Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61 +/- 10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal;however, no statistically significant changes of the renin-angiotensin-aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic-pituitary-adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425

CME: Volkskrankheit obstruktive Schlafapnoe

Zusammenfassung. Die obstruktive Schlafapnoe ist eine häufige schlafbezogene Atemregulationsstörung, wobei es durch einen Kollaps der oberen Atemwege zu repetitiven Sauerstoffdesaturationen und «micro arousals» kommt. Ist die physiologische Schlafarchitektur beeinträchtigt, sind vermehrte Tagesmüdigkeit und ein erhöhter Blutdruck die Folge. Zentrale Risikofaktoren sind Stammfettsucht, fortgeschrittenes Alter, männliches Geschlecht (und Schnarchen). Mittels Gewichtsabnahme, Alkoholabstinenz, und nächtlicher kontinuierlicher Überdruckbeatmung (CPAP) lässt sich das Schlafapnoesyndrom sehr gut behandeln, wobei eine Unterkieferprotusionsschiene die Therapie der zweiten Wahl darstellt. Abstract. Obstructive sleep apnea is a common sleep related breathing disorder with a collapse of the upper respiratory tract, leading to repetitive oxygen desaturations and ’micro arousals’. If the physiological sleep architecture is impaired, patients are at risk for an increased daytime sleepiness and an increased blood pressure. Main risk factors are central obesity, age, male sex, (and snoring). By means of weight loss, alcohol restriction, and continuous nocturnal positive pressure ventilation (CPAP), the obstructive sleep apnea syndrome can be treated, with mandibular advancement devices representing a second-choice therapy

Asthma, COPD oder Overlap? Symptomatik und Diagnostik

Asthma, COPD or overlap? Symptoms and diagnostic procedures Abstract. Medical history combined with spirometry before and after bronchodilation provides important information, and allows distinguishing between asthma and Chronic obstructive pulmonary disease (COPD) in most of the cases. COPD and asthma are sometimes difficult to discriminate, mainly in older patients with a smoking history and /or history of atopia. Symptoms and the results of diagnostic tests are the basis on which therapeutic decisions are made. Differentiation between asthma and COPD is of great importance because management approaches and goals for these conditions differ. Asthma-COPD-overlap has to be considered if a significant interleave of clinical features of both conditions is identified. If it is not possible to differentiate between the two conditions, ways of additional diagnostic testing are described in this article

Increased augmentation index in patients with Ehlers-Danlos syndrome

BACKGROUND Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls. METHODS We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis. RESULTS EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p < 0.001). EDS showed a positive association with AIx; independent of age, sex, height, blood pressure, medication, and pack years of smoking. CONCLUSIONS Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS

Efficacy of pharmacotherapy for OSA in adults: A systematic review and network meta-analysis

Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy of pharmacotherapy in adults with OSA and delineate the underlying mechanisms. Seven databases were systematically screened for randomised controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol (PROSPERO-ID-CRD42018086446) network meta-analysis was performed to obtain intervention effects on the apnoea-hypopnoea-index (AHI) based on data extracted from published reports. We identified 58 RCTs (n = 1710 patients) investigating 44 different drugs or drug-combinations. Interventions were classified into seven pathomechanism-groups and summarized narratively. A meta-analysis of 17 trials for seven drugs (acetazolamide, donepezil, mirtazapine, ondansetron, paroxetine, protriptyline, theophylline) indicated a small effect for acetazolamide (mean difference in AHI -9.6/h [-17.7; -1.4]; p = 0.02). In the network meta-analysis (I = 50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available

Effects of suboptimal adherence of CPAP-therapy on symptoms of obstructive sleep apnea: a randomised, double-blind, controlled trial

NTRODUCTION: Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnea (OSA), however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP-usage on objective and subjective sleepiness parameters in patients with OSA. MATERIAL AND METHODS: In this 2-week, parallel, double-blind, randomised controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (Epworth-Sleepiness-Scale [ESS] score >10 points) who had suboptimal CPAP adherence over at least 12 months (mean nightly usage time 3-4 h). Patients were allocated through minimisation to either subtherapeutic CPAP ("sham-CPAP") or continuation of CPAP (therapeutic-CPAP). A Bayesian analysis with historical priors calculated the posterior probability of superiority. RESULTS: Between May, 2016 and November, 2018, 57 patients (60±8 years, 79% men, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS-score increase was +2.4 points (95% CI +0.6 to +4.2; p=0.01) in the sham-CPAP-group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 90.4% for ESS, 90.1% for systolic, and 80.3% for diastolic blood pressure. CONCLUSIONS: Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials

Prevalence of Obstructive Sleep Apnea in Patients with Thoracic Aortic Aneurysm: A Prospective, Parallel Cohort Study

Background: The pathogenesis and etiology of thoracic aortic aneurysms (TAA) are largely unknown. Preliminary data from patients with aortic dissection and abdominal aneurysms suggest a causal link of obstructive sleep apnea (OSA) on aortic disease. Objectives: The aim of the study was to assess the prevalence of OSA in patients with TAA compared to a matched control group. Method: In this prospective parallel-cohort study, we 2-to-1 matched 208 patients with verified TAA (at the aortic sinus and/or ascending aorta) to 104 controls without TAA according to sex, age, height, weight, and left ventricular ejection fraction. All participants underwent an ultrasound of the thoracic aorta and a level III respiratory polygraphy. OSA was defined as apnea-hypopnea index ≥5/h. The prevalence of OSA was compared with conditional logistic regression and controlling for the matching variables. Results: A total of 312 patients (mean age 65 ± 11 years, 82% male, mean body mass index 27 ± 4 kg/m2) were successfully 2-to-1 matched in the final model. Prevalence of OSA was significantly higher in the TAA-group when compared to the matched control group (63 vs. 47%; odds ratio 1.87 [95% CI 1.05–3.34]; p = 0.03). When applying a higher apnea-hypopnea index threshold (≥15/h), the odds ratio increased to 3.25 (95% CI 1.65–6.42; p < 0.001). The median apnea-hypopnea index was higher in patients with TAA (9.2/h [3.3–20.0] vs. 4.5/h [2.2–11.1], p < 0.001). Conclusions: Patients with TAA have a higher prevalence of OSA when compared to the general population. Since OSA is effectively treatable and might contribute to the pathogenesis of TAA, further longitudinal trials are needed to assess the association between OSA and TAA