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

Authors: Bhatt, Surya P; Soler, Xavier; Wang, Xin; Murray, Susan; Anzueto, Antonio R; Beaty, Terri H; Boriek, Aladin M; Casaburi, Richard; Criner, Gerard J; Diaz, Alejandro A; Dransfield, Mark T; Curran-Everett, Douglas; Galbán, Craig J; Hoffman, Eric A; Hogg, James C; Kazerooni, Ella A; Kim, Victor; Kinney, Gregory L; Lagstein, Amir; Lynch, David A; Make, Barry J; Martinez, Fernando J; Ramsdell, Joe W; Reddy, Rishindra; Ross, Brian D; Rossiter, Harry B; Steiner, Robert M; Strand, Matthew J; van Beek, Edwin J R; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Chris H; Wise, Robert A; Silverman, Edwin K; Crapo, James D; Bowler, Russell P; Han, MeiLan K; COPDGene Investigators

Published In Am J Respir Crit Care Med, (2016 07 15)

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).

PubMed ID: 26808615 Exiting the NIEHS site

MeSH Terms: Female; Forced Expiratory Volume/physiology; Humans; Lung/diagnostic imaging; Lung/physiopathology; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive/diagnostic imaging; Pulmonary Disease, Chronic Obstructive/physiopathology*; Respiratory System/diagnostic imaging; Respiratory System/physiopathology*; Spirometry; Tomography, X-Ray Computed

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