Sex Differences in Cough Responses of Cats

In humans, women are more debilitated by chronic coughing, report to physicians for cough more frequently, and have a greater cough sensitivity than men. These sex differences between men and women begin to emerge at the end of puberty. We conducted a retrospective analysis in anesthetized cats to determine if sex differences could be identified in an animal model that is capable of intense repetitive coughing. Anesthetized cats (13 males, 10 females) were tracheotomized and allowed to breathe spontaneously. Electromyograms of parasternal, transversus abdominis/internal oblique, and laryngeal adductor muscles were recorded. Esophageal pressure (Pes) was recorded via small balloon placed in the midthoracic esophagus. Cough was induced by mechanical stimulation of the intrathoracic trachea with a small polyethylene tube via the trachea cannula. We evaluated the cough response before and after a protocol consisting of 20 consecutive mechanical stimulation trials separated by approximately one minute. This adaptation protocol typically results in a depression of coughing by approximately 50% with the subsequent cough response remaining stable for extended periods of time. There was no difference in the number of trials in the adaptation protocol between males and females (20±1 males, 20±1 females). Likewise, end tidal CO2, as an index of anesthetic level, did not differ between the groups (males 31±0.5, females 32±0.8). Cough frequency (CF‐number of coughs per second) declined significantly in both male and female cats during the adaptation protocol (males control CF 1.3±0.2, post adaptation CF‐0.8±0.1, P<0.001; females control CF‐1.0±0.06, post adaptation CF‐0.5±0.04, P<0.001). Control CF was not significantly different between males and females (P<0.2), but the post adaptation CF was higher in males (P<0.05). Pes declined significantly during the adaptation protocol in both males and females (males control 50±8 cm H 2 O, post adaptation 26±4 cm H 2 O, P<0.001; females control 22±3 cm H 2 O, post adaptation 14±3 cm H 2 O, P<0.04). Pes was higher in males both in the control period (P<0.05) and post adaptation (P<0.02). However, there was no significant difference between males and females when these changes were expressed as percentages or when normalized to body weight. The results indicate that sex differences in cough responses exist in this model of cough. Differences in cough intensity between sexes can be explained by body weight. CF is a metric of peripheral sensory and/or central excitability and females exhibit greater depression of coughing in a repetitive trial protocol than males. The mechanisms responsible for this sex difference are unknown. Support or Funding Information NIH HL 103415 and 1OT20D001983