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Chronic obstructive pulmonary disease upper airway microbiota alpha diversity is associated with exacerbation phenotype: a case-control observational study.
Pragman, Alexa A; Knutson, Katherine A; Gould, Trevor J; Isaacson, Richard E; Reilly, Cavan S; Wendt, Chris H.
Afiliação
  • Pragman AA; Department of Medicine, University of Minnesota and Minneapolis Veterans Affairs Medical Center, 1 Veterans Dr, Minneapolis, MN, 55417, USA. alexa@umn.edu.
  • Knutson KA; Minneapolis VA Health Care System, Attn: Dr. Alexa Pragman, Research Service (151), 1 Veterans Drive, Minneapolis, MN, 55417, USA. alexa@umn.edu.
  • Gould TJ; Division of Biostatistics, University of Minnesota School of Public Health, University Office Plaza, 2221 University Ave. SE - Suite 200, Minneapolis, MN, 55414, USA.
  • Isaacson RE; University of Minnesota Informatics Institute, Biological Science Dean's Office, Room 123 SnH, 6174A, 1475 Gortner Ave, St. Paul, MN, 55108, USA.
  • Reilly CS; Department of Veterinary and Biomedical Sciences, University of Minnesota, Room 205G VetS, 6187A, 1971 Commonwealth Ave, St. Paul, MN, 55108, USA.
  • Wendt CH; Division of Biostatistics, University of Minnesota School of Public Health, University Office Plaza, 2221 University Ave. SE - Suite 200, Minneapolis, MN, 55414, USA.
Respir Res ; 20(1): 114, 2019 Jun 07.
Article em En | MEDLINE | ID: mdl-31174538
ABSTRACT

BACKGROUND:

Chronic obstructive pulmonary disease (COPD) frequent exacerbators (FE) suffer increased morbidity and mortality compared to infrequent exacerbators (IE). The association between the oral and sputum microbiota and exacerbation phenotype is not well defined. The objective of this study was to determine key features that differentiate the oral and sputum microbiota of FEs from the microbiota of IEs during periods of clinical stability.

METHODS:

We recruited 11 FE and 11 IE who had not used antibiotics or systemic corticosteroids in the last 1 month. Subjects provided oral wash and sputum samples, which underwent 16S V4 MiSeq sequencing and qPCR of 16S rRNA. Data were analyzed using Dada2 and R.

RESULTS:

FE and IE were similar in terms of age, FEV1 percent predicted (FEV1pp), pack-years of tobacco exposure, and St. George's Respiratory Questionnaire score. 16S copy numbers were significantly greater in sputum vs. oral wash (p = 0.01), but phenotype was not associated with copy number. Shannon diversity was significantly greater in oral samples compared to sputum (p = 0.001), and IE samples were more diverse than FE samples (p < 0.001). Sputum samples from FE had more Haemophilus and Moraxella compared to IE sputum samples, due to dominance of these COPD-associated taxa in three FE sputum samples. Amplicon sequencing variant (ASV)-level analysis of sputum samples revealed one ASV (Actinomyces) was significantly more abundant in IE vs. FE sputum (padj = 0.048, Wilcoxon rank-sum test), and this persisted after controlling for FEV1pp. Principal coordinate analysis using Bray-Curtis distance with PERMANOVA analyses demonstrated clustering by anatomic site, phenotype, inhaled corticosteroid use, current tobacco use, COPD severity, and last professional dental cleaning.

CONCLUSIONS:

FE have less diverse oral and sputum microbiota than IE. Actinomyces was significantly more abundant in IE sputum than FE sputum. The oral and sputum microbiota of COPD subjects cluster based on multiple clinical factors, including exacerbation phenotype. Even during periods of clinical stability, the frequent exacerbator phenotype is associated with decreased alpha diversity, beta-diversity clustering, and changes in taxonomic abundance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Doença Pulmonar Obstrutiva Crônica / Microbiota / Pulmão Tipo de estudo: Observational_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Doença Pulmonar Obstrutiva Crônica / Microbiota / Pulmão Tipo de estudo: Observational_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article