Dataset Information

Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease.

ABSTRACT:

Rationale

The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.

Objectives

We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.

Methods

We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping.

Measurements and main results

Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM(fSAD) but not PRM(emph) was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRM(fSAD) and PRM(emph) were associated with FEV1 decline (P < 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM(fSAD) and PRM(emph) in GOLD 1/2 and 3/4, respectively.

Conclusions

CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

SUBMITTER: Bhatt SP

PROVIDER: S-EPMC5003216 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease.

Bhatt Surya P SP Soler Xavier X Wang Xin X Murray Susan S Anzueto Antonio R AR Beaty Terri H TH Boriek Aladin M AM Casaburi Richard R Criner Gerard J GJ Diaz Alejandro A AA Dransfield Mark T MT Curran-Everett Douglas D Galbán Craig J CJ Hoffman Eric A EA Hogg James C JC Kazerooni Ella A EA Kim Victor V Kinney Gregory L GL Lagstein Amir A Lynch David A DA Make Barry J BJ Martinez Fernando J FJ Ramsdell Joe W JW Reddy Rishindra R Ross Brian D BD Rossiter Harry B HB Steiner Robert M RM Strand Matthew J MJ van Beek Edwin J R EJ Wan Emily S ES Washko George R GR Wells J Michael JM Wendt Chris H CH Wise Robert A RA Silverman Edwin K EK Crapo James D JD Bowler Russell P RP Han MeiLan K MK

American journal of respiratory and critical care medicine 20160701 2

<h4>Rationale</h4>The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.<h4>Objectives</h4>We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.<h4>Methods</h4>We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with air ...[more]

PMID: 26808615

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Project description:<p>Progressive decline in lung function is a hallmark of chronic obstructive pulmonary disease (COPD). Although airway dysbiosis occurs in COPD, whether it contributes to disease progression remains unknown. Here, through a longitudinal analysis on 181 COPD individuals from two large cohorts involving four UK clinical centers, we showed that baseline airway dysbiosis, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. Co-presence of Moraxella, Staphylococcus and Stenotrophomonas was associated with an accelerated FEV1 decline by 139.7 mL/year. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at clinical stability, two critical events contributing to long-term FEV1 decline. The microbiota association with FEV1 decline was validated in a third, independent cohort in China. Human multi-omics, murine and cellular mechanistic studies showed that chronic airway colonization of Staphylococcus aureus promoted lung function decline through producing homocysteine, which elicited an apoptosis-to-NETosis shift in neutrophils toward persistent inflammation via AKT1-S100A8/A9 axis. Prophylactic and therapeutic depletion of S. aureus via bacteriophage restored lung function in emphysema mice. These results provide a fresh approach to slow COPD progression by targeting the airway microbiome.</p><p><br></p><p><strong>Linked studies:</strong></p><p><strong>UPLC-MS/MS assays</strong> of human samples are reported in this study.</p><p><strong>UPLC-MS/MS assays</strong> of murine samples are reported in<strong> </strong><a href='https://www.ebi.ac.uk/metabolights/MTBLS6894' rel='noopener noreferrer' target='_blank'><strong>MTBLS6894</strong></a>.</p><p><strong>UPLC-MS/MS assays</strong> of original cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4017' rel='noopener noreferrer' target='_blank'><strong>MTBLS4017</strong></a>.</p>

Dataset Information

Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease.

Similar Datasets

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