Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers

Abstract

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge.

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

“…CC16 levels in plasma correlated with CC16 levels in the alveolar fraction of BAL, and with the reactivity to inhaled mannitol. In contrast to previously reported increases after an exercise challenge (Bolger et al 2011a, Romberg et al 2011, Tufvesson et al 2013, the inhaled allergen challenge did not lead to increased urinary levels of CC16.…”

“…Levels of CC16 have been shown to increase in both plasma and urine after exercise (Romberg et al 2011, Tufvesson et al 2013, and in urine after mannitol inhalation challenge and EVH (Bolger et al 2011b, Kippelen et al 2013). An epithelial injury would also follow seemingly regardless of the integrity of the epithelium pre-challenge, considering there were no differences in increases of CC16 levels between asthmatics and healthy controls, or between those who responded with bronchoconstriction and those who did not.…”

Mechanisms of asthma development in elite athletes

“…Similarly the effect upon urinary CC16 levels was examined using an exercise test in swimmers compared with a mannitol test. Again there were increased CC16 levels in the swimmers after exercise both after positive and negative response, but not after the mannitol test [41]. Furthermore, HALLSTRAND [42] found increased number of columnar epithelial cells in induced sputum of asthmatic patients with EIB, compared with asthmatic patients without EIB, and also reported increased expression as measured by polymerase chain reaction of the gel-forming mucin, MUC5AC, in induced sputum.…”

Upper Airway Mucosal Inflammation : Proteomic Studies after Exposure to Irritants and Microbial Agents

“…In line, increased plasma levels of CC16, associated with disinfection by-products from the chlorinated water, are shown among swimmers, especially after short-term training [40,60]. However, some studies have instead linked the increase of CC16 in serum and urine to high intensity training, generating higher permeability in the lung epithelium, thereby enabling leakage to the blood stream [59,61]. When CC16 was measured in children regularly attending swimming pool facilities, not necessarily under intense training, the levels were instead lowered [62].…”