Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma: A Pilot Study

Author(s): Teodorescu, M; Xie, A; Sorkness, CA; Robbins, JA; Reeder, S; Gong, Y; Fedie, JE; Sexton, A; Miller, B; Huard, T; Hind, J; Bioty, N; Peterson, E; Kunselman, SJ; Chinchilli, VM; Soler, X; Ramsdell, J; Loredo, J; Israel, E; Eckert, DJ; Malhotra, A | Abstract: Study Objective: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness. Study design: 16-week single-arm study. Participants: 18 (14 females, mean [± SD] age 26 ± 6 years) corticosteroid-naive subjects with mild asthma (FEV189 ± 8% predicted). Interventions: High dose (1,760 mcg/day) inhaled FP. Measurements: (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure - Pmax, in KPa) and endurance - time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot) - at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects. Results: Pcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved. Conclusions: In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.