Association of positive airway pressure termination with mortality and non-fatal cardiovascular events in patients with obstructive sleep apnoea.

BACKGROUND AND AIMS: The recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether PAP termination is associated with an increased incidence of major adverse CV events (MACE) compared with adherent PAP continuation. METHODS: Data from the Pays de la Loire Sleep Cohort were linked to the French national health insurance database to identify incident MACE (composite outcome of mortality, stroke and cardiac diseases), and CV active drug (lipid-lowering, antihypertensive and antiplatelet drugs, beta-blockers) adherence (medication possession ratio ≥80%). The association of PAP termination with MACE was evaluated using a time-dependent survival Cox model, with adjustment for confounders including CV active drug status. RESULTS: After a median follow-up of 8 years, 969 of 4188 included patients (median age 58 years, 69.6% men) experienced MACE, 1485 had terminated PAP while 2703 continued PAP with at least 4 hours/night use. 38% of patients were adherent to all CV drugs in the PAP continuation group versus 28% in the PAP termination group (p<0.0001). After adjustment for confounders, PAP termination was associated with an increased risk of MACE (HR (95% CI): 1.39 (1.20 to 1.62); p<0.0001). PAP termination was not associated with incident heart failure and coronary artery disease. CONCLUSIONS: In this multicentre clinical-based cohort involving 4188 patients with OSA, PAP termination compared with adherent PAP continuation was associated with an increased risk of MACE. More research is needed to determine whether support programmes on PAP adherence could improve CV outcomes.

Exploring emotional regulation in insomnia with and without major depressive episode.

Previous studies have highlighted the pivotal role of emotional regulation impairment in the progression of depressive and insomnia disorders, individually. Nevertheless, to date, no study has undertaken a direct comparison of the emotional profiles in individuals experiencing insomnia with or without major depressive episode (MDE). In this study, our objective was to closely examine multiple aspects of emotional regulation among individuals experiencing insomnia, with or without concurrent depression. This descriptive observational study involved 57 participants, comprising 27 individuals with comorbid chronic insomnia and MDE, and 30 with chronic insomnia alone. All participants completed self-questionnaires assessing aspects of emotional regulation: the Affect Intensity Measure (intensity), Affective Lability Scale (lability), Temperament Evaluation of Memphis Pisa Paris and San Diego Autoquestionnaire (temperament), Cognitive Emotion Regulation Questionnaire (cognitive strategies), and Multidimensional Assessment of Thymic States (reactivity). There were statistically significant differences between the group with insomnia with MDE and insomnia without MDE in terms of anxiety/depression lability. Discrepancies also manifested in terms of activation or inhibition in motor activity and motivation. Additionally, a noteworthy variance in cognitive strategies for emotional regulation was observed, specifically in self-blame and catastrophising. From a cognitive perspective, patients with insomnia and a MDE exhibited a greater inclination towards self-blame and catastrophising, in contrast to those with insomnia only. Behaviourally, the former group demonstrated heightened inhibition of motivation and motor activity. These findings underscore the importance of larger-scale investigations to validate these insights and pave the way for clinical prospects centred around emotional regulation, ultimately fostering personalised treatments for insomnia.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

BACKGROUND AND OBJECTIVE: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. METHODS: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. RESULTS: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group. CONCLUSION: SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.

Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients. It has also been shown that small extracellular vesicles (sEVs) carrying PD-L1 induce lymphocyte dysfunction. Thus, the aim of our study was to analyze the expression of PD-L1 on sEVs of OSA patients and to evaluate the role of sEVs on lymphocyte activation and cytotoxicity. Circulating sEVs were isolated from OSA patients and the control group. Lymphocytes were isolated from the control group. Circulating sEVs were characterized by western blot, nanotracking analysis, and flow cytometry and were incubated with lymphocytes. Our results show no differences in the quantity and composition of sEVs in OSA patients and no significant effects of sEVs in OSA patients on lymphocyte activation and cytotoxicity. These results suggest that OSA does not modify PD-L1 expression on sEVs, which does not contribute to dysregulation of cytotoxic lymphocytes.

Prevalence of major depressive disorder and post-traumatic stress disorder among first-time sleep center attendees.

BACKGROUND: Sleep disorders and psychiatric disorders stand in a bidirectional relationship. Sleep complaints are prominent in populations with psychiatric disorders, especially amongst people with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Consultations at sleep clinics offer opportunities to screen psychiatric disorders and to propose primary psychiatric care. METHODS: This descriptive study was conducted on 755 patients making their first visit to sleep clinic, with 574 seeking consultation for suspected obstructive sleep apnoea-hypopnoea syndrome (OSAHS), 139 for complaints of insomnia, and 42 for complaints of hypersomnia. The results of 387 screening scales for MDD (BDI-II) and 403 for TSPT (PCL-5) were compared according to the reason given for the consultation. RESULTS: In the whole group, 12.1 % of patients presented a positive MDD screening and 4.9 % for PTSD. Among patients presenting with insomnia, 19.8 % had a positive screening for MDD, as compared to 9.3 % in patients presenting with suspected OSAHS (p = 0.02). Regarding PTSD, 9.7 % of patients seeking consultation because of insomnia had a positive screening, compared to 2.9 % among patients with suspected OSAHS (p = 0.03). Among patients with a positive screening for MDD, 40.5 % were not receiving antidepressant or mood stabilizer treatment. CONCLUSION: Positive screening for MDD and PTSD are frequent in patients who attend sleep centers, especially amongst those presenting with insomnia. Nearly half of the patients with positive screening for MDD or PTSD were not receiving a dedicated pharmacological treatment. These figures emphasize systematic screening for psychiatric disorders in sleep clinics.

Seasonal changes in positive airway pressure adherence.

Through their effects on sleep duration, bedroom environments, and pollen allergies, seasonal variations may impact positive airway pressure (PAP) adherence. We analyzed daily PAP telemonitoring data from 25,846 adults (median age 64 years, 67.8% male) treated with PAP for at least 4 months [mean (standard deviation, SD) duration of PAP: 5.5 years (SD 4.1)] to examine seasonal changes in PAP adherence, leaks, and residual apnea-hypopnea index. We demonstrate a significant decrease in PAP adherence in June compared to January (mean (SD): 0.37 (1.54) h/night) that achieved the minimal clinically important difference (MCID) of 30 min in 13.9% of adults. Furthermore, we provide novel data supporting the association of rising temperatures with seasonal changes in PAP use. Indeed, the most pronounced decline in PAP adherence was observed during the hottest days, while PAP adherence was only slightly reduced during the coolest days of June. Clinicians should be aware of seasonal changes in PAP adherence that are likely to be exacerbated by climate change.

Does PaCO2 correction have an impact on survival of patients with chronic respiratory failure and long-term non-invasive ventilation?

Background and objective: Non-invasive ventilation (NIV) improves survival of patients with chronic respiratory failure (CRF). Most often, pressure settings are made to normalize arterial blood gases. However, this objective is not always achieved due to intolerance to increased pressure or poor compliance. Few studies have assessed the effect of persistent hypercapnia on ventilated patients' survival. Data from the Pays de la Loire Respiratory Health Research Institute cohort were analyzed to answer this question. Study design and methods: NIV-treated adults enrolled between 2009 and 2019 were divided into 5 subgroups: obesity-hypoventilation syndrome (OHS), COPD, obese COPD, neuromuscular disease (NMD) and chest wall disease (CWD). PaCO2 correction was defined as the achievement of a PaCO2 < 6 kPa or a 20% decrease in baseline PaCO2 in COPD patients. The endpoint was all-cause mortality. Follow-up was censored in case of NIV discontinuation. Results: Data from 431 patients were analyzed. Median survival was 103 months and 148 patients died. Overall, PaCO2 correction was achieved in 74% of patients. Bivariate analysis did not show any survival difference between patients who achievedPaCO2 correction and those who remained hypercapnic: overall population: p = 0.74; COPD: p = 0.97; obese COPD: p = 0.28; OHS: p = 0.93; NMD: p = 0.84; CWD: p = 0.28. Conclusion: Moderate residual hypercapnia under NIV does not negatively impact survival in CRF patients. In individuals with poor tolerance of pressure increases, residual hypercapnia can therefore be tolerated under long-term NIV. Larger studies, especially with a higher number of patients with residual PaCO2 > 7 kPa, are needed to confirm these results.

The PAP-RES algorithm: Defining who, why and how to use positive airway pressure therapy for OSA.

Obstructive sleep apnea (OSA) is a common condition that is increasing in prevalence worldwide. Untreated OSA has a negative impact on health-related quality of life and is an independent risk factor for cardiovascular diseases. Despite available data suggesting that cardiovascular risk might differ according to clinical phenotypes and comorbidities, current approaches to OSA treatment usually take a "one size fits all" approach. Identification of cardiovascular vulnerability biomarkers and clinical phenotypes associated with response to positive airway pressure (PAP) therapy could help to redefine the standard treatment paradigm. The new PAP-RES (PAP-RESponsive) algorithm is based on the identification of OSA phenotypes that are likely to impact therapeutic goals and modalities. The paradigm shift is to propose a simplified approach that defines therapeutic goals based on OSA phenotype: from a predominantly "symptomatic phenotype" (individuals with high symptom burden that negatively impacts on daily life and/or accident risk or clinically significant insomnia) to a "vulnerable cardiovascular phenotype" (individuals with comorbidities [serious cardiovascular or respiratory disease or obesity] that have a negative impact on cardiovascular prognosis or a biomarker of hypoxic burden and/or autonomic nervous system dysfunction). Each phenotype requires a different PAP therapy care pathway based on differing health issues and treatment objectives.

Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA.

BACKGROUND: The healthy adherer effect has gained increasing attention as potential source of bias in observational studies examining the association of positive airway pressure (PAP) adherence with health outcomes in OSA. RESEARCH QUESTION: Is adherence to PAP associated with healthy behaviors and health care resource use prior to device prescription? STUDY DESIGN AND METHODS: Data from the IRSR Pays de la Loire Sleep Cohort were linked to health administrative data to identify proxies of heathy behaviors, including adherence to cardiovascular (CV) drugs (medical possession ratio), cancer screening tests, influenza vaccination, alcohol and smoking consumption, and drowsiness-related road accidents during the 2 years preceding PAP onset in patients with OSA. Multivariable regression analyses were conducted to evaluate the association of heathy behaviors with subsequent PAP adherence. Health care resource use was evaluated according to subsequent PAP adherence. RESULTS: We included 2,836 patients who had started PAP therapy between 2012 and 2018 (65% of whom were PAP adherent with mean daily use ≥ 4 h/night). Being adherent to CV active drugs (medical possession ratio ≥ 80%) and a person who does not smoke were associated with a higher likelihood of PAP adherence (OR, 1.43; 95% CI, 1.15-1.77 and OR, 1.37; 95% CI, 1.10-1.71, respectively). Patients with no history of drowsiness-related road accidents were more likely to continue PAP (OR, 1.39; 95% CI, 1.04-1.87). Patients who were PAP adherent used less health care resources 2 years before PAP initiation than patients who were nonadherent (mean number of outpatient consultations: 19.0 vs 17.2, P = .003; hospitalization days: 5.7 vs 5.0; P = .04; ED visits: 30.7% vs 24.0%, P = .0002, respectively). INTERPRETATION: Patients who adhere to PAP therapy for OSA were more health-seeking and used less health care resources prior to device initiation than patients who were nonadherent. Until the healthy adherer effect associated with PAP adherence is better understood, caution is warranted when interpreting the association of PAP adherence with CV health outcomes and health care resource use in nonrandomized cohorts.

Guidelines for the assessment and management of residual sleepiness in obstructive apnea-hypopnea syndrome: Endorsed by the French Sleep Research and Medicine Society (SFRMS) and the French Speaking Society of Respiratory Diseases (SPLF).

Excessive daytime sleepiness (EDS) is frequent among patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and can persist despite the optimal correction of respiratory events (apnea, hypopnea and respiratory efforts), using continuous positive airway pressure (CPAP) or mandibular advancement device. Symptoms like apathy and fatigue may be mistaken for EDS. In addition, EDS has multi-factorial origin, which makes its evaluation complex. The marketing authorization [Autorisation de Mise sur le Marché (AMM)] for two wake-promoting agents (solriamfetol and pitolisant) raises several practical issues for clinicians. This consensus paper presents recommendations of good clinical practice to identify and evaluate EDS in this context, and to manage and follow-up the patients. It was conducted under the mandate of the French Societies for sleep medicine and for pneumology [Société Française de Recherche et de Médecine du Sommeil (SFRMS) and Société de Pneumologie de Langue Française (SPLF)]. A management algorithm is suggested, as well as a list of conditions during which the patient should be referred to a sleep center or a sleep specialist. The benefit/risk balance of a wake-promoting drug in residual EDS in OSAHS patients must be regularly reevaluated, especially in elderly patients with increased cardiovascular and psychiatric disorders risks. This consensus is based on the scientific knowledge at the time of the publication and may be revised according to their evolution.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists anonymized to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).