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

ABSTRACT: 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.16-week single-arm study.18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).High dose (1,760 mcg/day) inhaled FP.(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.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.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.

SUBMITTER: Teodorescu M

PROVIDER: S-EPMC3899321 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

Teodorescu Mihaela M Xie Ailiang A Sorkness Christine A CA Robbins Joanne J Reeder Scott S Gong Yuanshen Y Fedie Jessica E JE Sexton Ann A Miller Barb B Huard Tiffany T Hind Jaqueline J Bioty Nora N Peterson Emily E Kunselman Susan J SJ Chinchilli Vernon M VM Soler Xavier X Ramsdell Joe J Loredo Jose J Israel Elliott E Eckert Danny J DJ Malhotra Atul A

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 20140215 2

<h4>Study objective</h4>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.<h4>Study design</h4>16-week single-arm study.<h4>Participants</h4>18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).<h4>Interventions</h4>High ...[more]

PMID: 24533002

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Project description:BackgroundFluticasone furoate/vilanterol trifenatate (FF/VI) is an inhaled therapy for the treatment of asthma, with a prolonged duration of anti-inflammatory and bronchodilatory action. This study investigated the global metabolomic and lipidomic profile following treatment with FF/VI or placebo and assessed whether changes correlated with exhaled nitric oxide levels as a measure of airway inflammation.MethodsThis was a single-center, randomized, double-blind, placebo-controlled, two-period, crossover, repeat-dose study. Adults with asthma (forced expiratory volume in 1 s ≥ 60% predicted; fraction of exhaled nitric oxide [FeNO] > 40 parts per billion) received once-daily FF/VI 100 µg/25 µg or placebo for 14 days, followed by a 21-day washout period. Serum samples were taken at pre-dose (T1), and 15 and 21 days (T2 and T3, respectively) post dose in each period. The metabolomic and lipidomic profiles were analyzed by liquid chromatography with tandem mass spectrometry and polar liquid chromatography platforms, and ions were matched to a library of standards for metabolite identification and quantification. FeNO values at each timepoint were evaluated for correlations with the biochemical data.ResultsOf 27 randomized participants (mean age 24.5 years, 63% male), 26 provided serum samples for metabolomic analysis. A total of 1969 metabolites were identified, 1634 of which corresponded to a named structure in a reference library. Treatment-related changes in the metabolome were generally subtle, with a modest increase in metabolite perturbations across timepoints. The percentage of metabolites with significant changes (p < 0.05 for all) (increases↑/decreases↓) versus placebo were: 2.1% (1.1%↑/1.0%↓), 6.7% (0.46%↑/6.2%↓) and 11.8% (0.86%↑/10.9%↓) at T1, T2 and T3, respectively. Treatment with FF/VI reduced FeNO levels by 60%, whereas the systemic intermediates involved in NO biosynthesis remained unaffected. Evidence of systemic anti-inflammatory activity was seen in complex lipid pathways, suggesting reduced phospholipase-A2 activity, but without downstream impact on free fatty acids or inflammatory mediators. Consistent with the pathogenesis of asthma, there was evidence of higher fatty acid β-oxidation and lower glycolysis in the placebo arm; this pattern was reversed in the treatment arm.ConclusionsDespite the prolonged airway anti-inflammatory action of FF/VI, this was accompanied by only subtle systemic metabolomic and lipidomic changes. Trial registration Prospectively registered on ClinicalTrials.gov registry number NCT02712047.

Project description:Study objectivesDrug-induced sleep endoscopy (DISE) using propofol is commonly used to identify the pharyngeal structure involved in collapse among patients with obstructive sleep apnea. DISE has never been compared with zolpidem-induced sleep endoscopy. We hypothesized that propofol at recommended sedation levels does not influence upper airway collapsibility nor the frequency of multilevel pharyngeal collapse as compared with zolpidem-induced sleep.MethodsTwenty-one patients with obstructive sleep apnea underwent polysomnography and sleep endoscopy during zolpidem-induced sleep and during DISE with propofol. A propofol target-controlled infusion was titrated to achieve a bispectral index between 50 and 70. Airway collapsibility was estimated and compared in both conditions by peak inspiratory flow and the magnitude of negative effort dependence. Respiratory drive was estimated by the difference between end-expiratory and peak-negative inspiratory pharyngeal pressure (driving pressure). Site and configuration of pharyngeal collapse during zolpidem-induced sleep and DISE with propofol were compared.ResultsThe frequency of multilevel collapse during zolpidem-induced sleep was similar to that observed during DISE with propofol (72% vs 86%, respectively; difference: 14%; 95% confidence interval: -12% to 40%; P = .453). The endoscopic classification of pharyngeal collapse during both conditions were similar. Peak inspiratory flow, respiratory drive (effect size: 0.05 and 0.03, respectively), and negative effort dependence (difference: -6%; 95% confidence interval: -16% to 4%) were also similar in both procedures.ConclusionsIn this pilot study, recommended propofol doses did not significantly increase multilevel pharyngeal collapse or affect upper airway collapsibility and respiratory drive as compared with zolpidem-induced sleep.Clinical trial registrationRegistry: clinicaltrials.gov; Name: Natural and Drug Sleep Endoscopy; URL: https://clinicaltrials.gov/ct2/show/study/NCT03004014; Identifier: NCT03004014.

Project description:IntroductionPharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies.MethodsWe performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios.ResultsA total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence.ConclusionIn this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Dataset Information

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

Publications

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

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