Associations between Vitamin D Status and Polysomnographic Parameters in Adults with Obstructive Sleep Apnea.

Vitamin D deficiency (VDD) may be associated with obstructive sleep apnea (OSA) presence and is more pronounced with increasing OSA severity; however, the relationship between these two entities remains unclear. This was a cross-sectional study among 262 adults with in-hospital-attended polysomnography-diagnosed OSA and no additional major comorbidities, aiming to explore possible associations between serum 25-hydroxyvitamin D [25(OH)D] levels and polysomnographic parameters. Data on demographics, medical history, anthropometric indices, and lifestyle habits were collected at enrolment. Serum 25(OH)D was evaluated using chemiluminescence, with VDD defined as 25(OH)D < 20 ng/mL. VDD was observed in 63% of the participants. Serum 25(OH)D correlated negatively with apnea-hypopnea index and other polysomnographic indices (all p < 0.05). In logistic regression analysis, adjusting for age, sex, smoking, body mass index, physical activity, dietary vitamin D intake, and season of blood sampling, serum 25(OH)D was associated with lower odds of severe OSA [odds ratio (95% confidence interval): 0.94 (0.90-0.98)]. In the same multivariate model, VDD was associated with ~threefold higher odds of severe OSA [2.75 (1.38-5.48)]. In stratified analyses, VDD predicted OSA severity in the group of participants ≥50 y [3.54 (1.29-9.68)] and among those with body mass index ≥ 30 kg/m2 [3.38 (1.52-7.52)], but not in the younger and non-obese adults. This study provides further evidence of an inverse association between vitamin D levels and OSA severity and underscores the importance of considering vitamin D status as a potential modifiable factor in the comprehensive management of OSA.

Associations between serum vitamin D status and the cardiometabolic profile of patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) and the metabolic syndrome (MetS) frequently coexist. Low serum vitamin D has been positively associated with OSA presence and severity; however, data on its link to cardiometabolic features in patients with OSA remain scarce. We aimed to assess serum 25-hydroxyvitamin D [25(OH)D] and explore its association with cardiometabolic parameters in OSA. METHODS: This was a cross-sectional study among 262 patients (49 ± 9 years old, 73% men) with polysomnography-diagnosed OSA. Participants were evaluated in terms of anthropometric indices, lifestyle habits, blood pressure, biochemical, plasma inflammatory and urinary oxidative stress markers, and the presence of MetS. Serum 25(OH)D was assessed by chemiluminescence, and vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. RESULTS: Median (1st, 3rd quartile) serum 25(OH)D levels were 17.7 (13.4, 22.9) ng/mL and 63% of participants had VDD. Serum 25(OH)D correlated negatively with body mass index (BMI), homeostasis model of assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), and urinary oxidized guanine species (oxG), and positively with high-density lipoprotein cholesterol (all P < 0.050). In logistic regression analysis, serum 25(OH)D was associated with lower odds of MetS [odds ratio (95% confidence interval): 0.94 (0.90-0.98)], after adjustment for age, sex, season of blood sampling, Mediterranean diet score, physical activity, smoking, apnea-hypopnea index, HOMA-IR, hsCRP, and oxG. In the same multivariate model, VDD was associated with ~ twofold greater odds of MetS [2.39 (1.15, 4.97)]. CONCLUSION: VDD is highly prevalent and is associated with a detrimental cardiometabolic profile among patients with OSA.

Sustained improvements in the cardiometabolic profile of patients with obstructive sleep apnea after a weight-loss Mediterranean diet/lifestyle intervention: 12-month follow-up (6 months post-intervention) of the "MIMOSA" randomized clinical trial.

BACKGROUND AND AIMS: Obstructive sleep apnea (OSA) and the metabolic syndrome (MS) frequently coexist and lead to increased cardiometabolic morbidity. We aimed to explore the long-term cardiometabolic benefits of a weight-loss Mediterranean diet/lifestyle intervention in OSA. METHODS AND RESULTS: As many as 180 adults with overweight/obesity and polysomnography-diagnosed moderate-to-severe OSA were randomized to a standard care (SCG, n = 62), a Mediterranean diet (MDG, n = 59) or a Mediterranean lifestyle group (MLG, n = 59). All groups were prescribed with continuous positive airway pressure (CPAP), while intervention arms (MDG/MLG) additionally participated in a 6-month weight-loss intervention based on the Mediterranean diet/lifestyle. Cardiometabolic parameters were evaluated at baseline and 12 months (6 months post-intervention). Data were analyzed using the intention-to-treat method, and 12-month between-group differences were explored while adjusting for age, sex, baseline status and CPAP use. Compared to the SCG, intervention arms exhibited lower insulin, triglycerides and high-sensitivity C-reactive protein, and higher high-density lipoprotein cholesterol; the MDG also exhibited lower diastolic blood pressure, while the MLG exhibited lower glucose and systolic blood pressure (all P < 0.050). The relative risk (95% confidence interval) of MS was 0.60 (0.36, 0.99) in the MDG versus the SCG, 0.33 (0.20, 0.55) in the MLG versus the SCG and 0.55 (0.32, 0.93) in the MLG versus the MDG. The risk of MS remained lower in the MLG versus the other study groups (both P < 0.050) after additional adjustment for body weight change. CONCLUSION: Cardiometabolic benefits of a 6-month healthy dietary/lifestyle intervention are sustainable 6 months post-intervention in OSA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02515357, August 4, 2015.

Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.

STUDY OBJECTIVES: Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. METHODS: This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. RESULTS: Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. CONCLUSIONS: Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION: Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.

A weight-loss Mediterranean diet/lifestyle intervention ameliorates inflammation and oxidative stress in patients with obstructive sleep apnea: results of the "MIMOSA" randomized clinical trial.

PURPOSE: Inflammation and oxidative stress are implicated in obstructive sleep apnea (OSA) pathophysiology. We aimed at exploring whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care, i.e., continuous positive airway pressure (CPAP) prescription, can lead to greater improvements in inflammation and oxidative stress, compared to standard care alone. METHODS: This was a randomized controlled clinical trial in 187 adult, overweight patients with moderate-to-severe OSA. Participants were randomized to a standard care (SCG, n = 65), a Mediterranean diet (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All groups received OSA standard care. Intervention arms participated in a 6-month behavioral weight-loss intervention based on the Mediterranean diet, while the MLG also received counselling on physical activity and sleep habits. RESULTS: Seven patients were excluded and 53/180 were lost to follow-up. In intention to treat analysis (n = 180), the SCG did not exhibit changes in any of the markers assessed. Post-intervention age-, sex-, baseline- and CPAP use-adjusted plasma high sensitivity C-reactive protein levels (mg/L) were lower in the MDG and the MLG compared to the SCG (mean difference - 1.33, P = 0.039 and - 1.68, P = 0.007, respectively). The MLG also exhibited lower urinary 8-iso prostaglandin F2a levels (ng/mg creatinine) compared to the SCG and the MDG (mean difference - 1.10, P < 0.0001 and - 0.80, P = 0.001, respectively). Adiponectin and oxidized guanine levels were not altered in any of the study groups. Results were similar in per protocol analysis (n = 127). CONCLUSION: A weight-loss Mediterranean diet/lifestyle intervention on top of CPAP has anti-inflammatory and antioxidant benefits in OSA. REGISTRATION: The trial was prospectively registered at ClinicalTrials.gov (NCT02515357) on August 4, 2015.

Common Susceptibility Loci for Male Breast Cancer.

BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.

The effectiveness of a weight-loss Mediterranean diet/lifestyle intervention in the management of obstructive sleep apnea: Results of the "MIMOSA" randomized clinical trial.

BACKGROUND & AIMS: Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), lifestyle interventions have also emerged as complementary therapeutic choices. We aimed to explore whether the addition of a weight-loss Mediterranean diet/lifestyle intervention to OSA standard care, i.e. CPAP prescription and brief written healthy lifestyle advice, has an incremental effect on improving OSA severity, over the effect of standard care alone. METHODS: We designed a parallel, randomized, controlled, superiority clinical trial. Eligible participants were adult, overweight men and women, diagnosed with moderate-to-severe OSA [apnea-hypopnea index (AHI)≥ 15 events/h] through an attended overnight polysomnography. Participants were blindly randomized to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three study groups were prescribed with CPAP. The SCG additionally received written healthy lifestyle advice, while intervention arms were subjected to a 6-month behavioral intervention aiming at weight loss and increasing adherence to the Mediterranean diet. The MLG also received counselling on physical activity and sleep habits. Polysomnographic data and OSA symptoms were evaluated pre- and post-intervention. RESULTS: A total of 187 OSA patients were recruited. Seven patients were excluded post-randomization and 53/180 (29%) were lost to follow-up. No harms from the interventions applied were reported. According to intention-to-treat analysis (n = 180), mean (95% confidence interval) AHI change was -4.2 (-7.4, -1.0) for the SCG, -24.7 (-30.4, -19.1) for the MDG and -27.3 (-33.9, -20.6) for the MLG. Post-intervention age-, sex-, baseline- and CPAP use-adjusted AHI was significantly lower in the MDG and the MLG compared to the SCG (mean difference: -18.0, and -21.2, respectively, both P < 0.001), and the differences remained significant after further adjustment for body-weight change (P = 0.004 and 0.008, respectively). Other respiratory event indices, daytime sleepiness and insomnia were also significantly lower in both intervention arms compared to the SCG (all P < 0.05). The MLG only presented higher percent rapid-eye-movement sleep and lower daytime sleepiness compared to the MDG (both P < 0.05). Results were similar in the per-protocol analysis (n = 127). CONCLUSIONS: A dietary/lifestyle intervention on top of standard care leads to greater improvements in OSA severity and symptomatology compared to standard care alone. Benefits are evident regardless of CPAP use and weight loss. TRIAL REGISTRATION: Clinicaltrials.gov NCT02515357, https://clinicaltrials.gov/ct2/show/NCT02515357.

Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The "MIMOSA" Randomized Clinical Trial.

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), its cardiometabolic benefits are questionable. Our aim was to explore whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care leads to greater cardiometabolic improvements compared with standard care alone. We randomly assigned 187 adult, overweight, polysomnography-diagnosed moderate-to-severe OSA patients to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three groups were prescribed with CPAP. Additionally, the SCG only received brief written healthy lifestyle advice, while intervention arms were subjected to a six-month weight-loss behavioral intervention based on the Mediterranean diet. The MLG also received guidance for improving physical activity and sleep habits. Glucose metabolism indices, blood lipids, liver enzymes and blood pressure improved only in intervention arms, and were significantly lower compared to the SCG post-intervention (all p < 0.05). The age-, sex-, baseline- and CPAP use-adjusted relative risk (95% confidence interval) of metabolic syndrome was 0.58 (0.34-0.99) for the MDG and 0.30 (0.17-0.52) for the MLG compared to the SCG. The MLG additionally presented a lower relative risk of metabolic syndrome compared to the MDG (0.52 (0.30-0.89)). After further adjustment for body-weight change, a lower relative risk of metabolic syndrome was still evident for the MLG compared to the SCG. In conclusion, although standard care alone does not improve OSA patients' cardiometabolic profile, its combination with a weight-loss Mediterranean diet/lifestyle intervention leads to significant cardiometabolic benefits.

Clinical and polysomnographic determinants of snoring.

Snoring is considered one of the hallmarks of sleep-disordered breathing, but its determinants remain obscure in both obstructive sleep apnoea (apnoeic) and non-apnoeic snorers. We aimed to document positional dependency of snoring along with its association with clinical and polysomnographic variables. Seventy-seven apnoeic and 27 non-apnoeic snorers who complained for every-night loud snoring and slept in supine and lateral positions in all sleep stages during overnight polysomnography were included. Snoring (i.e. sound intensity > 40 dB) was quantified by measuring the mean and maximum sound intensity, and snoring frequency. In apnoeic and non-apnoeic snorers, mean snoring intensity and snoring frequency were higher in supine than in lateral positions irrespective of sleep stage, and were also usually higher in N3 in comparison to rapid eye movement and/or N2 sleep stage in any given position. Positional change in snoring intensity as expressed by the ratio of mean intensity in the supine to lateral positions was independently and positively correlated with body mass index, tonsils size and age in the total of patients. Snoring is more prominent in the supine position and in N3 sleep stage in apnoeic and non-apnoeic snorers. Snoring positional dependence is determined by body mass index, tonsils size and age.

Average volume-assured pressure support in a 16-year-old girl with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is an uncommon disorder characterized by the absence of adequate autonomic control of respiration, which results in alveolar hypoventilation and decreased sensitivity to hypercarbia and hypoxemia, especially during sleep. Patients with CCHS need lifelong ventilatory support. The treatment options for CCHS include intermittent positive pressure ventilation administered via tracheostomy, noninvasive positive pressure ventilation, negative-pressure ventilation by body chamber or cuirass, and phrenic nerve pacing. However, it may be necessary to alter the mode of ventilation according to age, psychosocial reasons, complications of therapy, and emergence of new modes of ventilation. We present a case of a 16-year-old girl with CCHS who was mechanically ventilated via tracheostomy for 16 years and was successfully transitioned to a new modality of noninvasive ventilation (average volume-assured pressure support [AVAPS]) that automatically adjusts the pressure support level in order to provide a consistent tidal volume.

Determinants of subjective sleepiness in suspected obstructive sleep apnoea.

Although daytime sleepiness is commonly associated with obstructive sleep apnoea (OSA), the relationship between OSA severity and subjective sleepiness has been documented elusive. This study aimed to identify clinical and polysomnographic determinants of subjective sleepiness among patients suspected of having OSA. A sleep clinic-based sample of 915 patients was interviewed with a structured questionnaire and underwent diagnostic overnight polysomnography. Subjective sleepiness was quantified by Epworth Sleepiness Scale (ESS). Excessive daytime sleepiness (defined as ESS score > 10) was present in 38.8% of patients. In multiple linear regression analysis, respiratory disturbance index [RDI; used to define (whenever RDI was >5) and quantify OSA], depression and diabetes were the most important determinants of ESS score accounting for 17%, 11% and 6% of its variability respectively. Chronic obstructive pulmonary disease (COPD), stroke, heart disease, alcohol use and body mass index were less important determinants of ESS score explaining 1-3% of its variability. In conclusion, OSA should not be considered the sole potential cause of increased subjective sleepiness in patients suspected of having OSA. Primarily depression and diabetes, but also COPD, stroke, heart disease, alcohol use and increased body mass index may contribute to increased subjective sleepiness.

Exhaled breath markers in patients with obstructive sleep apnoea.

The objectives of the present study were to assess the level of exhaled breath markers indicating airway inflammation and oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) in comparison with non-apnoeic (obese and non-obese) subjects and investigate whether therapy with continuous positive airway pressure (CPAP) can modify them. The design was a retrospective observational study, set in Evgeneidio Hospital. Twenty-six OSAS patients and nine obese and 10 non-obese non-apnoeic subjects participated in this study. We measured nasal nitric oxide (nNO), exhaled nitric oxide (eNO), exhaled carbon monoxide (eCO) in exhaled breath, and 8-isoprostane, leukotriene B(4) (LTB(4)), nitrates, hydrogen peroxide (H(2)O(2)), and pH in exhaled breath condensate (EBC) before and after 1 month of CPAP therapy. The levels of eNO and eCO were higher in OSAS patients than in control subjects (p < 0.05). Nasal NO was higher in OSAS patients than in obese controls (p < 0.01). The level of H(2)O(2), 8-isoprostane, LTB(4), and nitrates were elevated in OSAS patients in comparison with obese subjects (p < 0.01). Conversely, pH was lower in OSAS patients than in non-apnoeic controls (p < 0.01). One month of CPAP therapy increased pH (p < 0.05) and reduced eNO (p < 0.001) and nNO (p < 0.05). Apnea/hypopnoea index was positively correlated with 8-isoprostane (r = 0.42; p < 0.05), LTB(4) (r = 0.35; p < 0.05), nitrates (r = 0.54; p < 0.001), and H(2)O(2) (r = 0.42; p < 0.05). Airway inflammation and oxidative stress are present in the airway of OSAS patients in contrast to non-apnoeic subjects. Exhaled breath markers are positively correlated with the severity of OSAS. One-month administration of CPAP improved airway inflammation and oxidative stress.

Ileocolic intussusception due to endometriosis.

Intussusception is a rare cause of bowel obstruction in adults. Clinical manifestations are not specific, making the preoperative diagnosis difficult to establish. We report a case of acute small-bowel obstruction due to ileocolic intussusception. An emergency explorative laparoscopy was performed and revealed a mass in the right colon proximal to the ileocecal valve. Conversion to open laparotomy allowed us to perform a right hemicolectomy. The pathologic examination of the resected sample revealed endometriosis of the terminal ileus.