Association between functional small airway disease and FEV1 decline in chronic obstructive pulmonary disease

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

Research output: Contribution to journalArticlepeer-review

258 Scopus citations


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 (PRMemph) and functional small airways disease (PRMfSAD), 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, PRMfSAD but not PRMemph was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRMfSAD and PRMemph 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 PRMfSAD and PRMemph 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 mildto-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with (NCT 00608764).

Original languageEnglish (US)
Pages (from-to)178-184
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number2
StatePublished - Jul 15 2016

Bibliographical note

Funding Information:
Supported by Award R01 HL089897, R01 HL089856, R01 HL122438, and R44 HL118837 from the NHLBI. The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion, and GlaxoSmithKline.


  • FEV
  • Lung function
  • Parametric response mapping


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