Nocturnal Hypoxemia Research Articles

Central Sleep Apnea and Cardiovascular Disease State-of-the-Art.

Central sleep apnea (CSA), a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke and use of certain cardiac-related medications. Polysomnographic findings of CSA with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, CSA is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose dependent relationship between nocturnal desaturation and mortality. Multiple small randomized controlled trials have shown mitigation of sympathetic activity when CSA is treated with nocturnal oxygen, continuous positive airway pressure and adaptive servoventilation. However, two early randomized controlled trials with positive airway pressure devices have shown either neutral effect on survival or excess premature mortality in the active treatment arm, compared to untreated CSA. In contrast, the results of the most recent trial using an advanced adaptive servoventilation device showed improved quality of life and no signal for mortality suggesting that treatment of CSA was at least safe. In addition to positive airway pressure devices, multiple medications have been shown to improve CSA, but no long-term trials of pharmacologic therapy have been published. Currently, phrenic nerve stimulation is approved for treatment of CSA, and the results of a randomized controlled trial showed significant improvement in sleep metrics and quality of life.

The Effects of Nocturnal Hypoxemia on Cognitive Performance in Andean Highlanders.

Background: Many Andean highlanders exposed to chronic hypoxemia are susceptible to excessive erythrocytosis (EE) and chronic mountain sickness (CMS). Nocturnal hypoxemia is more marked than diurnal hypoxemia and includes sustained and intermittent components. The potential for cognitive impairments related to nocturnal hypoxemia in this population has not been extensively studied, but improved understanding may provide opportunities for the prevention of long-term effects of EE and CMS. Methods: To examine this relationship, 48 participants residing permanently at 4,340 m completed an overnight sleep study and a battery of cognitive function tests that examined a broad range of cognitive domains. Results: Greater nocturnal hypoxemia was associated with longer reaction times on Balloon Analogue Risk Task (BART) (p < 0.01) and Emotion Recognition Test (ERT) (p < 0.01). Longer completion times of Trail Making Task were also associated with increased nocturnal hypoxemia (p = 0.03). Increased hematocrit was similarly associated with longer reaction times on the ERT (p = 0.01) and the BART (p = 0.01). Conclusion: Overall, our results showed that increased nocturnal hypoxemia and higher hematocrit were associated with impairments in cognitive performance in individuals residing permanently at high altitude.

Exploring phenotypes to improve long-term mortality risk stratification in obstructive sleep apnea through a machine learning approach: an observational cohort study.

Obstructive sleep apnea (OSA) is a heterogeneous sleep disorder for which the identification of phenotypes might help for risk stratification for long-term mortality. Thus, the aim of the study was to identify distinct phenotypes of OSA and to study the association of phenotypes features with long-term mortality by using machine learning. This retrospective study included patients diagnosed with OSA who completed a 15-year follow-up and were adherent to continuous positive airway pressure (CPAP) therapy. Multidimensional data were collected at baseline and were used to identify OSA phenotypes using the hierarchical approach. Associations between phenotypic features and long-term mortality were assessed using supervised analysis. A total of 402 patients, predominantly male (70 %), were included. Clustering analysis identified three distinct phenotypes: Cluster 1 (middle-aged, severely obese, very severe OSA with nocturnal hypoxemia), Cluster 2 (young, overweight, moderate OSA with limited nocturnal hypoxemia), and Cluster 3 (elderly, obese, multimorbid, severe OSA with nocturnal hypoxemia). Mortality was significantly higher in Clusters 1 and 3 (p < 0.001). Supervised methods identified eight main features of these clusters, among which nocturnal hypoxemia was found to be the main risk factor for mortality even after confounding factors-adjustment (hazard ratio 2.63, 95 % confidence interval 1.09-6.36, p = 0.032). This study demonstrated the interest of attributing OSA patients to distinct phenotypes including precise determination of nocturnal hypoxemia to improve mortality risk stratification.

A Single Night in Hypoxia Either with or without Ketone Ester Ingestion Reduces Sleep Quality Without Impacting Next Day Exercise Performance.

Sleeping at altitude is highly common in athletes as an integral part of altitude training camps or sport competitions. However, concerns have been raised due to expected negative effects on sleep quality, thereby potentially hampering exercise recovery and next-day exercise performance. We recently showed that ketone ester (KE) ingestion beneficially impacted sleep following strenuous, late evening exercise in normoxia, and alleviated hypoxemia. Therefore, we hypothesized that KE ingestion may be an effective strategy to attenuate hypox(em)ia-induced sleep dysregulations. Eleven healthy, male participants completed three experimental sessions including normoxic training and subsequent sleep in normoxia or at a simulated altitude of 3,000 m while receiving either KE or placebo post-exercise and pre-sleep. Sleep was evaluated using polysomnography, while next-day exercise performance was assessed through a 30-min all-out time trial (TT30'). Physiological measurements included oxygen status, heart rate variability, ventilatory parameters, blood acid-base balance and capillary blood gases. Hypoxia caused a ~3% drop in sleep efficiency, established through a doubled wakefulness after sleep onset and a ~22% reduction in slow wave sleep. KE ingestion alleviated the gradual drop in SpO2 throughout the first part of the night, but did not alter hypoxia-induced sleep dysregulations. Neither KE, nor nocturnal hypoxia affected TT30' performance, but nocturnal hypoxia hampered heart rate recovery following TT30'. We observed that sleeping at 3,000 m altitude impairs sleep efficiency. Although this hypoxia-induced sleep disruption was too subtle to limit exercise performance, we for the first time indicate that sleeping at altitude might impair next-day exercise recovery. KE alleviated nocturnal hypoxemia only when SpO2 values dropped below ~85%, but this did not translate into improved sleep or next-day exercise performance.

Obstructive sleep apnea in patients with fibrotic interstitial lung disease (non-idiopathic pulmonary fibrosis): what should be offered?

The frequency of obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is high. The clinical course of non-IPF interstitial lung disease (ILD) can be similar to that of IPF. We sought to assess the frequency and predictors of OSA in patients with non-IPF fibrotic ILD, as well as the impact of positive airway pressure (PAP) therapy on the quality of life of such patients. This was a prospective study in which non-IPF fibrotic ILD patients underwent a home sleep apnea test. The patients with and without OSA were compared, and a multivariate logistic regression model was used to identify independent predictors of OSA. At 3 months after initiation of PAP therapy, we evaluated the participating patients for respiratory events, nocturnal hypoxemia, and changes in quality of life. Of a total of 50 patients, 50% were male, and 76% were diagnosed with OSA. The mean age was 67.8 ± 8.3 years. The patients with OSA had significantly lower TLC (p = 0.033) and awake SpO2 (p = 0.023) than did those without OSA. In the multivariate logistic regression model, SpO2 (OR = 0.46; p = 0.016) and TLC (OR = 0.95; p = 0.026) remained significantly associated with OSA risk. A total of 12 patients received PAP therapy. At 3 months after initiation of PAP therapy, 91.7% were well controlled, Epworth Sleepiness Scale scores decreased significantly (p = 0.006), and emotional well-being tended to improve (p = 0.068). PAP therapy corrected nocturnal hypoxemia in all patients. We found a high frequency of OSA in patients with non-IPF fibrotic ILD. A low TLC was an independent predictor of a higher risk of OSA. PAP therapy can correct nocturnal hypoxemia. There should be a low threshold for suspicion of OSA and initiation of PAP therapy in patients with non-IPF fibrotic ILD.

Obstructive sleep apnoea and lung function, and their association with nocturnal hypoxemia: results from the Swedish CArdioPulmonary bioimage Study (SCAPIS) – a cross-sectional study

Obstructive sleep apnoea (OSA) and its associations with lung function.BackgroundOSA is highly prevalent and characterised by abnormal respiration during sleep. This large, population-based study aimed to investigate the associations between OSA and lung function in subjects aged 50–64 years.MethodThe population-based Swedish CArdioPulmonary bioimage Study includes information on anthropometry, comorbidities and spirometry. The current analysis included data from three centres (Gothenburg, Umeå and Uppsala) on whole-night respiratory polygraphy as a meta-analysis examining the overall effect size of lung function on sleep apnoea severity, expressed as ß-coefficient after stratifying for sex and adjusting for age, waist circumference and smoking status.ResultsData from9016participants (54%women, age58±4 years, body mass index27±4 kg/m2) with sleep recordings of good quality were included in the final analysis. Forced expiratory volume during1 s(FEV1) (ß=−0.10 (95% CI −0.16 to −0.03)),forced vital capacity(FVC) (−0.15 (−0.21 to −0.10)) anddiffusion capacity for carbon monoxide(DLCO) (−0.08 (−0.10 to −0.05)) were all negatively associated with theoxygen desaturation index(ODI) and also with per cent of registration with nocturnal oxygen saturation&lt;90% FVC(−0.44 (−0.87 to −0.01)), FEV1(−0.86 (−1.36 to −0.36)) and DLCO(−0.47 (−0.60 to −0.35)). Additionally, a positive association was observed between FEV1(0.13 (0.05 to 0.22)) and DLCO(0.07 (0.04 to 0.09)) with the mean nocturnal saturation. There was a negative association between DLCOandapnoea-hypopnoea index, AHI, (ß=−0.04 (95% CI−0.06 to −0.03)), while no associations were found between FEV1or FVC and AHI.ConclusionIn OSA, lower lung function is more distinctly associated with the nocturnal hypoxic burden than AHI. Potential lung function impairment should be investigated in OSA patients with a high ODI relative to AHI.

The Impact of Lung Function on Sleep Monitoring in Obstructive Sleep Apnea Associated with Obstructive Lung Diseases: Insights from a Clinical Study.

Background/Objectives: Obstructive sleep apnea (OSA) and obstructive lung diseases (OLD) are common and interdependent respiratory disorders, where one condition may contribute to the development and worsening of the other (OLDOSA syndrome). The term OLDOSA syndrome includes two different conditions: Overlap syndrome (OVS: OSA + chronic obstructive pulmonary disease, COPD) and Alternative Overlap syndrome (aOVS: OSA + Asthma). Data on the interactions between lung function and respiratory monitoring during sleep in OLDOSA patients are few and controversial. Our study aims to evaluate the impact of lung function impairment on sleep breathing disorders, paying attention to the lack of literature about comparisons between OVS, aOVS, and the impact of small airways disease (SAD) in these patients. Methods: In total, 101 patients with a diagnosis of OSA and asthma or COPD underwent pulmonary function tests (PFTs) and nocturnal home sleep cardiorespiratory monitoring (HSCM). Exclusion criteria: Obesity hypoventilation syndrome (OHS) and other non-respiratory sleep disorders. Results: Sleep time with oxygen saturation below 90% (T90) was negatively correlated with forced expiratory volume in the first second, % of predicted (%FEV1), forced vital capacity, % of predicted (%FVC), forced expiratory flow at 25-75% of the pulmonary volume, % of predicted (%FEF25-75), and, after multivariable linear regression analysis, %FEF25-75 remained an independent factor for T90 with a negative correlation in mild and moderate OSA. Obstructive apnea index (oAI) and FEV1/FVC were negatively correlated in mild and moderate OSA. OVS presented with more severe OSA (higher AHI, oAI, and T90) and SAD (lower FEF25-75) compared to aOVS. Conclusions: This study highlights a possible interdependence between OLD and OSA; obstruction of the large and small airways at PFTs contributes to the worsening of these patients' nocturnal hypoxemia and obstructive events of the upper airway during sleep. Furthermore, this study shows that patients with OVS should be carefully monitored, as they present worse data at HSCM and have greater small airways involvement compared to aOVS.

Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via CA1 hippocampal volume loss.

Obstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia. Older adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index-3% (REM-ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high-resolution hippocampus T2 scans. We determined whether the relationship between REM-ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non-REM sleep to determine whether the effects were REM-specific. Although there was not a direct effect of REM-ODI on verbal learning (p > 0.05) or memory (p > 0.05), mediation analyses showed a significant indirect effect of high REM-ODI on poorer verbal learning (β = -0.09, 95% confidence interval [CI] = -0.238 to -0.005) and memory (β = -0.100, 95% CI = -0.255 to -0.005), which was mediated by CA1 volume. These associations were absent in non-REM sleep (p > 0.05). Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.

Impact of sleep disturbance on longitudinal cognitive performance in patients with transient ischemic attack or mild stroke

IntroductionSleep disturbances including obstructive sleep apnea (OSA) and poor sleep quality are common after stroke, while its association with cognitive changes following transient ischemic attack (TIA) or mild stroke remains unclear. We aim to determine whether sleep duration, OSA parameters, or nocturnal hypoxemia is associated with a greater cognitive decline after stroke. MethodsWe prospectively followed-up patients with acute TIA/mild stroke [National Institute Health Stroke Scale (NIHSS) < 7] who underwent baseline sleep questionnaire [Pittsburgh Sleep Quality Index (PSQI)], and serial cognitive assessments [Montreal Cognitive Assessment (MoCA) 5-min, Stroop Test] at baseline and one-year. We also evaluated apnea-hypopnea index (AHI) and nocturnal hypoxemia by Home Sleep Apnea Test (HSAT) at one-year. Primary outcome was one-year change in MoCA 5-min score. ResultsOne hundred and five patients with TIA/mild stroke (mean age 63 years, 65 % male) were included. Baseline short sleep (< 6 hour/night) and AHI ≥ 20/hour at one-year were independently associated with a decline in the MoCA 5-min total score after covariates adjustment [short sleep: β = −2.36 95 % confidence interval (CI) (−4.13, −0.59), p = 0.009; AHI ≥ 20/hour: β = −1.79 (−3.26, −0.32), p = 0.017; remained significant after multiple comparisons correction]. A lower mean MinSpO2 was associated with a decline in executive function [Stroop interference index: β = 0.29 (0.04, 0.53), p = 0.021], but not with MoCA 5-min score at one-year. Moderation analysis indicated AHI ≥ 20/hour was associated with a pronounced decline in executive function only in men. ConclusionsShort sleep after stroke onset, AHI ≥ 20/hour and nocturnal hypoxemia at one-year contributed to an impaired cognitive trajectory at one-year following stroke in patients with TIA/mild stroke.

Images in sleep medicine sleep-disordered breathing in Wolfram's syndrome - A near-fatal event

Wolfram syndrome (WS) is a rare autosomal-recessive genetic disorder. The authors report a case of a patient with WS and undiagnosed/untreated obstructive sleep apnea (OSA) associated with prolonged periods of apnea and hypopnea and nocturnal hypoxemia, which may have predisposed him to the development of a near-fatal event during sleep. Addressing sleep-disordered breathing in patients with WS could improve their quality of life and potentially their longevity.

Associations between obstructive sleep apnea and sleep characteristics with chronic kidney disease in rural Pennsylvania

Study objectivesTo examine the association between moderate-severe obstructive sleep apnea (msOSA) and sleep characteristics with chronic kidney disease (CKD) in a population of rural and urban adults in Pennsylvania. MethodsA cross-sectional study of 23,643 adults who underwent polysomnography (PSG) at a rural healthcare system in Pennsylvania between 2009 and 2019. Serum creatinine was abstracted from electronic health records to calculate estimated glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 mL/min/1.73 m2. msOSA was defined as an apnea-hypoxia index (AHI) ≥15 events/hour. Poisson regression was performed to estimate the prevalence ratio (PR) of CKD for various sleep measures while adjusting for age, sex, race, smoking (never, former, current), body mass index, diabetes, and hypertension at time of PSG. ResultsIn this clinically-referred sample comprised of over one-third (35 %) rural individuals, the prevalence of CKD and msOSA was 9.4 % and 32.1 %, respectively. Patients with CKD had more severe OSA based on AHI and intermittent hypoxia profile and presented worse sleep quality across all studied measures. Having OSA was associated with a 13 % higher prevalence of CKD (95%CI: 1.04, 1.22). In addition, for every 5 % increment in sleep efficiency, the prevalence of CKD was 3 % lower (PR = 0.97, 95%CI: 0.96, 0.98). Significant associations that were in the expected direction were observed across most sleep characteristics in adjusted models. ConclusionsModerate-severe OSA, nocturnal hypoxemia, and disruptions to normal sleep duration, continuity, and architecture are associated with increased CKD prevalence in Pennsylvania adults. Management of OSA and/or sleep disturbances may be an opportunity to improve CKD outcomes. The unique health disparities among vulnerable rural populations are deserving of future study.

Randomized crossover trial of a demand oxygen delivery system in nocturnal hypoxemia

The newly developed portable oxygen concentrator with an auto-demand oxygen delivery system (auto-DODS) automatically switches between 3 sensitivities according to the negative pressure gradient of inhalation and supplies oxygen only during inhalation. The aim of this study was to verify the effectiveness and safety of auto-demand devices compared with a continuous flow oxygen concentrator, during sleep, in a randomized crossover noninferiority trial. We alternatively used an auto-DODS or a continuous-flow oxygen concentrator, all night on separate days for HOT (Home Oxygen Therapy) patients with nocturnal hypoxemic symptoms. The primary endpoints were the mean value of oxygen saturation (SpO2) over the total sleep time. The secondary endpoints included the efficacy endpoints and the safety endpoints. Regarding the primary endpoint, the difference in SpO2 between the auto-DODS and continuous flow was 0.835%. Since the upper limit of this difference did not exceed 2.8, which was set as the noninferiority margin, it was shown that the auto-DODS did not reduce SpO2 by at least 2.8% on average compared to continuous flow. No equipment failure or exacerbation of disease was observed, confirming the safety of the auto-DODS during the night.

Nocturnal Hypoxemia Is Associated with Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e., sarcopenia) in invitro models of COPD. Objectives: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in patients with COPD. Methods: Sleep studies from patients with COPD (n = 479) and control subjects without COPD (n = 275) were analyzed. Patients with obstructive sleep apnea, as defined by apnea-hypopnea index ⩾ 5, were excluded. Pectoralis muscle cross-sectional area (PMcsa) was quantified using computed tomography scans performed within 1 year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of control subjects, which was adjusted for age and body mass index (BMI) and stratified by sex. Youden's optimal cut-point criteria were used to predict sarcopenia based on mean oxygen saturation during sleep. Additional measures of nocturnal hypoxemia were analyzed. The pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. Results: On average, males with COPD had a 16.6% lower PMI than control males (1.41 ± 0.44 vs. 1.69 ± 0.56 cm2/BMI; P < 0.001), whereas females with COPD had a 9.4% lower PMI than control females (0.96 ± 0.27 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). Males with COPD with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33 ± 0.39 vs. 1.47 ± 0.46 cm2/BMI; P < 0.05) and a 23.6% decrease compared with control subjects (1.33 ± 0.39 vs. 1.74 ± 0.56 cm2/BMI; P < 0.001). Females with COPD with nocturnal hypoxemia had an 11.2% decrease versus COPD with normal O2 (0.87 ± 0.26 vs. 0.98 ± 0.28 cm2/BMI; P < 0.05) and a 17.9% decrease compared with control subjects (0.87 ± 0.26 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. Conclusions: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that patients with COPD have a lower PMI than patients without COPD and that nocturnal hypoxemia was associated with an additional decrease in the PMI of patients with COPD. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD.

Brain-Derived Neurotrophic Factor in the Acute and Early Recovery Period of Ischemic Stroke: The Role of Nocturnal Hypoxemia

Brain-Derived Neurotrophic Factor in the Acute and Early Recovery Period of Ischemic Stroke: The Role of Nocturnal Hypoxemia

Expanding TBCE-related phenotype-novel variant causing rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia.

We report three patients with the novel variant c.100 + 1G > A of the TBCE gene and describe the presented clinical phenotype in detail. We also systematically reviewed the literature for clinical similarities and dissimilarities among all known patients with pathogenic TBCE variants. The clinical phenotype observed in patients with pathogenic TBCE variants is broader than previously described. Homozygous carriers of the c.100 + 1G > A variant exhibit a markedly milder clinical course, with no deviations in the calcium-phosphate metabolism and central nervous system pathology in MRI studies. Additionally, two patients manifest highly specific symptoms such as a rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia. Furthermore, cryptorchidism was observed in male patients. The identification of the pathogenic c.100 + 1G > A variant has thus far been limited to patients of Central-Eastern European descent, suggesting a potential founder mutation in this population.

Gefapixant as a P2X3 receptor antagonist treatment for obstructive sleep apnea: a randomized controlled trial.

Obstructive sleep apnea (OSA) is a highly prevalent disorder with serious health consequences but limited therapeutic options. For a subset of those with OSA, a key underlying mechanism is hypersensitive chemoreflex control of breathing. There is no approved therapy that targets this endotypic trait. Here we determine whether the P2X3 receptor antagonist gefapixant, which is predicted to attenuate hypersensitive carotid chemoreflexes, reduces OSA severity in patients with chemoreflex-dependent OSA. In a randomized placebo-controlled crossover study, 24 patients with moderate-to-severe OSA (aged 39-68 years, non-continuous positive airway pressure users) whose disorder was partially responsive to supplemental oxygen (chemoreflex-dependent OSA) were treated with gefapixant 180 mg (or placebo) administered as tablets taken orally before bedtime for 7 days and assessed via overnight polysomnography. The primary analysis examined whether gefapixant treatment resulted in a greater reduction in the apnea-hypopnea index from baseline than placebo. Gefapixant did not lower the apnea-hypopnea index significantly more than placebo; the estimated ratio of the apnea-hypopnea index on gefapixant vs placebo was 0.92 (90% confidence interval: 0.73, 1.17). Notably, nocturnal hypoxemia was increased (ratio of total sleep time with saturated peripheral oxygen < 90% on gefapixant vs placebo = 2.08 [90% confidence interval: 1.53, 2.82]), consistent with reduced chemoreflex output. Commonly reported adverse events with gefapixant included ageusia, dysgeusia, oral hypoaesthesia, nausea, somnolence, and taste disorders. Gefapixant, while generally well tolerated, did not reduce OSA severity in patients with chemoreflex-dependent OSA. P2X3 receptor antagonism is unlikely to provide an avenue for therapeutic intervention in OSA. Registry: ClinicalTrials.gov; Name: Safety and Tolerability of Gefapixant (MK-7264) in Participants with Obstructive Sleep Apnea (MK-7264-039); URL: https://clinicaltrials.gov/study/NCT03882801; Identifier: NCT03882801. Robbins JA, Sands S, Maganti L, etal. Gefapixant as a P2X3 receptor antagonist treatment for obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2024;20(12):1905-1913.

Thoracic Society of Australia and New Zealand clinical practice guideline on adult home oxygen therapy.

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes

BackgroundMicro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D.MethodsThis cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non − specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease.ResultsPatients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non−specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD.ConclusionWhile hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.

Management of sleep-disordered breathing in patients with syndromic hemifacial macrosomia.

Patients with syndromic hemifacial microsomia (SHFM) are at risk of obstructive sleep apnea (OSA). The aim of the study was to describe the prevalence of OSA and its management, especially in patients with Goldenhar syndrome (GS). The respiratory polygraphies and clinical management of 15 patients, aged 2 to 23years, evaluated at a national reference center, were analyzed. Four (27%) patients had no OSA, 4 (27%) had mild OSA, and 7 (46%), of whom 5 were ≤ 2years old, had severe OSA. None of the patients had central apneas. Only one patient had alveolar hypoventilation, and another one had nocturnal hypoxemia. Two patients had severe OSA despite prior adenoidectomy or mandibular distraction osteogenesis. Median duration of follow-up was 3.5years (range 0.5-9years). None of the patients without OSA or with mild OSA at baseline respiratory polygraphy developed OSA during the follow up. Among the 7 patients with severe OSA, 3 required continuous positive airway pressure or noninvasive ventilation, and one patient required a tracheostomy. In conclusion, patients with SHFM are at high risk of severe OSA at any age, underlining the importance of systematic sleep studies to diagnose and evaluate the severity of OSA. Individualized treatment should be privileged, based on a careful examination of the entire upper airway, taking in account potential associated risk factors. All patients with SHFM should be managed by a pediatric expert multidisciplinary medical/surgical team until the end of post pubertal growth.

Effects of acetazolamide on sleep disordered breathing in pulmonary vascular disease: a randomised controlled trial.

Patients with pulmonary vascular disease (PVD) often suffer from nocturnal hypoxaemia, but also from sleep apnoea. Short-term use of acetazolamide increases ventilation due to metabolic acidosis and also reduces loop gain. We investigated whether prolonged use of acetazolamide improves sleep disordered breathing in PVD. In a randomised controlled crossover trial, patients with PVD were randomly assigned to acetazolamide 250 mg and placebo twice daily for 5 weeks. Patients underwent respiratory polygraphy at baseline and at the end of each intervention phase. Outcomes of interest were the effect of acetazolamide on mean nocturnal oxygen saturation (S pO2 ), time with oxygen saturation <90% (t <90), apnoea-hypopnoea index (AHI) and sleep apnoea severity. In 20 patients with PVD (55% women, nine with pulmonary arterial hypertension, 11 with distal chronic thromboembolic pulmonary hypertension; mean±sd nocturnal S pO2 88.8±3.5%, obstructive AHI 12.6±12.3 events·h-1), 5 weeks of acetazolamide resulted in a significant improvement in nocturnal oxygenation compared to placebo (mean nocturnal S pO2 +2.3% (95% CI 1.3-3.3%); p<0.001 and t <90 -18.8% (95% CI -29.6- -8.0%); p=0.001). Acetazolamide increased the proportion of patients with mean nocturnal S pO2 ≥90% from 45% to 85%. The percentage of patients with AHI >5 events·h-1 was reduced from 75% to 60% and with AHI >15 events·h-1 from 30% to 15%. Two patients discontinued the study because of mild side-effects. Acetazolamide given for 5 weeks reduces nocturnal hypoxaemia in PVD to a clinically relevant level and reduces the proportion of patients with obstructive sleep apnoea.