0
Original Research |

Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

Samuel Y. Ash, MD; Rola Harmouche, PhD; Rachel K. Putman, MD MPH; James C. Ross, PhD; Alejandro A. Diaz, MD MPH; Gary M. Hunninghake, MD MPH; Jorge Onieva Onieva, MSc; Fernando J. Martinez, MD MS; Augustine M. Choi, MD; David A. Lynch, MD; Hiroto Hatabu, MD PhD; Ivan O. Rosas, MD; Raul San Jose Estepar, PhD; George R. Washko, MD
Author and Funding Information

Summary of conflict of interest:

Financial and nonfinancial disclosures: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. Fundingfor this work includes: National Institutes of Health grants: 5-T32-HL007633-30 (Ash, Putman), R01-HL107246 (Washko, Estepar, Harmouche, Onieva Onieva), R01-HL116933 (Washko, Estepar, Ross, Harmouche, Onieva Onieva), R01-HL111024 (Hunninghake), P01-HL114501 (Choi, Rosas, Washko) and R01-HL089856 (Washko, Lynch, Estepar, Ross) and Boehringer-Ingelheim Pharmaceuticals, Inc. (Washko). Additionalsupportoutside of the submitted work includes: Dr. Diaz reports receiving speaker fees from Novartis and travel and accommodations from the COPD Foundation. Dr. Hunninghake reports consulting for Medna LLC, Gerson Lehrman Group, and Patients Like Me, and is on a scientific advisory board for Genentech. Dr. Martinez reports grants from GlaxoSmithKline, during the conduct of the study; personal fees from Bayer, personal fees, non-financial support and other from Boehringer Ingelheim, non-financial support and other from Centocor, non-financial support from Gilead Sciences, personal fees from Genentech, personal fees from Ikaria, personal fees from Kadmon, personal fees from Nycomed/Takeda, personal fees from Pfizer, personal fees from Veracyte, personal fees from American Thoracic Society, personal fees from Academic CME, personal fees from Falco, personal fees from National Association for Continuing Education, personal fees from Axon Communication, personal fees from Johnson & Johnson, non-financial support from Biogen/Stromedix, grants from National Institutes of Health, personal fees from Clarion, personal fees from Continuing Education, personal fees from Potomac, personal fees from Afferent, personal fees from Adept, personal fees from Forest , personal fees from Janssen, personal fees from GlaxoSmithKline, personal fees from Nycomed/Takeda, personal fees from Amgen, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Ikaria/Bellerophon, personal fees from Genentech, personal fees from Novartis, personal fees from Pearl, personal fees from Pfizer, personal fees from Roche, personal fees from Sunovion, personal fees from Theravane, personal fees from Axon, personal fees from CME Incite, personal fees from California Society for Allergy and Clinical Immunology, personal fees from Annenberg, personal fees from Integritas, personal fees from InThought, personal fees from Miller Medical, personal fees from National Association for Continuing Education, personal fees from Paradigm, personal fees from Peer Voice, personal fees from UpToDate, personal fees from Haymarket Communications, personal fees from Western Society of Allergy and Immunology, personal fees from Informa, from Bioscale, personal fees from Unity Biotechnology, personal fees from ConCert, personal fees from Lucid, personal fees from Methodist Hospital, personal fees from Columbia University, personal fees from Prime, personal fees from WebMD, personal fees from PeerView Network, outside the submitted work. Dr. Lynch reports grants from NHLBI, personal fees from Parexel, research support from Veracyte, personal fees from Boehringer Ingelheim, and personal fees from Genentech/Roche. Dr. Hatabu reports grant funding from Aze Inc, grant funding from Canon Inc, grant funding from Toshiba Medical System Inc, and is on an advisory board for Toshiba Medical System Inc. Dr. Washko reports other support from Genentech, GlaxoSmithKline, PulmonX, and Janssen.

Funding: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. Funding for the work was supported by National Institutes of Health grants: 5-T32-HL007633-30 (Ash, Putman), R01-HL107246 (Washko, Estepar, Harmouche, Onieva Onieva), R01-HL116933 (Washko, Estepar, Ross, Harmouche, Onieva Onieva), R01-HL111024 (Hunninghake), P01-HL114501 (Choi, Rosas, Washko) and R01-HL089856 (Washko, Lynch, Estepar, Ross) and Boehringer-Ingelheim Pharmaceuticals, Inc. (Washko).

aDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St., PBB, CA-3, Boston, MA 02115

bLaboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women’s Hospital, 1249 Boylston St., Boston, MA 02115

cDepartment of Medicine, Weil Cornell Medical College, 1300 York Avenue New York, NY 10065

dDepartment of Radiology, National Jewish Health, 1400 Jackson St, A330 Denver, CO 80206

eDepartment of Radiology, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115

Corresponding Author: Samuel Y. Ash MD Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St., PBB, CA-3, Boston, MA 02115, USA.


Copyright 2017, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2017.04.185
Text Size: A A A
Published online

Abstract

Background  Smoking related lung injury may manifest on computed tomography (CT) as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a MUC5B polymorphism.

Methods  Using CT scans from the COPDGene study, lung parenchyma was objectively labeled as a tissue subtype and the percentage of the lung occupied by interstitial subtypes was calculated.

Findings  8345 participants had clinical and CT data available. A 5% absolute increase in interstitial changes was associated with an absolute increase in percent predicted forced vital capacity of 2.47% (p<0.001) and a 1.36 point higher St. George’s Respiratory Questionnaire score (p<0.001). Among the 6827 participants with mortality data, a 5% increase in interstitial changes was associated with a 29% increased risk of death (p<0.001). These associations were present in a subgroup without visually defined interstitial lung abnormalities, as well as in those with normal spirometry, and in those without chronic respiratory symptoms. In non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter polymorphism there was a 0.63% (p=1x10-7) absolute increase in the percentage of lung with interstitial changes.

Conclusions  Objective interstitial changes on CT were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking related lung injury, detectable even in those who are normal by other measures.


Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543