Orthostatic Hypotension and Antihypertensive Treatment in Lung Transplant Recipients: A Cross-Sectional Study.

OBJECTIVES: Lung transplant is the ultimate treatment of many end-stage lung diseases. Calcineurin inhibitors, crucial in immunosuppression for lung transplant recipients, are linked to secondary hypertension, necessitating antihypertensive treatment. In addition, lung transplant recipients frequently experience orthostatic hypotension, occasionally stemming from autonomic dysfunction, but also commonly attributed as a negative side effect of antihypertensive treatment. Our study aimed to evaluate the frequency of orthostatic blood pressure irregularities and investigate the involvement of antihypertensive treatment as a potential risk factor in the occurrence among lung transplant recipients. MATERIALS AND METHODS: Fifty-six consecutive lung transplant recipients, both inpatient and outpatient, at the University Hospital Zurich (Switzerland) were monitored from 1999 to 2013. Transplant recipients underwent a Schellong test (an active standing test). Our evaluation encompassed their initial traits, such as the existence of supine hypertension. We computed the odds ratio for the comparison of the likelihood of experiencing orthostatic hypotension while using a minimum of 1 type of antihypertensive medication versus absence of antihypertensive drugs. RESULTS: Of the lung transplant recipients, 25% showed a positive Schellong test. Within this group, 64% had supine hypertension, and 29% displayed symptoms of orthostatic hypotension. Among the patients, 71% were using at least 1 type of antihypertensive medication. The odds ratio for showing orthostatic hypotension while taking at least 1 type of antihypertensive drug versus the absence of antihypertensive medications was 1.64 (95% exact CI, 0.39-6.90) with P = .50. This finding remained consistent regardless of age, sex, inpatient or outpatient status, and the duration since transplant. CONCLUSIONS: Orthostatic blood pressure dysregulation is prevalent among lung transplant recipients, frequently without noticeable symptoms. In our cohort, the use of antihypertensive medications did not elevate the risk of orthostatic hypotension.

ERS International Congress 2023: highlights from the Sleep Disordered Breathing Assembly.

The topic of sleep-related breathing disorders is always evolving, and during the European Respiratory Society (ERS) International Congress 2023 in Milan, Italy, the latest research and clinical topics in respiratory medicine were presented. The most interesting issues included new diagnostic tools, such as cardiovascular parameters and artificial intelligence, pathophysiological traits of sleep disordered breathing from routine polysomnography or polygraphy signals, and new biomarkers and the diagnostic approach in patients with excessive daytime sleepiness. This article summarises the most relevant studies and topics presented at the ERS International Congress 2023. Each section has been written by early career members of ERS Assembly 4.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-ß (Aß) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aß. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

Sleep and Breathing Conference highlights 2023: a summary by ERS Assembly 4.

This paper presents some of the highlights of the Sleep and Breathing Conference 2023 https://bit.ly/46MxJml.

ERS International Congress 2022: highlights from the Sleep Disordered Breathing Assembly.

During the European Respiratory Society (ERS) International Congress 2022 in Barcelona, Spain, the latest research and clinical topics in respiratory medicine were presented. The sleep medicine-focused presentations and symposia provided novel insights into the pathophysiology of sleep disordered breathing, its diagnostics, and new trends in translational research and clinical applications. The presented research trends focused mainly on the assessment of sleep disordered breathing-related intermittent hypoxia, inflammation and sleep fragmentation, and their implications, especially cardiovascular. The most promising methods for assessing these aspects encompass genomics, proteomics and cluster analysis. The currently available options include positive airway pressure and a combination of it and pharmacological agents (e.g. sulthiame). This article summarises the most relevant studies and topics on these subjects presented at the ERS International Congress 2022. Each section has been written by Early Career Members of the ERS Assembly 4.

Being (past and present) President of the ERS: interview about the role, perspectives on career development, and vision for the Society.

This article presents the views of the past and current Presidents of the ERS regarding their role, perspectives on career development and vision for the Society, along with important messages to inspire ECMs to build their own successful career. https://bit.ly/3kAvxIM.

Inspiring stories: the impact that being part of ERS activities can have on a professional career.

In this article, we provide an overview of the impact that being part of the @EuroRespSoc activities can have on a professional career, through the voices of Early Career Members (@EarlyCareerERS) https://bit.ly/32sHNW2.

Preview of the ERS Lung Science Conference 2023 and Sleep and Breathing Conference 2023.

In this article, we provide a brief description of the @EuroRespSoc 2023 Lung Science Conference and the Sleep and Breathing Conference https://bit.ly/3WsCzj6.

Highlights of the ERS Lung Science Conference and Sleep and Breathing Conference 2021 and the new ECMC members.

This article provides a brief description of some of the most remarkable sessions of the @EuroRespSoc Lung Science Conference and the Sleep and Breathing Conference 2021 and presents the new incoming members of the ECMC (@EarlyCareerERS) https://bit.ly/2RSDP40.

The Accuracy of Repeated Sleep Studies in OSA: A Longitudinal Observational Study With 14 Nights of Oxygen Saturation Monitoring.

BACKGROUND: Strong evidence exists for clinically relevant night-to-night variability of respiratory events in patients with suspected OSA. RESEARCH QUESTION: How many sleep study nights are required to diagnose OSA accurately? STUDY DESIGN AND METHODS: Patients with suspected OSA underwent up to 14 nights of pulse oximetry (PO) at home and one night of in-hospital respiratory polygraphy (RP). The accuracy of each of the 13 sleep study nights was analyzed using the mean oxygen desaturation index 3% (ODI3%) of all 14 nights as a reference. Multiple regression analyses assessed possible predictors for night-to-night variability. RESULTS: One hundred three patients underwent in-hospital RP. Using only the results of the RP, 19.7% were misdiagnosed using an ODI3% cutoff of 15/h. One hundred eight patients underwent properly performed PO studies at home with a coefficient of variation (CV) of 31.5% (SD, 14.7%) across all nights. The first PO night demonstrated a sensitivity of 71.4% (95% CI, 55.4%-84.3%) and a specificity of 89.4% (95% CI, 79.4%-95.6%) to diagnose moderate OSA. Using only the first PO night, the negative predictive value was 83.1%. Adding a second recording night increased sensitivity up to 88.1% (95% CI, 74.4%-96.0%) with a slightly lower specificity of 85.9% (95% CI, 74.9%-93.4%). The ODI3% of the in-hospital RP showed an independent negative association to the log-transformed CV (exponentiated coefficient, 0.989; 95% CI, 0.984-0.995). INTERPRETATION: One single night of in-hospital RP may miss relevant OSA. Multiple study nights, for example, using ambulatory oxygen saturation monitoring, increase accuracy for diagnosing moderate OSA. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03819361; URL: www.clinicaltrials.gov.

Nocturnal heart rate variability in obstructive sleep apnoea: a cross-sectional analysis of the Sleep Heart Health Study.

BACKGROUND: Obstructive sleep apnoea (OSA) results in sympathetic overdrive. Increased nocturnal heart rate variability (HRV) is a surrogate marker of autonomic disturbance. The aim was to study the association of the apnoea-hypopnea index (AHI), nocturnal hypoxaemia, and sleep fragmentation with nocturnal HRV to address the pathophysiological mechanisms underlying autonomic disturbance in OSA. METHODS: Participants of the Sleep Hearth Health Study with available data on nocturnal HRV and an AHI ≥10/h have been included in this cross-sectional analysis. The main outcome of interest was the association of sleep fragmentation, nocturnal hypoxaemia, and the AHI with nocturnal HRV. Multivariate regression modelling with the mean of the standard deviations of normal-sinus-to-normal-sinus-interbeat intervals in all 5-minute segments (SDNNIDX) and with low to high frequency power-ratio (LF/HF) as dependent variables controlling for prespecified confounders (age, sex, cups of coffee, beta blocker, nocturnal heart rate) was used to assess the contribution of the arousal index, total sleep time with an oxygen saturation <90% (TST90) and the AHI not due to arousals to HRV. The significance level was set at P<0.01. RESULTS: In 258 patients with OSA (mean ± SD age 62±10 years, BMI 29±4 kg/m2, median (IQR) AHI 18.6/h (14.0-25.6), the arousal index (coef =0.42, P=0.002) was independently positively associated with SDNNIDX also after having controlled for potential confounders, whereas the AHI (coef =0.22, P=0.030) and TST90 (coef =0.36, P=0.054) were not. The arousal index-but not TST and AHI-was also independently associated with LF/HF. CONCLUSIONS: In OSA, pronounced sleep fragmentation is associated with higher nocturnal HRV and a sympatho-vagal imbalance with sympathetic dominance. OSA severity and nocturnal hypoxaemia did not independently predict nocturnal HRV.

Patterns of nightly CPAP usage in OSA patients with suboptimal treatment adherence.

BACKGROUND AND OBJECTIVES: Low adherence impairs the effectiveness of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA), but knowledge on CPAP usage micro-patterns is mostly lacking. Thus, the aim of this study was to analyse usage micro-patterns among patients with suboptimal CPAP adherence. METHODS: We analysed CPAP usage datasets comprising the initial 31 nights of therapy. By employing a threshold of 4 h usage in at least 70% of nights, we subdivided the patients into suboptimal and optimal users. We investigated single CPAP start- and stop-points, and introduced the parameter "interruption-rate", by dividing the amount of therapy interruptions per night by the usage duration per night. This parameter represents the amount of interruptions per 1 h of CPAP usage. Group comparison analysis was performed via t-test, Wilcoxon rank sum-test, and via Chi2-test. RESULTS: We included datasets of 48 suboptimal and 48 optimal users (55.9 ± 11.3 years, 83.3% men) in the analysis. Interruption-rate was significantly higher among suboptimal users, when compared with optimal users (median (quartiles) 0.24 (0.14/0.45) versus 0.15 (0.05/0.28), p < 0.001∗). Suboptimal users were more likely to report that CPAP reduced their sleep quality, waked them up at night, and that CPAP side effects or problems with the device impaired their adherence. CONCLUSIONS: CPAP usage micro-patterns are more fragmented among OSA patients with lower overall adherence. These patterns might result from impaired sleep quality, due to CPAP side effects, and device-associated problems.

Night-to-night variability of respiratory events in obstructive sleep apnoea: a systematic review and meta-analysis.

BACKGROUND: It is current practice to use a single diagnostic sleep study in the diagnostic workup of obstructive sleep apnoea (OSA). However, a relevant night-to-night variability (NtNV) of respiratory events has been reported. METHODS: We evaluated the NtNV of respiratory events in adults with suspected or already diagnosed OSA who underwent more than one diagnostic sleep study. Data sources were PubMed, Cochrane and Embase up to 23 January 2019. Random-effects models were used for evidence synthesis. For moderator analysis, mixed-effects regression analysis was performed. The study was registered with PROSPERO (CRD42019135277). RESULTS: Of 2143 identified papers, 24 studies, comprising 3250 participants, were included. The mean Apnoea-Hypopnoea Index (AHI) difference between the first and second night was -1.70/hour (95% CI -3.61 to 0.02). REM time differences (first to second night) were significantly positive associated with differences in mean AHI (ß coefficient 0.262 (95% CI 0.096 to 0.428). On average, 41% (95% CI 27% to 57%) of all participants showed changes of respiratory events >10/hour from night to night. Furthermore, 49% (95% CI 32% to 65%) of participants changed OSA severity class (severity thresholds at 5/hour, 15/hour and 30/hour) at least once in sequential sleep studies. Depending on the diagnostic threshold (5/hour, 10/hour or 15/hour), on average 12% (95% CI 9% to 15%), 12% (95% CI 8% to 19%) and 10% (95% CI 8% to 13%) of patients would have been missed during the first night due to single night testing. CONCLUSION: While there was no significant difference between mean AHI in two sequential study nights on a group level, there was a remarkable intraindividual NtNV of respiratory events, leading to misdiagnosis and misclassification of patients with suspected OSA.

Smoking status and second-hand smoke biomarkers in COPD, asthma and healthy controls.

INTRODUCTION: Tobacco smoke worsens COPD and asthma. For healthy individuals, quantifying active and second-hand smoke (SHS) exposure clarifies the epidemiology of tobacco consumption and the efficacy of nonsmoking measures. Identifying tobacco exposure biomarkers and cut-offs might allow the creation of sensitive and specific tests. AIM: We describe the state-of-the-art serum, urinary cotinine and exhaled carbon monoxide (CO) cut-offs for assessing smoking status and SHS exposure in adult patients with COPD or asthma, and healthy controls. METHODOLOGY: After a keyword research in the PubMed database, we included papers reporting on the cut-offs of the investigated biomarkers in one of the populations of interest. Papers published before 2000, not in English, or reporting only data on nonadult subjects or on pregnant women were excluded from the analysis. 14 papers were included in the final analysis. We summarised diagnostic cut-offs for smoking status or SHS exposure in COPD, asthmatic and healthy control cohorts, reporting sensitivity and specificity when available. CONCLUSION: Serum and urinary cotinine and exhaled CO are easy-to-standardise, affordable and objective tests for assessing smoking status and SHS exposure. Evidence on cut-offs with good sensitivity and specificity values is available mainly for healthy controls. For COPD and asthmatic patients, most of the currently available evidence focuses on exhaled CO, while studies on the use of cotinine with definite sensitivity and specificity values are still missing. Solid evidence on SHS exposure is available only for healthy controls. An integrated approach with a combination of these markers still needs evaluation.

ERS International Congress, Madrid, 2019: highlights from the Sleep and Clinical Physiology Assembly.

The 2019 European Respiratory Society (ERS) International Congress took place in Madrid, Spain, and served as a platform to find out the latest advances in respiratory diseases research. The research aims are to understand the physiology and consequences of those diseases, as well as the improvement in their diagnoses, treatments and patient care. In particular, the scientific sessions arranged by ERS Assembly 4 provided novel insights into sleep-disordered breathing and new knowledge in respiratory physiology. This article, divided by session, will summarise the most relevant studies presented at the ERS International Congress. Each section has been written by Early Career Members specialising in the different fields of this interdisciplinary assembly.

Compliance of Pharmacotherapy with GOLD Guidelines: A Longitudinal Study in Patients with COPD.

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.

Low repeatability of Epworth Sleepiness Scale after short intervals in a sleep clinic population.

STUDY OBJECTIVES: The purpose of this study was to evaluate the short-term repeatability of the Epworth Sleepiness Scale (ESS) in patients with suspected obstructive sleep apnea and to determine whether transitory sleepiness of the patient influenced ESS results. METHODS: Adult participants with suspected obstructive sleep apnea taking part in a study on the diagnostic accuracy of repeated sleep studies were eligible. For assessment of repeatability, the agreement between 2 sequential ESS scores obtained within 1 day (same-day group) or on different days within 1 week (same-week group) was evaluated. By analyzing the within-day repeatability, a possible influence of situational sleepiness on ESS results was assessed. By comparing correlations of sequential scores between both groups, a potential influence of test day-specific sleepiness on ESS results was evaluated. Data were analyzed using Bland-Altman plots, intraclass correlation coefficients, standard error of measurement analysis, and relative amounts of ESS discrepancies beyond 2, 3, 5, and 7 points. RESULTS: Forty participants (mean age, 47.7 ± 15.4 years; 67.5% men) were included in this study, with 20 in each group. Bland-Altman analysis demonstrated considerable variability of repeated scores (mean ± 1.96 × SD = 1.93 [-3.81 to 7.66]). Discrepancies of at least 3 points between sequential ESS scores were found in 48% of all participants. Comparison of ESS repeatability between both groups showed no evidence for a difference. CONCLUSIONS: A clinically relevant variability in ESS scores was found, even when repeated on the same day, possibly because of situational sleepiness influencing ESS results. Changes in ESS in response to interventions should be interpreted with caution because of its low test-retest reliability.

Distinct profile of inflammatory and remodelling biomarkers in sputum of severe asthmatic patients with or without persistent airway obstruction.

BACKGROUND: Both inflammatory and remodelling processes are associated with irreversible airway obstruction observed in severe asthma. Our aim was to characterize a group of severe asthmatic patients with or without persistent airway obstruction in relation to specific sputum inflammatory and remodelling biomarkers. METHODS: Forty-five patients under regular high-dose inhaled corticosteroid/ß-2agonist treatment were studied, after a follow-up period of at least 2 years, with a minimum of 4 visits. Periostin, TGF-ß, RANTES, IL-8, GM-CSF, FGF-2, and cell counts were measured in induced sputum. Serum periostin was also measured. RESULTS: Sputum induction was successfully performed in all but 5 patients. There were no significant differences in demographic and clinical data between patients with non-persistent obstruction (NO: FEV1/VC>88%pred.) and those with persistent obstruction (O: a not completely reversible obstruction with FEV1/VC<88%pred. at each visit before the study visit). Patients with persistent obstruction had significantly higher sputum periostin and TGF-ß concentrations than NO patients and a trend of higher serum periostin levels. GM-CSF and FGF-2 were significantly increased in NO compared to O patients. No differences between groups were found for RANTES, IL-8 and differential cell counts. Sputum periostin inversely correlated with functional parameters (prebronch. FEV1: rho = -0.36, p < 0.05; postbronch. FEV1: rho = -0.33, p = 0.05). Patients with high sputum periostin concentration (>103.3 pg/ml: median value) showed an absolute number of sputum eosinophils significantly higher than patients with low sputum periostin; this behavior was unobserved when serum periostin was considered. CONCLUSIONS: Only periostin and TGF-ß identified a subgroup of severe asthmatic patients with persistent airway obstruction. Sputum periostin was also inversely associated with FEV1 and proved to be a more sensitive biomarker than serum periostin to identify severe asthmatics with higher sputum eosinophilia.