Bronchial Hyperresponsiveness May Predict Cough-Variant Asthma in Adults With Chronic Cough

The study found that cough severity and cough-related quality of life were not related to the severity of bronchial hyperresponsiveness in nonsmoking adults with cough-variant asthma.

Due to its high positive predictive value (PPV), bronchial hyperresponsiveness (BHR) could be considered as a predictor of cough-variant asthma (CVA) in nonsmoking adults with chronic cough, a study published in Respiratory Research found.

The study found that cough severity and cough-related quality of life (QOL) were not related to the severity of BHR in patients with CVA, which is a common cause of CC; instead, BHR had a high PPV for establishing a diagnosis of CVA in this population.

“To the best of our knowledge, there have been no previous studies on the response to anti-asthmatic therapy in CC adults with BHR,” the study authors wrote. “High PPV of BHR in CVA diagnosing in our study suggests that CVA should be considered as a major cause of cough in patients with CC presenting with BHR.”

CVA is a phenotype of asthma, characterized by BHR—increased sensitivity to a wide variety of airway-narrowing stimuli—and cough as primary symptoms.

This prospective, single-center, observational included 55 patients with CC and confirmed BHR, although only 49 patients completed the entire study. The study was performed in the Department of Internal Medicine, Pulmonary Diseases, and Allergy of the Medical University of Warsaw between 2016 and 2020.

The inclusion criteria were as follows:

  • Aged 18 to 85 years
  • CC lasting more than 8 weeks
  • No history of wheezing or dyspnea (labored breathing)
  • Normal spirometry (functional breathing)
  • BHR in methacholine challenge test (methacholine concentration causing 20% fall in FEV1 [PC20] below 16 mg/mL)

The participants had BHR confirmed in the methacholine provocation test, and an antiasthmatic, gradually intensified treatment was introduced. CVA was diagnosed when improvements in cough severity and cough-related QOL were noted.

Out of 49 patients with CC and BHR, 43 (87.8%) responded to antiasthmatic therapy, and the PPV of BHR in establishing the diagnosis of CVA was 87.8%. Of those 43, 31 (72%) participants showed significant and rapid improvement after the first-step treatment, which was a 4-week treatment of inhaled corticosteroids and long-acting β2-agonists. Ten (23.3%) participants showed improvement after add-on leukotriene receptor antagonist and 2 (4.6%) more improved after a short course of oral corticosteroids.

However, 12.2% of patients did not respond to treatment despite a high clinical probability of CVA. All patients with BHR who did not respond to antiasthmatic therapy presented symptoms of gastroesophageal reflux (GER); the authors wrote that they cannot assume the presence of BHR in CC signifies clear-cut diagnosis of CVA.

“Low capsaicin threshold in cough challenge, symptoms of GER and high neutrophil percentage in sputum were related to poor response to treatment,” the authors noted. “The severity of BHR was related to BMI [body mass index] but was ineffective in the prediction of cough reduction after therapy.”

The study did not identify any clinical factors that could predict the response after each step of therapy.

BHR severity was not a predictor of response to antiasthmatic therapy. Further, PC20 had a negative correlation with BMI, which is consistent with previous studies and indicates obesity’s role in the pathomechanism of CC.

“The results of our study support the opinion that asthmatic cough diagnosis and further decision making on continuation or discontinuation of anti-asthmatic treatment should be based on thorough and objective assessment of response to therapy in patients with suspicion of CVA,” the authors wrote. Referring to guidelines from European Respiratory Journal and CHEST, they added that this approach “is consistent with the recent guidelines.”


Rybka-Fraczek A, Dabrowska M, Grabczak EM, et al. Does bronchial hyperresponsivenes predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study. Respir Res. 2021;22:252. doi:10.1186/s12931-021-01845-2