Analysis Explores Possible Reasons for Gender Differences in Chronic Cough

A recent review explored gender differences in chronic cough and considered several possible explanations for these differences.

Understanding why this difference exists could assist with finding new therapies, said the authors, writing in Frontiers of Physiology.

Chronic cough, which lasts longer than 8 weeks, affects quality of life and is one of the main reasons people seek medical treatment, the authors noted. Reasons for chronic cough in nonsmokers include asthma, bronchitis, postnasal drip, and cough related to gastroesophageal reflux disease (GERD).

Worldwide, about 2/3 of all patients with chronic cough are female, although in China it varies by region and prevalence may be about the same between both sexes. This apparent lack of a gender difference in China may be due to the types of patients enrolled in studies or to certain aspects of their health care system.

One reason that more women have chronic cough may be their increased sensitivity. In people with or without chronic cough, women have more cough sensitivity than men as seen by differences in cough receptors, of which there are 2 types: myelinated Aδ-fiber and unmyelinated C-fiber.

Unmyelinated C-fiber is sensitive to chemical substances such as capsaicin and endogenous mediators, but their function is affected by the expression of different ion channels, which include transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1). Cough challenges can be provoked by the selective TRPA1 agonist allyl isothiocyanate (AITC) or the TRPV1 agonist capsaicin.

Women have more obvious AITC and capsaicin cough sensitivity than men, wrote the authors, citing a 2019 study.

They also noted a 2015 study that indicated a P2X3 receptor antagonist could reduce cough frequency, as P2X3, an ATP-gated ion channel, mediates cough neuronal hypersensitivity.

The female sex hormones estrogen and progesterone mediates these ion channels, but this cannot fully account for chronic cough in postmenopausal women. These hormones also have an effect on eosinophils, mast cells, histamine, and inflammatory mediators, but more research is needed to examine the effect of sex hormones on mediators related to atopic disease, which is linked to cough.

The 2 hormones can also affect laryngeal dysfunction, GERD, and obstructive sleep apnea, but again, further research is needed in this areas as well, the authors reported.

Allison Inserro contributed to this report.

Reference

Bai B, Sha B, Xu X, Yu L. Gender difference in chronic cough: Are women more likely to cough? Front Physiol. Published online May 7, 2021. doi: 10.3389/fphys.2021.654797