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=Volume 9 - 2018

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=Background: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps in Japanease. 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). 
Objective: To evaluate fine-particle ICS ETN treatment as a potential therapeutic option in ECRS with asthma.
Methods: Twenty-three patients with severe ECRS under refractory to intranasal corticosteroid treatment were randomized in a double-blind fashion to receive either HFA-BDP metered-dose inhaler (MDI) ETN (n = 11) or placebo MDI ETN (n = 12) for four 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 roll of eosinophils on airway inflammation, BEAS-2B human bronchial epithelial cells were co-incubated with purified eosinophils to determine corticosteroid sensitivity.
Results: 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.
Conclusions: 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) (http://www.umin.ac.jp/ctr/index.htm)