Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications

Abstract

Background: Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs).

Methods: We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov.

Results: BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test).

Conclusions: Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort.

Keywords: Bronchiectasis; bronchiectasis exacerbation (BE); bronchodilator response (BDR); clinical parameter.

Conflict of interest statement

Conflicts of Interest: Profs. NS Zhong and RC Chen declared that they had received Changjiang Scholars and Innovative Research Team in University ITR0961, The National Key Technology R&D Program of the 12th National Five-year Development Plan 2012BAI05B01 and National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer No. 2013BAI09B09. Dr. Guan declared that he has received National Natural Science Foundation No. 81400010 and 2014 Scientific Research Projects for Medical Doctors and Researchers from Overseas, Guangzhou Medical University No. 2014C21. None of the funding sources had any role on this study. All other authors declared no potential conflicts of interest.

Figures

Figure 1

Recruitment flow chart. There were 129 bronchiectasis patients at baseline measurements and during longitudinal follow-up. A total of 101 bronchiectasis patients were followed-up for 1 year, and 65 patients (56 patients with non-significant bronchodilator responses, 9 patients with significant bronchodilator responses) were included in the analysis of the lung function trajectories and bronchiectasis exacerbations. BEs were defined as having 3 of the following items that persisted for at least 24 h: significantly increased sputum purulence/volume; dyspnea; considerably increased cough frequency; T >37.5 °C; hemoptysis; exercise intolerance or fatigue; increased crackles; increased pulmonary infiltrations. BDR, bronchodilator response.

Figure 2

Correlations between changes in FEV1 following bronchial dilation and baseline FEV1 and eosinophil count. A total of 129 bronchiectasis patients were included in the analysis. The dotted lines indicated the 95% confidence interval for the correlation. (A) Correlations between baseline FEV1 predicted and changes in FEV1 (%); (B) correlations between post-bronchodilator changes in FEV1 (%) and blood eosinophil percentage (r=0.15, P=0.18); (C) correlations between post-bronchodilator changes in FEV1 (%) and sputum eosinophil percentage (r=0.07, P=0.64).

Figure 3

Trajectories of FEV1% predicted and FEV1/FVC% during 1-year follow-up. A total of 65 bronchiectasis patients were included in the analysis because 28 patients were lost to follow-up. (A) Trajectories of FEV1% predicted during 1-year follow-up; (B) trajectories of FEV1/FVC% during 1-year follow-up.

Figure 4

Time to the first BEs within 1-year follow-up. Subgroup 0 (n=56): patients with non-significant bronchodilator responses; subgroup 1 (n=9): patients with significant bronchodilator responses; patients who were lost to follow-up were not included in the survival analysis. Patients with FEV1 >80% predicted at baseline were also not included in the analysis; subgroup 2 (n=51): patients with FEV1 >80% predicted at baseline.