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There is strong evidence for clinically relevant night‐to‐night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in‐laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea–hypopnea index in the respiratory polygraphy was < 5 per hr, but the mean oxygen desaturation index of 14 nights of pulse oximetry was ≥ 5 per hr. The additional information of 14 nights of pulse oximetry helped to diagnose obstructive sleep apnea with a 70% consensus in two of those patients (16.7% [95% confidence interval: 4.7/44.8]). In eight patients, experts could not agree to a 70% consensus regarding continuous positive airway pressure therapy recommendation after respiratory polygraphy. The additional information of multiple‐night testing led to a consensus in three of those cases (37.5% [95% confidence interval: 14/69]). Change of obstructive sleep apnea diagnosis and continuous positive airway pressure recommendation was significantly negatively associated with the number of treated obstructive sleep apnea patients > 100 per year compared with 0–29 patients per year (Coef. [95% confidence interval] −0.63 [−1.22/−0.04] and −0.61 [−1.07/−0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty.

Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.

Background: Obstructive sleep apnea (OSA) and sarcoidosis have both been implied to be risk factors for increased arterial stiffness. However, it is unclear whether an elevated apnea–hypopnea index (AHI) in sarcoidosis patients increases arterial stiffness and thus the cardiovascular risk. Methods: We performed non-invasive applanation tonometry in 57 adults with sarcoidosis. The participants underwent SphygmoCor to assess arterial stiffness using an aortic augmentation index with a heart rate of 75/min (AIx) and level-3 respiratory polygraphy. An AHI of ≥5/h, ≥15/h, and ≥30/h defined mild, moderate, and severe OSA, respectively. Multivariate regression analysis was used to investigate the association between AIx and AHI, adjusted for prespecified risk factors for AIx. Results: 23 (40%) sarcoidosis patients had at least mild OSA (AHI ≥ 5), while 7 (12%) patients showed AHI ≥ 15/h. AHI was significantly associated with AIx (coef. (95%CI) of 0.31 (0.09/0.52), p = 0.006) even after adjustment for known risk factors of arterial stiffness. While severe OSA was positively associated with increased AIx, mild and moderate OSA were not associated with increased AIx after adjusting for known risk factors. Conclusions: Increased AHI is independently associated with increased arterial stiffness in sarcoidosis patients. Further investigations are needed to underline the association between OSA severity and the magnitude of arterial stiffness.

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5–8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.

Thoracic aortic aneurysms (TAA) may be associated with complications such as rupture and dissection, which can lead to a fatal outcome. Increased central arterial stiffness has been proposed to be present in patients with TAA compared to unmatched controls. We aimed to assess whether wall properties in patients with TAA are also altered when compared to a matched control group. Applanation tonometry was performed in 74 adults with TAA and 74 sex, age, weight, height, and left ventricular ejection fraction matched controls. Subsequently analysis of the pulse wave was done using the SphygmoCor System. For comparing the two groups, AIx was adjusted to a heart rate of 75/min (AIx@75). 148 1-to-1 matched participants were included in the final model. There was no significant difference in the Alx@75 between the TAA group and the matched control group [mean (SD) of 24.7 (11.2) % and 22.8 (11.2) %, p = 0.240]. Adjusted for known cardiovascular risk factors, there was no association between TAA and AIx@75. Patients with TAA showed comparable arterial wall properties to cardiovascular risk factor matched controls. Since higher arterial stiffness is associated with TAA progression, it remains to be investigated if increased central arterial stiffness is a relevant factor of TAA emergence. Keywords: thoracic aortic aneurysm; augmentation index; arterial stiffness

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.

Maurice Roeder,1 Noriane A Sievi,1 Dario Kohlbrenner,1 Christian F Clarenbach,1 Malcolm Kohler1,2 1Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland; 2Centre for Interdisciplinary Sleep Research, University of Zurich, Zurich, SwitzerlandCorrespondence: Malcolm KohlerPulmonary Division, University Hospital Zurich, Raemistrasse 100, Zurich 8091, SwitzerlandEmail malcolm.kohler@usz.chBackground: Cardiovascular events are, after cancer, the most common cause of death in COPD patients. Arterial stiffness is an independent predictor of all-cause mortality and cardiovascular events. Several cross-sectional studies have confirmed increased arterial stiffness in patients with COPD. Various mechanisms in the development of arterial stiffness in COPD such as reduced lung function or systemic inflammation have been proposed. However, clinical predictors of arterial stiffness that had been reported in cross-sectional studies have not yet been confirmed in a longitudinal setting. We have assessed the course of augmentation index (AIx) - a measure of systemic arterial stiffness - and possible predictors in a cohort of COPD patients over a period of up to 7 years.Methods: COPD patients underwent annual AIx measurement by applanation tonometry for a maximum duration of 7 years. Additionally, we performed annual assessments of lung function, blood gases, systemic inflammation, serum lipids and blood pressure. Associations between the course of AIx and potential predictors were investigated through a mixed effect model.Results: Seventy-six patients (mean (SD) age 62.4 (7.1), male 67%) were included. The AIx showed a significant annual increase of 0.91% (95% CI 0.21/1.60) adjusted for baseline. The change in diffusion capacity (DLco), low-density lipoprotein (LDL), and high-sensitivity c-reactive protein (hsCRP) was independently associated with the increasing evolution of AIx (Coef. - 0.10, p< 0.001, Coef. 1.37, p=0.003, and Coef. 0.07, p=0.033, respectivel

Fabian A Grewe,1 Noriane A Sievi,1 Matteo Bradicich,1 Maurice Roeder,1 Thomas Brack,2 Martin H Brutsche,3 Martin Frey,4 Sarosh Irani,5 Jörg D Leuppi,6 Robert Thurnheer,7 Christian F Clarenbach,1 Malcolm Kohler1,8 1Pulmonary Division, University Hospital Zurich, Zurich, Switzerland; 2Pulmonary Division, Cantonal Hospital of Glarus, Glarus, Switzerland; 3Pulmonary Division, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland; 4Pulmonary Division, Clinic Barmelweid, Erlinsbach, Switzerland; 5Pulmonary Division, Cantonal Hospital of Aarau, Aarau, Switzerland; 6University Department of Medicine, Cantonal Hospital Baselland and University of Basel, Basel, Switzerland; 7Pulmonary Division, Cantonal Hospital of Münsterlingen, Münsterlingen, Switzerland; 8Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, SwitzerlandCorrespondence: Malcolm KohlerPulmonary Division, University Hospital Zurich, Raemistrasse 100, Zurich 8091, SwitzerlandEmail malcolm.kohler@usz.chObjective: To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.Methods: This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland. Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016. For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline. We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication. Groups were compared via ANOVA.Results: Data of 305 patients (62± 7 years, 66% men) were analysed. In 59.1% of visits, the prescribed medication conforme

Objective: To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting. Methods: This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland. Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016. For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline. We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication. Groups were compared via ANOVA. Results: Data of 305 patients (62±7 years, 66% men) were analysed. In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline. Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines. Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively. Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%). Conclusion: The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups. The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. Keywords: Global Initiative for Chronic Obstructive Lung Disease guidelines; chronic obstructive pulmonary disease; guideline-compliance.

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.