Abstract
Background The lung microbiome is an inflammatory stimulus whose role in chronic obstructive pulmonary disease (COPD) pathogenesis is incompletely understood. We hypothesized that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome, and inflammation longitudinally during exacerbation-free periods.
Methods We conducted a case-control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. Eighty-one subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral, and sputum microbiome samples at two visits over 2–4 months. Exacerbation phenotype, relevant clinical factors, and sputum cytokine values were associated with microbiome findings.
Results The frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit β-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025, p=0.014). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. IL-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012, p=0.0496). IL-22, IL-17A, and IL-5 levels were positively associated with Moraxella abundance (p=0.027, p=0.0014, p=0.0020).
Conclusions Even during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased β-diversity. Decreased sputum microbiome α-diversity and Moraxella abundance are associated with lung inflammation.
Footnotes
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Conflict of interest: Alexa Pragman reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH. Support for attending meetings and/or travel from US Department of Veterans Affairs, outside the submitted work.
Conflict of interest: Shane Hodgson reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH.
Conflict of interest: Tianhua Wu reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH.
Conflict of interest: Allison Zank reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH.
Conflict of interest: Cavan Reilly reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH. Grants or contracts from NIH, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for Mayo Clinic, and Washington University, outside the submitted work.
Conflict of interest: Chris Wendt reports support for the present manuscript from US Department of Veterans Affairs Office of Research and Development, and NIH.
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- Received August 14, 2023.
- Accepted November 7, 2023.
- Copyright ©The authors 2023
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