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J Asthma. 2019 Jun 19:1-9. doi: 10.1080/02770903.2019.1628251. [Epub ahead of print]

Small airway inflammation is associated with residual airway hyperresponsiveness in Th2-high asthma.

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a Department of Respiratory Medicine, Allergy and Clinical Immunology , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.


Background: Asthma is characterized by airway inflammation, variable airflow obstruction, and airway hyperresponsiveness (AHR). Generally, AHR takes longer to resolve than does airflow obstruction or clinical symptoms. AHR occasionally persists despite adequate asthma treatment. Objective: To evaluate factors which associates with residual AHR in patients with seemingly remitted airway inflammation. Methods: Patients who exhibited high fractional exhaled nitric oxide (FeNO) levels (>25 ppb) at the first visit (Visit 1) and normalized FeNO levels (<25 ppb) after adequate asthma treatment, including inhaled corticosteroid administration (Visit 2), were analyzed. Patients underwent a blood test, FeNO and small airway/alveolar nitric oxide concentration (CANO) measurements and a methacholine challenge test (continuous inhalation method) at both visits. Clinical indices were compared between patients with and without residual AHR. Results: Fifty patients were analyzed. All exhibited high FeNO levels at Visit 1 [mean, 54.0 ppb (95% confidence interval, 42.4-65.5)] and improvement of FeNO levels at Visit 2 [20.4 (19.2-21.6)] (p < 0.0001). Thirty-three patients (66%) had remission of AHR at Visit 2. No significant differences were observed between patients with and without residual AHR in terms of FeNO levels, lung function parameters and blood eosinophil counts at both visits. CANO level at Visit 2 was the only factor that significantly differed between patients with residual AHR [2.7 (1.9-3.6)] and those who achieved AHR remission [0.8 (0.5-1.0)] (p < 0.0001). Conclusion: Small airway inflammation, as assessed by CANO, was associated with residual AHR in patients with Th2-high asthma.


Biomarkers; Control/Management; airway hyperresponsiveness; alveolar nitric oxide; exhaled nitric oxide

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