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).
Highlights
Eosinophilic chronic rhinosinusitis (ECRS) characterized by ethmoid-predominant sinusitis with eosinophilic inflammation is a refractory airway disease categorized as a subgroup of chronic rhinosinusitis with nasal polyps [1, 2]
Fine particles travel toward the upper airway during inhalation through the mouth followed by exhalation through the nose (ETN) [7], suggesting that these fine particles could be delivered to the lower airway and to the inflammatory sites in the upper airway, such as the middle meatus to which the ethmoid sinus opens
In the particle deposition model using a human nasal cavity cast, we found that fine particles flowing from the pharynx to the external naris at flow rates of 10–30 L/min were deposited in the middle meatus where the sinus ostia are located, the deposition was less in the epipharynx area (Figure 4A)
Summary
Eosinophilic chronic rhinosinusitis (ECRS) characterized by ethmoid-predominant sinusitis with eosinophilic inflammation is a refractory airway disease categorized as a subgroup of chronic rhinosinusitis with nasal polyps [1, 2]. Fine particles travel toward the upper airway during inhalation through the mouth followed by exhalation through the nose (ETN) [7], suggesting that these fine particles could be delivered to the lower airway and to the inflammatory sites in the upper airway, such as the middle meatus to which the ethmoid sinus opens. These reports included retrospective evaluation as a case series, and the ETN methods were inconsistent. We recently reported a series of ECRS patients with asthma treated with fine-particle inhaled corticosteroid (ICS) exhalation through the nose (ETN)
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