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.

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

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.

A biphasic effect of age on CPAP adherence: a cross-sectional study of 26,343 patients.

BACKGROUND: As the prevalence of OSA increases in older patients, the proportion of elderly patients treated with CPAP is expected to become even higher. We studied CPAP-adherence in a real-life cohort involving a large population of elderly patients with OSA. METHODS: eQUALISAS is a cross-sectional study of CPAP treated OSA patients for at least 4 months who received remote monitoring during 2021. CPAP adherence, device-reported residual AHI (AHICPAP) and 95th percentile non-intentional leaks were software collected during January 2021. Age and sex were also collected. RESULTS: Data from 26,343 patients including 1656 patients aged [80-85] years and 639 patients aged ≥ 85 years were analysed. Median CPAP adherence increases from 6.3 h (< 50 years) to 7 h (75-80 years) and decreases after this age (p < 0.001). The decrease in CPAP adherence observed after the age of 80 was associated with an increase in the proportion of patients with a CPAP-adherence < 4 h/day (p < 0.001). Proportion of CPAP treated female, patients having AHICPAP mean ≥ 10 events per hour or 95th percentile non-intentional leaks mean over 24 l/min increase with aging of the population. However, for patients over 80 years old, Chi square test showed no association of adherence with gender, AHICPAP and leaks (p > 0.05). CONCLUSION: This study demonstrates that adherence gradually increases with age until 80 years. The proportion of non-adherent patients grows with age after 80 years old. No significative relationship was found between adherence after 80 years old and gender, leaks and AHICPAP. TRIAL REGISTRATION: The study is registered on Health Data Hub platform (No. F20220715144543).

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Sleep Apnea-Specific Hypoxic Burden, Symptom Subtypes, and Risk of Cardiovascular Events and All-Cause Mortality.

Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation <90% were the only predictors of MACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.

Positive Airway Pressure Adherence, Mortality, and Cardiovascular Events in Patients with Sleep Apnea.

Rationale: Randomized controlled trials showed no effect of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on cardiovascular (CV) risk. However, patient selection and low PAP adherence preclude the generalization of their data to clinical samples. Objectives: To evaluate the association between hours of PAP use, mortality, and CV morbidity in real-life conditions. Methods: Data from the Pays de la Loire Cohort were linked to health administrative data to identify incident major adverse cardiovascular events (MACEs; a composite outcome of mortality, stroke, and cardiac diseases) in patients with OSA who were prescribed PAP. Cox proportional hazards analyses were conducted to evaluate the association between MACEs and quartiles of average daily PAP use over the study period. Measurements and Main Results: After a median follow-up of 6.6 years, 961 of 5,138 patients experienced MACEs. Considering nonadherent patients (0-4 h/night) as the reference group, adjusted hazard ratios (95% confidence intervals) for MACEs were 0.87 (0.73-1.04) for the 4-6 h/night group, 0.75 (0.62-0.92) for the 6-7 h/night group, and 0.78 (0.65-0.93) for the ⩾7 h/night group (P = 0.0130). Sensitivity analyses using causal inference approaches confirmed the association of PAP use with MACEs. The association was stronger in male patients (P value for interaction = 0.0004), patients without overt CV disease at diagnosis (P < 0.0001), and those belonging to the excessively sleepy symptom subtype (P = 0.060). Conclusions: These real-life clinical data demonstrate a dose-response relationship between PAP adherence and incident MACEs in OSA. Patient support programs may help improve PAP adherence and CV outcomes in patients with OSA.

Adherence to continuous positive airway pressure treatment in a cohort of elderly adults with newly diagnosed obstructive sleep apnea.

PURPOSE: To evaluate adherence to continuous positive airway pressure (CPAP) treatment in elderly patients newly diagnosed with obstructive sleep apnea syndrome (OSAS). METHODS: Consecutive patients ≥ 70 years attending one of the participating centers, requiring CPAP treatment and agreeing to participate, were included. Mean hours of CPAP during the first 5 months of treatment defined adherence as CPAP ≥ 4 h/day on 70% of nights over a 30-day period. RESULTS: From January 2014 to April 2019, 262 patients aged between 76.7 and 87.7 years (mean age, 82.6 years) were included and fully evaluated; 224 (85.5%) were adherent. Mean adherence time was 6.9 h in adherent patients, vs 2 h in non-adherent patients (p < 0.0001). Compared to non-adherent patients, adherent patients tended to have higher baseline AHI without reaching statistical significance (44.7 vs 39.5, p = 0.0913). They less frequently presented with dementia (3.7% vs 21.6%, p < 0.0001). The somnolence (ODSI and Epworth), nocturia, and depression (QD2A) scores of adherent patients improved significantly from baseline to the fifth month: ODSI decreased from 7 to 3.7 (p < 0.0001), Epworth from 8.7 to 6.2 (p < 0.0001), nocturia from 6.6 to 4.1 (p = 0.0015), and QD2A from 3.7 to 3 (p = 0.0025). Many more patients in the non-adherent group used nasal plugs than in the adherent group (14.7% vs 2.1%, p = 0.0006). CONCLUSION: The present real-world study showed the ability of newly diagnosed elderly adults (including the very old) to adhere to CPAP therapy and the benefit of 5 months' well-conducted CPAP treatment. REGISTRATION NUMBER: Not applicable.

Cancer risk in patients with sleep apnoea following adherent 5-year CPAP therapy.

BACKGROUND: Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA. METHODS: The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk. RESULTS: After a median (interquartile range) follow-up of 5.4 (3.1-8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78-1.14). CONCLUSIONS: Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Did COVID-19 impact Positive Airway Pressure adherence in 2020? A cross-sectional study of 8477 patients with sleep apnea.

BACKGROUND: Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. METHODS: With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. RESULTS: 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25-75: 61-77], 25.6% < 62 years old, initial Apnea-Hypopnea Index (AHI) of 41 (31-59)/h. Median PAP adherence was 7.21 (6.12-8.10) h/day in 2020 versus 7.12 (6.05-8.02) h/day in 2019, p < 0.001. The median difference in PAP adherence between the first 2020 lockdown and the corresponding 2019 weeks was 9.75 (CI95% 8.75-10.75) min/day, p < 0.001. The median difference in PAP adherence between the second 2020 lockdown and the corresponding 2019 weeks was 5.00 (CI95% 4.00-6.00) min/day, p < 0.001. If we consider the minimal clinically important difference of 30 min for PAP adherence, 30.4% and 26% of the patients increased their PAP adherence by at least 30 min during the first and second lockdowns respectively; 17.6% and 19.3% of the patients lowered their PAP adherence by at least 30 min in the first and second lockdowns, respectively. CONCLUSION: During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases. Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966).

Large Extracellular Vesicle-Associated Rap1 Accumulates in Atherosclerotic Plaques, Correlates With Vascular Risks and Is Involved in Atherosclerosis.

RATIONALE: Metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular diseases and atherosclerosis. Circulating levels of large extracellular vesicles (lEVs), submicrometer-sized vesicles released from plasma membrane, from MetS patients were shown to induce endothelial dysfunction, but their role in early stage of atherosclerosis and on vascular smooth muscle cells (SMC) remain to be fully elucidated. OBJECTIVE: To determine the mechanisms by which lEVs lead to the progression of atherosclerosis in the setting of MetS. METHODS AND RESULTS: Proteomic analysis revealed that the small GTPase, Rap1 was overexpressed in lEVs from MetS patients compared with those from non-MetS subjects. Rap1 was in GTP-associated active state in both types of lEVs, and Rap1-lEVs levels correlated with increased cardiovascular risks, including stenosis. MetS-lEVs, but not non-MetS-lEVs, increased Rap1-dependent endothelial cell permeability. MetS-lEVs significantly promoted migration and proliferation of human aortic SMC and increased expression of proinflammatory molecules and activation of ERK (extracellular signal-regulated kinase) 5/p38 pathways. Neutralization of Rap1 by specific antibody or pharmacological inhibition of Rap1 completely prevented the effects of lEVs from MetS patients. High-fat diet-fed ApoE-/- mice displayed an increased expression of Rap1 both in aortas and circulating lEVs. lEVs accumulated in plaque atherosclerotic lesions depending on the progression of atherosclerosis. lEVs from high-fat diet-fed ApoE-/- mice, but not those from mice fed with a standard diet, enhanced SMC proliferation. Human atherosclerotic lesions were enriched in lEVs expressing Rap1. CONCLUSIONS: These data demonstrate that Rap1 carried by MetS-lEVs participates in the enhanced SMC proliferation, migration, proinflammatory profile, and activation of ERK5/p38 pathways leading to vascular inflammation and remodeling, and atherosclerosis. These results highlight that Rap1 carried by MetS-lEVs may be a novel determinant of diagnostic value for cardiometabolic risk factors and suggest Rap1 as a promising therapeutic target against the development of atherosclerosis. Graphical Abstract: A graphical abstract is available for this article.

Long-term dentoskeletal side effects of mandibular advancement therapy in patients with obstructive sleep apnea: data from the Pays de la Loire sleep cohort.

OBJECTIVES: Mandibular advancement devices (MADs) are the main therapeutic alternative to continuous positive airway pressure for obstructive sleep apnea. Our aim was to evaluate the long-term dentoskeletal side effects of MADs and to identify the predictive factors for these side effects. MATERIALS AND METHODS: Patients from the Pays de la Loire cohort treated with a custom-made MAD for at least 1 year were included in this retrospective study. Digital cephalometric analyses were performed at baseline and at follow-up. RESULTS: We included a total of 117 patients, treated with a MAD for a median [interquartile range] of 4.6 [2.6-6.6] years. The main significant side effects were a decrease in overbite (- 0.5 ± 1 mm), overjet (- 0.7 ± 1 mm) and maxillary incisor inclination (- 2.5 ± 2.8°) and an increase in mandibular incisor inclination (+ 2.2 ± 2.7°). Subjective side effects were not linked to the observed dentoskeletal changes. Current smokers were at higher risk of overjet modifications. A pre-existing anterior open-bite was associated with a greater decrease in overbite. Treatment duration was associated with a more pronounced mandibular incisor proclination. Propulsion was negatively associated with maxillary incisor retroclination. CONCLUSIONS: Long-term dentoskeletal side effects were mainly moderate dental side effects. Some predictive factors were shown to be associated with more pronounced changes. Subjective side effects did not appear to be reliable tools to detect dentoskeletal side effects. CLINICAL RELEVANCE: Regular follow-up with clinical examination and regular radiographs is mandatory. The predictive factors could be of interest for a better selection of patients and to individualize follow-up.

Pulmonary Hypertension in Patients with Common Variable Immunodeficiency.

PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.

A CPAP data-based algorithm for automatic early prediction of therapy adherence.

OBJECTIVE: Adherence is a critical issue in the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP). Approximately 40% of patients treated with CPAP are at risk of discontinuation or insufficient use (< 4 h/night). Assuming that the first few days on CPAP are critical for continued treatment, we tested the predictive value at day 14 (D14) of the Philips Adherence Profiler™ (AP) algorithm for adherence at 3 months (D90). METHOD: The AP™ algorithm uses CPAP machine data hosted in the database of EncoreAnywhere™. This retrospective study involved 457 patients (66% men, 60.0 ± 11.9 years; BMI = 31.2 ± 5.9 kg/m2; AHI = 37.8 ± 19.2; Epworth score = 10.0 ± 4.8) from the Pays de la Loire Sleep Cohort. At D90, 88% of the patients were adherent as defined by a mean daily CPAP use of ≥ 4 h. RESULTS: In a univariate analysis, the factors significantly associated with CPAP adherence at D90 were older age, lower BMI, CPAP adherence (≥ 4 h/night) at D14, and AP™ prediction at D14. In a multivariate analysis, only older age (OR 2.10 [1.29-3.41], p = 0.003) and the AP™ prediction at D14 (OR 16.99 [7.26-39.75], p < 0.0001) were significant predictors. CPAP adherence at D90 was not associated with device-derived residual events, nor with the levels of pressure or leakage except in the case of very significant leakage when it persisted for 90 days. CONCLUSION: Automatic telemonitoring algorithms are relevant tools for early prediction of CPAP therapy adherence and may make it possible to focus therapeutic follow-up efforts on patients who are at risk of non-adherence.

Predicting treatment response to mandibular advancement therapy using a titratable thermoplastic device.

OBJECTIVES: Mandibular advancement device (MAD) therapy is the most commonly used second-line treatment for obstructive sleep apnea (OSA), but MAD may be ineffective in a subgroup of patients. We describe the use of a trial of a titratable thermoplastic MAD to predict treatment outcomes with a custom-made MAD. MATERIALS AND METHODS: Patients treated with a thermoplastic MAD as a trial before custom-made MAD manufacturing were included in the study. Sleep recordings and clinical outcomes assessed after 6 months of treatment with each device were compared. Predictive utility of thermoplastic MAD to identify custom-made MAD treatment success defined as a reduction greater than 50% and final apnea-hypopnea index (AHI) less than 10 events/h was evaluated. RESULTS: Thermoplastic MADs were installed in 111 patients, but only 36 patients were finally treated with both devices and were included in the analysis. A significant correlation was observed between the impact of the two devices on the AHI (r=0.85, p<0.0001), oxygen desaturation index (r=0.73, p<0.0001), snoring index (r=0.85, p<0.0001), and Epworth sleepiness scale (r=0.77, p<0.0001). A high positive predictive value (86%) but a low negative predictive value (46%) was observed regarding AHI decrease. CONCLUSIONS: Similar impacts of both MADs were observed on major OSA severity markers and symptoms. The ability of thermoplastic MAD to indicate likelihood of success with custom-made MAD will require further controlled studies. CLINICAL RELEVANCE: Thermoplastic MADs could represent a useful and easily implemented tool to predict the likelihood of success of a custom-made MAD as treatment for OSA.

Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms.

IMPORTANCE: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. OBJECTIVE: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. EXPOSURES: Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURES: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441). CONCLUSIONS AND RELEVANCE: Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.