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Systemic Biomarker Pattern in Different Chronic Obstructive Pulmonary Disease Phenotypes Independent of Smoking Status

Department of Pulmonary, Allergy, and Critical Care Medicine; University of Pittsburgh Cancer Institute; and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Frank C. Sciurba, M.D., Associate Professor of Medicine, Director, Emphysema Research Center, Division of Pulmonary and Critical Care Medicine, University of Pittsburgh, 3471 5th Avenue, Suite 1211, Pittsburgh, PA 15212. E-mail: sciurbafc{at}upmc.edu

Background: Chronic obstructive pulmonary disease (COPD) is a disease consisting of a spectrum of distinct and often unassociated clinical and physiologic phenotypic domains, such as impariment in FEV₁, hyperinflation, diffusion, dyspnea, sputum production, and body mass index (BMI). We hypothesized that variations in these phenotypes would be associated with differences in systemic inflammatory profiles and independent of tobacco status.

Methods: We analyzed 32 inflammatory biomarkers from peripheral blood samples using a protein suspended bead array platform (LabMAP; Luminex Corp., Austin, TX). Phenotype categories included the following: (1) FEV₁ severity (0 = FEV₁ > 80% pred, 1 = FEV₁ 40–65%, 2 = FEV₁ < 40%), (2) sputum production (0 = never or only with infections, 1 = few to several days/week, 2 = most days/week), (3) dyspnea (Medical Research Council [MRC] scale), (4) DL_CO (triads), (5) hyperinflation (residual volume [RV] triads), (6) BMI, and (7) smoking status. Relationships between biomarkers and phenotype categories were adjusted to be independent of FEV₁. Comparisons used analysis of covariance and Tukey's biweight robust method.

Results: Thirty-nine subjects (age, 63 ± 8 yr; 20 male) with COPD (FEV₁, 59 ± 27%; range, 14–101%) were studied. A subset (n = 34) also had DL_CO (52 ± 18%) measured. FEV₁ was associated with differences in epidermal growth factor (EGF) and monocyte chemoattractant protein-1 (MCP-1) levels. After adjustment for FEV₁, unique inflammatory biomarker profiles were demonstrated among several phenotypes. Sputum production was associated with differences in interleukin (IL)-8, macrophage inflammatory protein (MIP)-1b, eotaxin, and IP-10, whereas smoking status was associated with differences in eotaxin, interferon gamma-inducible protein 10 (IP-10), and IL-12p40. Dyspnea severity was associated with differences IL-12p40 and RANTES (regulated upon activation, T-cell expressed and secreted). DL_CO was associated with differences in IL-1a and IL-6. No biomarkers were associated with hyperinflation or BMI.

Conclusions: Various clinical and physiologic phenotypes are associated with differences in systemic inflammatory biomarker profiles. These differences may elucidate pathophysiologic mechanisms of disease and contribute to the molecular understanding of the clinical and physiologic heterogeneity of patients with COPD. Furthermore, these inflammatory profiles do not parallel those induced by current smoking status, supporting an independent COPD-related inflammatory process.

FOOTNOTES

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form March 20, 2006; accepted in final form March 28, 2006)

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, S. A. Articles by Sciurba, F. C. Search for Related Content PubMed Articles by Patel, S. A. Articles by Sciurba, F. C.