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Systemic Cytokines, Clinical and Physiological Changes in Patients Hospitalized for Exacerbation of COPD^*

^* From the Division of Pulmonary and Critical Care Medicine (Drs. Pinto-Plata, Livnat, Girish, Dew, Kenney, and Celli), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA; Boston University School of Public Health (Dr. Cabral), Boston, MA; and Respiratory and Human Biomarkers Centers (Dr. Masdin and Mr. Linacre), GlaxoSmithKline, Stevenage-Ware, UK.

Correspondence to: Bartolome R. Celli, MD, FCCP, St. Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135; e-mail: bcelli{at}copdnet.org

Abstract

Background: Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited information relating levels of systemic inflammatory markers with symptoms and physiologic changes during an exacerbation

Methods: We measured dyspnea using the visual analog scale, pulmonary function tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene B₄ (LTB4), tumor necrosis factor-, and secretory leukocyte protease inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge (recovery).

Results: Dyspnea was present in all patients. Inspiratory capacity improved faster than FEV₁. Compared to recovery, there was a significant increase in the mean (± SD) hospital admission plasma levels of IL-6 (6.38 ± 0.72 to 2.80 ± 0.79 pg/mL; p = 0.0001), IL-8 (8.18 ± 0.85 to 3.72 ± 0.85 pg/mL; p = 0.002), and LTB4 (8,675 ± 1,652 to 2,534 ± 1,813 pg/mL; p = 0.003), and the percentages of segmented neutrophils (79 to 69%; p < 0.02) and band forms (7.3 to 1.0%; p < 0.01) in peripheral blood, with no changes in TNF- and SLPI. There were significant correlations between changes in IL-6 (r = 0.61; p = 0.01) and IL-8 (r = 0.56; p = 0.04) with changes in dyspnea and levels of IL-6 (r = –0.51; p = 0.04) and TNF- (r = –0.71; p < 0.02) with changes in FEV_1.

Conclusions: Hospitalized patients with ECOPDs experience significant changes in systemic cytokine levels that correlate with symptoms and lung function. An ECOPD represents not only a worsening of airflow obstruction but also increased systemic demand in a host with limited ventilatory reserve.

Key Words: chronic obstructive lung disease • cytokines • dyspnea • exacerbation

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