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Am J Respir Crit Care Med. 2015 Nov 15;192(10):1171-8. doi: 10.1164/rccm.201504-0736OC.

Clinical and Immunological Factors in Emphysema Progression. Five-Year Prospective Longitudinal Exacerbation Study of Chronic Obstructive Pulmonary Disease (LES-COPD).

Author information

1
1 Department of Medicine.
2
2 Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
3
3 Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
4
4 Department of Radiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and.
5
5 Michael E. DeBakey Veterans Affairs Center for Translational Research on Inflammatory Diseases, Houston Texas.
6
6 Department of Pathology and Immunology, and.
7
7 Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas.

Abstract

RATIONALE:

Cross-sectional studies of T-cell responses to self-antigens correlate with baseline emphysema severity.

OBJECTIVES:

We investigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEV1, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study.

METHODS:

We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history.

MEASUREMENTS AND MAIN RESULTS:

Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was +0.46 (0.92), ranging from -1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5-unit decrease in BMI; 95% confidence interval, +0.03 to +0.29). In active smokers, increased IFN-γ and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD.

CONCLUSIONS:

The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema.

KEYWORDS:

IFN-γ; IL-17; IL-6; T cells; emphysema progression

Comment in

PMID:
26241705
PMCID:
PMC4731622
DOI:
10.1164/rccm.201504-0736OC
[Indexed for MEDLINE]
Free PMC Article

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