title: Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease.
abstract: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.
  
  
  
  We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
authors.affiliation: 1 Division of Pulmonary, Allergy and Critical Care Medicine, and.|2 UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Surya P
authors.initials: SP
authors.lastname: Bhatt
authors.affiliation: 3 Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
authors.forename: Xavier
authors.initials: X
authors.lastname: Soler
authors.affiliation: 4 School of Public Health.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: 4 School of Public Health.
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.affiliation: 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.
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Anzueto
authors.affiliation: 6 Department of Epidemiology, School of Public Health, and.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: 7 Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Aladin M
authors.initials: AM
authors.lastname: Boriek
authors.affiliation: 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.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.affiliation: 9 Pulmonary and Critical Care Medicine, and.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.affiliation: 10 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Diaz
authors.affiliation: 1 Division of Pulmonary, Allergy and Critical Care Medicine, and.|2 UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: 11 Department of Biostatistics and Bioinformatics.|12 Department of Biostatistics and Informatics, and.
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.affiliation: 13 Department of Radiology, Center for Molecular Imaging.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Galbán
authors.affiliation: 14 Department of Radiology.|15 Department of Medicine, and.|16 Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: 17 Department of Pathology and Laboratory Medicine, University of British Columbia, and James Hogg Research Centre, St. Paul's Hospital, Vancouver, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
authors.affiliation: 18 Department of Radiology.
authors.forename: Ella A
authors.initials: EA
authors.lastname: Kazerooni
authors.affiliation: 9 Pulmonary and Critical Care Medicine, and.
authors.forename: Victor
authors.initials: V
authors.lastname: Kim
authors.affiliation: 19 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kinney
authors.affiliation: 20 Department of Pathology.
authors.forename: Amir
authors.initials: A
authors.lastname: Lagstein
authors.affiliation: 21 Department of Radiology, and.
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.affiliation: 22 Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.affiliation: 23 Division of Pulmonary & Critical Care Medicine, and.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: 3 Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramsdell
authors.affiliation: 24 Division of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Rishindra
authors.initials: R
authors.lastname: Reddy
authors.affiliation: 13 Department of Radiology, Center for Molecular Imaging.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.affiliation: 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.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Rossiter
authors.affiliation: 25 Department of Radiology, Temple University Hospital, Philadelphia, Pennsylvania.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Steiner
authors.affiliation: 11 Department of Biostatistics and Bioinformatics.|12 Department of Biostatistics and Informatics, and.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Strand
authors.affiliation: 26 Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.affiliation: 27 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.affiliation: 10 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.affiliation: 1 Division of Pulmonary, Allergy and Critical Care Medicine, and.|2 UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wells
authors.affiliation: 28 Minneapolis VAMC, Pulmonary, Allergy, Critical Care and Sleep Medicine Section, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Wendt
authors.affiliation: 29 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.affiliation: 27 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: 22 Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado.
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.affiliation: 22 Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.affiliation: 23 Division of Pulmonary & Critical Care Medicine, and.
authors.forename: MeiLan K
authors.initials: MK
authors.lastname: Han
mesh_terms: D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012137:Respiratory System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013147:Spirometry; D014057:Tomography, X-Ray Computed
keywords: FEV1; lung function; parametric response mapping