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

doi:10.1016/j.jaci.2007.08.045

Journal of Allergy and Clinical Immunology

Volume 120, Issue 5, November 2007, Pages 1118-1125

https://doi.org/10.1016/j.jaci.2007.08.045 Get rights and content

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.

Section snippets

Study subjects

Subjects with COPD were recruited based on chest CT scan evidence of emphysema, pulmonary function studies, and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) clinical evaluation (history of chronic cough, sputum production, and dyspnea).¹⁰ They also completed a standardized COPD questionnaire (ie, St George Questionnaire; possible score, 0-100).¹¹ Healthy individuals were nonsmokers who had no evidence of disease on history and physical examination and had a normal chest CT

COPD study subject CT scan results, pulmonary function test results, and clinical characteristics

The subjects with COPD (n = 16) had evidence of significant emphysema based on their chest CT scan results and FEV₁ values (Fig 1). In contrast, none of the subjects in either the healthy nonsmoking group (n = 7) or the current smoker group (n = 8) had evidence of COPD on chest CT scan or abnormalities of pulmonary function (Fig 1).

Subjects with COPD-E had a significantly higher chest CT scan score (36.8% ± 4.0% voxels < −920 HU) compared with those of either the healthy nonsmoking group (3.3%

Discussion

In this study we have demonstrated that subjects with GOLD stage III moderate-to-severe COPD-E (enrolled on the basis of CT scan evidence of emphysema rather than pulmonary function testing) express a biomarker profile (ECP-1 and eotaxin-1) associated with bronchodilator responsiveness and also correlated with the extent of emphysema on CT scanning. The significant correlation between BAL fluid ECP level and the extent of emphysema on chest CT scanning raises the possibility that activated

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: Supported by National Institutes of Health grants HL72342 and GCRC MO1RR000827.

: Disclosure of potential conflict of interest: M. Miller, J. Ramsdell, P. J. Friedman, J. Y. Cho, M. Renvall, and D. H. Broide have received grant support from the National Institutes of Health.

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

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Study subjects

COPD study subject CT scan results, pulmonary function test results, and clinical characteristics

Discussion

Lancet

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

Chronic obstructive pulmonary disease

N Engl J Med

Asthma

N Engl J Med

Bronchodilator response in chronic obstructive pulmonary disease

Am Rev Respir Dis

Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Factors associated with persistent airflow limitation in severe asthma

Am J Respir Crit Care Med

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