Evidence of Airway Inflammation and Remodeling in Ski Athletes with and without Bronchial Hyperresponsiveness to Methacholine

Abstract

Asthma-like symptoms, methacholine hyperresponsiveness, and use of asthma medication are prevalent in elite cross-country skiers. We quantitated mucosal inflammatory cell infiltration and tenascin expression in the subepithelial basement membrane in endobronchial biopsy specimens of the proximal airways from 40 elite, competitive skiers (mean: 17.5; range: 16 to 20 yr) without a diagnosis of asthma, in 12 subjects with mild asthma, and in 12 healthy controls, through immunohistochemistry and indirect immunofluorescence, respectively. All of the subjects were nonsmokers. T-lymphocyte, macrophage, and eosinophil counts were, respectively, greater by 43-fold (p < 0.001), 26-fold (p < 0.001), and twofold (p < 0.001) in skiers, and by 70-fold (p < 0.001), 63-fold (p < 0.001), and eightfold (p < 0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than twofold greater than in asthmatic subjects, and mast cell counts were not significantly different than in controls. Tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) was increased in skiers (median: 6.7 microm; interquartile range [IQR]: 5.3 to 8.5 microm, p < 0.001) and asthmatic subjects (mean: 8.8 microm; IQR: 7.2 to 10.8 microm, p < 0. 001) compared with controls (mean: 0.8 microm; IQR: 0 to 3.1 microm) and did not correlate with inflammatory cell counts. Inflammatory changes were present irrespective of asthmalike symptoms, hyperresponsiveness, or atopy. Prolonged repeated exposure of the airways to inadequately conditioned air may induce inflammation and remodeling in competitive skiers.

Physical training does not increase allergic inflammation in asthmatic children

“…In contrast with asthmatics, the increased numbers of inflammatory cells in healthy athletes' airways do not correlate with exercise-induced symptoms or bronchial responsiveness [28]. Recently, it has been observed that healthy children undertaking outdoor recreational activities exhibit a significant increase in eNO, dependent on ambient ozone levels, but with no changes in lung function test results [29].…”

Airway Remodeling in Asthma and its Influence on Clinical Pathophysiology

“…Thickening of epithelial basement membrane has been observed as a characteristic remodeling for asthma for a long time but was also found in early asthma (Karjalainen et al 2000(Karjalainen et al , 2003. Thickening of basement membrane observed with microscopy correspond to the deposition of extracellular matrix (ECM) at subepithelial space observed by electron microscopy, and it is called subepithelial fibrosis (Roche et al 1989;Jeffery et al 1992).…”

Cold air-provoked respiratory symptoms: the mechanisms and management

“…Indeed, a high prevalence of respiratory symptoms and airway hyperresponsiveness has been found in skiers, swimmers and long-distance runners (75). Endobronchial biopsies of elite, competitive skiers demonstrate elevated numbers of clustered lymphocytes, neutrophils and macrophages (76,77). The increased expression of tenascin possibly reflects ongoing healing and repair processes and remodeling of the airways (77).…”

“…Endobronchial biopsies of elite, competitive skiers demonstrate elevated numbers of clustered lymphocytes, neutrophils and macrophages (76,77). The increased expression of tenascin possibly reflects ongoing healing and repair processes and remodeling of the airways (77). The mucosal cellular infiltrate in the skiers' airways differs from that in asthma, with a greater number of neutrophils and a lesser number of eosinophils, mast cells and macrophages (77).…”

“…The increased expression of tenascin possibly reflects ongoing healing and repair processes and remodeling of the airways (77). The mucosal cellular infiltrate in the skiers' airways differs from that in asthma, with a greater number of neutrophils and a lesser number of eosinophils, mast cells and macrophages (77). Therefore, the term "ski asthma" (78) should probably be avoided.…”