Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study

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-naïve subjects with mild asthma (FEV1 89 ± 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.

Keywords: Asthma; genioglossus; inhaled corticosteroid; lung; obstructive; sleep apnea.

Figures

Figure 1. Study outline and procedures performed.

*Visits for phenotyping/eligibility assessment. †Asthma control was assessed with the Asthma Control Questionnaire (ACQ), standardized asthma quality of life questionnaire (AQLQs), spirometry and diaries (except at V2). ‡Questionnaires included: 1) the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), 2) Pittsburgh Sleep Quality Index (PSQI), and 3) Epworth Sleepiness Scale (ESS). Scans were obtained in the last three subjects. V, visit; Pcrit, critical closing pressure of the upper airway; MRI, magnetic resonance imaging; FP, inhaled fluticasone propionate; MDI, metered dose inhaler; LSE, lingual strength and endurance, measured using the Iowa Oral Performance Instrument; ACQ, Asthma Control Questionnaire (symptoms and rescue use) which was administered via phone.

Figure 2. Flow diagram of subjects through the study.

Figure 3. Group and individual data showing the change in Pcrit with inhaled fluticasone treatment.

Following treatment, overall the Pcrit significantly improved on average (p = 0.04). However, variability in the response was noted, as some subjects improved (Pcrit became more negative), others remained unchanged and others deteriorated (Pcrit became less negative). Data are presented as mean ± standard error (SE).

Figure 4. Changes in tongue strength with inhaled fluticasone treatment, at anterior (A) and posterior (B) locations.

A significant improvement in strength was seen with treatment at both anterior (A) (p = 0.02) and posterior (B) (p = 0.002) locations. Data are presented as mean ± standard error (SE).

Figure 5. Changes in tongue endurance (first trial—T1 and the sum of all 3 trials—Ttot) with inhaled fluticasone treatment, at anterior (A and B) and posterior (C and D) locations.

Tongue endurance significantly subsided at anterior location (A) (p = 0.007) and (B) (p = 0.0007); likewise, at the posterior location, endurance generally subsided (C) (p = 0.02) and (D) (p = 0.06). Data are presented as mean ± standard error (SE).