer A.
AU - Busse, William W.
AU - Gern, James E.
AU - Jackson, Daniel J.
AU - Altman, Matthew C.
AU - Lynch, Susan V.
N1 - Publisher Copyright:
© 2022
PY - 2022/7
Y1 - 2022/7
N2 - Background: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown. Objective: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe–host interactions modify risk of asthma exacerbation in a season-specific manner. Methods: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data were examined for seasonal dynamics and integrative analyses. Results: Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically, in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in virus-positive respiratory illnesses and those that progressed to exacerbations. The abundance of 2 discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus, exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase the odds of subsequent exacerbation (odds ratio = 14.7, 95% confidence interval = 1.50-144, P = .02; odds ratio = 39.17, 95% confidence interval = 2.44-626, P = .008, respectively). Conclusions: Upper airway microbiomes covary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally adjusted analyses reveal specific bacteria–host interactions that significantly increase risk of asthma exacerbation in these children.
AB - Background: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown. Objective: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe–host interactions modify risk of asthma exacerbation in a season-specific manner. Methods: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data were examined for seasonal dynamics and integrative analyses. Results: Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically, in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in virus-positive respiratory illnesses and those that progressed to exacerbations. The abundance of 2 discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus, exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase the odds of subsequent exacerbation (odds ratio = 14.7, 95% confidence interval = 1.50-144, P = .02; odds ratio = 39.17, 95% confidence interval = 2.44-626, P = .008, respectively). Conclusions: Upper airway microbiomes covary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally adjusted analyses reveal specific bacteria–host interactions that significantly increase risk of asthma exacerbation in these children.
KW - Microbiome
KW - exacerbations
KW - pediatric asthma
KW - respiratory illness
KW - transcriptomics
KW - virus infection
UR - http://www.scopus.com/inward/record.url?scp=85125628670&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2022.01.020
DO - 10.1016/j.jaci.2022.01.020
M3 - Article
C2 - 35149044
AN - SCOPUS:85125628670
SN - 0091-6749
VL - 150
SP - 204
EP - 213
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -