In order to investigate the relationship between airways inflammation and disease severity, and improve the understanding of persistent asthma, 74 asthmatics, with disease severity ranging from intermittent, to mild to moderate and severe persistent (classified according to the Global Initiative for Asthma [GINA] guidelines), and 22 nonatopic control subjects were studied using the method of induced sputum. Sputum was analyzed for total and differential cell counts concentrations of albumin, and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase, inflammatory mediators reflecting eosinophil, neutrophil, and mast cell activation. Asthma severity (assessed by FEV(1), peak expiratory flow [PEF] variability, and daily symptom scores) and methacholine airways responsiveness were related to sputum eosinophilia and ECP. In addition, sputum neutrophilia and MPO levels correlated, albeit weakly, with PEF variability and symptom scores, respectively. Tryptase concentrations were raised in mild to moderate asthmatics. Albumin concentrations were significantly raised across the spectrum of asthma severity and correlated with those of tryptase and ECP. Despite treatment with either high doses of inhaled corticosteroids or oral corticosteroids, prominent eosinophilic inflammation with raised ECP was noted. This study points to persistent, disease severity-related airways inflammation in asthma, involving eosinophils, mast cells, and neutrophils, which is evident despite treatment with corticosteroids.

The beneficial effects of high-altitude treatment in asthma have been attributed to allergen avoidance. Recent evidence shows that this treatment also improves airway inflammation in nonallergic patients. We hypothesised that high-altitude treatment is clinically equally effective in patients with severe refractory asthma, with or without allergic sensitisation.In a prospective observational cohort study, 137 adults with severe refractory asthma (92 with allergic sensitisation), referred for high-altitude (1,600 m) treatment in Davos, Switzerland, were consecutively included. We measured asthma control (Asthma Control Questionnaire (ACQ)), asthma-related quality of life (Asthma-Related Quality of Life Questionnaire (AQLQ)), sino-nasal symptoms (Sino-Nasal Outcome Test (SNOT-20)), medication requirement, postbronchodilator (post-BD) forced expiratory volume in 1 s (FEV1), 6-min walking distance (6MWD), total immunoglobulin (Ig)E, blood eosinophils and exhaled nitric oxide fraction (FeNO) at admission and after 12 weeks.Sensitised and nonsensitised patients showed similar improvements in ACQ (-1.4 and -1.5, respectively; p50.79), AQLQ (1.6 and 1.5, respectively; p50.94), SNOT-20 (-0.7 and -0.5, respectively; p50.18), post-BD FEV1 (6.1% and 5.8% pred, respectively; p50.87), 6MWD (+125 m and +147 m, respectively; p50.43) and oral steroids (40% versus 44%, respectively; p50.51). Sensitised patients showed a larger decrease in total IgE, blood eosinophils and FeNO.High-altitude treatment improves clinical and functional parameters, and decreases oral corticosteroid requirement in patients with severe refractory asthma, irrespective of allergic sensitisation.

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