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.

Tenascin and fibronectin are extracellular matrix glycoproteins expressed during morphogenesis and tissue repair. In the present study bronchial biopsies were studied by the morphometric method of immunocytochemistry to reveal the distribution of different tenascin and fibronectin isoforms as well as the presence of inflammatory cells in the airway mucosa of patients with chronic asthma (n = 32) and those with seasonal birch-pollen-sensitive asthma out of season (n = 17), both in comparison with healthy control subjects (n = 12). The results showed an increase in tenascin immunoreactivity in the bronchial subepithelial reticular basement membrane layer in patients with chronic asthma (p < 0.0001) and in those with seasonal asthma (p < 0.01) compared with control subjects. The tenascin immunoreactivity, appearing as an intense wide subepithelial band in asthma, was seen only occasionally in the basement membrane of control specimens. Instead, a diffuse immunoreaction against both total fibronectin and locally produced extradomain A fibronectin was similarly visible in the airway mucosa of both patients and control subjects. Despite the significant increase in the airway mucosa of eosinophils and lymphocytes in patients with chronic asthma (p < 0.0001 and p < 0.0001, respectively) and of eosinophils in patients with seasonal asthma (p < 0.001), there was no correlation between the number of these cell types and level of tenascin expression. In patients with birch-pollen-sensitive asthma during the birch-pollen season, inhaled corticosteroid treatment, budesonide 400 micrograms twice daily, decreased tenascin immunoreactivity, in comparison with effects of placebo (p = 0.01). Our results suggest that the higher amount of tenascin reflects disease activity in asthma and may be an indicator of a remodeling process rather than of injury itself.

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Treatment outcome in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is often unsuccessful, but the particular determinants of poor treatment outcome have remained obscure. The present authors therefore analysed treatment effectiveness and predictors of poor treatment outcome in pulmonary MDR-TB and XDR-TB in Estonia, a European country with one of the highest MDR-TB and XDR-TB rates in the world.All culture-confirmed pulmonary MDR-TB and XDR-TB patients who started TB treatment in 2003-2005 were included. Multivariate analysis was performed on two models of predictors: 1) patients' HIV-status, demographic and socioeconomic characteristics; and 2) TB-related data.In the 235 MDR-TB patients, the proportion of overall successful treatment outcome was 60.4%, rising to 72.8% among adherent patients. Among the 54 XDR-TB patients, these proportions were 42.6% and 50.0%, respectively. Risk factors for poor treatment outcome in MDR-TB were HIV infection, previous TB treatment, resistance to ofloxacin and positive acid-fast bacilli (AFB) smear at the start of treatment. Predictors of poor treatment outcome in XDR-TB were urban residence and positive AFB smear.This country-wide study provides evidence that to improve treatment outcome in multidrugresistant and extensively drug-resistant tuberculosis, special care should be taken to treat HIVinfected patients and urban residents, as well as to make efforts to diminish re-treatment cases by increasing patient adherence.