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Systemic inflammation and COPD: The Framingham Heart Study

Robert E. Walter, MD, MPH^,,*; Jemma B. Wilk, DSc; Martin G. Larson, ScD^,*; Ramachandran S. Vasan, MD^,,+; John F. Keaney, Jr., MD^,+; Izabella Lipinska, PhD; George T. O'Connor, MD, MS^,,* and Emelia J. Benjamin, MD, ScM^,,+,#,*

Section of Pulmonary, Allergy, and Critical Care Medicine, Boston University School of Medicine Evans Memorial Department of Medicine, Boston University School of Medicine Department of Neurology, Boston University School of Medicine, Boston University School of Medicine Whitaker Cardiovascular Institute ⁺Department of Cardiology and Preventive Medicine, Boston University School of Medicine Department of Mathematics and Statistics, Boston University, Boston, MA ^#Epidemiology Department, Boston University School of Public Health, Boston, MA ^*NHLBI's Framingham Study, Framingham, MA

walterb{at}bu.edu

Abstract

BackgroundThe current paradigm for the pathogenesis of chronic obstructive pulmonary disease (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.

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

ResultsInterleukin-6 was consistently associated with impaired lung function; one standard deviation higher concentration of interleukin-6 was associated with a 41mL lower FEV₁ (95%CI: -61, -20) and a borderline 15% higher odds of COPD (OR=1.15, 95%CI: 0.99, 1.34). Additionally, P-selectin was associated with lower FEV₁ levels; after adjusting for the other biomarkers, one standard deviation higher concentration of P-selectin predicted an FEV₁ that was on average 19mL lower (95% CI: -37, 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function-biomarker association; the relations of intercellular adhesion molecule-1 to FEV₁, and ICAM and CD40 ligand to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40 ligand and COPD appeared greater in individuals with more extensive smoking histories.

ConclusionsAmong participants in the Framingham 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.

Key Words: Pulmonary Disease • Chronic Obstructive • Forced expiratory volume • Inflammation • Interleukin-6 • CD40 Ligand • Intercellular Adhesion Molecule-1 • Monocyte Chemoattractant Protein-1 • P-selectin • myeloperoxidase

Related Editorial

Interleukin-6: A Red Herring or a Real Catch in COPD?

Don D. Sin and S. F. Paul Man
Chest 2008 133: 4-6. [Full Text] [PDF]

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				D. D. Sin and S. F. P. Man Interleukin-6: A Red Herring or a Real Catch in COPD? Chest, January 1, 2008; 133(1): 4 - 6. [Full Text] [PDF]