Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide in children with asthma

Objective: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and obstruction. AHR to stimuli that indirectly cause bronchial smooth muscle (BSM) contractions via release of endogenous mediators is thought to better reflect airway inflammation than AHR to stimuli that act directly on BSM. Fractional exhaled nitric oxide (FeNO) is a useful parameter for noninvasive clinical airway inflammation assessments. Accordingly, this study aimed to examine the relationships of mannitol and methacholine challenge test outcomes with FeNO and the influence of inhaled corticosteroid treatment in children with asthma. Methods: One hundred thirty-four asthmatic children (89 males; ages: 5-17 years, median: 9 years) underwent spirometry, FeNO measurement, serum total/specific IgE testing, and blood eosinophil count. All subjects were challenged with mannitol dry powder (MDP; AridolH, Pharmaxis, Australia) and methacholine at 7-day intervals. Data of steroid-treated and steroid-naive children were compared. Results: Positive responses to MDP and methacholine challenge tests were observed in 74.6% and 67.2% of total subject group, respectively, and 72 children had positive response to both challenge tests. The median FeNO level, response-dose ratio (RDR) of PC20 methacholine, and RDR of PD15 MDP were significantly higher in the steroid-treated group than in the steroid-naive group (p < 0.001, 0.226, and 0.004, respectively). FeNO levels associated significantly with PD15 MDP and RDR PD15 MDP in total subject populations (p = 0.016 and 0.003, respectively); however, a significant correlation between FeNO and RDR PD15 MDP was observed only in the steroid-naive group. Conclusions: Compared with AHR to methacholine, AHR to MDP more closely reflected the level of FeNO in steroid-naive asthmatic children.