Paradoxical Effect From Bronchodilators Linked to Worse Quality of Life in COPD

March 22, 2021
Skylar Jeremias

A study of Korean patients with chronic obstructive pulmonary disease (COPD) found that a paradoxical response to short-acting bronchodilators may reduce lung function and quality of life.

A decrease in lung function after bronchodilator administration may be independently linked with chronic airway inflammation and poor quality of life in patients with chronic obstructive pulmonary disease (COPD), according to a Korean study published in the Journal of Thoracic Disease.

The study is the first to assess COPD clinical outcomes associated with this paradoxical bronchodilator response (BDR) in an Asian population, the authors said.

Although post-bronchodilator spirometry is necessary to diagnosis COPD, the role of BDR, which the investigators defined as a decrease in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after administering a short-acting bronchodilator, is not well characterized in COPD.

It has been suggested in previous studies that a paradoxical BDR may be linked to inhaler use errors or a response to certain inhaler ingredients, but the mechanisms that causes this response is unclear.

The investigators gathered data from January 2012 and December 2017 from patients enrolled in the Korea COPD Subgroup Study (KOCOSS), an ongoing, longitudinal, noninterventional, observational study. Patients included in the analysis were over age 40, had an FEV1 or FVC value post-bronchodilator greater than 0.7, and experienced symptoms including cough, sputum, and dyspnea.

The evaluation contained information from patients’ pulmonary function tests, 6-minute walk distance tests, COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, COPD-specific St George’s Respiratory Questionnaire (SGRQ-C), exacerbations in the past year, smoking status, medications, and comorbidities.

Out of the 2279 patients included in the analyzed cohort from the KOCOSS, 1991 patients were included in this analysis. The investigators found that 2.9% (n = 57) of patients had a paradoxical BDR. The mean ages of the patients were 68.8 years for the paradoxical BDR group and 69.2 years for the nonparadoxical BDR group. Men represented 87.7% of the paradoxical BDR group and 90.8% of the nonparadoxical BDR group.

The FEV1 values pre-bronchodilator was higher among patients in the paradoxical BDR group compared with those in the nonparadoxical BDR group. However, post-bronchodilator FEV1 and FVC values were significantly higher in the nonparadoxical BDR group.

Additionally, the multivariate analysis, which adjusted for confounding variables, revealed that higher mMRC, CAT, and SGRQ-C scores were associated with paradoxical BDR, indicating more functional limitations and a poor quality of life.

In the univariate logistic regression analysis, paradoxical BDR was associated with vital capacity, pre-bronchodilator BDR, C-reactive protein (CRP), and diffusing capacity for carbon monoxide (DLCO). However, multivariate logistic regression analysis showed that high CRP (odds ratio [OR], 1.05; 95% CI, 1.01-1.09; P = .003) and DLCO (OR, 0.95; 95% CI, 0.92-0.98; P = .004) were significantly associated with paradoxical BDR.

During the first year after the logistic regression analysis, paradoxical BDR was not found to be associated with severe acute exacerbation after adjusting for confounding factors. Additionally, compared with post-bronchodilator FEV1, pre-bronchodilator FEV1 had a higher area under the curve (AUC) for predicting severe acute exacerbations in the paradoxical BDR group (AUC, 0.752; 95% CI, 0.567–0.936; P = .094 vs AUC, 0.788; 95% CI, 0.649-0.927; P = .040).

“While there was no difference between the pre-bronchodilator and post-bronchodilator FEV1 (% predicted) AUC at predicting severe acute exacerbations, pre-bronchodilator FEV1 measurements may be helpful in assessing disease prognosis in patients with a paradoxical BDR,” wrote the investigators.

The investigators identified several study limitations, including that they did not assess serial reversibility tests, there is no validated definition of paradoxical BDR, and the inability to fully exclude the influence of other chronic conditions, such as heart disease, diabetes mellitus, hypertension, and asthma.


Shin HJ, Kim TO, Kim YI, et al. The paradoxical response to short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease. J Thorac Dis. 2021;13(2): 511-520. doi: 10.21037/jtd-20-985