The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma

Background: Chronic inflammation of the airways and airway hyperresponsiveness (AHR) are key pathological features of asthma. The fraction of exhaled nitric oxide (FeNO) is closely related to eosinophilic airway inflammation and corticosteroid responsiveness. AHR is being used as an indirect marker of the degree of airway inflammation, and AHR to mannitol is more closely related to airway inflammation compared with AHR to methacholine. We sought to evaluate the association between FeNO and AHR in adults with and without asthma..

Methods: In 304 patients with symptoms suggestive of asthma, FeNO and AHR to mannitol or methacholine were measured. A total of 180 who underwent both tests were analyzed and were divided into four groups : low (<25ppb)/high FeNO and with/ without AHR.

Results: FeNO and response to mannitol was measured in 90 patients (group±), and FeNO and response to methacholine in 90 (groupII). Current asthma was diagnosed in 31 (group±, 34.4%) and 37 (groupII, 41.1%). In non-asthmatics, those with low FeNO/-AHR, low FeNO/+AHR, high FeNO/-AHR, high FeNO/+AHR was 78%, 1.7%, 18.6%, 1.7% in group ±; 66%, 0%, 34%, 0% in groupII. Of the asthmatics, 45.2%, 3.2%, 12.9%, 38.7% in group±; 27%, 24.3%, 8.15, 40.6% in groupII, and neither showed significant difference in atopy, duration of asthma, use of inhaled corticosteroid, blood and sputum eosinohils with regard to distribution of FeNO or AHR, except only in FEV1. A significant correlation was observed between log FeNO and log response-dose rate (RDR) mannitol (r=0.411, P=0.024) and also between log FeNO and log RDR methacholine (r=0.336, P=0.042) in only asthma patients.

Conclusions: In asthma patients, the association between FeNO and AHR was stronger in mannitol than in methacholine. However, a significant proportion of patients had high FeNO and no AHR to mannitol and low FeNO and AHR to methacholine.