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Background: In patients with obstructive sleep apnea syndrome (OSAS), the preference-based, health-related quality of life in terms of utility has not been extensively studied., Objective: To address this point, we compared the performance of different instruments assessing utility in patients with OSAS undergoing continuous positive airway pressure (CPAP) therapy., Materials and Methods: Data of 208 patients with OSAS (28 women, mean ± SE age 54.4 ± 0.7 years, apnea-hypopnea index (AHI) 51.9 ± 1.8/h, Epworth sleepiness score 13.4 ± 0.2) participating in a randomized trial of different CPAP modalities over 2 years were analyzed. Evaluations included sleep studies, Epworth sleepiness scale, and several utility instruments that measure subjective health preference on a scale ranging from 1 (most preferred and perfect health) to 0 (least preferred and very poor health)., Results: After 2 years of CPAP therapy, the mean ± SE AHI was 6.7 ± 1.5/h and Epworth score 7.9 ± 0.4, both p < 0.001 versus baseline. Baseline utilities and changes (95% confidence interval) after 2 years of CPAP therapy were EuroQol 5-dimensions 0.79 ± 0.01, 0.02 (0.00-0.05, p = 0.064); short-form 6-dimension medical outcome questionnaire 0.72 ± 0.01, 0.06 (0.04-0.08, p < 0.001); Euro-thermometer visual analog scale 0.70 ± 0.01, 0.09 (0.07-0.12, p < 0.001); time trade-off 0.82 ± 0.01, 0.03 (0.01-0.06, p = 0.002); and standard gamble 0.82 ± 0.01, -0.01 (-0.03 to 0.02, p = 0.712)., Conclusion: The short-form 6-dimensions questionnaire, the Euro-thermometer, and the time trade-off instruments reflected the major clinical improvements in OSAS, while the EuroQoL 5-dimensions and standard gamble tests were not sensitive to CPAP effects. These results indicate that the evaluation of utility of a treatment for OSAS depends critically on the instrument used, which is important from an individual and societal perspective., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

A Difficult-to-Treat Asthma Bronchiale Is Not Necessarily a Severe Asthma Abstract. New biologicals offer the opportunity for treatment of 'difficult-to-treat' asthma. Before prescribing these medications, each 'difficult-to-treat' asthma bronchiale has to be checked for factors aggravating asthma control (e.g. insufficient inhalation technique and adherence, persistent allergen exposure) and asthma-related comorbidities (e.g. rhinosinusitis, gastro-esophageal reflux disease or obstructive sleep apnea) rendering the asthma 'controlled'. Asthma phenotyping s essential for the understanding of different treatment modalities.

Background: The obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term., Methods: In this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5-15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2-4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals., Results: At 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change -6.3, 95% CI -7.1 to -5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change -6.2, 95% CI -7.0 to -5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was -0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was -2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups., Conclusions: AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar., Trial Registration Number: ClinicalTrials.gov NCT00280800., Competing Interests: Competing interests: KEB reports grants to his institution from Swiss National Science Foundation, Zurich Lung League, Respironics Foundation, ResMed Switzerland, during the conduct of the study. The other authors report no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Study Objectives: Obstructive sleep apnea (OSA) promotes myocardial electrical instability and may predispose to nocturnal sudden cardiac death. We evaluated whether hypobaric hypoxia during altitude travel further impairs cardiac repolarization in patients with OSA, and whether this is prevented by acetazolamide, a drug known to improve oxygenation and central sleep apnea at altitude., Methods: Thirty-nine OSA patients living < 600 m, discontinued continuous positive airway pressure therapy during studies at 490 m and during two sojourns of 3 days at altitude (2 days at 1860 m, 1 day at 2590 m). During one altitude sojourn, patients took acetazolamide, during the other placebo, or vice versa, according to a randomized, double-blind crossover design. Twelve-lead electrocardiography and pulse oximetry (SpO2) were recorded during nocturnal polysomnography. Heart rate corrected mean QT intervals during the entire night (meanQTc) and during 1 min of the night with the longest meanQTc (maxQTc) were determined., Results: At 490 m the median nocturnal SpO2 was 93%, medians of meanQTc and maxQTc were 420 ms and 478 ms. At 2590 m, on placebo, SpO2 was lower (85%), and meanQTc and maxQTc were prolonged to 430 ms and 510 ms (P < 0.02 vs. 490 m, all corresponding comparisons). At 2590 m on acetazolamide, median SpO2 was increased to 88% (P < 0.05 vs. placebo), meanQTc was reduced to 427 ms (P < 0.05 vs. placebo), whereas maxQTc remained increased at 502 ms (P = ns vs. placebo)., Conclusions: At 2590 m OSA patients experienced cardiac repolarization disturbances in association with hypoxemia. Prolongation of meanQTc at altitude was prevented and hypoxemia was improved by acetazolamide, whereas maxQTc remained increased suggesting imperfect protection from repolarization disturbances., Clinical Trial Registration: ClinicalTrials.gov ID: NTC-00714740. URL: www.clinicaltrials.gov., (© 2016 Associated Professional Sleep Societies, LLC.)

Background: Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient's phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS)., Methods: Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern., Results: 30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p<0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%., Conclusion: Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individual's metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible., Trial Registration Number: NCT02050425 (registered at ClinicalTrials.gov)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Sleep-disordered breathing may impair cerebral oxygenation in patients with OSA syndrome, in particular during altitude travel. We studied cerebral tissue oxygenation (CTO) at low and moderate altitude in patients with OSA and evaluated whether acetazolamide improved CTO., Methods: Eighteen patients with OSA living at < 600 m discontinued CPAP therapy during studies in Zurich (490 m) and during two sojourns of 3 days in the Swiss Alps (2 days at 1,860 m and 1 day at 2,590 m) separated by a 2-week washout period at < 600 m. Patients received acetazolamide (2 × 250 mg/d) or placebo at altitude in a randomized, double-blind, crossover design. Nocturnal polysomnography, including CTO monitoring by near-infrared spectroscopy (NIRS), was performed., Results: At 490 m, medians of CTO, peripheral oxygen saturation as measured by pulse oximetry (Spo2), and apnea/hypopnea index were 65%, 93%, and 57.3/h, respectively. At 2,590 m, on placebo, the corresponding values were 59%, 86%, and 86.4/h, respectively (P < .05, all corresponding comparisons). Acetazolamide increased CTO and Spo2 at 2,590 m by mean values of 2% (95% CI, 0%-4%) and 2% (95% CI, 1%-3%), respectively, and reduced the apnea/hypopnea index by 23.4/h (95% CI, 14.0-32.8/h) (P < .05, all changes). Cerebral total hemoglobin concentration, a NIRS-derived surrogate reflecting regional cerebral blood volume, increased by a similar degree in response to apneas at 490 m and 2,590 m and during acetazolamide and placebo treatment., Conclusions: In patients with OSA staying at altitude, nocturnal cerebral and arterial oxygenation were reduced in association with exacerbated sleep apnea. Acetazolamide partially improved CTO, Spo2, and sleep apnea without impairing the cerebral blood flow response to apneas., Trial Registry: ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov.

Study Objectives: 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy., Design: Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed., Setting: Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m., Patients: Study 1: 39 OSAS patients. Study 2: 41 OSAS patients., Interventions: Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500-750 mg) or placebo at moderate altitudes., Measurements and Results: An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5-10%) and increase in beta activity (approximately 25%)., Conclusions: The higher evening dose of 500 mg acetazolamide showed the "spectral fingerprint" of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.

Context: Many patients with obstructive sleep apnea syndrome (OSA) living near sea level travel to altitude, but this may expose them to hypoxemia and exacerbation of sleep apnea. The treatment in this setting is not established., Objective: To evaluate whether acetazolamide and autoadjusted continuous positive airway pressure (autoCPAP) control breathing disturbances in OSA patients at altitude., Design, Setting, and Participants: Randomized, placebo-controlled, double-blind, crossover trial involving 51 patients with OSA living below an altitude of 800 m and receiving CPAP therapy who underwent studies at a university hospital at 490 m and resorts in Swiss mountain villages at 1630 m and 2590 m in summer 2009., Interventions: Patients were studied during 2 sojourns of 3 days each in mountain villages, 2 days at 1630 m, 1 day at 2590 m, separated by a 2-week washout period at less than 800 m. At altitude, patients either took acetazolamide (750 mg/d) or placebo in addition to autoCPAP., Main Outcome Measures: Primary outcomes were nocturnal oxygen saturation and the apnea/hypopnea index; secondary outcomes were sleep structure, vigilance, symptoms, adverse effects, and exercise performance., Results: Acetazolamide and autoCPAP treatment was associated with higher nocturnal oxygen saturation at 1630 m and 2590 m than placebo and autoCPAP: medians, 94% (interquartile range [IQR], 93%-95%) and 91% (IQR, 90%-92%) vs 93% (IQR, 92%-94%) and 89% (IQR, 87%-91%), respectively. Median increases were 1.0% (95% CI, 0.3%-1.0%) and 2.0% (95% CI, 2.0%-2.0). Median night-time spent with oxygen saturation less than 90% at 2590 m was 13% (IQR, 2%-38%) vs 57% (IQR, 28%-82%; P < .001). Acetazolamide and autoCPAP resulted in better control of sleep apnea at 1630 m and 2590 m than placebo and autoCPAP: median apnea/hypopnea index was 5.8 events per hour (5.8/h) (IQR, 3.0/h-10.1/h) and 6.8/h (IQR, 3.5/h-10.1/h) vs 10.7/h (IQR, 5.1/h-17.7/h) and 19.3/h (IQR, 9.3/h-29.0/h), respectively; median reduction was 3.2/h (95% CI, 1.3/h-7.5/h) and 9.2 (95% CI, 5.1/h-14.6/h)., Conclusion: Among patients with OSA spending 3 days at moderately elevated altitude, a combination of acetazolamide and autoCPAP therapy, compared with autoCPAP alone, resulted in improvement in nocturnal oxygen saturation and apnea/hypopnea index., Trial Registration: clinicaltrials.gov Identifier: NCT00928655.

Background: Many patients with obstructive sleep apnea syndrome (OSA) are unable or unwilling to use continuous positive airway pressure (CPAP) therapy when traveling to the mountains for work or recreation even though they risk pronounced hypoxemia and exacerbation of sleep apnea. Because the treatment of OSA at altitude has not been established, we tested the hypothesis that acetazolamide improves hypoxemia, sleep, and breathing disturbances in otherwise untreated patients with OSA at altitude., Methods: Forty-five patients with OSA on long-term CPAP, median age 64 years, living at < 600 m underwent a placebo-controlled, double-blind, crossover trial randomized for the sequence of drug and altitude exposure (490 m, 1,860 m, and 2,590 m). Patients spent two 3-day periods at altitude and a 2-week wash-out period at < 600 m. At altitude, patients discontinued CPAP and received acetazolamide 2 × 250 mg daily or placebo. Polysomnography, vigilance, and symptoms were evaluated., Results: At 490 m, off CPAP, median nocturnal oxygen saturation was 93%, and the apnea/hypopnea index was 51.2/h. On placebo at 1,860 m and 2,590 m, the corresponding values were 89% and 85% and 63.6/h and 86.2/h, respectively (P < .01 vs 490 m, both instances). On acetazolamide at 1,860 m and 2,590 m, oxygen saturation was higher (91% and 88%) and apnea/hypopnea indices were lower (48.0/h and 61.4/h) than on placebo (P < .01 all instances). Acetazolamide reduced nocturnal transcutaneous Pco(2), improved sleep efficiency and subjective insomnia, and prevented excessive BP elevations at altitude., Conclusions: In patients with OSA discontinuing CPAP during an altitude sojourn, acetazolamide improves oxygenation, breathing disturbances, and sleep quality by stimulating ventilation. Therefore, patients with OSA may benefit from acetazolamide at altitude if CPAP therapy is not feasible., Trial Registry: ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov.

BACKGROUND Many patients with the obstructive sleep apnoea syndrome (OSA) travel to the mountains for recreational and professional activities while temporarily discontinuing continuous positive airway pressure (CPAP) treatment. A study was undertaken to evaluate the hypothesis that altitude would aggravate their hypoxaemia, sleep-related breathing disturbances and impair daytime performance. METHODS Thirty-four patients with OSA of median age 62 years (IQR 57-65), median apnoea/hypopnoea index (AHI) 47.5 events/h (IQR 32.4-72.8), residing at <600 m were enrolled. A crossover trial randomised for the sequence of altitude exposure was carried out: patients spent 1 day in Zurich (490 m) and 4 days in the Swiss Alps at 1860 m and 2590 m (2 days each) during which continuous positive airway pressure was discontinued. Daily evaluations included polysomnography, symptom questionnaires, physical examination and driving simulator tests. RESULTS Polysomnography revealed median oxygen saturations at 490 m and in the first and second nights at 1860 and 2590 m, respectively, of 94%, 90%, 90%, 86% and 87% (p<0.01 between altitudes). Corresponding median AHI were 47.5, 85.1, 74.6, 90.0 and 90.9 events/h (p<0.01 between altitudes) with ratios of central to obstructive events of 0.1, 0.8, 1.0, 1.9 and 1.9 (p<0.01 between altitudes). Tracking performance during simulated driving was significantly impaired at 2590 m compared with 490 m. Systolic blood pressure and cardiac arrhythmias were increased at altitude. CONCLUSIONS Altitude exposure in untreated patients with OSA aggravates hypoxaemia, increases sleep-related breathing disturbances due to frequent central apnoeas/hypopnoeas, impairs driving simulator performance and induces cardiovascular stress. These findings have implications for counselling and treating patients with OSA planning to travel to high altitude. ClinicalTrials.gov identifier NCT00514826.