Published ahead of print on August 29, 2007, doi:10.1164/rccm.200707-980OC Am. J. Respir. Crit. Care Med., Volume 176, Number 12, December 2007, 1200-1207 A more recent version of this article appeared on December 15, 2007
Submitted on July 3, 2007 Impaired Flow-mediated Dilation is Associated with Low Pulmonary Function and Emphysema in Ex-smokersR Graham Barr1*,1 Department of Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA, 2 Department of Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA, 3 Department of Radiology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA, 4 Department of Biomedical Engineering, College of Engineering, Cornell University, Ithaca, NY, USA, 5 School of Electrical and Computer Engineering, College of Engineering, Cornell University, Ithaca, NY, USA * To whom correspondence should be addressed. E-mail: rgb9{at}columbia.edu.
Rationale: Basic science research suggests a causal role for endothelial dysfunction in COPD. Clinical studies examining endothelial function are lacking, particularly early in the disease. Flow-mediated dilatation (FMD) is a physiologic measure of endothelial reactivity to endogenous nitric oxide. Objectives: We hypothesized that lower FMD among former smokers would be associated with lower post-bronchodilator FEV1, higher CT percent emphysema and lower diffusing capacity. Methods: We measured FMD, pulmonary function and CT percent emphysema in a random sample of 107 cotinine-confirmed former smokers in the ongoing EMCAP Study. FMD was defined as percent change in the brachial artery diameter with reactive hyperemia. Generalized additive models were used to adjust for potential confounders and assess linearity. Measurements and Main Results: Mean age of participants was 71±5 years, 46% were female,and packyears averaged 48±26. Mean FMD was 3.8±3.1%; mean post-bronchodilator FEV1, 2.3±0.8 L; and mean CT percent emphysema, 26±10%. A one SD decrease in FMD was associated with a 132 mL (95% CI: 16, 248; P=0.03) decrement in post-bronchodilator FEV1 and a 2.6% (95% CI 0.5, 4.7; P=0.02) increase in CT percent emphysema in fully adjusted models. These associations were linear across the spectrum from normality to disease, independent of smoking history, and also significant among participants without COPD. Associations with diffusing capacity were consistent but non-significant (P=0.09). The FMD-FEV1 association was entirely attributable to percent emphysema. Conclusions: Impaired endothelial function, as measured by FMD, was associated with lower FEV1 and higher CT percent emphysema in former smokers early in COPD. Key words: pulmonary disease, chronic obstructive; bronchitis, chronic; pulmonary emphysema; endothelial dysfunction
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