Identifying Consistent Characteristics Among Patients With Refractory, Unexplained Chronic Cough

Individuals with refractory or unexplained chronic cough had characteristics consistent of those with chronic cough in general, including cough duration, severity, and 24-hour frequency.

Patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) showed characteristics consistent with already-published profiles associated with chronic cough, according to a study published in Annals of Allergy, Asthma & Immunology.

These characteristics include cough duration, severity, and 24-hour frequency.

The study also found that individuals with RCC or UCC reported substantial burden arising from the condition and demonstrated symptoms consistent with cough-reflex hypersensitivity.

To come to these findings, the study authors included 2044 adult participants with chronic cough enrolled in the COUGH-1 and COUGH-2 trials. Three-quarters of participants were women, the mean (SD) age was 58 (12) years, and mean cough duration was approximately 11 years, with all participants experiencing chronic cough for at least 1 year.

The authors noted that most participants (73%) received a diagnosis of asthma, gastroesophageal reflux disease (GERD), or upper airway cough syndrome prior to the study.

On a 100-mm cough severity visual analog scale (VAS) at screening and baseline, all included patients had a score greater than 40 mm, with a mean (SD) weekly cough severity VAS of 68 (14) mm. Additionally, geometric mean 24-hour cough frequency was 19.2 coughs per hour in this study.

According to the authors, these results are generally consistent with prior research findings. They noted, though, that many previous studies recruited patients from specialized cough clinics or did not stratify by cough severity, which may affect the results.

The proportion of women in this study was higher than in prior chronic cough research, but supports the observation that individuals with chronic cough are more likely to be female. The mean age and cough duration were also similar to those found in similar studies.

“The overall characterization of participants with RCC or UCC reported in this study is also generally consistent with a previous analysis of baseline characteristics of a smaller population of participants from the United States and United Kingdom with RCC or UCC, in a phase 2 clinical trial of gefapixant,” the authors noted. “In contrast, the current analysis includes participants from 26 countries across several geographic regions, highlighting the global nature of RCC and UCC.”

Regarding other similarities, mean Leicester Cough Questionnaire (LCQ) total score was 10.4 in this study, similar to the mean LCQ score of 11.3 in other studies. Mean Hull Airway Reflux Questionnaire score was similar but slightly higher in this study, with a score of 39.6 in this study and 33 in past research.

Rates of asthma, GERD, and upper airway cough syndrome comorbidities in the COUGH-1 and COUGH-2 trials were also consistent, and history of medication use was reflective of conditions and treatments associated with the patient’s cough.

“This analysis of participants diagnosed with RCC or UCC reflects a global population with severe and long-lasting cough who share characteristics with individuals in previous studies of CC,” the authors wrote. “These data highlight the existing burden of cough that is unresponsive to treatment of presumed associated conditions and reinforces the need for an effective treatment of chronic cough.”


Dicpinigaitis PV, Birring SS, Blaiss M, et al. Demographic, clinical, and patient-reported outcome data from two global, phase 3 trials of chronic cough. Ann Allergy Asthma Immunol. Published online May 12, 2022. doi:10.1016/j.anai.2022.05.003