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Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction: A Cohort StudyEmphysema-like Lung on CT and All-Cause Mortality

Elizabeth C. Oelsner, MD, MPH; Eric A. Hoffman, PhD; Aaron R. Folsom, MD, MPH; J. Jeffrey Carr, MD; Paul L. Enright, MD; Steven M. Kawut, MD, MS; Richard Kronmal, PhD; David Lederer, MD, MS; Joao A.C. Lima, MD; Gina S. Lovasi, PhD; Steven Shea, MD, MS; and R. Graham Barr, MD, DrPH
[+] Article, Author, and Disclosure Information

From Columbia University, New York, New York; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; Wake Forest University, Winston-Salem, North Carolina; University of Arizona, Tucson, Arizona; University of Pennsylvania, Philadelphia, Pennsylvania; University of Washington, Seattle, Washington; and Johns Hopkins University, Baltimore, Maryland.

Note: Dr. Oelsner was primarily responsible for data analysis and drafting of the manuscript and vouches for the integrity of the data and analyses presented. All authors were involved in manuscript preparation, and all have approved the final manuscript.

Acknowledgment: The authors thank the other investigators, the staff, and the participants of MESA for their valuable contributions. A full list of participating MESA investigators and institutions can be found at www.mesa-nhlbi.org. The authors also thank the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene for providing data from which some of the information contained herein was derived.

Financial Support: MESA is supported by the NHLBI and was designed and conducted by the MESA investigators in collaboration with NHLBI staff. Support for MESA is provided by contracts N01-HC-95159 through N01-HC-95169, UL1-RR-024156, and UL1-RR-025005. The MESA Lung Study is funded by R01-HL077612, RC1-100543, and R01-93081 from the NHLBI.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2570.

Reproducible Research Statement:Study protocol (for the MESA Lung Study) and statistical code: Available from Dr. Oelsner (e-mail, eco7@cumc.columbia.edu). Data set: Available as a limited access data set from the NHLBI (www.mesa-nhlbi.org).

Requests for Single Reprints: Elizabeth C. Oelsner, MD, MPH, Columbia University Medical Center, 630 West 168th Street, PH 9 East Room 105, New York, NY 10032; e-mail, eco7@cumc.columbia.edu.

Current Author Addresses: Drs. Oelsner, Shea, and Barr: Columbia University Medical Center, 630 West 168th Street, PH 9 East Room 105, New York, NY 10032.

Dr. Hoffman: Department of Radiology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242.

Dr. Folsom: Division of Epidemiology and Community Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454.

Dr. Carr: Department of Radiology, Vanderbilt University Medical Center, 1161 21st Avenue South, CCC-1108 Medical Center North, Nashville, TN 37232-2675.

Dr. Enright: Department of Medicine, University of Arizona, 4460 East Ina Road, Tucson, AZ 85718.

Dr. Kawut: University of Pennsylvania, 718 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Dr. Kronmal: Collaborative Health Studies Coordinating Center, University of Washington, 6200 NE 74th Street 310, Seattle, WA 98115.

Dr. Lederer: Columbia University, 622 West 168th Street, PH-14, Room 104, New York, NY 10032.

Dr. Lima: Johns Hopkins University, 600 North Wolfe Street, Blalock 524, Baltimore, MD 21287.

Dr. Lovasi: Columbia University, 722 West 168th Street, 8th Floor, New York, NY 10032.

Author Contributions: Conception and design: E.C. Oelsner, E.A. Hoffman, S.M. Kawut, J.A.C. Lima, G.S. Lovasi, R.G. Barr.

Analysis and interpretation of the data: E.C. Oelsner, E.A. Hoffman, S.M. Kawut, D. Lederer, G.S. Lovasi, R.G. Barr.

Drafting of the article: E.C. Oelsner, S.M. Kawut, J.A.C. Lima.

Critical revision of the article for important intellectual content: A.R. Folsom, J.J. Carr, P.L. Enright, S.M. Kawut, D. Lederer, J.A.C. Lima, G.S. Lovasi, S. Shea, R.G. Barr.

Final approval of the article: E.A. Hoffman, A.R. Folsom, J.J. Carr, S.M. Kawut, R. Kronmal, D. Lederer, J.A.C. Lima, G.S. Lovasi, S. Shea, R.G. Barr.

Provision of study materials or patients: E.A. Hoffman, J.J. Carr, S. Shea.

Statistical expertise: R. Kronmal, G.S. Lovasi, R.G. Barr.

Obtaining of funding: E.A. Hoffman, J.J. Carr, S. Shea, R.G. Barr.

Administrative, technical, or logistic support: E.A. Hoffman, J.J. Carr, R. Kronmal.

Collection and assembly of data: E.C. Oelsner, E.A. Hoffman, J.J. Carr, P.L. Enright, R.G. Barr.

Ann Intern Med. 2014;161(12):863-873. doi:10.7326/M13-2570
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Background: Low lung function is known to predict mortality in the general population, but the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) is uncertain.

Objective: To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons in the general population without airflow obstruction or COPD.

Design: Prospective cohort study.

Setting: Population-based, multiethnic sample from 6 U.S. communities.

Participants: 2965 participants aged 45 to 84 years without airflow obstruction on spirometry.

Measurements: Emphysema-like lung was defined as the number of lung voxels with attenuation less than −950 Hounsfield units on cardiac CT and was adjusted for the number of total imaged lung voxels.

Results: Among 2965 participants, 50.9% of whom had never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio per one-half interquartile range, 1.14 [95% CI, 1.04 to 1.24]; P  = 0.004) after adjustment for potential confounders, including cardiovascular risk factors and FEV1. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status.

Limitations: Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses.

Conclusion: Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted.

Primary Funding Source: National Heart, Lung, and Blood Institute.


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Appendix Figure 1.

Study flow diagram.

CT = computed tomography; MESA = Multi-Ethnic Study of Atherosclerosis.

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Figure 1.

Lung windows from cardiac and full-lung CT scans in a MESA participant.

CT = computed tomography; MESA = Multi-Ethnic Study of Atherosclerosis.

Left. Cardiac CT scan. The dashed lines indicate the cephalad one eighth and caudal one third, which demarcate the upper-lobe and basilar regions, respectively. Right. Full-lung CT scan.

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Appendix Figure 2.

Bland–Altman plot of imaged lung volume on paired cardiac CT scans at the MESA baseline examination, 2000 to 2002, for all MESA Lung Study participants.

The average imaged lung volume among the paired scans is shown on the x-axis, and the difference in imaged lung volume between the paired scans is shown on the y-axis. The red lines correspond to the limits of agreement. There was a high level of agreement with respect to imaged lung volume between the paired scans (intraclass correlation coefficient, 0.93) and no evidence for systematic bias across the range of imaged lung volume values. CT = computed tomography; MESA = Multi-Ethnic Study of Atherosclerosis.

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Figure 2.

Regions of emphysema-like lung and all-cause mortality among all participants without airflow obstruction ( n  = 2965).

Dotted lines indicate 95% CIs. Dashed line indicates a hazard ratio of 1.

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Figure 3.

Regions of emphysema-like lung and all-cause mortality, stratified by smoking status.

Dotted lines indicate 95% CIs. Dashed line indicates a hazard ratio of 1.

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