To our knowledge, this is the first study to evaluate seasonal variations of cough reflex sensitivity to capsaicin in athletes. Athletes are known to frequently experience respiratory symptoms, cough being the most prevalent . In our study, athletes had significantly more self-reported cough after exercise than non-athlete subjects, mostly within the first hour following exercise. Moreover, athletes also experienced cough 2 to 8 h after exercise, suggesting the presence of a late cough response. When analyzing all seasons together, athletes had C5 values ranging from 42 to 91 μM and non-athlete subjects had values between 123-144 μM. Although the difference in cough reflex sensitivity to capsaicin is not statistically significant, athletes' C5 values are lower than what is reported in the literature in healthy subjects (C5: 125-186 μM), while our non-athlete subjects were in the same range. In athletes, the cough reflex sensitivity to capsaicin is unlikely due to the amount of training, as no significant correlations were found between cough reflex sensitivity to capsaicin and the number of years of training or the number of hours of training per week.
It was also observed that athletes had a higher prevalence of cough, one hour post-exercise, in winter compared with summer. However, the cough reflex sensitivity to capsaicin was unchanged through the seasons in both athletes and non-athlete subjects. Therefore, this could not explain the increase in exercise-induced cough during winter.
Cough reflex sensitivity to capsaicin did not seem to be related to airway hyperresponsiveness or exercise-induced bronchoconstriction, as there was no relationships found between cough reflex sensitivity to capsaicin and airway responsiveness to methacholine, atopy, response to EVH (% fall in FEV1), or airway inflammation assessed by sputum. This may suggest that in athletes, cough is closely related to airway cough receptors' sensitivity to dehydration, possibly with an associated release of mediators. Cold air inhalation could induce neurogenic inflammation with release of tachykinins and kinins . This is supported by our observation that some athletes experienced an increase in cough symptoms while at rest, 2 to 8 h following exercise. This suggests that in these subjects, exercise is the key factor inducing cough, but without changes in the cough reflex sensitivity to capsaicin. In this regard, intense training can induce the release of long-acting mediators such as leukotrienes, triggering cough receptors, but without a significant impact on cough reflex sensitivity to capsaicin. Thus there may be a dual early and late response pattern, such as the one observed after allergenic challenge or after physical exertion in children [26–28] and adult asthmatic subjects [38-41].
Exercise-induced bronchoconstriction has been shown to result from water loss; this might be true for cough as well [29, 30]. It is conceivable that cough receptors may respond to thermal stimuli or to mediators that are produced or released as a consequence of airway cooling. Banner et al.  showed that hyperpnea with poorly conditioned air results in coughing, the frequency of which is directly related to the rate of respiratory heat loss. Hyperaemia occurs following the airway rewarming process and may lead to the activation of cough receptors by physical deformation of nerve ending. This could trigger cough receptors, despite not sufficiently to induce airway narrowing . Respiratory water loss has tussive consequences by alteration of mucosal fluid osmolarity [33, 34]. Water loss produces a hyperosmotic milieu in the bronchial mucosa that may alter the water-flux junctions between epithelial cells, leading to the discharge of nerve receptors lying close to these junctions . Further supporting this possibility is the observation that hypertonic aerosols such as saline or mannitol have tussive effects in humans. If respiratory water loss is indeed a tussive stimulus, high rates of water loss would lead to coughing when cough reflex sensitivity is increased. Exercise-induced cough may result by a mechanism related to hyperpnea. Forced manoeuvres may cause cough, by deformation of airway receptors. Lung distortion or stretching may also release prostaglandins which have been shown to provoke cough by discharge of airway C-fibers [36, 37]. However, the precise mechanism of cough without bronchoconstriction during cold air inhalation is unclear. In our study, cooling-induced cough was not associated with exercise-induced bronchoconstriction. This is in keeping with other authors who observed that exercise-induced bronchoconstriction may be prevented by a beta-2-agonist without affecting cough .
Contrary to our hypothesis, cold-air athletes did not have a significant increased cough reflex sensitivity to capsaicin. One possible explanation for these findings is that capsaicin challenge was perhaps not the appropriate test to assess cough reflex sensitivity in this population. It is possible that in cold-air athletes, cough receptors could be damaged. Long-term exposure to cold and dry air may desensitize the cough receptors residing within the airway epithelium and could make them less sensitive to capsaicin. This could explain why we observed a high prevalence of symptoms in athletes without an increase in cough reflex sensitivity to capsaicin. Alternatively, inhalation of cold and dry air may induce changes in the airway mucus and modulate cough reflex sensitivity. Enhanced mucus volume may provide a barrier shielding the superficial airway cough receptors from tussive stimuli of capsaicin, inducing an inhibition of C-fibers or the depletion of neuropeptides. This could possibly explain the diminished sensitivity to capsaicin [25, 26].
Interestingly, Xing et al.  have shown that a subpopulation of vagal afferent neurons innervating bronchopulmonary tissues expresse TRPM8 receptors and that these receptors could be excited by cold. These findings provide a possible molecular mechanism by which cold induces autonomic responses in the respiratory system. Thus, TRPM8 receptors have functions beyond encoding for consciousness of cold sensation in somatic sensory system. Temperature in the upper airway, such as the laryngeal tracheal region, may be below 25°C in a cold air environment. It is possible that TRPM8 receptors are mainly expressed in upper airway trees, where the receptors serve as a cold temperature sensor to mediate reflexive responses.