Obstructive sleep apnea, chronic obstructive pulmonary disease and NAFLD: an individual participant data meta-analysis.

RATIONALE: Chronic intermittent hypoxia occurring in obstructive sleep apnea (OSA) is independently associated with nonalcoholic fatty liver disease (NAFLD). Chronic obstructive pulmonary disease (COPD) has also been suggested to be linked with liver disease. OBJECTIVE: In this individual participant data meta-analysis, we investigated the association between liver damage and OSA and COPD severity. METHODS AND MEASUREMENTS: Patients suspected of OSA underwent polysomnography (PSG) or home sleep apnea testing (HSAT). Non-invasive tests were used to evaluate liver steatosis (Hepatic Steatosis Index) and fibrosis (Fibrotest or FibroMeter). An individual participant data meta-analysis approach was used to determine if the severity of OSA/COPD affects the type and severity of liver disease. Results were confirmed by multivariate and causal mediation analysis. Sub-group analyses were performed to investigate specific populations. MAIN RESULTS: Among 2120 patients, 1584 had steatosis (75%). In multivariable analysis, risk factors for steatosis were an apnea-hypopnea index (AHI) > 5/h, body mass index (BMI) > 26 kg/m2, age, type 2 diabetes (all p-values <0.01) and male gender (p = 0.02). Concerning fibrosis, among 2218 patients 397 had fibrosis (18%). Risk factors associated with fibrosis were BMI>26 kg/m2, age, male gender, and type 2 diabetes (all p-values <0.01). AHI severity was not associated with fibrosis. A combination of AHI >30/h and COPD stage 1 was associated with an increased risk of steatosis. CONCLUSION: This meta-analysis confirms the strong association between steatosis and the severity of OSA. The relation between OSA and fibrosis is mainly due to BMI as shown by causal mediation analysis.

Long-term variations of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular co-morbidities and mortality. Arterial stiffness is an independent predictor of cardiovascular risk and mortality, and is influenced by the presence of OSA and related comorbidities. There is a paucity of data regarding long-term evolution of arterial stiffness in CPAP-treated OSA patients. We aimed to prospectively study long term PWV variations and determinants of PWV deterioration. METHODS: In a prospective obese OSA cohort, at time of diagnosis and after several years of follow-up we collected arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), clinical and metabolic parameters, and CPAP adherence. Univariate and multivariate analyses were performed in order to determine contributing factors. RESULTS: Seventy two OSA patients (men: 52.8%, median age: 55.8 years and median BMI of 38.5 kg/m2) with a prevalence of hypertension: 58.3%, type 2 diabetes: 20.8%, hypercholesterolemia: 33.3%, current or past smoking: 59.7%, were evaluated after a median follow-up of 7.4 [5.8; 8.3] years. Over the period of follow-up, the median increase in PWV was 1.34 [0.10; 2.37] m/s. In multivariate analysis, the increase in PWV was associated with older age (10 extra years was associated with a 5.24 [1.35; 9.12] % increase in PWV) and hypertension (a significant increase in PWV of 8.24 [1.02; 15.57] %). No impact of CPAP adherence on PWV evolution was found. CONCLUSION: PWV progression in CPAP-treated OSA patients is mainly related to pre-existing cardio-metabolic comorbidities and not influenced by CPAP adherence. In this high cardiovascular risk population, it is crucial to associated weight management and exercise with CPAP treatment.

Clinical presentation and comorbidities of obstructive sleep apnea-COPD overlap syndrome.

BACKGROUND: More advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as 'overlap syndrome' (OVS), impacts on cardiovascular health. OBJECTIVE: To investigate differences between patients with OVS and those with moderate-to-severe OSA alone. METHODS: A cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017. Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health. RESULTS: 46,786 patients had moderate-to-severe OSA. Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS. A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P <0.02). Similarly, a lower proportion of OVS patients (35.6% versus 39.4%, respectively; P <0.01) experienced sleepiness while driving. In contrast, 63.5% of the OVS population experienced nocturia compared to 58.0% of the OSA population (P<0.01). Apnea hypopnea index (36 [25; 52] vs 33.1 [23.3; 50]), oxygen desaturation index (28 [15; 48] vs 25.2 [14; 45]) and mean nocturnal SaO2 (92 [90; 93.8] vs 93 [91.3; 94]) were significantly more altered in the OVS group. Associated COPD had no effect on the prevalence of hypertension and stroke. After controlling for main confounders, COPD severity was associated in a dose-response relationship with a higher prevalence of coronary heart disease, heart failure and peripheral arteriopathy. CONCLUSIONS: In adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy.

A demonstration project of Global Alliance against Chronic Respiratory Diseases: Prediction of interactions between air pollution and allergen exposure-the Mobile Airways Sentinel NetworK-Impact of air POLLution on Asthma and Rhinitis approach.

This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers. For decades, information available for the patients and allergologists consisted of pollen counts, which are vital but insufficient. New technology paves the way to substantial increase in amount and diversity of the data. This paper reviews old and newly suggested methods to predict pollen and air pollutant concentrations in the air and proposes an allergy risk concept, which combines the pollen and pollution information and transforms it into a qualitative risk index. This new index is available in an app (Mobile Airways Sentinel NetworK-air) that was developed in the frame of the European Union grant Impact of Air POLLution on sleep, Asthma and Rhinitis (a project of European Institute of Innovation and Technology-Health). On-going transformation of the pollen allergy information support is based on new technological solutions for pollen and air quality monitoring and predictions. The new information-technology and artificial-intelligence-based solutions help to convert this information into easy-to-use services for both medical practitioners and allergy sufferers.

Digital transformation of health and care to sustain Planetary Health: The MASK proof-of-concept for airway diseases-POLLAR symposium under the auspices of Finland's Presidency of the EU, 2019 and MACVIA-France, Global Alliance against Chronic Respiratory Diseases (GARD, WH0) demonstration project, Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing.

In December 2019, a conference entitled "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki. It was co-organized by the Finnish Institute for Health and Welfare, the Finnish Environment Institute and the European Commission, under the auspices of Finland's Presidency of the EU. As a side event, a symposium organized as the final POLLAR (Impact of air POLLution on Asthma and Rhinitis) meeting explored the digital transformation of health and care to sustain planetary health in airway diseases. The Finnish Allergy Programme collaborates with MASK (Mobile Airways Sentinel NetworK) and can be considered as a proof-of-concept to impact Planetary Health. The Good Practice of DG Santé (The Directorate-General for Health and Food Safety) on digitally-enabled, patient-centred care pathways is in line with the objectives of the Finnish Allergy Programme. The ARIACARE-Digital network has been deployed in 25 countries. It represents an example of the digital cross-border exchange of real-world data and experience with the aim to improve patient care. The integration of information technology tools for climate, weather, air pollution and aerobiology in mobile Health applications will enable the development of an alert system. Citizens will thus be informed about personal environmental threats, which may also be linked to indicators of Planetary Health and sustainability. The digital transformation of the public health policy was also proposed, following the experience of the Agency for Health Quality and Assessment of Catalonia (AQuAS).

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.51. Subgroup analyses were performed to investigate this relationship in specific populations. Among 730 patients without overt CV disease, 387 (53.0%) had severe OSA (apnoea-hypopnea index ≥30) and 164 (22.5%) exhibited endothelial dysfunction. After adjustment for age, gender, diastolic blood pressure, obesity, diabetes and chronic obstructive pulmonary disease, endothelial dysfunction was associated with severe OSA (odds ratio, OR [95% confidence interval]: 2.27 [1.12-4.60]; p = 0.02), and nocturnal hypoxemia defined by >20 min with oxygen saturation <90% (OR: 1.83 [1.22-2.92]; p = 0.004) or mean oxygen saturation <92% (OR: 1.52 [1.17-1.96]; p = 0.002). On subgroup analyses, the association between severe OSA and endothelial dysfunction was not significant in patients with hypertension, obesity and/or diabetes. Among adults without overt CV disease, severe OSA is independently associated with an increased risk of endothelial dysfunction that may predispose to late CV events.

Who May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study.

BACKGROUND: Diuretics have been reported as effective for reducing OSA severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending on the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry "Observatoire Sommeil de la Fédération de Pneumologie." RESEARCH QUESTION: Which phenotypic subtypes of OSA may benefit from diuretics? STUDY DESIGN AND METHODS: A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h, and the usefulness of diuretics was assessed by using a logistic regression model. RESULTS: The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years (interquartile range: 47.4; 65.6), 67% were men, and the median AHI was 28 (14; 43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = .03) and in patients with hypertension (P < .01), particularly in patients with hypertension with a BMI between 25 and 35 (P < .01). Diuretics had no significant effect on OSA severity in patients with self-reported low physical activity or heart failure. INTERPRETATION: Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.

Partial failure of CPAP treatment for sleep apnoea: Analysis of the French national sleep database.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) is the first-line therapy for obstructive sleep apnoea (OSA). Residual apnoea and/or hypopnoea events, that is an apnoea-hypopnoea index (AHI) > 5, during CPAP contribute to treatment drop-out. The clinical scenarios triggering residual events during CPAP use are poorly described. Underlying co-morbidities, especially cardiovascular diseases, lifestyle factors, OSA characteristics at diagnosis and type of mask have been suggested as potential contributors. METHODS: Patients from the prospective French sleep apnoea registry diagnosed with OSA (AHI ≥ 15 events/h) treated with CPAP were included. Logistic regression analysis identified factors associated with a risk of residual AHI > 5 events/h on CPAP. RESULTS: The 12 285 OSA patients were predominantly men (n = 8715, 70.9%), middle-aged (58.2 (49.8; 66.1) years) and obese (median body mass index: 31.3 (27.7; 35.6) kg/m2 ). Most had an AHI ≤ 5 events/h (n = 9573, 77.9%) versus 22.1% with AHI > 5/h. The latter were less CPAP adherent (5.75 (4.01; 7.00) vs 6.00 (4.53; 7.00) h/night). In multivariable analysis, factors associated with residual AHI >5/h were male sex, age, sedentary lifestyle, OSA severity, cardiovascular co-morbidities (heart failure and arrhythmia) and type of interface (orofacial mask versus nasal mask: OR = 2.15 (95%CI: 1.95; 2.37)). A subgroup analysis found that patients using pressures above 10 cm H2 O were 1.43 (95% CI: 1.3; 1.57) times more likely to have residual AHI > 5/h. CONCLUSION: Knowing about risk factors for residual apnoeic-hypopnoeic events may assist in the timely provision of personalized care including the type of PAP therapy, attention to co-morbidities and choice of interface.

Diagnosis and management of central sleep apnea syndrome.

Introduction: Central sleep apnea (CSA) syndrome has gained a considerable interest in the sleep field within the last 10 years. It is overrepresented in particular subpopulations such as patients with stroke or heart failure. Early detection and diagnosis, as well as appropriate treatment of central breathing disturbances during sleep remain challenging. Areas covered: Based on a systematic review of CSA in adults the clinical evidence and polysomnographic patterns useful for discerning central from obstructive events are discussed. Current therapeutic indications of CSA and perspectives are presented, according to the type of respiratory disturbances during sleep, alterations in blood gases and ventilatory control. Expert opinion: The precise identification of central events during polysomnographic recording is mandatory. Therapeutic choices for CSA depend on the typology of respiratory disturbances observed by polysomnography, changes in blood gases and ventilatory control. In CSA with normocapnia and ventilatory instability, adaptive servo-ventilation is recommended. In CSA with hypercapnia and/or rapid-eye movement sleep hypoventilation, non-invasive ventilation is required. Further studies are required as strong evidence is lacking regarding the long-term consequences of CSA and the long-term impact of current treatment strategies.

[What prospects for the sleep apnea syndrome and connected health?] / Quelles perspectives pour le syndrome d'apnées du sommeil et la santé connectée ?

Connected health is a growing field and can be viewed from different perspectives, particularly in sleep apnea syndrome. The purpose of this review is to show how all these aspects of connected health are already used in the management of sleep apnea syndrome (SAS) and its comorbidities. First, it can give patients a better understanding and a better assessment of their health. It also facilitates their healthcare by allowing them a greater role in their care pathway. For healthcare providers, connected health tools make it possible to set up new procedures for diagnosing and monitoring ambulatory patients, and for the making of joint decisions by health professionals and patients. Finally, for researchers, e-health generates massive amounts of data, thus facilitating the acquisition of knowledge in real life situations and the development of new methodologies for clinical studies that are faster, less expensive and just as reliable. All these considerations are already applicable in the field of sleep apnea, both for proposed treatments and for comorbidities management and for the patient's involvement in his/her care pathway.

Multimodal Remote Monitoring of High Cardiovascular Risk Patients With OSA Initiating CPAP: A Randomized Trial.

BACKGROUND: The management of patients with high cardiovascular risk and OSA must target not only improving adherence to CPAP, but should also include strategies aimed at reducing BP and increasing physical activity. The study aims to evaluate the effectiveness of an integrated intervention using remote patient telemonitoring in reducing BP in high cardiovascular risk patients with OSA. METHODS: In a multicenter, open, randomized trial, patients with OSA were randomly assigned at CPAP initiation to usual care or multimodal telemonitoring for 6 months. Telemonitoring used electronic equipment collecting information about BP, symptoms, CPAP side effects, and physical activity with home care providers prespecified protocoled actions. The primary effectiveness outcome was assessed using home self-measured BP on 3 consecutive days. Secondary outcomes included CPAP compliance, symptoms, and physical activity. RESULTS: Of 306 patients with a median age of 61.3 years [interquartile range, 54.1; 66.1], who were predominantly men, 226 (74%) with a BMI of 32.0 [28.7; 35.6] kg/m2 and an apnea-hypopnea index of 46 [35; 61] events/h, 149 received usual care and 157 received telemonitoring. After 6 months of CPAP, home self-measured BP did not differ significantly between groups. In secondary analyses, there was no significant difference in steps per day, but a significant increase in CPAP adherence and an improvement in daytime sleepiness and quality of life in favor of the multimodal telemonitoring. CONCLUSIONS: In OSA patients with high cardiovascular risk, multimodal telemonitoring was not superior to usual CPAP care for improving home BP; however, telemonitoring improved adherence and patient-centered outcomes.

Impact of Non-alcoholic Fatty Liver Disease on long-term cardiovascular events and death in Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk. We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients. The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up. Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis. Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology. In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively. During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died. In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]). We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality. To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients.

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project.

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients' literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.