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.

The aim of this study was to compare mandibular advancement device (MAd) therapy and continuous positive airway pressure (CPAP) for obstructive sleep apnoea/hypopnoea syndrome (OSAHS) after one-night polysomnographic (PSG) titration of both treatments.59 OSAHS patients (apnoea/hypopnoea index (AHI): 34±13 events·h⁻¹; Epworth scale: 10.6±4.5) were included in a crossover trial of 8 weeks of MAd and 8 weeks of CPAP after effective titration. Outcome measurements included home sleep study, sleepiness, health-related quality of life (HRQoL), cognitive tests, side-effects, compliance and preference.The median (interquartile range) AHI was 2 (1–8) events·h⁻¹with CPAP and 6 (3–14) events·h⁻¹with MAd (p<0.001). Positive and negative predictive values of MAd titration PSG for treatment success were 85% and 45%, respectively. Both treatments significantly improved subjective and objective sleepiness, cognitive tests and HRQoL. The reported compliance was higher for MAd (p70% of patients preferring this treatment.These results support titrated MAd as an effective therapy in moderately sleepy and overweight OSAHS patients. Although less effective than CPAP, successfully titrated MAd was very effective at reducing the AHI and was associated with a higher reported compliance. Both treatments improved functional outcomes to a similar degree. One-night titration of MAd had a low negative predictive value for treatment success.

Regional chemotherapy has been proposed as a treatment modality in a number of cancer settings. In primary or metastatic lung cancer, administration of chemotherapy via inhalation could increase exposure of lung tumor to the drug, while minimizing systemic side effects. Several proof of concept studies in animal models of metastatic or primary lung cancer have demonstrated the safety, pharmacokinetic advantage, and antitumor effect of aerosol administration of several chemotherapeutic agents including doxorubicin, gemcitabine and liposome-encapsulated formulations of paclitaxel and 9-nitrocamptothecin (9-NC). Recent phase I studies have demonstrated the feasibility of aerosol delivery of doxorubicin and liposomal formulations of 9-NC and cisplatin in patients with primary and metastatic lung cancer with a limited pharmacokinetic profile consistent with the observed low systemic toxicity. Further studies integrating safety, pharmacokinetic, and efficacy considerations are required to determine whether there is a place for local administration of chemotherapy via inhalation in lung cancer.

Long-term adherence is a major issue in patients receiving home continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de Recherche en Santé Respiratoire des Pays de la Loire [IRSR] sleep cohort) of consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days, we studied the impact on long-term treatment adherence of socioeconomic factors, patients and disease characteristics prior to CPAP initiation. Among 1,141 patients in whom CPAP had been prescribed for an average of 504±251 days (range: 91 to 1035), 674 (59%) were adherent with a mean daily use of CPAP≥4 h (mean: 6.42±1.35 h). Stepwise regression analysis identified 4 independent factors of CPAP adherence including apnea-hypopnea index (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI≥30 vs. AHI<30; p = 0.003), body mass index (BMI) (OR: 1.786, 95%CI 1.131 to 2.822 for BMI≥25 and <30 kg/m², p = 0.01; OR: 1.768, 95%CI 1.145–2.731 for BMI≥30 kg/m², p = 0.01 vs. BMI<25 kg/m²), employment status (OR: 1.414, 95%CI 1.097–1.821 for retired vs. employed; p = 0.007) and marital status (OR: 1.482, 95%CI 1.088–2.019 for married or living as a couple vs. living alone; p = 0.01). Age, gender, Epworth sleepiness scale, depressive syndrome, associated cardiovascular morbidities, educational attainment and occupation category did not influence CPAP adherence. Marital status and employment status are independent factors of CPAP adherence in addition to BMI and disease severity. Patients living alone and/or working patients are at greater risk of non-adherence, whereas adherence is higher in married and retired patients. These findings suggest that the social context of daily life should be taken into account in risk screening for CPAP non-adherence. Future interventional studies targeting at-risk patients should be designed to address social motivating factors and work-related barriers to CPAP adherence.

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.