Mannitol challenge for assessment of airway responsiveness, airway inflammation and inflammatory phenotype in asthma

Abstract

Assessment of airway inflammation in asthma is becoming increasingly important, as the inflammatory phenotype underpins the treatment response. This study aimed to evaluate mannitol as a tool for assessing airway responsiveness and airway inflammation in asthma, compared with hypertonic saline. Fifty-five subjects with stable asthma completed a hypertonic (4.5%) saline challenge and a mannitol challenge at two separate visits, performed 48-72 h apart, in random order. Induced sputum was obtained from 49 (89%) subjects during the saline challenge and 42 (76%) subjects during the mannitol challenge (P>0.05). There was a significant correlation between the greatest percentage fall in forced expiratory volume in 1 s (FEV(1)) (r=0.6, P<0.0001), the dose-response slope (r=0.73), cumulative dose (r=0.55) and PD15 (r=0.46) for mannitol and hypertonic saline. The greatest percentage fall in FEV(1) to mannitol was less in non-eosinophilic asthma. There was a lower total cell count in mannitol vs. hypertonic-saline-induced sputum. However, sputum eosinophils and neutrophils were not significantly different. Using mannitol, a higher proportion of subjects were classified as having eosinophilic asthma. There were no differences in IL-8, neutrophil elastase or matrix-metalloproteinase 9 concentrations in sputum samples induced with mannitol or hypertonic saline. We conclude that mannitol can be used to induce good-quality sputum, useful for analysis of inflammatory mediators and for predicting the inflammatory phenotype in asthma.