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

Background

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.

Objective

We investigated whether subjects with COPD and a bronchodilator response had increased levels of bronchoalveolar lavage (BAL) fluid eosinophil biomarkers, T_H2 cytokines, CC chemokines, and serum allergen-specific IgE.

Methods

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.

Results

CT scan score, FEV₁, 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_H2 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.

Conclusion

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_H2 cytokines.

Clinical implications

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.

Key words: Asthma, eosinophil, eotaxin, cytokines, chemokines

Abbreviations used: BAL, Bronchoalveolar lavage, COPD, Chronic obstructive pulmonary disease, COPD-E, Chronic obstructive pulmonary disease–emphysema, COPD-E (BD+), Chronic obstructive pulmonary disease–emphysema with bronchodilator response, COPD-E (BD−), Chronic obstructive pulmonary disease–emphysema with no bronchodilator response, CT, Computed tomography, Dlco, Carbon monoxide single-breath diffusion capacity, ECP, Eosinophil cationic protein, GOLD, Global Initiative for Chronic Obstructive Lung Disease, LTB₄, Leukotriene B₄, MPO, Myeloperoxidase, UCSD, University of California San Diego