Chest

Chest

Volume 133, Issue 1, January 2008, Pages 19-25
Journal home page for Chest

Original Research
COPD
Systemic Inflammation and COPD: The Framingham Heart Study

https://doi.org/10.1378/chest.07-0058Get rights and content

Background

The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking.

Methods

Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function.

Results

IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV1 (95% confidence interval [CI], − 61 to − 20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV1 levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV1 that was on average 19 mL lower (95% CI, − 37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV1, and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories.

Conclusions

Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited.

Section snippets

Subjects, Covariates, and Measures of Pulmonary Function and Systemic Inflammation

Participants attending the most recent completed examination (ie, seventh, from 1998 to 2001) of the Offspring Cohort4 were eligible for inclusion. Informed consent was obtained in accordance with the protocol approved by the Institutional Review Board of Boston University Medical Center. The single-day examination included a variety of procedures, with phlebotomy after an overnight fast (typically between 8:00 am and 9:00 am) and subsequent spirometry without bronchodilator testing performed

Subject Characteristics

Participant characteristics are described in Table 1; the majority were female and had a history of cigarette smoking. Compared to those without evidence of chronic airflow obstruction, those with COPD were older, were more likely to be smokers, and had more pack-years of smoking exposure. Such differences between subjects with and without COPD also existed among the subgroup with at least 10 pack-years of cigarette smoking. Additionally, subjects with COPD generally had higher concentrations

Discussion

We observed significant cross-sectional associations between a number of the biomarkers of systemic inflammation and impaired lung function. Although there appeared to be some differences in the associations with impaired lung function between the smoking strata, in our exploratory analyses these differences were statistically significant only for the relation of CD40L to COPD.

CRP may have direct immunomodulatory effects in the lung1314151617 and has been previously associated with impaired

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    • Cited by (0)

    Support was provided by National Institutes of Health/National Heart, Lung, and Blood Institute contracts N01-HC-25195, N01-HV-28178, HL076784, HL064753, and AG028321. Drs. Walter and Wilk are each recipients of a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute.

    The authors have no conflicts of interests to disclose.

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    Copyright © 2008 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.