Relationship of Mannitol Challenge to Methacholine Challenge and Inflammatory Markers in Persistent Asthmatics Receiving Inhaled Corticosteroids

Abstract

Mannitol is a novel osmotic indirect bronchial challenge agent used to aid asthma diagnosis and management and is thought to reflect underlying inflammatory processes in asthma. Our objective was to evaluate relationships between mannitol airway hyperresponsiveness (AHR) and other measures of airway inflammation as well as direct-acting methacholine challenge in persistent asthmatics receiving inhaled corticosteroids. We analysed screening data of mild to moderate persistent asthmatics, all receiving inhaled corticosteroids (ICS), who had mannitol and/or methacholine challenges, fractional exhaled nitric oxide (FeNO), and salivary eosinophilic cationic protein (ECP) performed as part of the same screen. Mannitol AHR was grouped by PD(10) (cumulative provocative dose required to produce a 10% fall in FEV(1)): mild (315-635mg), moderate (75-315mg), and severe (0-75mg). FeNO groups were low (<25ppb), medium (25-50ppb), and high (>50ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20% fall in FEV(1)) groups were mild (2-8mg/ml), moderate (0.5-2mg/ml), and severe (0-0.5mg/ml). Mannitol PD(10) groups were significantly different overall for FeNO (p=0.023): 43% higher in the severe vs. the mild group. There was a significant overall difference for methacholine PC(20) (p=0.006): a 2.1 doubling dilution difference between severe vs. mild mannitol groups. FeNO groups were significantly different overall for mannitol PD(10) (p=0.01) and methacholine PC(20) (p=0.029). Methacholine PC(20) groups were significantly different overall for mannitol PD(10) (p<0.001) and FeNO (p=0.005). No significant differences were found across any groups for salivary ECP, FEV(1) % predicted, or ICS dose. Mannitol PD(10), methacholine PC(20), and FeNO as continuous variables all correlated with each other. Mannitol challenge reflects underlying inflammation using FeNO and direct AHR using methacholine. Thus, mannitol may be a useful screening tool for the assessment of asthmatic patients receiving inhaled corticosteroids.