Esther I. Schwarz

Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: A systematic review and meta‐analysis

Obstructive sleep apnoea (OSA) is a prevalent sleep‐related breathing disorder associated with adverse cardiovascular outcome. Endothelial dysfunction is one of the proposed mechanistic links between OSA and the increased cardiovascular risk. Treatment with continuous positive airway pressure (CPAP) may reverse this detrimental pathophysiological consequence of OSA. Most studies on the effect of CPAP on endothelial function in OSA are limited by their low sample size. The objective of this systematic review was to assess the effect CPAP therapy on endothelial function in patients with OSA. We conducted a systematic review and meta‐analysis searching literature databases up to August 2013 for randomized controlled trials (RCTs) on the effect of CPAP on endothelial function in OSA, assessed by flow‐mediated dilatation (FMD) and other validated techniques. The primary outcome for the meta‐analysis (DerSimonian/Laird random‐effects method) was the treatment effect on FMD. Eight RCTs comparing the effects of therapeutic CPAP versus subtherapeutic CPAP (or no intervention) on endothelial function involving 245 OSA patients were included in the systematic review. The studies are consistent in effect direction, showing an improvement of endothelial function by CPAP. Four RCTs involving 150 patients could be used for the meta‐analysis. Compared to the control group, CPAP therapy (range 2–24 weeks) significantly increased absolute % FMD by 3.87% (95% confidence interval: 1.93–5.80, P < 0.001). In patients with OSA, CPAP therapy improves endothelial function significantly and to a clinically important extent.

Biomarkers of oxidative stress following continuous positive airway pressure withdrawal: data from two randomised trials

There is conflicting evidence whether intermittent hypoxia in obstructive sleep apnoea (OSA) influences oxidative stress. We hypothesised that withdrawal of continuous positive airway pressure (CPAP) from patients with OSA would raise markers of oxidative stress. 59 patients with CPAP-treated moderate-to-severe OSA (oxygen desaturation index (ODI) >20 events·h−1) were randomised 1:1 to either stay on CPAP (n=30) or change to sham CPAP (n=29) for 2 weeks. Using samples from two similar studies at two sites, we measured early morning blood malondialdehyde (MDA, a primary outcome in one study and a secondary outcome in the other), lipid hydroperoxides, total antioxidant capacity, superoxide generation from mononuclear cells and urinary F2-isoprostane. We also measured superoxide dismutase as a marker of hypoxic preconditioning. “Treatment” effects (sham CPAP versus CPAP) were calculated via linear regression. Sham CPAP provoked moderate-to-severe OSA (mean ODI 46 events·h−1), but blood markers of oxidative stress did not change significantly (MDA “treatment” effect (95% CI) −0.02 (−0.23 to +0.19) μmol·L−1). Urinary F2-isoprostane fell significantly by ∼30% (−0.26 (−0.42 to −0.10) ng·mL−1) and superoxide dismutase increased similarly (+0.17 (+0.02 to +0.30) ng·mL−1). We found no direct evidence of increased oxidative stress in patients experiencing a return of their moderate-to-severe OSA. The fall in urinary F2-isoprostane and rise in superoxide dismutase implies that hypoxic preconditioning may have reduced oxidative stress. Obstructive sleep apnoea may induce hypoxic preconditioning and reduce, rather than increase, oxidative stress http://ow.ly/MaUoN

Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea

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 patients 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 individuals metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible. Trial registration number NCT02050425 (registered at ClinicalTrials.gov).

FDG-positive Warthin's tumors in cervical lymph nodes mimicking metastases in tongue cancer staging with PET/CT

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) is increasingly used for staging of patients with head and neck squamous cell cancers (HNSCC) with significant impact on therapy decisions. Additional applications are detection of carcinomas of unknown primary (CUP), detection of secondary cancers, and response assessment after therapy. FDG uptake is not specific for malignant tumors. Many nonmalignant tissues and inflammatory or infectious lesions can take up FDG and cause misinterpretations in cancer patients. We present the case of a 42-year-old male smoker with biopsy-proven SCC of the right anterolateral border of the oral tongue. Partial glossectomy was performed one week prior. Large lymph nodes were palpable in the right neck. The contrast-enhanced neck CT demonstrated two ipsilateral large, partially necrotic neck nodes at level II, suspicious for lymph node metastases, and the patient was referred for further staging to our institution. A partial-body PET/CT after injection of 350 Mbq FDG was performed (Fig 1). PET/CT demonstrated intense radiotracer uptake with a maximum standardized uptake value (SUV max. 5.2) at the resection site of the former primary tumor on the right-sided anterior border of the oral tongue representing postoperative changes. Additionally, intense FDG uptake (SUV max. 9.5 and 5.7) in the ipsilateral enlarged lymph nodes of level II was observed. Again, the diagnosis of SCC lymph node metastases was established by FDG-PET/CT. By imaging, the tumor was staged pT2cN2bcM0 according to the UICC staging system. Bilateral elective supraomohyoid neck dissection was carried out subsequently. In pathology three Warthin’s tumors (cystadenolymphomas) in three right-sided lymph nodes, 4.5 cm in greatest dimension, were found. All the other lymph nodes in the neck dissection were free of tumor. Finally, the tumor was classified as pT2pN0cM0. We have Institutional Review Board approval for this study.

Effects of CPAP and Mandibular Advancement Devices on Health-Related Quality of Life in OSA: A Systematic Review and Meta-analysis

Background Untreated OSA is associated with impaired health‐related quality of life (QoL) and excessive daytime sleepiness, which have been shown to improve with treatment. The aim was to compare the effects of CPAP and a mandibular advancement device (MAD) on health‐related QoL in OSA. Methods MEDLINE and the Cochrane Library were searched up to November 2015 for randomized controlled trials (RCTs) comparing the effect of CPAP, MADs, or an inactive control treatment on health‐related QoL assessed by the 36‐Item Short Form Health Survey (SF‐36) in OSA. Extraction of study characteristics, quality, and bias assessment were independently performed by three authors. A network meta‐analysis using multivariate random‐effects meta‐regression was performed to assess treatment effects on the mental component score (MCS) and the physical component score (PCS) of the SF‐36. Results Of 1,491 identified studies, 23 RCTs were included in the meta‐analysis (2,342 patients). Compared with an inactive control, CPAP was associated with a 1.7 point (95% CI, 0.1‐3.2; P = .036) improvement in the MCS and a 1.7 point (95% CI, 0.5‐2.9; P = .005) improvement in the PCS. MADs were associated with a 2.4 point (95% CI, 0.0‐4.9; P = .053) and a 1.5 point (95% CI, –0.2 to 3.2; P = .076) improvement in the MCS and PCS, respectively, compared with inactive control treatments. There were no statistically significant differences between treatment effects of CPAP and MAD on the SF‐36 scores. Conclusions CPAP is effective in improving health‐related QoL in OSA, and MADs may be just as effective, but further RCTs comparing the two treatments are required.

Is continuous positive airway pressure necessarily an everyday therapy in patients with obstructive sleep apnoea

There are limited data on the evolution of obstructive sleep apnoea (OSA) during continuous positive airway pressure (CPAP) therapy and whether this treatment is required every night. 125 OSA patients with an original oxygen desaturation index (ODI) >10 events per hour, established on CPAP, were asked to withdraw CPAP for four nights and performed ambulatory nocturnal pulse oximetry on the fourth night of CPAP withdrawal. An ODI >10 events per hour during pulse oximetry was considered to indicate persistent OSA. Patients not experiencing recurrence of OSA underwent repeat ambulatory pulse oximetry after a further 2-week period off CPAP. In 71% of the patients, OSA recurred after four nights of CPAP withdrawal (group 1); thus, OSA did not recur in 29% (group 2). 55% of group 2 had an ODI >10 events per hour after 2 weeks off CPAP; thus, 45% remained without a recurrence. In multivariate analysis, higher original ODI, longer duration of CPAP therapy, current smoking status and larger neck circumference were independently associated with a higher ODI after four nights of CPAP withdrawal (all p<0.05). Following CPAP withdrawal, a third of CPAP-treated patients do not experience significant recurrence of oxygen desaturations after 4 days and ∼10% do not after 2 weeks. Thus, a significant proportion of patients may be able to stop CPAP for short periods. OSA does not recur in one-third of patients after 4 nights of CPAP withdrawal and in ∼10% after 2 weeks http://ow.ly/sxqIl

Effect of CPAP Withdrawal on myocardial perfusion in OSA: A randomized controlled trial.

Obstructive sleep apnoea (OSA) is highly prevalent and associated with an increased incidence of cardiovascular events. Endothelial dysfunction is the proposed causative mechanism. Continuous positive airway pressure (CPAP) is presumed to improve cardiovascular outcome in OSA. CPAP withdrawal was recently shown to lead to peripheral endothelial dysfunction. However, it is not known whether short‐term CPAP withdrawal reduces myocardial perfusion in OSA.

Coronary artery calcification, epicardial fat burden, and cardiovascular events in chronic obstructive pulmonary disease.

Rationale Patients with chronic obstructive pulmonary disease (COPD) suffer from significantly more cardiovascular comorbidity and mortality than would be anticipated from conventional risk factors. The aim of this study was to determine whether COPD patients have a higher coronary artery calcium score (CACS) and epicardial fat burden, compared to control subjects, and their association with cardiovascular events. Methods From a registry of 1906 patients 81 patients with clinically diagnosed COPD were one-to-one matched to 81 non-COPD control subjects with a smoking history, according to their age, sex, and the number of classic cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, family history of premature coronary artery disease). CACS, epicardial fat, and subsequent major adverse cardiovascular events (MACE) during follow-up were compared between groups. Results Patients with COPD (Global Initiative for Chronic Obstructive Lung Disease-classification I: 5%, II: 23%, III: 16% and IV: 56%) showed no difference in CACS (median difference 68 Agatston Units [95% confidence interval -176.5 to 192.5], p=0.899) or epicardial fat volume (mean difference -0.5 cm3 [95% confidence interval -20.9 to 21.9], p=0.961) compared with controls. After a median follow-up of 42.6 months a higher incidence of MACE was observed in COPD patients (RR=2.80, p=0.016) compared with controls. Cox proportional hazard regression identified cardiac ischemias and CACS as independent predictors for MACE. Conclusion COPD patients experienced a higher MACE incidence compared to controls despite no baseline differences in coronary calcification and epicardial fat burden. Other mechanisms such as undersupply of medication seem to account for an excess cardiovascular comorbidity in COPD patients.

Salmonella aortitis treated with endovascular aortic repair: a case report

IntroductionSalmonella is a typical cause of aortitis, which is associated with high morbidity and mortality. In infrarenal disease, besides open surgery, endovascular aortic repair as an alternative treatment has been reported. To the best of our knowledge, we report the first successful endovascular aortic repair documented by necropsy to date.Case presentationA 67-year-old Caucasian man presented with low back pain, fever and positive blood cultures for Salmonella Enteritidis. A computed tomography scan showed an enlargement and intramural hematoma of the infrarenal aortic wall; a Salmonella aortitis was suspected and antimicrobial therapy initiated. Because of substantial comorbidities, endovascular aortic repair was favored over open surgery; postoperatively the antibiotic treatment was continued for 12 months. Post-mortem there were neither macroscopic nor microscopic signs of aortitis or graft infection.ConclusionsWe could demonstrate by necropsy that endovascular aortic repair of infrarenal aortitis with prolonged pre- and postinterventional antibiotic therapy for 12 months was a minimally invasive alternative and should be considered in selected clinically stable patients with substantial co-morbidities.

Intrathoracic pressure swings induced by simulated obstructive sleep apnoea promote arrhythmias in paroxysmal atrial fibrillation

AIMS There is preliminary evidence for a link between obstructive sleep apnoea (OSA) and arrhythmias such as paroxysmal atrial fibrillation (PAF) and sudden cardiac death but underlying mechanisms remain largely unknown. METHODS AND RESULTS In this interventional crossover study, we evaluated whether intrathoracic pressure changes, induced by simulated OSA, trigger premature cardiac beats, and alter measures of ventricular repolarization [QTc and Tpeak-to-Tend (TpTec) intervals] in patients with PAF. 12-Lead-electrocardiograms were recorded continuously in 44 patients, while simulating obstructive apnoea (Mueller manoeuvre, MM), obstructive hypopnoea (inspiration through a threshold load, ITH), end-expiratory central apnoea (AP), and during normal breathing (NB) in randomized order. The prevalence of OSA in these 44 patients was assessed by a sleep study. Atrial premature beats (APBs) occurred more frequently during MM (55% of patients) and ITH (32%), but not during AP (14%), compared with NB (9%) (P < 0.001, P = 0.006 and P = 0.688, respectively). Mueller manoeuvre led to a significant prolongation of QTc and TpTec intervals (+17.3 ms, P < 0.001 and +4.3 ms, P = 0.005). Inspiration through a threshold load significantly increased QTc (+9.6 ms, P < 0.001) but not TpTec. End-expiratory central apnoea did not alter QTc and TpTec intervals. According to the sleep study, 56% of patients had OSA (apnoea hypopnoea index ≥5). CONCLUSION Simulated OSA induces APBs which may be important in patients with PAF, because the majority of episodes of PAF has been shown to be triggered by APBs. Simulated OSA leads to a significant prolongation of ventricular repolarization.