Continued Cough Reflex Hypersensitivity After COPD Exacerbation Predicts More Attacks

August 5, 2020

Researchers found that cough reflex sensitivity is amplified during chronic obstructive pulmonary disease (COPD) exacerbation and reduces after recovery, while its persistence can help serve as a predictor for future exacerbations.

It’s been established that coughing serves as an indicator of chronic obstructive pulmonary disease (COPD) exacerbation. Probing the importance of cough reflex sensitivity specifically, researchers have found that cough reflex sensitivity is heightened during exacerbation of COPD and falls after recovery.

However, the researchers were able to show that continued cough reflex hypersensitivity at recovery can help serve as a predictor for future exacerbations.

While hospitalized for COPD exacerbation during the 2017-2018 winter seasons, 20 patients participated in inhaled capsaicin challenge in which thresholds to elicit 5 coughs were documented. Patients continued the challenge for 6 weeks following their recovery. Analyzing at the results, the researchers found that the capsaicin cough thresholds were significantly lower while patients had their exacerbation than when they were 6 weeks post recovery (1.76 vs 809 μmol L−1, respectively).

“Capsaicin is a selective agonist of transient receptor potential vanilloid 1 ion channel receptors (TRPV1), which are expressed on C-fibre sensory nerves. Bronchopulmonary C fibres are relatively quiescent in health and can be sensitised or activated by inflammatory mediators,” explained the researchers. “Exposure to ozone, lactic acid, cationic proteins and prostaglandin-E2 are known to enhance pulmonary C-fibre responses to mechanical and chemical stimuli in a reversible fashion. Airway inflammation in exacerbation of COPD could therefore lead to sensitisation or activation of C fibres.”

Notably, there was no association between the change in the doubling dosing from the time of exacerbation to recovery and age, forced expiratory volume in 1 second, or history of COPD exacerbations prior to the study exacerbation.

Seventeen patients were followed for 12 months to monitor any future exacerbations. The year of follow-up revealed that persistence of cough reflex hypersensitivity at recovery was linked with the frequency of future exacerbations, which are commonly characterized by increased cough and/or sputum volume or purulence.

“Such episodes are associated with impaired quality of life, accelerated decline in lung function and increased health care utilisation,” wrote the researchers, who added, “The identification of individuals with COPD who are more susceptible to exacerbation may lead to targeted preventive therapies.”

During the year of follow-up, 15 of the 17 patients had a mean 2.5 subsequent exacerbations. Of the 42 total exacerbations, 30 led to seeking out primary care services, 12 led to emergency department visits, and 9 led to hospital admissions. According to the researchers, subsequent exacerbations were more common in patients who had a lower reduction in cough reflex sensitivity at 6 weeks following the initial exacerbation.

Reference: Cho P, Fletcher H, Turner R, Patel I, Jolley C, Birring S. The relationship between cough reflex sensitivity and exacerbation frequency in chronic obstructive pulmonary disease. Lung. Published June 19, 2020. doi: 10.1007/s00408-020-00366-x