Symptomatic response to CPAP in obstructive sleep apnea versus COPD- obstructive sleep apnea overlap syndrome: Insights from a large national registry.

BACKGROUND: The symptomatic response to continuous positive airway pressure (CPAP) therapy in COPD-obstructive sleep apnea overlap syndrome (OVS) compared to OSA syndrome (OSA) alone has not been well studied so far. The aim of this study is to explore main differences in the clinical response to CPAP treatment in OVS compared to OSA alone. STUDY DESIGN AND METHODS: Using prospective data from the French National Sleep Apnea Registry, we conducted an observational study among 6320 patients with moderate-to-severe OSA, available spirometry, and at least one follow-up visit under CPAP therapy. RESULTS: CPAP efficacy measured on the residual apnea-hypopnea index and median adherence were similar between OVS and OSA patients. In both groups, the overall burden of symptoms related to sleep apnea improved with CPAP treatment. In a multivariable model adjusted for age, gender, body mass index, adherence to treatment and residual apnea-hypopnea index, OVS was associated with higher odds for persistent morning headaches (OR: 1.37 [95% CI; 1.04; 1.79]; P = 0.02), morning tiredness (OR: 1.33 [95% CI: 1.12; 1.59]; P<0.01), daytime sleepiness (OR; 1.24 [95% CI: 1.4; 1.46]: P<0.01) and exertional dyspnea (OR: 1.26 [95% CI: 1.00;1.58]; P = 0.04) when compared with OSA alone. INTERPRETATION: CPAP therapy was effective in normalizing the apnea-hypopnea index and significantly improved OSA-related symptoms, regardless of COPD status. CPAP should be offered to patients with OVS on a trial basis as a significant improvement in OSA-related symptoms can be expected, although the range of response may be less dramatic than in OSA alone.

Management of acute COPD exacerbations in France: A qualitative survey in a private practice setting.

BACKGROUND: The current prevalence of chronic obstructive pulmonary disease (COPD) in France is estimated to be 2.6 million and is predicted to increase to 2.8 million by 2025. Presently, there is a lack of data on COPD management within the private healthcare setting. The aim of this study was to investigate the management of COPD exacerbations by pulmonologists within private practices in France. METHODS: A prospective, online, qualitative survey was distributed to private practice pulmonologists in France. The survey covered all aspects of COPD management from diagnosis and therapeutic management, to secondary prevention and organization of care. Survey responses were collected between 27 January 2018 and 18 June 2018 and all data were summarized descriptively. RESULTS: The survey had a response rate of 20.6%, with 116 out of 563 pulmonologists providing responses. Overall, 87.4% of respondents stated that the management of COPD represented over 15% of their total clinical activity. Most respondents indicated that they work closely with general practitioners and a large multidisciplinary team to manage patients with numerous comorbidities. Following a COPD exacerbation, the majority of respondents (78.4%) were in favor of using respiratory-connected devices (class 2a-connected medical device according to the French HAS classification and available on medical prescription) to assist with patient follow-up at home. CONCLUSIONS: COPD management forms part of the core clinical activity for pulmonologists within the private practice setting in France. Patients with COPD generally have multiple comorbidities and are managed by a multidisciplinary team in line with French guidelines. The use of respiratory-connected devices was highlighted as an important new strategy for improving patient care following a COPD exacerbation.

The Somatotropic Axis in the Sleep Apnea-Obesity Comorbid Duo.

Background: Growth hormone (GH) stimulates the production of insulin-like growth factor 1 (IGF-1) in most tissues and together GH and IGF-1 profoundly impact adipose tissue deposition, glucose metabolism and cardiovascular function. A low serum IGF-I level has been reported as being associated with obstructive sleep apnea (OSA) and might be one of the mechanisms underlying cardio-metabolic risk in OSA patients. Methods: In a multicenter national study, 817 patients consulting for suspicion of OSA (OSA confirmed for 567 patients) underwent serum IGF-1 measurements. We analyzed the association between an IGF-1 level below the median value of the population and variables related to cardio-metabolic risk: body mass index (BMI) and waist circumference, apnea hypopnea index (AHI), cholesterol and triglycerides (expressed as median and divided into quartiles for continuous variables). Results: After adjustment for age and gender, low IGF-1 levels were associated with increased BMI and AHI (Odds ratios (OR) = 2.83; p < 0.0001 and OR = 3.03, p < 0.0001 for Quartile 4 vs. Quartile1, respectively), with elevated cholesterol levels (OR = 1.36, p = 0.0444), and elevated triglyceride levels (OR = 1.36; p = 0.0008). Conclusions: Both adiposity and sleep apnea synergistically predict low levels of IGF-1 and thus could together contribute toward cardio-metabolic risk. Further work are needed to confirm whether IGF-1 levels allow grading severity and predicting response to treatments to aim at a personalized medicine for patients suffering from OSA.

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.

Impact of a Multimodal Telemonitoring Intervention on CPAP Adherence in Symptomatic OSA and Low Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: One of the major challenges in treating OSA is to achieve adequate CPAP adherence. Telemonitoring has the potential to provide individualized management and early recognition of problems during treatment. RESEARCH QUESTION: What is the effect of a multimodal telemonitoring intervention on treatment adherence, quality of life, and functional status in symptomatic patients with OSA and low cardiovascular risk? STUDY DESIGN AND METHODS: In a multicenter, randomized controlled trial, patients newly diagnosed with OSA were randomly assigned to multimodal telemonitoring for 6 months vs usual care (UC). Telemonitoring consisted of built-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks, or persistent residual events. The primary outcome was CPAP adherence (in hours per night). Secondary outcomes included daily symptoms such as fatigue and sleepiness, and quality of life measured by using self-reported questionnaires. RESULTS: A total of 206 patients with OSA and a median age of 50.6 years (interquartile range [IQR], 42.1; 58.1 years) were included in the study; they were predominantly male (63%) with a median BMI of 30.6 kg/m2 (IQR, 26.8; 35.1 kg/m2) and a median apnea-hypopnea index of 45.2 events/h (IQR, 34.0; 60.0 events/h). Of these, 102 received UC and 104 received telemonitoring. After 6 months of treatment, CPAP adherence was similar in the two groups when assessed either by mean duration of usage (4.73 ± 2.48 h per night in the telemonitoring group and 5.08 ± 2.44 h per night in the UC group; P = .30) or in percentage of patients adherent to treatment (> 4 h usage per night, > 70% nights; 64% in the telemonitoring group vs 72% in the UC group; P = .24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. INTERPRETATION: In patients with severe OSA and low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both the telemonitoring and UC groups, similar improvements in daytime symptoms were achieved. TRIAL REGISTRY: ClinicalTrials.gov; No.: 01796769; URL: www.clinicaltrials.gov.

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.

Obstructive Sleep Apnea: A Cluster Analysis at Time of Diagnosis.

BACKGROUND: The classification of obstructive sleep apnea is on the basis of sleep study criteria that may not adequately capture disease heterogeneity. Improved phenotyping may improve prognosis prediction and help select therapeutic strategies. OBJECTIVES: This study used cluster analysis to investigate the clinical clusters of obstructive sleep apnea. METHODS: An ascending hierarchical cluster analysis was performed on baseline symptoms, physical examination, risk factor exposure and co-morbidities from 18,263 participants in the OSFP (French national registry of sleep apnea). The probability for criteria to be associated with a given cluster was assessed using odds ratios, determined by univariate logistic regression. RESULTS: Six clusters were identified, in which patients varied considerably in age, sex, symptoms, obesity, co-morbidities and environmental risk factors. The main significant differences between clusters were minimally symptomatic versus sleepy obstructive sleep apnea patients, lean versus obese, and among obese patients different combinations of co-morbidities and environmental risk factors. CONCLUSIONS: Our cluster analysis identified six distinct clusters of obstructive sleep apnea. Our findings underscore the high degree of heterogeneity that exists within obstructive sleep apnea patients regarding clinical presentation, risk factors and consequences. This may help in both research and clinical practice for validating new prevention programs, in diagnosis and in decisions regarding therapeutic strategies.

Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to determine whether nocturia is an independent predictor for prevalent hypertension in obstructive sleep apnea (OSA). METHODS: We analyzed data from a national prospective clinical cohort of OSA patients participating in the French national prospective registry. Anthropometric data, comorbidities, OSA severity, and number of voids/night were included in multivariate analyses to determine the independent variables associated with prevalent hypertension. RESULTS: A total of 22,674 OSA patients were included, of which 11,332 were hypertensive. The prevalence of hypertension among OSA patients was about 1.3 times higher in patients suffering from nocturia at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p <0.001). There was a significant positive relationship between hypertension and the severity of nocturia beyond two voids/night: two voids/night versus none: odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association was enhanced in patients over 64 years of age. CONCLUSIONS: Nocturia is a strong independent predictor of prevalent hypertension in OSA. This association exhibited a "dose-response" relationship beyond two voids/night. The resolution of nocturia after continuous positive airway pressure (CPAP) treatment might be an important outcome to consider for the response of hypertension to CPAP.

Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines.

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

Association between glaucoma and sleep apnea in a large French multicenter prospective cohort.

OBJECTIVE: Several reports suggest that glaucoma may be linked to obstructive sleep apnea (OSA). Herein, we investigated this hypothesis in the largest reported sample to date. METHODS: Data were from the French multicenter prospective cohort study including OSA-suspected patients from private practice, general and teaching hospitals. Demographics, history, comorbidities and sleep studies from patients aged >50 years were analyzed. Univariate and multivariate logistic regression were used to predict the odds ratio of prevalent glaucoma depending on sleep apnea status and other potential anthropometric, metabolic, cardiovascular and respiratory confounders. RESULTS: A total of 9580 patients aged >50 years were included. Among these patients, 6754 had sleep apnea and 330 had glaucoma. Glaucoma prevalence was 3.55% in patients with OSA and 3.14% in patients without OSA. OSA diagnosis did not significantly influence the risk of glaucoma in univariate analysis (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.87-1.47). The variables significantly influencing the odds of glaucoma with multivariate regression were age >61.4 years (OR, 1.55; 95% CI, 1.23-1.95), body mass index <30 kg/m2 (OR, 1.58; 95% CI, 1.26-1.99), female gender (OR, 1.40; 95% CI, 1.11-1.78), arterial hypertension (OR, 1.32; 95% CI, 1.05-1.67), high triglyceride levels (OR, 2.03; 95% CI, 1.43-2.88) and thyroid dysfunction (OR, 1.52; 95% CI, 1.09-2.11). CONCLUSIONS: When confounders are taken into account, patients with OSA do not have higher odds of glaucoma compared with patients who do not have OSA in a large multicenter prospective cohort.

Type of mask may impact on continuous positive airway pressure adherence in apneic patients.

RATIONALE: In obstructive sleep apnea patients (OSA), continuous positive airway pressure (CPAP) adherence is crucial to improve symptoms and cardiometabolic outcomes. The choice of mask may influence CPAP adherence but this issue has never been addressed properly. OBJECTIVE: To evaluate the impact of nasal pillows, nasal and oronasal masks on CPAP adherence in a cohort of OSA. METHODS: Newly CPAP treated OSA participating in "Observatoire Sommeil de la Fédération de Pneumologie", a French national prospective cohort, were included between March 2009 and December 2011. Anthropometric data, medical history, OSA severity, sleepiness, depressive status, treatment modalities (auto-CPAP versus fixed pressure, pressure level, interface type, use of humidifiers) and CPAP-related side effects were included in multivariate analysis to determine independent variables associated with CPAP adherence. RESULTS: 2311 OSA (age = 57(12) years, apnea+hypopnea index = 41(21)/h, 29% female) were included. Nasal masks, oronasal masks and nasal pillows were used by 62.4, 26.2 and 11.4% of the patients, respectively. In univariate analysis, oronasal masks and nasal pillows were associated with higher risk of CPAP non-adherence. CPAP non-adherence was also associated with younger age, female gender, mild OSA, gastroesophageal reflux, depression status, low effective pressure and CPAP-related side effects. In multivariate analysis, CPAP non-adherence was associated with the use of oronasal masks (OR = 2.0; 95%CI = 1.6; 2.5), depression, low effective pressure, and side effects. CONCLUSION: As oronasal masks negatively impact on CPAP adherence, a nasal mask should be preferred as the first option. Patients on oronasal masks should be carefully followed.

Residual sleepiness in sleep apnea patients treated by continuous positive airway pressure.

Hypoxic brain damage might explain persistent sleepiness in some continuous positive airway pressure-compliant obstructive sleep apnea called residual excessive sleepiness. Although continuous positive airway pressure may not be fully efficient in treating this symptom, wake-promoting drug prescription in residual excessive sleepiness is no longer allowed by the European Medicines Agency. The aim of this study is to describe residual excessive sleepiness phenotypes in a large prospective sample of patients with obstructive sleep apnea. Residual excessive sleepiness was defined by an Epworth Sleepiness Scale score ≥ 11. Eligible patients from the French National Sleep Registry attending follow-up continuous positive airway pressure visits numbered 1047. Patients using continuous positive airway pressure < 3 h (n = 275), with residual apnea-hypopnea index > 15 h⁻¹ (n = 31) or with major depression were excluded (n = 150). Residual excessive sleepiness prevalence in continuous positive airway pressure-treated obstructive sleep apnea was 13% (18% for those with an initial Epworth Sleepiness Scale score > 11), and significantly decreased with continuous positive airway pressure use (9% in ≥ 6 h night⁻¹ continuous positive airway pressure users, P < 0.005). At the time of diagnosis, patients with residual excessive sleepiness had worse subjective appreciation of their disease (general health scale, Epworth Sleepiness Scale and fatigue score), and complained more frequently of continuous positive airway pressure side-effects. Residual excessive sleepiness prevalence was lower in severe obstructive sleep apnea than in moderate obstructive sleep apnea (11% when AHI > 30 h⁻¹ versus 18% when AHI 15-30, P < 0.005). There was no relationship between residual excessive sleepiness and body mass index, cardiovascular co-morbidities or diabetes. Continuous positive airway pressure improved symptoms in the whole population, but to a lower extent in patients with residual excessive sleepiness (fatigue scale: -5.2 versus -2.7 in residual excessive sleepiness- and residual excessive sleepiness+ patients, respectively, P < 0.001). Residual excessive sleepiness prevalence decreased with continuous positive airway pressure compliance. Hypoxic insult is unlikely to explain residual excessive sleepiness as obstructive sleep apnea severity does not seem to be critical. Residual symptoms are not limited to sleepiness, suggesting a true 'continuous positive airway pressure-resistant syndrome', which may justify treatment by wake-promoting drugs.