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

Front Immunol. 2018 Sep 25:9:2192. doi: 10.3389/fimmu.2018.02192. eCollection 2018.

Abstract

Background: 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). 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-134a-beclomethasone dipropionate (HFA-BDP) metered-dose inhaler (MDI) ETN (n = 11) or placebo MDI ETN (n = 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. 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).

Keywords: airway medicine; asthma; eosinophilic chronic rhinosinusitis; exhalation through the nose; inhaled corticosteroid; united airway.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Anti-Asthmatic Agents / administration & dosage*
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / immunology
  • Beclomethasone / administration & dosage
  • Cells, Cultured
  • Chronic Disease / drug therapy
  • Double-Blind Method
  • Drug Combinations
  • Eosinophils / immunology
  • Exhalation / immunology*
  • Female
  • Humans
  • Hydrocarbons, Fluorinated / administration & dosage
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Nasal Mucosa / cytology
  • Nasal Mucosa / immunology
  • Placebos / administration & dosage
  • Primary Cell Culture
  • Rhinitis / complications
  • Rhinitis / drug therapy*
  • Rhinitis / immunology
  • Sinusitis / complications
  • Sinusitis / drug therapy*
  • Sinusitis / immunology
  • Treatment Outcome

Substances

  • Anti-Asthmatic Agents
  • Drug Combinations
  • Hydrocarbons, Fluorinated
  • Placebos
  • norflurane
  • Beclomethasone