A Narrative Review of the Clinical Trials in Sleep-Related Breathing Disorders from 2022 to Present.

Sleep-related breathing disorders (SRBD) comprise obstructive sleep apnea (OSA), central sleep apnea (CSA), obesity-hypoventilation syndrome (OHS), as well as isolated sleep-related hypoxemia (ISRH), according to the recent International Classification of Sleep Disorders 3. During the last decades, there have been cumulative research reports indicating an association between the SRBD and increased cardiometabolic illness and death, as well as decreased quality of life. Notwithstanding, the results have been inconclusive, and the evidence level was not high regarding the effect of treatment for the SRBD on adverse outcomes. In the current work, we aim to give a comprehensive review of the clinical trials published from January 2022 to August 31, 2023. We highlight the heterogeneity of cardiometabolic disorders among adults with SRBD and particularly emphasize OSA management, drug therapy for OSA, positive airway pressure (PAP) therapy and cardiovascular outcomes, other effects of PAP in pregnancy and neurocognitive function, as well as the effects of surgical treatment and oral appliances. We also underline future directions in OSA management, telemonitoring, and druginduced sleep endoscopy in managing the SRBD, especially OSA. We ascertain that more studies are needed within the CSA, OHS, and ISRH research fields.

Diaphragmatic dysfunction at the first visit to a chest diseases outpatient clinic in 500 patients with amyotrophic lateral sclerosis.

INTRODUCTION: In this study, we aimed to evaluate diaphragmatic dysfunction (DD) by using a practical approach in patients with amyotrophic lateral sclerosis (ALS) at the first visit to a chest diseases outpatient clinic. METHODS: Patients with ALS seen in our outpatient clinic for the past 5 y and followed up for at least 1 y, were retrospectively evaluated. Having at least one of the following three criteria was accepted as DD: (a) paradoxical abdominal movement (PAM), (b) sitting-supine forced vital capacity (FVC) difference ≥ 20%, (c) sitting-supine arterial oxygen saturation measured by pulse oximetry (SpO2 ) difference ≥ 4%. Respiratory symptoms, arterial blood gas analysis, sleep studies, noninvasive mechanical ventilation use, and mortality were recorded. RESULTS: Five-hundred patients with ALS were included (female/male: 220/280, age: 58.9 ± 11.3 y). Of the patients, 22.8% had daytime hypercapnia. DD was observed in 55% of the patients (PAM in 112, sitting-supine FVC difference ≥ 20% in 50, and sitting-supine SpO2 difference ≥ 4% in 113 patients). Of the patients with DD, 31.6% (n = 87) had no respiratory symptoms, 46.4% had FVC > 70% and 33.5% had FVC <50%. Nocturnal hypoxemia (sleep time spent with SpO2 < 90% ≥30%) was present in 59.7%, and all patients with nocturnal hypoxemia had DD. Obstructive sleep apnea (8 severe, 14 moderate, 39 mild) was detected in 55% of the patients with polysomnography (n = 61) or polygraphy (n = 50). During follow-up, 52.2% of the patients died. Mean survival time was shorter in patients with DD (P < .001). CONCLUSION: Paradoxical abdomimal movement (PAM), sitting-supine SpO2 difference ≥ 4% and sitting-supine FVC difference ≥ 20% are indicators of DD, which should be routinely evaluated at every outpatient visit.

Serum endocan levels in patients with stable COPD.

BACKGROUND: Endothelial cell specific molecule-1, also called as endocan, is a dermatan sulfate proteoglycan, which is expressed by endothelial cells in alveolar walls of the lung and kidney. High endocan levels are found associated with endothelial dysfunction and inflammation. We hypothesize that endocan level is also high in COPD due to systemic inflammation and endothelial dysfunction. We aimed to investigate the expression of endocan in patients with stable COPD. MATERIAL AND METHODS: The study included patients with COPD and control subjects. COPD patients were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 criteria. Demographics, body mass index, smoking history, and comorbidities were recorded. Endocan levels of COPD patients and controls were compared. RESULTS: Totally, 88 subjects (47 stable COPD patients, 41 controls) were evaluated. Endocan levels were significantly higher in COPD patients than control group (860.1±259.8 vs 647.3±316.9 pg/mL, P=0.001). There was no relationship between GOLD COPD categories and endocan levels. Also endocan levels were similar between COPD patients with or without hypoxemia. CONCLUSION: Serum endocan level was significantly higher in patients with stable COPD. Further studies should be performed to better understand the relationship between endocan and COPD.

Obstructive sleep apnea is a risk factor for osteoarthritis.

INTRODUCTION: Obstructive sleep apnea (OSA) syndrome is closely associated with cardiovascular and metabolic disorders. Recent studies reported that osteoarthritis (OA) is associated with cardiovascular disease as well as inflammation defined as "metabolic disorder". Due to the strong association of metabolic disorders with both OA and OSA, we aimed to investigate the association between severity of OSA and osteoarthritis grade based on X-Ray. MATERIALS AND METHODS: Patients who underwent polysomnography due to suspicion of OSA were recruited in a cross-sectional study. Included patients were grouped according to apnea-hypopnea index (AHI) as mild (AHI between 5 and 14.9), moderately (AHI between 15 and 29.9), and severe OSA (AHI ≥ 30). Patients with AHI p< 5 served as the control group. Kellgren-Lawrence scoring system was used to express OA severity, which was graded as Grade 0, 1, 2, 3 and 4. RESULT: One hundred twenty patients were enrolled into the study. Mean age was 52.4 ± 11.5 years and 56% (68/120) of the patients were male. A strong correlation was present between severity of OSA and severity of OA. Among those with Grade 4 OA group (33 patients), all patients had severe OSA and this association was independent from body-mass index. In the Grade 1 OA group, none of the patients had severe OSA (p< 0.05). A positive correlation was also seen between severity of OSA, OA and hs-CRP. CONCLUSIONS: There is a strong association between OSA and OA. OSA might be a novel risk factor for the development OA. Further studies should evaluate the effect of OSA treatment on OA.

The Predictors of Obesity Hypoventilation Syndrome in Obstructive Sleep Apnea.

BACKGROUND: As obesity increases, the frequency of obstructive sleep apnea and obesity hypoventilation syndrome increases also. However, obesity hypoventilation syndrome frequency is not known, as capnography and arterial blood gas analysis are not routinely performed in sleep laboratories. AIMS: To investigate the frequency and predictors of obesity hypoventilation syndrome in obese subjects. STUDY DESIGN: Retrospective clinical study. METHODS: Obese subjects who had arterial blood gas analysis admitted to the sleep laboratory and polysomnography were retrospectively analyzed. Subjects with restrictive (except obesity) and obstructive pulmonary pathologies were excluded. Demographics, Epworth-Sleepiness-Scale scores, polysomnographic data, arterial blood gas analysis, and spirometric measurements were recorded. RESULTS: Of the 419 subjects, 45.1% had obesity hypoventilation syndrome. Apnea hypopnea index (p<0.001), oxygen desaturation index (p<0.001) and sleep time with SpO2<90% (p<0.001) were statistically higher in subjects with obesity hypoventilation syndrome compared to subjects with eucapnic obstructive sleep apnea. The nocturnal mean SpO2 (p<0.001) and lowest SpO2 (p<0.001) were also statistically lower in subjects with obesity hypoventilation syndrome. Logistic regression analysis showed that the lowest SpO2, oxygen desaturation index, apnea hypopnea index and sleep time with SpO2 <90% were related factors for obesity hypoventilation syndrome. CONCLUSION: Obesity hypoventilation syndrome should be considered when oxygen desaturation index, apnea hypopnea index and sleep time with SpO2 <90% are high.

Vocal Cord Paralysis and Hypercapnic Respiratory Failure in a Patient with Familial Amyloidotic Polyneuropathy.

We herein report a patient case with familial amyloidotic polyneuropathy (FAP) who presented with vocal cord paralysis (VCP). A 60-year-old man with FAP (Gly89Gln) presented with hoarseness and snoring for the previous two years. A chest X-ray demonstrated cardiomegaly and bilateral diaphragmatic elevation. The findings of a restrictive pattern on spirometry and daytime hypercapnia were consistent with respiratory muscle weakness related to neuropathy [forced expiratory volume (FEV1): 38%, forced vital capacity (FVC): 39%, FEV1/FVC: 77, partial pressure of arterial oxygen (PaO2): 80 mmHg, partial pressure of carbon dioxide in arterial blood (PaCO2): 52 mmHg]. An ear-nose-throat examination showed VCP. Polysomnography revealed severe obstructive sleep apnea (OSA). FAP may cause OSA by VCP and hypercapnic respiratory failure by respiratory muscle weakness. Therefore, an ear-nose-throat examination, spirometry, arterial blood gases analysis and polysomnography are important for these patients.

Serum endothelial cell specific molecule-1 (endocan) levels in patients with obstructive sleep apnea.

OBJECTIVE: To investigate the level of endothelial cell specific molecule-1 (endocan) in obstructive sleep apnea (OSA). METHODS: Study group included subjects with OSA. Control group included subjects who had no OSA on polysomnography and nonobese healthy subjects from population who had no OSA symptoms. Endocan levels of OSA and non-OSA subjects were compared. RESULTS: Totally 106 individuals (63 OSA, 43 non-OSA) were included. Endocan levels were higher in OSA subjects than controls (1.25 ± 0.4 ng/ml vs 0.93 ± 0.3 ng/ml, p < 0.001). Endocan levels were correlated with BMI (r = 0.456, p < 0.001) and daytime PaO2 (r = -0.266, p < 0.042). In linear regression analysis there was no factor related to endocan level. CONCLUSION: Serum endocan is significantly higher in OSA. Further studies should be performed to better understand the relationship between endocan and OSA.

Modified STOP-BANG questionnaire to predict obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea.

PURPOSE: The STOP-BANG questionnaire (SBQ) has never been studied in the context of its ability to predict obesity hypoventilation syndrome (OHS). Our aim was to evaluate the predictive performance of the original and modified SBQs for OHS in obese subjects with obstructive sleep apnea (OSA). METHODS: Demographics, polysomnographic data, body mass index (BMI), Epworth Sleepiness Scale (ESS) scores, arterial blood gases, spirometric measurements, and SBQ scores were recorded. The modified SBQ was created by dividing BMI into ranges and adding the serum bicarbonate ranges. RESULTS: The study included 196 obese subjects, of whom 17 had normal polysomnography. Of the remaining subjects, 105 had pure OSA and 74 had OHS with OSA. Both the original and modified SBQs scores were higher for the OHS subjects than for those with pure OSA (p < 0.001). An original SBQ score of ≥6 gave a satisfactory discrimination for OHS diagnosis (sensitivity 71.6 %, specificity 59.1 %, positive predictive value (PPV) 55.2 %, and negative predictive value (NPV) 74.7 %). The diagnostic OR for an original SBQ score of ≥6 for predicting OHS was 3.7. The sensitivity and NPV were increased for the modified SBQ (sensitivity 89.2 %, specificity 47.6 %, PPV 54.6 %, NPV 86.2 %), and the OR was 7.5. Both the original and modified SBQ scores were moderately correlated with ESS, AHI, ODI, lowest SpO2, and sleep time spent with SpO2 <90 %. CONCLUSIONS: The modified SBQ can be used to screen for OHS in obese subjects.

Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea.

BACKGROUND: Arterial blood gas (ABG) analysis is not a routine test in sleep laboratories due to its invasive nature. Therefore, the diagnosis of obesity hypoventilation syndrome (OHS) is underestimated. We aimed to evaluate the differences in subjects with OHS and pure obstructive sleep apnea (OSA) and to determine clinical predictors of OHS in obese subjects. METHODS: Demographics, body mass index (BMI), Epworth Sleepiness Scale score, polysomnographic data, ABG, spirometric measurements, and serum bicarbonate levels were recorded. RESULTS: Of 152 obese subjects with OSA (79 females/73 males, mean age of 50.3 ± 10.6 y, BMI of 40.1 ± 5.6 kg/m(2), 51.9% with severe OSA), 42.1% (n = 64) had OHS. Subjects with OHS had higher BMI (P = .02), neck circumference (P < .001), waist circumference (P < .001), waist/hip ratio (P = .02), Epworth Sleepiness Scale scores (P = .036), ABG and serum bicarbonate levels (P < .001), apnea-hypopnea index (P = .01), oxygen desaturation index (P < .001), and total sleep time with S(pO2) < 90% (P < .001) compared with subjects with pure OSA (n = 88). They also had lower daytime PaO2 (P < .001), sleep efficiency (P = .032), mean S(pO2) (P < .001), and nadir S(pO2) (P < .001). Serum bicarbonate levels and nadir S(pO2) were the only independent predictive factors for OHS. A serum bicarbonate level of ≥ 27 mmol/L as the cutoff gives a satisfactory discrimination for the diagnosis of OHS (sensitivity of 76.6%, specificity of 74.6%, positive predictive value of 54.5%, negative predictive value of 88.9%). A nadir S(pO2) of < 80% as the cutoff gives a satisfactory discrimination for the diagnosis of OHS (sensitivity of 82.8%, specificity of 54.5%, positive predictive value of 56.9%, negative predictive value of 81.4%). When we used a serum bicarbonate level of ≥ 27 mmol/L and/or a nadir S(pO2) of < 80% as a screening measure, only 3 of 64 subjects with OHS were missed. CONCLUSIONS: Serum bicarbonate level and nadir saturation were independent predictive factors for the diagnosis of OHS.

Relationship between parenchymal involvement and obstructive sleep apnea in subjects with sarcoidosis.

INTRODUCTION: Increased obstructive sleep apnea (OSA) incidence has been reported in sarcoidosis. However, no research has been conducted to determine the relation between OSA and pulmonary parenchymal involvement in sarcoidosis. OBJECTIVES: We investigated OSA frequency and association between pulmonary parenchymal involvement and OSA in sarcoidosis. Additionally, relationship between lung functions and polysomnography data was assessed. METHODS: The study enrolled sarcoidosis subjects with or without pulmonary parenchymal involvement. Spirometry, diffusion capacity, 6-min walking test, arterial blood gases, chest X-ray, Epworth sleepiness scale (ESS) and polysomnography were performed. Subjects with body mass index (BMI) ≥30 or significant upper airway pathologies that might cause OSA were excluded. RESULTS: A total of 29 sarcoidosis subjects (15 with, 14 without parenchymal involvement) with mean age 43.8 ± 9.4 years were analyzed. Twenty-seven of them were female. BMI was 26.8 ± 4.2 kg/m(2) . Mean forced expiratory volume 1 s (FEV1 ) was 97.89% ± 20.21%, and forced vital capacity (FVC) was 102.86 ± 18.14%. ESS score was 4 ± 1.6. OSA was identified in 51.7% (n = 15) of subjects. Apnea-hypopnea index (AHI) was 16.16 ± 19/h and oxygen desaturation index (ODI) was 22.3 ± 25.99 among subjects with OSA. Sleep apnea related with rapid eye movement was present in 40% of OSA subjects. AHI and ODI were higher among sarcoidosis subjects with parenchymal involvement (P = 0.019, P = 0.026). OSA frequency was higher in the group with parenchymal involvement, but the difference was not statistically significant (n = 10/15, %66 vs n = 5/14, %35). FEV1 and FVC were not related with AHI and ODI. CONCLUSION: We found a high rate of OSA in sarcoidosis. There was a trend of high OSA frequency in sarcoidosis subjects with parenchymal involvement.

Evidence for the efficacy of a bioresonance method in smoking cessation: a pilot study.

BACKGROUND: Since the 1970s, MORA bioresonance therapy has globally been applied in the context of complementary medicine for various indications. In this regard, practitioners also report successful application in smoking cessation. The present study aims to verify these reports in a controlled study setting. METHODS: In order to achieve the aforementioned objective, we subjected the bioresonance method to a prospective, placebo-controlled, double-blind, parallel-group study involving 190 smokers. In both study groups (placebo n = 95; active bioresonance group; n = 95) the course of treatment and study conditions were standardized. RESULTS: 1 week (77.2% vs. 54.8%), 2 weeks (62.4% vs. 34.4%), 1 month (51.1% vs. 28.6%), and 1 year (28.6% vs. 16.1%) after treatment, the success rate in the verum group differed significantly from the results in the placebo group. Also, the subjective health condition after treatment and subjective assessment of efficacy, polled after 1 week, were significantly more positive among participants in the active bioresonance therapy group than among those in the placebo group. Adverse side effects were not observed. CONCLUSION: According to the findings attained by this pilot study, bioresonance therapy is clinically effective in smoking cessation and does not show any adverse side effects.

Obstructive sleep apnea is common in patients with interstitial lung disease.

PURPOSE: The incidence of obstructive sleep apnea (OSA) in interstitial lung disease (ILD) has been reported at different frequencies in several studies. The aims of our study were to evaluate the frequency of OSA in ILD and to analyze the relationship between polysomnography (PSG) findings and pulmonary function, disease severity, parenchymal involvement, and Epworth Sleepiness Scale (ESS) scores. METHODS: ILD patients with parenchymal involvement were evaluated. The disease severity was assessed using an index consisting of body mass index (BMI), carbon monoxide diffusion capacity, the Modified Medical Research Council dyspnea scale, and the 6-min walking distance. All of the patients had lung function, chest X-ray, PSG, ESS scoring, and an upper airway examination. Patients with a BMI ≥ 30 or significant upper airway pathologies were excluded. RESULTS: Of 62 patients, 50 patients comprised the study group (14 male, 36 female; mean age 54 ± 12.35 years, mean BMI 25.9 ± 3.44 kg/m(2)) with diagnoses of idiopathic pulmonary fibrosis (IPF; n = 17), stage II-III sarcoidosis (n = 15), or scleroderma (n = 18). The frequency of OSA was 68 %. The mean apnea-hypopnea index (AHI) was 11.4 ± 12.5. OSA was more common in IPF patients (p = 0.009). The frequency of rapid eye movement-related sleep apnea was 52.9 %. The frequency of OSA was higher in patients with a disease severity index ≥3 (p = 0.04). The oxygen desaturation index and the AHI were higher in patients with diffuse radiological involvement (p = 0.007 and p = 0.043, respectively). CONCLUSIONS: OSA is common in ILD. PSG or at minimum nocturnal oximetry should be performed, particularly in patients with functionally and radiologically severe disease.