Dataset Information

Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF_25-75). Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition. Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera. Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD.

SUBMITTER: Opron K

PROVIDER: S-EPMC7865064 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort.

Opron Kristopher K Begley Lesa A LA Erb-Downward John R JR Freeman Christine C Madapoosi Siddharth S Alexis Neil E NE Barjaktarevic Igor I Graham Barr R R Bleecker Eugene R ER Bowler Russell P RP Christenson Stephanie A SA Comellas Alejandro P AP Cooper Christopher B CB Couper David J DJ Doerschuk Claire M CM Dransfield Mark T MT Han MeiLan K MK Hansel Nadia N NN Hastie Annette T AT Hoffman Eric A EA Kaner Robert J RJ Krishnan Jerry J O'Neal Wanda K WK Ortega Victor E VE Paine Robert R Peters Stephen P SP Michael Wells J J Woodruff Prescott G PG Martinez Fernando J FJ Curtis Jeffrey L JL Huffnagle Gary B GB Huang Yvonne J YJ

NPJ biofilms and microbiomes 20210205 1

Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome ...[more]

PMID: 33547327

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Project description:BackgroundThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD.Research questionAre there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes?Study design and methodsWe used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS.ResultsWe identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, -50 vs -39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of -68 mL/y vs -23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029).InterpretationIn non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment.Clinical trial registrationClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov.

Project description:BACKGROUNDMitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown.METHODSCell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters - including FEV1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure - were examined.RESULTSU-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.CONCLUSIONU-mtDNA levels may help to identify distinct clinical phenotypes and underlying pathobiological differences in males versus females with COPD.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov ( NCT01969344).FUNDINGUS NIH, National Heart, Lung and Blood Institute, supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics, Boehringer-Ingelheim Pharmaceuticals Inc., Chiesi Farmaceutici S.p.A., Forest Research Institute Inc., GlaxoSmithKline, Grifols Therapeutics Inc., Ikaria Inc., Novartis Pharmaceuticals Corporation, Nycomed GmbH, ProterixBio, Regeneron Pharmaceuticals Inc., Sanofi, Sunovion, Takeda Pharmaceutical Company, and Theravance Biopharma and Mylan.

Project description:RATIONALE:Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. OBJECTIVE:To determine the independent association between rural residence and COPD-related outcomes including COPD exacerbations, airflow obstruction and symptom burden. METHODS:A total of 1684 Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) participants with FEV1/FVC<0.70 had geocoding-defined rural-urban residence status determined (N=204 rural and N=1480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of home address to the block level at time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures.The primary outcome measures were exacerbations determined over the one-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. Odds ratio and incidence rate of exacerbations that required treatment with medications including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates. RESULTS:Rural residence was independently associated with 70% increase in odds of total exacerbations [OR 1.70 (95% CI 1.13-2.56); p=0.012] and 46% higher incidence rate of total exacerbations [IRR 1.46 (95% CI 1.02-2.10); p=0.039]. There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation to analysis attenuated the association between rural residence and odds and incidence rate of total exacerbations [OR 1.52 (95% CI 1.00-2.32; p=0.05) and IRR 1.39 (95% CI 0.97 - 1.99); p=0.07]. There was no difference in symptoms or airflow obstruction between rural and urban participants. CONCLUSIONS:Rural residence is independently associated with increased odds and incidence of total, but not severe COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of increased risk of COPD exacerbations in the rural population.

Project description:BackgroundQuantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.MethodsAn imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration.ResultsWe derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema.ConclusionsQCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.

Dataset Information

Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort.

Publications

Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort.

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