Relationship of mannitol challenge to methacholine challenge and inflammatory markers in persistent asthmatics receiving inhaled corticosteroids.
BACKGROUND
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.


METHODS
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 (315-635 mg), moderate (75-315 mg), and severe (0-75 mg). FeNO groups were low (<25 ppb), medium (25-50 ppb), and high (> 50 ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20 % fall in FEV(1)) groups were mild (2-8 mg/ml), moderate (0.5-2 mg/ml), and severe (0-0.5 mg/ml).


RESULTS
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.


CONCLUSIONS
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.
Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Asthma and Allergy Research Group, Ninewells Hospital & Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK. drwjanderson@gmail.com
William J
WJ
Anderson
Brian J
BJ
Lipworth
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001944:Breath Tests; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008353:Mannitol; D016210:Methacholine Chloride; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D012463:Saliva; D012720:Severity of Illness Index
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide; D008353:Mannitol; D047150:Eosinophil Cationic Protein