AUTHOR=Kobayashi Yoshiki , Yasuba Hirotaka , Asako Mikiya , Yamamoto Takahisa , Takano Hiroshi , Tomoda Koichi , Kanda Akira , Iwai Hiroshi 

TITLE=HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02192

DOI=10.3389/fimmu.2018.02192

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps in Japanese. ECRS highly associated with asthma is a refractory eosinophilic airway inflammation and requires comprehensive care as part of the united airway concept. We recently reported a series of ECRS patients with asthma treated with fine-particle inhaled corticosteroid (ICS) exhalation through the nose (ETN).</p><p><bold>Objective:</bold> To evaluate fine-particle ICS ETN treatment as a potential therapeutic option in ECRS with asthma.</p><p><bold>Methods:</bold> Twenty-three patients with severe ECRS under refractory to intranasal corticosteroid treatment were randomized in a double-blind fashion to receive either HFA-134a-beclomethasone dipropionate (HFA-BDP) metered-dose inhaler (MDI) ETN (<italic>n</italic> = 11) or placebo MDI ETN (<italic>n</italic> = 12) for 4 weeks. Changes in nasal polyp score, computed tomographic (CT) score, smell test, and quality of life (QOL) score from baseline were assessed. Fractionated exhaled nitric oxide (FENO) was measured as a marker of eosinophilic airway inflammation. Response to corticosteroids was evaluated before and after treatment. Additionally, deposition of fine-particles was visualized using a particle deposition model. To examine the role of eosinophils on airway inflammation, BEAS-2B human bronchial epithelial cells were co-incubated with purified eosinophils to determine corticosteroid sensitivity.</p><p><bold>Results:</bold> HFA-BDP MDI ETN treatment improved all assessed clinical endpoints and corticosteroid sensitivity without any deterioration in pulmonary function. FENO and blood eosinophil number were reduced by HFA-BDP MDI ETN treatment. The visualization study suggested that ETN at expiratory flow rates of 10–30 L/min led to fine particle deposition in the middle meatus, including the sinus ostia. Co-incubation of eosinophils with BEAS-2B cells induced corticosteroid resistance.</p><p><bold>Conclusions:</bold> Additional HFA-BDP MDI ETN treatment was beneficial in patients with ECRS and should be considered as a potential therapeutic option for eosinophilic airway inflammation such as ECRS with asthma. (UMIN-CTR: R000019325) (<ext-link ext-link-type="uri" xlink:href="http://www.umin.ac.jp/ctr/index.htm" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.umin.ac.jp/ctr/index.htm</ext-link>).</p>