Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.

BACKGROUND: Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness. METHODS: In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: >20% of the bronchial tissue area) and low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively, and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 µg twice daily). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/placebo and followed for 12 months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1 s (FEV1) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS. RESULTS: In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV1 change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year-1 within the group of patients with LASMC and 183.0 mL·year-1 within the group of patients with HASMC. CONCLUSION: COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.

Copeptin, pro-atrial natriuretic peptide and pro-adrenomedullin as markers of hypoxic stress in patients with obstructive sleep apnea-a prospective intervention study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) might lead to oxidative stress, inflammation and elevated circulating copeptin, proANP and proADM levels. We aimed to evaluate whether the levels of these prohormones are higher in patients with OSA and whether they might change under continuous positive airway pressure (CPAP) therapy, serving as potential proxies for the diagnosis and therapy-response in OSA. METHODS: A total of 310 patients with suspicion of OSA were recruited. Screening for OSA was performed using overnight pulse oximetry followed by polygraphy and a venous puncture in the morning. All patients diagnosed with OSA underwent CPAP adaptation. A venous puncture was conducted in the night before CPAP and in the following morning. At 1 and 6 months of treatment, polygraphy was performed, followed by a venous puncture in the morning. In the acquired blood, copeptin, proANP and proADM levels were measured. RESULTS: We analyzed 232 patients with OSA and 30 patients without OSA. Our results indicated that only copeptin levels differed significantly among patients with and without OSA at baseline. In OSA patients, the levels of proADM significantly changed after 1 and 6 months on CPAP therapy, when compared to baseline (p < 0.001 and p = 0.020). Additionally, proANP levels significantly decreased after 12 h on CPAP therapy, as compared to baseline levels (p < 0.001). CONCLUSIONS: Copeptin is significantly associated with the presence of OSA. ProANP levels might serve as a potential proxy for the acute response to non-invasive ventilation (12 h), while proADM reflects the long-term response (1 and 6 months).

Oxygen desaturation during flexible bronchoscopy with propofol sedation is associated with sleep apnea: the PROSA-Study.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of complete or partial obstruction of the upper airways during sleep. Conscious sedation for flexible bronchoscopy (FB) places patients in a sleep-like condition. We hypothesize that oxygen desaturation during flexible bronchoscopy may help to detect undiagnosed sleep apnea. METHODS: Single-centre, investigator-initiated and driven study including consecutive patients undergoing FB for clinical indication. Patients completed the Epworth Sleepiness Scale (ESS), Lausanne NoSAS score, STOP-BANG questionnaire and the Berlin questionnaire and underwent polygraphy within 7 days of FB. FB was performed under conscious sedation with propofol. Oxygen desaturation during bronchoscopy was measured with continuous monitoring of peripheral oxygen saturation with ixTrend (ixellence GmbH, Germany). RESULTS: 145 patients were included in the study, 62% were male, and the average age was 65.8 ± 1.1 years. The vast majority of patients (n = 131, 90%) proved to fulfill OSA criteria based on polygraphy results: 52/131 patients (40%) had mild sleep apnea, 49/131 patients (37%) moderate sleep apnea and 30/131 patients (23%) severe sleep apnea. Patients with no oxygen desaturation had a significantly lower apnea-hypopnea index than patients with oxygen desaturation during bronchoscopy (AHI 11.94/h vs 21.02/h, p = 0.011). This association remained significant when adjusting for the duration of bronchoscopy and propofol dose (p = 0.023; 95% CI 1.382; 18.243) but did not hold when also adjusting for age and BMI. CONCLUSION: The severity of sleep apnea was associated to oxygen desaturation during flexible bronchoscopy under conscious sedation. Patients with oxygen desaturation during bronchoscopy might be considered for sleep apnea screening. TRIAL REGISTRATION: The Study was approved by the Ethics Committee northwest/central Switzerland, EKNZ (EK 16/13) and was carried out according to the Declaration of Helsinki and Good Clinical Practice guidelines. Due to its observational character, the study did not require registration at a clinical trial registry.

Endothelial dysfunction is not a predictor of outcome in chronic obstructive pulmonary disease.

BACKGROUND: Local airway inflammation may cause systemic changes which result in endothelial dysfunction. Only a few studies have used reactive hyperemia peripheral arterial tonometry (RH-PAT) in patients with chronic obstructive pulmonary disease (COPD) in order to measure their endothelial dysfunction. OBJECTIVE: To determine the efficacy of endothelial dysfunction, measured by RH-PAT, in assessing disease severity and systemic burden in a cohort of COPD patients. METHODS: In this prospective, monocentric study, 157 patients with moderate to very severe COPD (GOLD class II-IV) were examined for endothelial dysfunction using RH-PAT (Itamar medical Ltd., Caesarea, Israel). In a nested-cohort, examination was repeated at exacerbation. The association between reactive hyperemia index (RHI), augmentation index (AI) and disease severity and outcome parameters was analysed. RESULTS: 57% of the COPD patients had a dysfunctional endothelium and the median (IQR) RHI was 1.42 (1.27-1.53). Exacerbation of COPD was not associated with a significant change in RHI (p = 0.625) or ΑΙ (p = 0.530). None of the diagnostic or clinical outcomes of COPD was associated with RHI or arterial stiffness. CONCLUSION: Endothelial dysfunction is common in COPD. However, it does not seem to be a predictor neither of disease severity, nor of outcome and does not change during exacerbations of the disease.

Long-Term Mechanical Ventilation: Recommendations of the Swiss Society of Pulmonology.

Long-term mechanical ventilation is a well-established treatment for chronic hypercapnic respiratory failure (CHRF). It is aimed at improving CHRF-related symptoms, health-related quality of life, survival, and decreasing hospital admissions. In Switzerland, long-term mechanical ventilation has been increasingly used since the 1980s in hospital and home care settings. Over the years, its application has considerably expanded with accumulating evidence of beneficial effects in a broad range of conditions associated with CHRF. Most frequent indications for long-term mechanical ventilation are chronic obstructive pulmonary disease, obesity hypoventilation syndrome, neuromuscular and chest wall diseases. In the current consensus document, the Special Interest Group of the Swiss Society of Pulmonology reviews the most recent scientific literature on long-term mechanical ventilation and provides recommendations adapted to the particular setting of the Swiss healthcare system with a focus on the practice of non-invasive and invasive home ventilation in adults.

Time-course of upper respiratory tract viral infection and COPD exacerbation.

Viral respiratory tract infections have been implicated as the predominant risk factor for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to evaluate, longitudinally, the association between upper respiratory tract infections (URTI) caused by viruses and AECOPD.Detection of 18 viruses was performed in naso- and orοpharyngeal swabs from 450 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) who were followed for a mean of 27 months. Swabs were taken during stable periods (n=1909), at URTI onset (n=391), 10 days after the URTI (n=356) and during an AECOPD (n=177) and tested using a multiplex nucleic acid amplification test.Evidence of at least one respiratory virus was significantly higher at URTI onset (52.7%), 10 days after the URTI (15.2%) and during an AECOPD (38.4%), compared with the stable period (5.3%, p<0.001). During stable visits, rhinovirus accounted for 54.2% of all viral infections, followed by coronavirus (20.5%). None of the viruses were identified in two consecutive stable visits. Patients with a viral infection at URTI onset did not have a higher incidence of exacerbation than patients without viral infection (p=0.993). Τhe incidence of any viral infection during an AECOPD was similar between URTI-related AECOPD and non-URTI-related AECOPD (p=0.359). Only 24% of the patients that had a URTI-related AECOPD had the same virus at URTI onset and during an AECOPD. Detection of parainfluenza 3 at URTI onset was associated with a higher risk of an AECOPD (p=0.003). Rhinovirus and coronavirus were the most frequently detected viruses during AECOPD visits, accounting for 35.7% and 25.9% of all viral infections, respectively.The prevalence of viral infection during the stable period of COPD was low. The risk of exacerbation following the onset of URTI symptoms depends on the particular virus associated with the event and was significant only for parainfluenza 3.

Fighting Sleep at Night: Brain Correlates and Vulnerability to Sleep Loss.

OBJECTIVE: Even though wakefulness at night leads to profound performance deterioration and is regularly experienced by shift workers, its cerebral correlates remain virtually unexplored. METHODS: We assessed brain activity in young healthy adults during a vigilant attention task under high and low sleep pressure during night-time, coinciding with strongest circadian sleep drive. We examined sleep-loss-related attentional vulnerability by considering a PERIOD3 polymorphism presumably impacting on sleep homeostasis. RESULTS: Our results link higher sleep-loss-related attentional vulnerability to cortical and subcortical deactivation patterns during slow reaction times (i.e., suboptimal vigilant attention). Concomitantly, thalamic regions were progressively less recruited with time-on-task and functionally less connected to task-related and arousal-promoting brain regions in those volunteers showing higher attentional instability in their behavior. The data further suggest that the latter is linked to shifts into a task-inactive default-mode network in between task-relevant stimulus occurrence. INTERPRETATION: We provide a multifaceted view on cerebral correlates of sleep loss at night and propose that genetic predisposition entails differential cerebral coping mechanisms, potentially compromising adequate performance during night work.

Peripheral arterial tonometry versus polysomnography in suspected obstructive sleep apnoea.

BACKGROUND: Polysomnography (PSG) is the gold standard for the diagnosis of obstructive sleep apnoea (OSA). Home sleep apnoea testing with peripheral arterial tonometry (PAT) is a recommended diagnostic alternative for patients with an increased risk for OSA. In a large clinical cohort, we investigated concordance and predictors for discordance in diagnosing OSA using PAT and PSG, and three-year cardiovascular risk in patients with discordant OSA diagnosis. METHODS: Retrospective monocentric cohort study. Patients with a PAT AHI ≥ 5/h followed by an in-hospital PSG within three months were included. All patients with a PAT AHI ≥ 5/h but a PSG AHI < 5/h were classified as discordant. Patients with PAT and PSG AHI ≥ 5/h were classified as concordant. To ascertain cardiovascular risk, major adverse cardiovascular events (MACE) were analyzed in discordant patients and sex, age, body mass index (BMI) and cardiovascular disease-matched concordant patients over a follow-up time of 3.1 ± 0.06 years. RESULTS: A total of 940 patients, 66% male with an average age of 55 ± 0.4 years and BMI of 31 ± 0.2 kg/m2 were included. Agreement in OSA diagnosis was observed in 80% of patients (55% in mild and 86% in moderate and severe OSA). Factors significantly associated with a discordant diagnosis were female sex, younger age and lower BMI, but not comorbidities. There was no significant difference in MACE (p = 0.920) between discordant patients (n = 155) and matched concordant patients (n = 274) with or without therapy. CONCLUSIONS: Concordance between PAT and PSG diagnosis of sleep apnoea is good, particularly in moderate and severe OSA. Predictors for discordant results between PAT and PSG were age, sex and BMI. MACE risk is similar in those with OSA diagnosed by PAT or PSG.

Enhanced didactic methods of smoking cessation training for medical students--a randomized study.

BACKGROUND: It is essential that medical students are adequately trained in smoking cessation. A web-based tobacco abstinence training program might supplement or replace traditional didactic methods. METHODS: One-hundred and forty third-year medical students were all provided access to a self-directed web-based learning module on smoking cessation. Thereafter, they were randomly allocated to attend 1 of 4 education approaches: (a) web-based training using the same tool, (b) lecture, (c) role playing, and (d) supervised interaction with real patients. RESULTS: Success of the intervention was measured in an objective structured clinical examination. Scores were highest in Group 4 (35.9 ± 8.7), followed by Groups 3 (35.7 ± 6.5), 2 (33.5 ± 9.4), and 1 (28.0 ± 9.6; p = .007). Students in Groups 4 (60.7%) and 3 (57.7%) achieved adequate counseling skills more frequently than those in Groups 2 (34.8%) and 1 (30%; p = .043). There was no difference in the scores reflecting theoretical knowledge (p = .439). Self-assessment of cessation skills and students' satisfaction with training was significantly better in Groups 3 and 4 as compared with 1 and 2 (p < .001 and p = .006, respectively). CONCLUSIONS: Role playing and interaction with real patients are equally efficient and both more powerful learning tools than web-based learning with or without a lecture.

Multiplex bacterial PCR in the bronchoalveolar lavage fluid of non-intubated patients with suspected pulmonary infection: a quasi-experimental study.

Background: Early pathogen identification in pulmonary infection is crucial to guide antibacterial therapy and decrease length of hospital stay. We hypothesise that compared to conventional diagnostic methods, a multiplex bacterial polymerase chain reaction assay has a higher diagnostic yield in bronchoalveolar lavage (BAL) fluid and improved clinical outcomes in patients with suspicion of pulmonary infection. Methods: A prospective, monocentric, quasi-experimental, observational study was carried out. Unselected patients with suspected pulmonary infection who underwent bronchoscopy with BAL were included in the study over a period of 1 year. In addition to conventional diagnostic methods, a multiplex PCR bacterial assay was performed in BAL on a 2 week on: 1 week off pre-determined schedule. No therapeutic recommendations were provided to the treating physician. Results: 605 cases were included, 54% of whom were immunosuppressed. Conventional diagnostic methods detected 56% of the bacteria evidenced by PCR. PCR failed to detect bacteria in 4% of the cases with a positive conventional diagnostic result. After bronchoscopy, 42% of the patients received antibacterial therapy for pulmonary infection for a median of 12 antibiotic days. There was no statistically significant difference in length of hospital stay (median 8 versus 8; p=0.839), antibiotic exposure (median 11 versus 14; p=0.362) or number of antibiotics prescribed (median 2 versus 2; p=0.595) between the two groups. Conclusions: A multiplex bacterial PCR detected more bacteria in BAL fluid than conventional diagnostic methods. However, without a specific antibiotic stewardship approach and a clear understanding of the clinical implications of a positive or negative PCR result, the PCR results did not influence clinical outcomes.

Insomnia and other sleep disorders in dermatology patients: A questionnaire-based study with 634 patients.

Insufficient sleep duration and quality are associated with various adverse health outcomes. Whereas sleep disorders have been studied in a few skin conditions, data in a more comprehensive dermatology population are lacking. We sought to describe the prevalence, causes, and consequences of sleep disorders in dermatology patients. In this cross-sectional, single-center study, dermatology patients completed a questionnaire addressing skin-related and non-skin-related health, sleep behavior, causes, and consequences of sleep disorders. According to the Regensburg Insomnia Scale, 27.92% of the 634 participants had insomnia (177 of 634 patients). Of these 177 patients, 115 (64.97%) were subjectively sleep disturbed, with skin-related causes accounting for 55.65% (64 of 115 patients), non-skin-related accounting for 33.04% (38 of 115 patients), and combined accounting for 11.30% (13 of 115 patients). Itch was the leading cause of skin-related sleep disorders (64.49%, 50 of 77 patients), followed by skin-related pain (55.84%, 43 of 77 patients) and skin-related fearful thoughts (54.55%, 42 of 77 patients). Sleep disorders reduced daytime performance in 68.70% (79 of 115 patients) and sleep quality of relatives in 20.87% (24 of 115 patients). The prevalence of insomnia among different diagnostic categories ranged from 20.31% to 50.00%. The most common strategy to improve sleep was taking sleep medication (57.39%, 66 of 115 patients). We conclude that sleep disorders are highly prevalent in dermatology patients, often leading to reduced daytime performance, impaired sleep among the patients' relatives, and increased use of substances.

Choir singing improves respiratory muscle strength and quality of life in patients with structural heart disease - HeartChoir: a randomised clinical trial.

AIMS OF THE STUDY: Most patients with reduced exercise capacity and acquired or congenital structural heart disease also have a reduced respiratory muscle strength. The aim of this pilot study was to investigate whether choir singing in combination with respiratory muscle training positively influences respiratory muscle strength, exercise capacity and quality of life in this population. METHODS: In this single-centre, randomised and open-label interventional study we compared respiratory muscle strength, exercise capacity and quality of life in patients with acquired or congenital structural heart disease who received either standard of care and a 12-week intervention (weekly choir rehearsal and daily breathing exercises) or standard of care alone. The primary endpoint was the difference in change in maximum inspiratory pressure (∆MIP%predicted). Secondary endpoints included the difference in change in maximum expiratory pressure (∆MEP%predicted), exercise capacity quantified as maximal oxygen uptake during exercise (∆MVO2%predicted) and quality of life quantified by the Minnesota living with heart failure questionnaire (∆MLHFQ score). RESULTS: Overall 24 patients (mean age 65, standard deviation [SD] 19 years, 46% male) were randomised after exclusion. ∆MIP%predicted was significantly higher in the intervention group (∆MIP%predicted +14, SD 21% vs −14, SD 23%; p = 0.008) and quality of life improved significantly (∆MLHFQ score −5, SD 6 vs 3, SD 5; p = 0.006) after 12 weeks. ∆MEP%predicted and ∆MVO2%predicted did not differ between both groups (∆MEP%predicted −3, SD 26% vs −3, SD 16%; p = 1.0 and ∆MVO2%predicted 18, SD 12% vs 10, SD 15%; p = 0.2). CONCLUSIONS: Choir singing in combination with respiratory muscle training improved respiratory muscle strength and quality of life in patients with structural heart disease and may therefore be valuable supplements in cardiac rehabilitation. (Clinical trial registration number: NCT03297918)  .

Recurrent bilateral pneumothorax.

A 71-year-old male with a history of coronary artery bypass surgery 7 years ago underwent a transthoracic needle aspiration biopsy of a pulmonary nodule in the right lung. Three hours later, the patient complained of dyspnea and left sided thoracic pain. The chest x-ray showed bilateral apical pneumothoraces. A second chest x-ray two hours later showed an increase in pneumothorax size on the left side. An intercostal drainage tube (size 24 French) was inserted into the fourth intercostal space on the X side and continuous suction was applied with 20 cm H2O. One day later, the chest x-ray revealed resolution on both sides with only minimal residual bilateral pneumothoraces. There was no air leak and hence the chest tube was removed. Histology revealed a non small cell lung cancer and a lobectomy was performed. At the second postoperative day a chylothorax was diagnosed because of elevated triglycerides. Parenteral nutrition was begun and the quantity of drained effusion diminished. Nine days after successful lobectomy the patient accidentally removed the chest tube and bilateral pneumothoraces were seen in the x-ray again.

Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations.

The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.

The impact of postoperative nasal packing on sleep-disordered breathing and nocturnal oxygen saturation in patients with obstructive sleep apnea syndrome.

Nasal septum surgery is frequently performed to establish a functional nasal airway. In these patients obstructive sleep apnea syndrome (OSAS) is frequently present. Although patients with OSAS are at increased risk for hypoxemia, the impact of postoperative nasal packing (PNP) on sleep-disordered breathing and oxygen desaturations in patients with OSAS is unknown. We consecutively investigated 40 patients undergoing endonasal surgery receiving PNP. Fifteen of these patients had previously diagnosed OSAS (Group 2) and 25 did not (Group 1). In the control group, 12 healthy patients underwent elective ear or neck surgery without PNP. During the preoperative and postoperative nights, we continuously measured oronasal flow, thoracoabdominal movements, and oxygen saturation. We calculated the apnea-hypopnea index (AHI) and the oxygen-desaturation index (ODI). Compared with the preoperative values, after the operation, neither AHI nor ODI changed in the control group. In contrast, in Group 1, AHI (from 11 [5-19] to 37 [22-49]) and ODI (from 4 [2-8] to 13 [6-21]) significantly increased (P < 0.05), whereas in Group 2, only AHI significantly increased (from 14 [10-21] to 39 [26-50]); ODI remained similar (13 [8-27] versus 11 [4-37]). Because ODI did not increase in patients with OSAS and PNP who received postoperative oxygen overnight, postoperative intensive care monitoring might not be necessary on a routine basis for all patients with PNP and OSAS.

Utility of Transcutaneous Capnography for Optimization of Non-Invasive Ventilation Pressures.

INTRODUCTION: Nocturnal Non-invasive Positive Pressure Ventilation (NPPV) is the treatment of choice in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous oxygen saturation measured with a pulse oximeter provides a surrogate measure of arterial oxygen saturation but does not completely reflect ventilation. Currently, Partial Pressure of Arterial (PaCO2) measured by arterial blood analysis is used for estimating the adequacy of ventilatory support and serves as the gold standard. AIM: To examine the safety, feasibility and utility of cutaneous capnography to re-titrate the non-invasive positive pressure ventilation settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. MATERIALS AND METHODS: Twelve patients with chronic hypercapnic respiratory failure prospectively underwent complete polysomnography and cutaneous capnography measurement on the ear lobe. Non-invasive ventilation pressures were adjusted with the aim of normalizing cutaneous carbon dioxide or at least reducing it by 10 to 15 mmHg. Sensor drift for cutaneous carbon dioxide of 0.7 mmHg per hour was integrated in the analysis. RESULTS: Mean baseline cutaneous carbon dioxide was 45.4 ± 6.5 mmHg and drift corrected awake value was 45.1 ± 8.3 mmHg. The correlation of baseline cutaneous carbon dioxide and the corrected awake cutaneous carbon dioxide with arterial blood gas values were 0.91 and 0.85 respectively. Inspiratory positive airway pressures were changed in nine patients (75%) and expiratory positive airway pressures in eight patients (66%). Epworth sleepiness score before and after the study showed no change in five patients, improvement in six patients and deterioration in one patient. CONCLUSION: Cutaneous capnography is feasible and permits the optimization of non-invasive ventilation pressure settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous cutaneous capnography might serve as an important additional tool to complement diurnal arterial carbon dioxide tension values.

Comprehensive biomarker profiling in patients with obstructive sleep apnea.

OBJECTIVES: The pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism. DESIGN AND METHODS: In 65 patients with moderate or severe OSAS [apnea-hypopnea index (AHI) 39±20/h] and 33 patients with no or mild OSAS (AHI 8+4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP). RESULTS: Patients with moderate/severe OSAS had higher insulin before sleep [median (interquartile range), 36.4 (21.9-52.1) vs. 20.8 (10.6-32.8)mU/mL; p=0.006], higher IL-6 after sleep [1.00 (0.73-1.58) vs. 0.72 (0.48-0.94)pg/mL; p=0.005], and larger relative overnight reduction in BNP [-9 (-35-0) vs. -3 (-21-13)%; p=0.04] than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69-0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep. CONCLUSIONS: Significant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.