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Am J Respir Crit Care Med. 2016 Jul 15;194(2):178-84. doi: 10.1164/rccm.201511-2219OC.

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

Author information

1
1 Division of Pulmonary, Allergy and Critical Care Medicine, and.
2
2 UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
3
3 Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
4
4 School of Public Health.
5
5 Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System, San Antonio, Texas.
6
6 Department of Epidemiology, School of Public Health, and.
7
7 Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
8
8 Division of Pulmonary and Critical Care Physiology and Medicine, and Rehabilitation Clinical Trials Center Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
9
9 Pulmonary and Critical Care Medicine, and.
10
10 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
11
11 Department of Biostatistics and Bioinformatics.
12
12 Department of Biostatistics and Informatics, and.
13
13 Department of Radiology, Center for Molecular Imaging.
14
14 Department of Radiology.
15
15 Department of Medicine, and.
16
16 Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa.
17
17 Department of Pathology and Laboratory Medicine, University of British Columbia, and James Hogg Research Centre, St. Paul's Hospital, Vancouver, Canada.
18
18 Department of Radiology.
19
19 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado.
20
20 Department of Pathology.
21
21 Department of Radiology, and.
22
22 Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado.
23
23 Division of Pulmonary & Critical Care Medicine, and.
24
24 Division of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan.
25
25 Department of Radiology, Temple University Hospital, Philadelphia, Pennsylvania.
26
26 Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom.
27
27 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and.
28
28 Minneapolis VAMC, Pulmonary, Allergy, Critical Care and Sleep Medicine Section, University of Minnesota, Minneapolis, Minnesota.
29
29 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

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).

KEYWORDS:

FEV1; lung function; parametric response mapping

PMID:
26808615
PMCID:
PMC5003216
DOI:
10.1164/rccm.201511-2219OC
[Indexed for MEDLINE]
Free PMC Article

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