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Micha T Maeder,1 Otto D Schoch,2 Hans Rickli1 1Department of Cardiology, 2Department of Respiratory Medicine, Kantonsspital St Gallen, St Gallen, Switzerland Abstract: Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP) has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA. Keywords: obstructive sleep apnea, cardiovascular, risk, heart failure, atrial fibrillation, hypertension

Study Objectives: To design a national antinoise policy, we need to know the monetary value that people attach to the reduction of sleep disturbance due to road traffic noise.Principles: Patients with obstructive sleep apnea syndrome (OSAS) controlled by nasal continuous positive airway pressure (nCPAP) underwent one-to-one structured interviews to determine the monetary value of their resultant undisturbed sleep. This was then converted into a value for sleep undisturbed by noise, using a severity ratio.Setting: Outpatient interviews in 67 OSAS patients (54 males, 28 to 73 years old) managed by the Center for Sleep Medicine, Kantonsspital, St. Gallen, Switzerland.Materials and Methods: The interview questions addressed the outcome and difficulties of nCPAP therapy, the self-rated severity of pretreatment sleep disturbance and self-rated monetary value of sleep improvement. Thirteen OSAS patients who had also experienced noise-related sleep disturbance rated its severity on a visual analogue scale (VAS).Results: The mean monetary value of nCPAP-controlled sleep disturbance was Swiss francs (CHF) 70/night (CHF1 = US$ 0.877, year end 2004; 25th and 75th percentiles: CHF 35 and CHF 100). Interviewees maintained this high estimate after learning that the actual treatment costs were only approximately 6 CHF/night. A severity ratio ranging from 2.3:1 to 4.7:1 for sleep disturbance resulting from OSAS or from noise was derived from patients' responses and literature. The value of noise-free sleep was CHF 7.45-23.81 per night.Conclusion: Sleep undisturbed by noise has a remarkably high monetary value for people, which should be considered in political decision-making. [ABSTRACT FROM AUTHOR]

Rationale: To assess feasibility and yield of diagnostic procedures after active case finding for tuberculosis with radiologic screening at the three main entry points for asylum seekers to Switzerland. Method: Prospective multicenter study on the value of symptoms, spontaneous and induced sputum, and bronchoscopy for the confirmation of tuberculosis in radiologically selected cases. Results: Among 101 asylum seekers examined, spontaneous sputum was collected "on the spot" in 83 and yielded 7 (54%) of 13 smear-positive and 13 (39%) of 33 culture-positive cases. Morning sputum, collected in 84, yielded 8 (62%) and 16 (49%), and the two spontaneous sputa combined 9 (69%) and 20 (61%), respectively. Two additional induced sputa, collected in 91 persons, yielded no additional smear-positive, but yielded seven culture-positive cases (yield, 82%). Bronchoscopy, performed in 87 of 92 sputum smear-negative cases, yielded four additional smear-positive and six culture-positive cases. Culture confirmation was independently and significantly predicted by obtaining a specimen using bronchoscopy (adjusted odds ratio, 11.0; 95% confidence interval, 1.9-62) and a prior decision to treat (adjusted odds ratio, 3.0; confidence interval, 1.1-8.1). Conclusion: Radiographic anomalies compatible with tuberculosis found during screening are a poor guide to initiation of treatment. Respiratory and systemic symptoms correlated weakly with culture confirmation of tuberculosis. All radiologically selected cases must be examined with on-the-spot and early-morning sputum, regardless of symptoms. If both specimens are smear negative, the yield is increased by bronchoscopy and, to a lesser extent, by two samples of induced sputum. The examination of any single specimen has a low yield of 36 to 63% and is insufficient to exclude active tuberculosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The microbiological analysis of respiratory specimens is the most reliable approach to diagnose active pulmonary tuberculosis. PATIENT AND METHODS: We report a 60-year-old female patient (index patient) who underwent diagnostic bronchoscopy for chronic cough. No acid-fast bacilli were detected in bronchial washings. Although cough subsided with symptomatic treatment, Mycobacterium tuberculosis grew on egg-based media after 12 weeks. A false-positive culture result was suspected. Chart review and DNA fingerprinting were carried out. RESULTS: The bronchoscope used to examine the index patient was previously used for a 30-year-old patient (source patient) with smear- and culture-positive pulmonary tuberculosis. Restriction fragment length polymorphism (RFLP) analysis based on the IS 6110 element confirmed that the two strains were identical. CONCLUSION: Cross-contamination is a reason for false-positive cultures with M. tuberculosis and should be suspected in patients with a low clinical probability for active tuberculosis. [ABSTRACT FROM AUTHOR]

Sleep apnea (SA) is a prevalent disorder characterized by recurrent events of nocturnal apnea. Polysomnography (PSG) represents the gold standard for SA diagnosis. This laboratory-based procedure is complex and costly, and less cumbersome wearable devices have been proposed for SA detection and monitoring. A novel textile multi-sensor monitoring belt recording electrocardiogram (ECG) and breathing frequency (BF) measured by thorax excursion was developed and tested in a sleep laboratory for validation purposes. The aim of the current study was to evaluate the diagnostic performance of ECG-derived heart rate variability and BF-derived breathing rate variability and their combination for the detection of sleep apnea in a population of patients with a suspicion of SA. Fifty-one patients with a suspicion of SA were recruited in the sleep laboratory of the Cantonal Hospital St. Gallen. Patients were equipped with the monitoring belt and underwent a single overnight laboratory-based PSG. In addition, some patients further tested the monitoring belt at home. The ECG and BF signals from the belt were compared to PSG signals using the Bland-Altman methodology. Heart rate and breathing rate variability analyses were performed. Features derived from these analyses were used to build a support vector machine (SVM) classifier for the prediction of SA severity. Model performance was assessed using receiver operating characteristics (ROC) curves. Patients included 35 males and 16 females with a median age of 49 years (range: 21 to 65) and a median apnea-hypopnea index (AHI) of 33 (IQR: 16 to 58). Belt-derived data provided ECG and BF signals with a low bias and in good agreement with PSG-derived signals. The combined ECG and BF signals improved the classification accuracy for SA (area under the ROC curve: 0.98; sensitivity and specificity greater than 90%) compared to single parameter classification based on either ECG or BF alone. This novel wearable device combining ECG and BF provided accurate signals in good agreement with the gold standard PSG. Due to its unobtrusive nature, it is potentially interesting for multi-night assessments and home-based patient follow-up.

Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Children exposed to a tuberculosis (TB) index case are at risk of TB infection and disease., Objectives: The aim of this study was to describe the proportion of child contacts who developed TB infection or disease after exposure and to assess the diagnostic pathways and adherence to current guidelines., Methods: Retrospective observational study including children ≤16 years of age who had contact to a TB index case between January 2019 and July 2021. Analysis was stratified by age groups 0-4, 5-11, and 12-16 years., Results: Of 401 TB-exposed children, data were available for 380 (95%). Of those, 7 (2%) were diagnosed with TB disease and 35 (9%) with TB infection. We identified several deviations in the management compared to recommendations in national Swiss guidelines: In the children aged 0-4 years, only 82% were examined with an immunodiagnostic test or a chest radiography within 2 weeks after last contact. Recommended prophylactic treatment was prescribed in 66% of the children only. In the children aged 5-11 years, 64% were tested with an immunodiagnostic test in a first examination and 75% in a second examination, 2 weeks and 2 months after last contact, respectively., Conclusions: Contact investigations of children exposed to a TB index case identified a significant proportion of children with TB infection and disease in a low TB incidence setting. We observed significant deviations from the guidelines in the contact investigations suggesting the need for improved implementation., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Sleep apnea (SA) is a prevalent disorder characterized by recurrent events of nocturnal apnea originating from obstructive and/or central mechanisms. SA disrupts normal sleep and can lead to a series of complications when left untreated. SA results in intermittent hypoxia which has an impact on the cardio- and cerebrovascular system. Hospitalized patients with SA typically have a greater burden of comorbidity, a longer length of hospital stay, but may show an improvement of in-hospital mortality compared to patients without diagnosed SA. The reason for this survival benefit is controversial and we aimed to clarify this protective effect in the light of predictive factors including SA-associated comorbidities using a nation-wide hospitalization database., Methods and Findings: Data were extracted from a nation-wide hospitalization database provided by the Swiss Federal Office for Statistics. Hospitalized patients with a SA co-diagnosis were extracted from the database together with a 1:1-matched control population without SA. Overall, 212'581 patients with SA were hospitalized in Switzerland between 2002 and 2018. Compared to the controls, SA cases had a longer median length of hospital stay (7 days; 95% CI: 3 to 15 vs. 4 days; 95% CI: 2 to 10) (p < 0.001) and a higher median number of comorbidities (8 comorbidities; IQR: 5 to 11 vs. 3 comorbidities; IQR: 1 to 6) (p < 0.001). The risk of in-hospital mortality was lower in the SA cases compared to the controls (OR: 0.73; 95% CI: 0.7 to 0.76; p < 0.001). SA was associated with a survival benefit in hospitalizations related to 28 of 47 conditions with the highest rate of in-hospital death. Sixty-three comorbidities were significantly over-represented in SA cases among which obesity, hypertension and anatomic nasal deviations were associated with a significant decrease of in-hospital mortality., Conclusions: Compared to matched controls, SA was associated with significant and relevant inpatient survival benefit in a number of most deadly conditions. Within SA-patients, associated comorbidities mostly correlated with a poorer prognosis, whereas obesity and hypertension were associated with an improved in-hospital mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: The new 2018 pulmonary hypertension (PH) definition includes a lower mean pulmonary artery pressure (mPAP) cut-off (>20 mmHg rather than ≥25 mmHg) and the compulsory requirement of a pulmonary vascular resistance (PVR) ≥3 Wood units (WU) to define precapillary PH. We assessed the clinical impact of the 2018 compared to the 2015 PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR)., Methods: Severe AS patients (n = 487) undergoing pre-AVR right heart catheterization were classified according to the 2015 and 2018 definitions. Post-AVR mortality (median follow-up 44 months) was assessed., Results: Based on the 2015 definition, 66 (13%) patients exhibited combined pre and postcapillary PH (CpcPH), 116 (24%) isolated post-capillary PH (IpcPH), 28 (6%) precapillary PH, and 277 (57%) no PH at all. Overall, 52 (11%) patients were reclassified: 23 no PH into IpcPH; 8 no PH into precapillary PH; 20 precapillary PH into no PH; 1 CpcPH into IpcPH. By the 2015 definition, only CpcPH patients displayed increased mortality, whereas by the 2018 definition, precapillary PH patients also experienced higher mortality than those without PH. Among the PH definition components, PVR ≥3 WU was the strongest predictor of death (hazard ratio > 4)., Conclusions: In severe AS, a higher number of IpcPH patients are diagnosed by the 2018 definition, even though they have the same prognosis as those without PH. Patients with true precapillary PH are more accurately identified by the 2018 definition that includes a pulmonary vascular disease criterion, that is, PVR ≥3 WU, a strong mortality predictor., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Numerous ECG alterations due to pneumothorax have been reported. The objective of the study was to establish the presence of ECG changes associated with pneumothorax in the literature, and in a cohort of patients with proven pneumothorax compared with age- and sex-matched healthy controls., Methods: A systematic review for ECG alterations associated with pneumothorax was performed. We then reviewed our hospital database for patients with pneumothorax and identified all patients with an ECG available at this time. The retrieved ECG alterations in the systematic review were identified in our pneumothorax patients and compared with a healthy sex- and age-matched control group. Accordingly, we calculated sensitivity and specificity for all alterations., Results: Seventeen ECG alterations were found and defined from the systematic review. Our pneumothorax cohort consisted of 82 pneumothorax patients and 82 control patients. Specificity was mostly more than 90%, but sensitivities were low. Phasic R voltage (pneumothorax group 25.6% vs control group 1.2%), T-wave inversion (31.7% vs 2.4%), prolonged QTc (11.0% vs 2.4%), right axis deviation (14.6% vs 3.6%) and QRS voltage ratio in aVF/I >2 (41.5% vs 22.0%) were significantly more frequent in pneumothorax patients compared with controls., Conclusion: The sensitivity of published ECG signs in predicting pneumothorax in our cohort was low, which means that ECG findings are an unsuitable tool for pneumothorax screening. However, presence of these ECG signs might raise a suspicion of pneumothorax in patients presenting with dyspnoea, or unclear chest discomfort.

An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD., (© 2021 S. Karger AG, Basel.)

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.)

BACKGROUND: Although most guidelines overwhelmingly recommend outpatient TB treatment, hospitalisations are common. We investigated the proportion of TB patients hospitalised and determined factors associated with length of stay (LOS) in Switzerland. METHODS: Cases with TB as the primary diagnosis were retrieved from a nation-wide hospitalisation database and compared to TB notifications. Month and year of admission, hospital site, type of TB, age, sex, LOS and up to 50 ICD-10 coded comorbidities were compared with controls matched for age, sex and admission date. RESULTS: From 2002 to 2015, the estimated TB hospitalisation rate was 81%. The median LOS of 6,234 TB patients was stable at 14 days (IQR 6-22), but increased in patients with miliary TB, old patients and with hospital location. TB-associated comorbidities included HIV, liver disease, anaemia, malnutrition and genitourinary tract diseases. LOS was associated with three comorbidity clusters: 1) malnutrition, cachexia and anaemia (median LOS 20 days, IQR 13-31); 2) toxic liver disease and hepatitis (median LOS 23 days, IQR 14-37.5); and 3) adverse drug events (median LOS 20 days, IQR 13-30). CONCLUSION: Most TB patients were hospitalised. LOS was related to TB type, comorbidities and hospital location. Promoting outpatient care is a priority to improve TB management in Switzerland.

Sleep apnea (SA) is a prevalent disorder diagnosed by polysomnography (PSG) based on the number of apnea-hypopnea events per hour of sleep (apnea-hypopnea index, AHI). PSG is expensive and technically complex; therefore, its use is rather limited to the initial diagnostic phase and simpler devices are required for long-term follow-up. The validity of single-parameter wearable devices for the assessment of sleep apnea severity is still debated. In this context, a wearable electrocardiogram (ECG) acquisition system (ECG belt) was developed and its suitability for the classification of sleep apnea severity was investigated using heart rate variability analysis with or without data pre-filtering. Several classification algorithms were compared and support vector machine was preferred due to its simplicity and overall performance. Whole-night ECG signals from 241 patients with a suspicion of sleep apnea were recorded using both the ECG belt and patched ECG during PSG recordings. 65% of patients had an obstructive sleep apnea and the median AHI was 21 [IQR: 7-40] h - 1 . The classification accuracy obtained from the ECG belt (accuracy: 72%, sensitivity: 70%, specificity: 74%) was comparable to the patched ECG (accuracy: 74%, sensitivity: 88%, specificity: 61%). The highest classification accuracy was obtained for the discrimination between individuals with no or mild SA vs. moderate to severe SA. In conclusion, the ECG belt provided signals comparable to patched ECG and could be used for the assessment of sleep apnea severity, especially during follow-up.

Rationale: Continuous positive airway pressure (CPAP) is the standard treatment for the obstructive sleep apnea syndrome (OSAS), but long-term adherence remains a challenge. In a pilot study, we observed that telemedicine combined with telemetrically triggered interventions was associated with improved CPAP adherence in the first month of treatment. Objectives: In the current randomized, controlled phase III trial, we aimed to collect pivotal data for the use of telemedicine in CPAP treatment of patients with OSAS. Methods: Symptomatic patients with OSAS were randomized to a telemedicine or control arm and initiated CPAP treatment. Phone calls were triggered in the telemedicine group during the first month of treatment upon either poor use or excessive mask leakage. Patients were followed for 6 months. Measures of CPAP use at 6 months were the main study endpoints. Results: Among 240 patients enrolled, 71 (30%) discontinued CPAP treatment over the course of the study. The primary outcome measure, the proportion of nights with CPAP use greater than 1 hour, was not statistically different in the telemedicine group (92.0%) versus the control group (88.2%) ( P  = 0.565). The daily hours of CPAP use at 6 months also did not differ significantly between the telemedicine group (5.6 h) and the control group (4.8 h) ( P  = 0.663). However, in a post hoc analysis, telemedicine led to increased device use in a subgroup of patients with a mild form of disease (5.6 h vs. 3.4 h; P  = 0.026). The telemedicine-based intervention had a positive impact on sleep-related quality of life as measured with the Quebec Sleep Questionnaire (5.55 vs. 5.49 at 1 mo [ P  = 0.020]; 5.61 vs. 5.46 at 6 mo [ P  = 0.013]). Conclusions: A telemetrically triggered intervention in the first month of treatment did not improve CPAP use in the study population overall, but it had positive effects in patients with a mild form of OSAS and led to an improvement in sleep-related quality of life.Clinical trial registered with www.clinicaltrials.gov (NCT01715194).

Sleep monitoring in an unattended home setting provides important information complementing and extending the clinical polysomnography findings. The validity of a wearable textile electrocardiography (ECG)-belt has been proven in a clinical setting. For evaluation in a home setting, ECG signals and features were acquired from 12 patients (10 males and 2 females, showing an interquartile range for age of 48-59 years and for body mass indexes (BMIs) of 28.0-35.5) over 28 nights. The signal quality was assessed by artefacts detection, signal-to-noise ratio, and Poincaré plots. To assess the validity, the data were compared to previously reported data from the clinical setting. It was found that the artefact percentage was slightly reduced for the ECG-belt from 9.7% ± 14.7% in the clinical setting, to 7.5% ± 10.8% in the home setting. The signal-to-noise ratio was improved in the home setting and reached similar values to the gel electrodes in the clinical setting. Finally, it was found that for artefact percentages above 3%, Poincaré plots are instrumental to evaluate the origin of artefacts. In conclusion, the application of the ECG-belt in a home setting did not result in a reduction in signal quality compared to the ECG-belt used in the clinical setting, and thus provides new opportunities for patient pre-screening or follow-up.

Even for 1-lead electrocardiography (ECG), single-use gel conductive electrodes are employed in a clinical setting. However, gel electrodes show limited applicability for long-term monitoring due to skin irritation and detachment. In the present study, we investigated the validity of a textile ECG-belt suitable for long-term measurements in clinical use. In order to assess the signal quality and validity of the ECG-belt during sleep, 242 patients (186 males and 56 females, age 52 (interquartile range 42-60) years, body mass index 29 (interquartile range 26-33) kg·m -2 ) with suspected sleep apnoea underwent overnight polysomnography including standard 1-lead ECG recording. The single intervals between R-peaks (RR-intervals) were calculated from the ECG-signals. We found a mean difference for average RR-intervals of -2.9 ms, a standard error of estimate of 0.39%, as well as a Pearson r of 0.91. Furthermore, we found that the validity of the ECG-belt decreases when lying on the side, which was potentially due to the fitting of the belt. In conclusion, the validity of RR-interval measurements using the ECG-belt is high and it may be further improved for future applications by optimizing wear fitting.

Background: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan., Methods: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control., Findings: Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation., Interpretation: Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto., Funding: The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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.)

Non-invasive ventilatory support is frequently used in patients with severe respiratory failure (SRF), but is often limited to intensive care units (ICU). We hypothesized that an instantaneous short course of NIV (up to 2 h), limited to regular working hours as an additional therapy on the emergency department (ED) would be feasible and could improve patient´s dyspnoea measured by respiratory rate and Borg visual dyspnea scale. NIV was set up by an interdisciplinary respiratory care team. Outside these predefined hours NIV was performed in the ICU. This is an observational cohort study over 1 year in the ED in a non-university hospital. Fifty-one % of medical emergencies arrived during regular working hours (5475 of 10,718 patients). In total, 63 patients were treated with instantaneous NIV. Door to NIV in the ED was 56 (31-97) min, door to ICU outside regular working hours was 84 (57-166) min. Within 1 h of NIV, the respiratory rate decreased from 30/min (25-35) to 19/min (14-24, p < 0.001), the Borg dyspnoea scale improved from 7 (5-8) to 2 (0-3, p < 0.001). In hypercapnic patients, the blood-pH increased from 7.29 (7.24-7.33) to 7.35 (7.29-7.40) and the pCO 2 dropped from 8.82 (8.13-10.15) to 7.45 (6.60-8.75) kPa. In patients with SRF of varying origin, instantaneous NIV in the ED during regular working hours was feasible in a non-university hospital setting, and rapidly and significantly alleviated dyspnoea and reduced respiratory rate. This approach proved to be useful as a bridge to the ICU as well as an efficient palliative dyspnoea treatment.

Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany., Competing Interests: Interessenkonflikt: Siehe Interessenkonflikterklärung auf www.awmf.org, (© Georg Thieme Verlag KG Stuttgart · New York.)

Pulmonary hypertension associated with left-sided heart disease (PH-LHD) is the most common type of pulmonary hypertension. In patients with left-sided heart disease, the presence of pulmonary hypertension is typically a marker of more advanced disease, more severe symptoms, and worse prognosis. In contrast to pulmonary arterial hypertension, PH-LHD is characterised by an elevated pulmonary artery wedge pressure (postcapillary pulmonary hypertension) without or with an additional precapillary component (isolated postcapillary versus combined postcapillary and precapillary pulmonary hypertension). Transthoracic echocardiography is the primary nonin-vasive imaging tool to estimate the probability of pulmonary hypertension and to establish a working diagnosis on the mechanism of pulmonary hyperten-sion. However, right heart catheterisation is always required if significant pulmonary hypertension is sus-pected and exact knowledge of the haemodynamic constellation is necessary. The haemodynamic con-stellation (mean pulmonary artery pressure, mean pulmonary artery wedge pressure, left ventricular end-diastolic pressure) in combination with clinical infor-mation and imaging findings (mainly echocardiog-raphy, coronary angiography and cardiac magnetic resonance imaging) will usually allow the exact mech-anism underlying PH-LHD to be defined, which is a prerequisite for appropriate treatment. The general principle for the management of PH-LHD is to treat the underlying left-sided heart disease in an optimal man-ner using drugs and/or interventional or surgical ther-apy. There is currently no established indication for pulmonary arterial hypertension-specific therapies in PH-LHD, and specific therapies may even cause harm in patients with PH-LHD.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder associated with "cardiovascular stress", i.e. cardiovascular risk factors, cardiovascular diseases, and an increased risk of heart failure, stroke, and death. Experimental and clinical studies have characterized potential underlying mechanisms including biventricular dysfunction, atherosclerosis, and arrhythmia. Assessment of these cardiovascular features of OSA requires a spectrum of clinical tools including ECG, echocardiography, exercise testing, and angiography. In contrast to many cardiovascular diseases, the role of blood biomarkers to characterize cardiovascular function and cardiovascular risk in OSA is poorly defined. In the present review we summarize the available data on biomarkers potentially providing information on cardiovascular features in OSA patients without overt cardiovascular disease. The vast majority of studies on biomarkers of cardiovascular stress in OSA evaluated B-type natriuretic peptide (BNP)/N-terminal-B-type natriuretic peptide (NT-proBNP), and cardiac troponins (cTn). Although some studies found significant associations between these cardiac biomarkers and the presence and severity of OSA, data remain conflicting. Also, the detailed pathophysiological mechanisms underlying the link between OSA and hemodynamic cardiac stress (BNP/NT-proBNP) and cardiomyocyte damage (cTn) are poorly understood. Major research efforts are required to establish the clinical role of cardiovascular biomarkers in patients with OSA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Obstructive sleep apnoea syndrome (OSAS) is characterised by repetitive collapse of the upper airway during sleep. Continuous positive airway pressure (CPAP) applied via a mask is the standard treatment for OSAS. CPAP adherence is crucial in therapy to prevent the deleterious consequences of OSAS. We hypothesised that a combination of supervision by telemetry together with targeted telephone support in the first month of CPAP would increase CPAP adherence and treatment success. A total of 113 OSAS patients followed by telemetry-triggered interventions used the device for 5.3 h/night on 28/30 nights, significantly more than the 110 OSAS patients in the control group with 4.6 h/night and 27/30 nights. Telemetry-triggered interventions have a significant impact on adherence rate in early CPAP treatment. These results can be reached with an acceptable additional effort., (© The Author(s) 2015.)

Introduction: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher temperatures could affect IFN-γ and IP-10 responsiveness in order to improve the performance of IP-10 release assays and IGRAs., Aim: The aim of this study was to assess the robustness of whole blood based IP-10 release assay and IGRAs and the effect of hyper-thermic incubation (39 °C) on the diagnostic accuracy of IP-10 release assay and IGRAs., Results: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0.57-1.02) fold, with 39 °C compared to 37 °C incubation temperature. At 37 °C IGRA sensitivity was 85% and IP-10 sensitivity was 82%, whereas specificity was 97% for both tests (p > 0.8). These minor changes observed as a result of hyper-thermic incubation were not sufficient to impact IGRA and IP-10 release assay test performance., Conclusion: The performance of IGRA and IP-10 release assays is robust despite variations in the incubation temperature between 37 °C and 39 °C., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.

Background: Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea syndrome (OSAS)., Objectives: The aim of the current study was to determine operational long-term adherence to PAP and its predictors., Methods: In a retrospective single-center observational cohort study, we analyzed all patients referred to our center with suspected OSAS between November 2001 and November 2011. Baseline results and last follow-up data of each patient were analyzed. Kaplan-Meier estimates of adherence and Cox proportional hazard regression for age, gender, Epworth sleepiness scale (ESS) scores, body mass index, apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were performed. Evolution of adherence was analyzed in yearly cohorts comparing the proportion of patients discontinuing PAP within 6 and 12 months., Results: Of 4,638 referrals, 2,187 confirmed OSAS patients started PAP, 297 (14%) were referred out to other centers to follow-up, 42 (2%) died, and 92 (5%) no longer needed PAP. Of 1,756 patients, the median follow-up was 36 months [95% confidence interval (CI) 33.6-37.8], and adherence at 1, 5 and 10 years was 74 (CI 71-75; n = 1,028), 55 (CI 53-58; n = 281) and 51% (CI 48-55; n = 10), respectively. Adherence is associated with ESS score [hazard ratio (HR) 0.60; CI 0.47-0.78], ODI (HR 0.50; CI 0.32-0.77) and AHI (HR 0.56; CI 0.37-0.85). In yearly cohorts according to inclusion date, the absconder rate at 6 and 12 months was 20 (CI 18-22) and 27% (CI 25-30) for the first 8 years and improved to 10 (CI 7-15) and 14% (CI 10-19) for the last 2 years, respectively., Conclusions: Long-term adherence to PAP in OSAS is associated with baseline measures of disease severity. After 2009, an improvement in the adherence rate was observed.

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6-7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (W(max)) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6-7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max ) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6-7 (5533 m), VO(2) at 75% W(max) (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO(2) was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO(2) to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5-6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions., (© 2011 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Impairment of cognitive performance during and after high-altitude climbing has been described in numerous studies and has mostly been attributed to cerebral hypoxia and resulting functional and structural cerebral alterations. To investigate the hypothesis that high-altitude climbing leads to cognitive impairment, we used of neuropsychological tests and measurements of eye movement (EM) performance during different stimulus conditions. The study was conducted in 32 mountaineers participating in an expedition to Muztagh Ata (7,546 m). Neuropsychological tests comprised figural fluency, line bisection, letter and number cancellation, and a modified pegboard task. Saccadic performance was evaluated under three stimulus conditions with varying degrees of cortical involvement: visually guided pro- and anti-saccades, and visuo-visual interaction. Typical saccade parameters (latency, mean sequence, post-saccadic stability, and error rate) were computed off-line. Measurements were taken at a baseline level of 440 m and at altitudes of 4,497, 5,533, 6,265, and again at 440 m. All subjects reached 5,533 m, and 28 reached 6,265 m. The neuropsychological test results did not reveal any cognitive impairment. Complete eye movement recordings for all stimulus conditions were obtained in 24 subjects at baseline and at least two altitudes and in 10 subjects at baseline and all altitudes. Measurements of saccade performances showed no dependence on any altitude-related parameter and were well within normal limits. Our data indicates that acclimatized climbers do not seem to suffer from significant cognitive deficits during or after climbs to altitudes above 7,500 m. We demonstrated that investigation of EMs is feasible during high-altitude expeditions.

Background: Percutaneous endoscopic gastrostomy (PEG) tube placement in amyotrophic lateral sclerosis (ALS) patients with impaired respiratory function is associated with an increased risk of peri-procedural and post-interventional complications. It was the aim of the study to analyze peri- and post-interventional complications and survival after PEG tube placement under noninvasive ventilation (NIV) in ALS patients with various degrees of respiratory impairment., Methods: Twenty-six subjects were included in this retrospective case study. Prior to PEG tube placement, training with ventilatory support via an oronasal mask was performed with ALS subjects on the pneumology ward. PEG placement was then performed under continuous NIV. FVC, sniff nasal inspiratory pressure, and demographic data were assessed. Complication rates and 1-month and overall survival rates were analyzed., Results: There were no deaths within 24 hours after PEG placement. One subject died within the first month. The mean survival rate after PEG was 12 ± 10 months (range 0.6-42 months). There was no difference in post-PEG survival between subjects with moderately (> 50%) and severely (< 50%) impaired FVC., Conclusions: In this case series, PEG tube insertion was associated with minimal peri- and post-procedural complications. The low complication rate might be due to the systematic use of procedural NIV in ALS subjects.

Immigration from high tuberculosis (TB) prevalence countries has a substantial impact on the epidemiology of TB in receiving countries with low TB incidence. Cross-border migration offers an ideal opportunity for active case finding that will result in a lower caseload in the host country and a reduced spread of disease to both the indigenous and migrant populations. Screening strategies can start 'offshore', thereby indirectly assisting and empowering public health systems in the source countries, or be performed at ports of entry with or without long-term engagement of 'onshore' facilities and systems to provide either preventive therapy or surveillance for reactivation of latent TB. The chest radiograph seems to be playing a key role in this process, but questions remain regarding when, where and in whom radiographs are best done for optimal yield and cost-effectiveness, and with what other tests they might best be combined to further increase the usefulness of transborder TB control., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Background: The role of drainage, intrapleural fibrinolytics, and/or surgery in the management of thoracic empyema is controversial., Objectives: We aimed to investigate the operational practice of empyema management at our hospital., Methods: Between January 2001 and December 2008, all patients with thoracic empyema were retrieved. After exclusion of patients with malignant effusion, traumatic or iatrogenic empyema, and a history of pleurodesis or tuberculosis, we compared the characteristics of medically versus surgically treated empyema patients., Results: Seventy-eight of 215 retrieved patients were acute bacterial empyema cases. All received intravenous antibiotics. Fifty-eight (74.4%) initially received tube thoracostomy, 34 (43.6%) were treated with intrapleural urokinase, and 30 (38.5%) were operated on. Of 20 patients without initial tube thoracostomy, 15 (75%) were operated on, compared to 9 (37.5%) who were initially treated by tube thoracostomy without intrapleural fibrinolytics (OR 5; 95% CI 1.4-18.5, p = 0.01) and 6 (17.7%) who were initially treated with tube thoracostomy and intrapleural urokinase (OR 14; 95% CI 3.6-53.6, p < 0.001). The surgery patients were not different in demographic and clinical characteristics but were more likely to describe significant chest pain 12 months after discharge., Conclusions: In this retrospective cohort study of thoracic empyema patients, initial chest tube insertion and intrapleural fibrinolytics were associated with less surgical therapy. Other predictors of the need for surgery could not be identified. Surgery patients were more likely to suffer from residual chest pain 12 months after discharge. Initial treatment with IV antibiotics, chest tube, and intrapleural fibrinolytics was successful in the majority of patients., (Copyright © 2013 S. Karger AG, Basel.)

Objectives: The aim of this study was to assess serum tumor necrosis factor alpha (TNFA) concentrations 8 months of continuous positive airway pressure (CPAP) therapy., Design: This study used prospective, observational clinical trial., Patients: Sixty-six patients with newly diagnosed sleep apnea syndrome (12 women, 54 men), age 52.3 ± 9.8 (mean ± SD) with a body mass index of 29.7 ± 4.4 and an apnea-hypopnea index of 39.7 ± 26.8, were studied., Intervention: CPAP was administered for a mean of 7.8 ± 1.3 months., Measurements and Results: TNFA concentrations using an ultrasensitive ELISA assay at baseline and follow-up. TNFA decreased in men with high (5.2 ± 1.7 h/night, -0.46 ± 1.1 ng/l, p = 0.001) and with low (2.5 ± 1.0 h/night -0.63 ± 0.77 ng/l, p = 0.001) adherence but not in women. Average number of hours of CPAP use correlated positively with delta TNFA (R (2) 0.08, p = 0.04), Conclusion: Long-term CPAP positively affects TNFA even in men with poor adherence to CPAP.

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value &#60; 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value &#60; 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value &#60; 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Rationale: Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m)., Objectives: To investigate whether periodic breathing persists during prolonged stay at very high altitude., Methods: A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19-20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained., Measurements and Main Results: Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5-8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing., Conclusions: Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).

Objective: To investigate the long-term effects of nasal continuous positive airway pressure (CPAP) ventilation in patients with obstructive sleep apnea syndrome (OSAS) on body composition (BC) and IGF1., Design: Observational study., Subjects: Seventy-eight (11 females and 67 males) OSAS patients who were compliant with CPAP (age 51+/-1.1 years) participated in the study. We assessed body mass index (BMI), total body mass (TBM), total body fat (TBF; kg) and lean body mass (LBM; kg), abdominal subcutaneous (SC) and visceral (V) fat (cm(2)), and waist circumference (WC; cm) by magnetic resonance imaging, and IGF1 (ng/ml) before and after 7.8+/-1.3 months of CPAP use of an average of 5.9+/-1.2 h., Results: Women had a higher BMI, WC; TBM, TBF, and more SC fat. Men had a higher LBM and more V fat. CPAP increased WC (+2.8+/-9.6 cm, P=0.02) and LBM (2.2+/-0.5 kg, P=0.006), but not IGF1. In men, CPAP increased BMI (0.5+/-0.2 kg/m(2), P=0.02), WC (1.7+/-6.9 cm, P=0.002), TBM (1.7+/-0.4 kg, P=0.0001), LBM (1.5+/-0.4 kg, P=0.0003), SC fat (12.9+/-5.1 cm(2), P=0.02), and IGF1 (13.6+/-4.2 ng/ml, P=0.002). Compliance with CPAP increased LBM in men aged <60 years, but not in those aged >60 years, and IGF1 increased in men aged 40-60 years only., Conclusions: Long-term CPAP increased LBM in both sexes and IGF1 in men, while fat mass remained unchanged, suggesting a sexually dimorphic response of IGF1 to CPAP. The role of the GH axis activity and age to this response is unclear. The metabolic consequences of changes in LBM are still to be determined. Future studies on the effects of CPAP on BC should include LBM as an outcome.