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Original Research |

A novel spirometric measure identifies mild chronic obstructive pulmonary disease unidentified by standard criteria

Asli Gorek Dilektasli, MD; Janos Porszasz, MD, PhD; Richard Casaburi, PhD, MD; William W. Stringer, MD; Surya P. Bhatt, MD; Youngju Pak, PhD; Harry B. Rossiter, PhD; George Washko, MD; Peter J. Castaldi, MD; Raul San Jose Estepar, PhD; James E. Hansen, MD
Author and Funding Information

Conflicts of interest statement: None declared (AGD, JP, RC, WWS, YP, HBR, PJC, RSJE, JEH). SPB is supported by NIH KL2 Scholarship, 1KL2TR001419. GW reports consultancies with GlaxoSmithKline and Genentech.

Funding: COPDGene is funded by Award Numbers R01HL089856 and R01HL089897 from the National Heart, Lung, and Blood Institute.

Some of the results of this study have been reported in the form of an abstract (Dilektasli AG, Porszasz J, Casaburi R, Stringer W, Bhatt SP, Pak Y, Washko G, Castaldi P, Estepar RSJ, Hansen JE, and the COPDGene Investigators. Diagnostic Value of Isolated Prebronchodilator FEV3/FEV6 Abnormality in Early Undiagnosed COPD. CHEST 2015;148:749A-749A.).

This article has an online data supplement.

1Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA

2Faculty of Medicine, Department of Pulmonary Medicine, Uludağ University, Turkey

3University of Alabama at Birmingham and UAB Lung Health Center, Birmingham, AL

4UCLA Clinical and Translational Science Institute at LA BioMed Harbor-UCLA Medical Center, Torrance, CA

5Faculty of Biological Sciences, University of Leeds, Leeds, UK

6Brigham and Women’s Hospital Clinics, Boston, MA

7Channing Division of Network Medicine and Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, Boston, MA

Corresponding author: Richard Casaburi, PhD, MD, Rehabilitation Clinical Trials Center Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center 1124 W. Carson St., Building CDCRC Torrance, California 90502


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.06.047
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Abstract

Rationale  In chronic obstructive pulmonary disease both smaller and larger airways are affected. Forced expiratory volume in one second (FEV1) mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow.

Objective  To evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6 seconds (FEV3/FEV6), and small airway measures and gas trapping in quantitative chest computed tomography (CT), and clinical outcomes in the COPDGene cohort.

Methods  7,853 current and ex-smokers were evaluated for airflow obstruction using recently-defined linear iteratively-derived equations of Hansen et al.1 to determine lower limits of normal equations for pre-bronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6 and FEV3/FVC. General linear and ordinal regression models were applied to the relation between pre-bronchodilator spirometry and radiologic and clinical data.

Main Results  Of the 10,311 participants included in the COPDGene Phase 1 study, participants with incomplete quantitative CT or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with ratio of FEV1 to forced vital capacity (FEV1/FVC) greater than lower limit of normal, 15.4% had abnormal FEV3/FEV6. Compared to participants with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping, St. George Respiratory Questionnaire score, mMRC dyspnea score, BODE index, and shorter six-minute walking distance (all P < 0.0001), but not CT-evidence of emphysema.

Conclusions  Current and ex-smokers with pre-bronchodilator FEV3/FEV6 < lower limit of normal as the sole abnormality identifies a distinct population with evidence of small airway disease in quantitative CT, impaired indices of physical function and quality of life otherwise deemed normal by current spirometric definition.


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