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

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).

Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis

“…In addition to improvements in the above outcomes, RWE studies reported that non-biologics improved SNOT-22 scores, Lund-Kennedy CT and endoscopic scores, total symptom scores by VAS, and nasal polyp scores (Supplementary Tables 5, 7 , 9, 11, 13, and 14). Four RCTs [77][78][79][80] and 4 RWE studies [81][82][83][84] reported on non-biologics (corticosteroids and ESS) for patients with eCRSwNP. All eight studies demonstrated improvement in clinical outcomes.…”

Systematic literature review of humanistic and economic burdens of chronic rhinosinusitis with nasal polyposis

“…Ten RCTs [14][15][16][17][18][19][20][21][22][23] and 42 RWE studies reported mean or median baseline SNOT-22 scores for study populations consisting of surgical candidates. In all studies, baseline SNOT-22 score was assessed prior to surgical interventions.…”

“…Of the 10 RCTs 14-23 and 42 RWE studies reporting baseline SNOT-22 scores for surgical candidates, all ranged from moderate to severe (Table 4) 91 . Five RCTs [14][15][16][17][18] and 25 RWE studies 65 reported mean baseline SNOT-22 scores in the moderate range. Five RCTs [19][20][21][22][23] and 17 RWE studies [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] reported severe mean baseline SNOT-22 scores.…”

Eosinophilic Cholecystitis Occurred in a Patient With Refractory Eosinophilic Airway Inflammation: A Case Report

“…A second ESS was performed for his refractory ECRS. In addition, inhaled corticosteroid (ICS) exhalation through the nose (ETN) treatment, which provides better control for both asthma and nasal symptoms, 5,6 was initiated instead of conventional ICS exhalation through the mouth treatment. To prevent recurrence of ECRS and reduce asthma symptoms, the doses of ICS were increased to up to 1800 mg. Thirty months after the second ESS, cholecystitis occurred concomitantly with the recurrence of nasal polyps while the doses of ICS were decreased to 1400 mg, 2 months before the onset of biliary colic.…”