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

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.

Asthma Control and Its Relationship with Obstructive Sleep Apnea (OSA) in Older Adults.

Background/Objectives. Asthma in older individuals is poorly understood. We aimed to characterize the older asthma phenotype and test its association with obstructive sleep apnea (OSA). Design. Cross-sectional. Setting. Pulmonary and Asthma/Allergy clinics. Participants. 659 asthma subjects aged 18-59 years (younger) and 154 aged 60-75 (older). Measurements. Sleep Apnea scale of Sleep Disorders Questionnaire (SA-SDQ), asthma severity step (1-4, severe if step 3 or 4), established OSA diagnosis, continuous positive airway pressure (CPAP) use, and comorbidities. Results. Older versus younger had worse control, as assessed by asthma step, lung function, and inhaled corticosteroid use. Among older subjects, after controlling for known asthma aggravators, OSA diagnosis was the only factor robustly associated with severe asthma: on average, OSA was associated with nearly 7 times greater likelihood of severe asthma in an older individual (OR = 6.67). This relationship was of greater magnitude than in younger subjects (OR = 2.16). CPAP use attenuated the likelihood of severe asthma in older subjects by 91% (P = 0.005), much more than in the younger asthmatics. Conclusion. Diagnosed OSA increases the risk for worse asthma control in older patients, while CPAP therapy may have greater impact on asthma outcomes. Unrecognized OSA may be a reason for poor asthma control, particularly among older patients.

Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea.

To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 newly diagnosed OSA patients [apnea-hypopnea index (AHI) 42 ± 5 events/h with 92% of apneas obstructive] who were treated with O2 supplementation, an isocapnic rebreathing system in which CO2 was added only during hyperpnea to prevent transient hypocapnia, and a continuous rebreathing system. We also measured each patient's controller gain below eupnea [change in minute volume/change in end-tidal Pco2 (ΔVe/ΔPetCO2)], CO2 reserve (eupnea-apnea threshold PetCO2), and plant gain (ΔPetCO2/ΔVe), as well as passive upper airway closing pressure (Pcrit). With isocapnic rebreathing, 14/26 reduced their AHI to 31 ± 6% of control (P < 0.01) (responder); 12/26 did not show significant change (nonresponder). The responders vs. nonresponders had a greater controller gain (6.5 ± 1.7 vs. 2.1 ± 0.2 l·min(-1)·mmHg(-1), P < 0.01) and a smaller CO2 reserve (1.9 ± 0.3 vs. 4.3 ± 0.4 mmHg, P < 0.01) with no differences in Pcrit (-0.1 ± 1.2 vs. 0.2 ± 0.9 cmH2O, P > 0.05). Hypercapnic rebreathing (+4.2 ± 1 mmHg PetCO2) reduced AHI to 15 ± 4% of control (P < 0.001) in 17/21 subjects with a wide range of CO2 reserve. Hyperoxia (SaO2 ∼95-98%) reduced AHI to 36 ± 11% of control in 7/19 OSA patients tested. We concluded that stabilizing central respiratory motor output via prevention of transient hypocapnia prevents most OSA in selected patients with a high chemosensitivity and a collapsible upper airway, whereas increasing respiratory motor output via moderate hypercapnia eliminates OSA in most patients with a wider range of chemosensitivity and CO2 reserve. Reducing chemosensitivity via hyperoxia had a limited and unpredictable effect on OSA.