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.

Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease.

Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities.

Impact of concomitant medications on obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is characterized by repeated episodes of apnoea and hypopnoea during sleep. Little is known about the potential impact of therapy drugs on the underlying respiratory disorder. Any influence should be taken into account and appropriate action taken, including drug withdrawal if necessary. Here, we review drugs in terms of their possible impact on OSA; drugs which (1) may worsen OSA; (2) are unlikely to have an impact on OSA; (3) those for which data are scarce or contradictory; and (4) drugs with a potentially improving effect. The level of evidence is ranked according to three grades: A - randomized controlled trials (RCTs) with high statistical power; B - RCTs with lower power, non-randomized comparative studies and observational studies; C - retrospective studies and case reports. Our review enabled us to propose clinical recommendations. Briefly, agents worsening OSA or inducing weight gain, that must be avoided, are clearly identified. Drugs such as 'Z drugs' and sodium oxybate should be used with caution as the literature contains conflicting results. Finally, larger trials are needed to clarify the potential positive impact of certain drugs on OSA. In the meantime, some, such as diuretics or other antihypertensive medications, are helpful in reducing OSA-associated cardiovascular morbidity.

Prevalence of obesity hypoventilation syndrome in ambulatory obese patients attending pathology laboratories.

BACKGROUND AND OBJECTIVE: The prevalence of obesity hypoventilation syndrome (OHS) in the unselected obese is unknown. Our objectives were: (i) to determine the prevalence of OHS in ambulatory obese patients not previously referred to a pulmonologist for suspicion of sleep breathing disorders and (ii) to assess whether venous bicarbonate concentration [HCO3-v ] can be used to detect OHS. METHODS: In this prospective multicentric study, we measured [HCO3-v ] in consenting obese patients attending pathology analysis laboratories. Patients with [HCO3-v ] ≥ 27 mmol/L were referred to a pulmonologist for comprehensive sleep and respiratory evaluations. Those with [HCO3-v ] < 27 mmol/L were randomized to either referral to a pulmonologist or ended the study. RESULTS: For the 1004 screened patients, the [HCO3-v ] was ≥27 mmol/L in 24.6% and <27 mmol/L in 45.9%. A total of 29.5% who had previously consulted a pulmonologist were excluded. A population of 241 obese patients underwent sleep and respiratory assessments. The prevalence of OHS in this population was 1.10 (95% CI = 0.51; 2.27). In multivariate analysis, PaCO2 , forced expiratory volume in 1 s (FEV1 ), apnoea-hypopnoea index (AHI), BMI, use of ≥3 anti-hypertensive drugs, anti-diabetics, proton pump inhibitors and/or paracetamol were related to raised [HCO3-v ]. CONCLUSION: The prevalence of OHS in our obese population was lower than previous estimations based on hospitalized patients or clinical cohorts with sleep breathing disorders. Apart from hypercapnia, increased [HCO3-v ] may also reflect multimorbidity and polypharmacy, which should be taken into account when using [HCO3-v ] to screen for OHS.

Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: Data from randomized trials.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) could be an independent risk factor for non-alcoholic fatty liver disease (NAFLD) occurrence and progression. The impact of continuous positive airway pressure (CPAP) treatment on non-invasive markers of NAFLD has not been studied. The aim of this study was to evaluate the effect of 6-12 weeks of effective CPAP on the FibroMax test (comprising components including the SteatoTest, NashTest and FibroTest) through three randomized sham controlled studies. METHODS: The FibroMax test was performed in 103 obstructive sleep apnoea patients (apnoea + hypopnoea index > 15/h) enrolled in a randomized study comparing sham versus effective CPAP. RESULTS: At baseline, 40.4% of patients in the sham CPAP group and 45.5% in the CPAP group exhibited liver steatosis. Furthermore, 39.6% of patients in the sham CPAP group and 58.4% in the CPAP group displayed borderline or possible non-alcoholic steatohepatitis (NASH). Six to twelve weeks of effective CPAP did not demonstrate any impact on reducing steatosis, NASH or liver fibrosis even after adjustment for gender, BMI, baseline apnoea + hypopnoea index and severity of liver injury. CONCLUSION: A number of non-invasive markers of liver damage are increased in untreated obstructive sleep apnoea patients, potentially contributing to cardiometabolic risk, but they do not improve after 6-12 weeks of effective CPAP treatment. CLINICAL TRIAL REGISTRATION: NCT01196845 (ADISAS), NCT00464659 (MneSAS) and NCT00669695 (StatinflaSAS) at ClinicalTrials.gov.

Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study.

BACKGROUND AND OBJECTIVE: Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. METHODS: In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m(2) ; apnoea-hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. RESULTS: In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was -3.1 (-6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. CONCLUSION: In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

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.

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.

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.

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.

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).

[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.

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.

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.