Computed tomographic scan-diagnosed chronic obstructive pulmonary disease-emphysema: eotaxin-1 is associated with bronchodilator response and extent of emphysema.

Abstract

Bronchodilator responses are a hallmark of asthma and a subset of chronic obstructive pulmonary disease (COPD). We evaluated subjects with COPD and computed tomographic (CT) scan evidence of emphysema to determine the biomarker profile associated with a bronchodilator response. We investigated whether subjects with COPD and a bronchodilator response had increased levels of bronchoalveolar lavage (BAL) fluid eosinophil biomarkers, T(H)2 cytokines, CC chemokines, and serum allergen-specific IgE. All patients with COPD and control subjects (n = 31) had chest CT scans to detect emphysema and subsequent pulmonary function studies, BAL for biomarkers, and serum IgE measurements. CT scan score, FEV(1), carbon monoxide single-breath diffusion capacity, and BAL fluid neutrophil biomarker levels were similar in subjects with COPD who had or did not have a bronchodilator response of greater than 12%. In contrast, levels of BAL fluid eosinophil biomarkers (eosinophil cationic protein [ECP] and eotaxin-1) were greater in patients with COPD with a bronchodilator response, whereas T(H)2 cytokines were not detectable in any patients with COPD. BAL fluid ECP and eotaxin-1 levels correlated with CT scan extent of emphysema. Immunostaining of COPD lung sections from a separate cohort of subjects with COPD and healthy subjects demonstrated epithelial expression of eotaxin-1 but no lung expression of IL-4 or IL-5. Subjects with COPD diagnosed on the basis of the presence of emphysema on CT scan who have a bronchodilator response have increased levels of BAL ECP and eotaxin-1 but not T(H)2 cytokines. Eosinophil biomarkers (ECP-1 and eotaxin-1) might identify a subset of subjects with COPD with emphysema on CT scans who have a bronchodilator response and an increased extent of emphysema on CT scanning.