Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: A randomized controlled study.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. METHODS: This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). FINDINGS: Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. INTERPRETATION: IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.

Thyroid dysfunction in the wake of Omicron: understanding its role in COVID-19 severity and mortality.

Purpose: SARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase. Methods: This was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups. Results: A history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism. Conclusion: COVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19.

This prospective, randomized, controlled clinical trial assessed the therapeutic effects of major ozone autohemotherapy (O3-MAH) in patients with post-acute sequelae of COVID-19 (PASC). Seventy-three eligible participants were randomly assigned to an O3-MAH plus conventional therapy group (n = 35) or a conventional therapy alone group (n = 38). Symptom score, pulmonary function, 6-minute walk distance (6MWD), and hematological, biochemical, and immunological parameters were evaluated before and after the interventions. Both groups demonstrated improvements in various parameters post-intervention, but efficacy was greater in the O3-MAH group than the conventional treatment group; with intervention effectiveness defined as a ≥ 50 % reduction in symptom score, 25 of 35 patients (71 %) responded to O3-MAH, while 17/38 patients (45 %) responded to conventional treatment alone (P = 0.0325). Significant improvements in symptom scores (P = 0.0478), tidal volume (P = 0.0374), predicted 6MWD (P = 0.0032), and coagulation and inflammatory indicators were noted in the O3-MAH group compared with the conventional treatment group. O3-MAH was more likely to be effective in patients with elevated CRP levels. Furthermore, O3-MAH markedly improved cellular immunity, and this improvement became more pronounced with extended treatment duration. In summary, combining O3-MAH with conventional treatment was more effective than conventional therapy alone in improving symptoms, pulmonary function, inflammation, coagulation, and cellular immunity in patients with PASC. Further research is now warranted to validate these findings and individualize the regimen.

Bioluminescence-optogenetics-mediated gene therapy in a sleep-disordered breathing mouse model.

Obstructive sleep apnea (OSA) incurs a huge individual, societal, and economic burden. Specific and selective targeting of hypoglossal motor neurons could be an effective means to treat OSA. Bioluminescent-optogenetics (BL-OG) is a novel genetic regulatory approach in which luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels, increase neuronal excitability when exposed to a suitable substrate. Here we develop and validate the feasibility of BL-OG for sleep-disordered breathing (SDB). Upon confirming that diet-induced obese mice represent an excellent SDB model, we employed a method of targeting the hypoglossal nucleus (12 N) by peripherally injecting retrogradely transported rAAV2/Retro. With AAV transduction, the eLMO3 protein is expressed in hypoglossal motor neurons (HMN); administration of CTZ results in production of bioluminescence that in turn activates the tethered channelrhodopsin, leading to an increase in the firing of HMN and a 2.7 ± 0.8-fold increase in phasic activity of the genioglossus muscle, a 7.6 ± 1.8-fold increase in tonic activity, and improvements in hypoventilation and apnea index without impacting sleep structure. This is therefore the first study to leverage the rAAV2/Retro vector to execute the BL-OG approach in SDB, which amplified genioglossus muscle discharge activity and increased airflow in mice after activation. This study marks the pioneering utilization of BL-OG in SDB research.

Combination of acute intermittent hypoxia and intermittent transcutaneous electrical stimulation in obstructive sleep apnea: a randomized controlled crossover trial.

Intermittent hypoxia (IH) and intermittent transcutaneous electrical stimulation (ITES) might benefit patients with obstructive sleep apnea (OSA). However, the therapeutic value of combined IH and ITES in OSA is unknown. In this prospective, randomized, controlled crossover study, normoxia (air exposure for 50 min before sleep and sham stimulation for 6 h during sleep), IH (5 repeats of 5 min 10-12 % O2 alternating with 5 min air for 50 min, and sham stimulation for 6 h), ITES (air exposure for 50 min and 6 repeats of 30 min transcutaneous electrical stimulation alternating with 30 min of sham stimulation for 6 h), and IH&ITES (10-12 % O2 alternating with air for 50 min and transcutaneous electrical stimulation alternating with sham stimulation for 6 h) were administered to patients with OSA over four single-night sessions. The primary endpoint was difference in OSA severity between the interventions according to apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). The efficacy was response to IH, ITES, IH&ITES defined as a ≥50 % reduction in AHI compared with normoxia. Twenty participants (17 male, 3 female) completed the trial. The median (IQR) AHI decreased from 14.5 (10.8, 17.5) events/h with normoxia to 6.9 (3.9, 14.8) events/h with IH (p=0.020), 5.7 (3.4, 9.1) events/h with ITES (p=0.001), and 3.5 (1.8, 6.4) events/h with IH&ITES (p=0.001). AHI was significantly different between IH and IH&ITES (p=0.042) but not between ITES and IH&ITES (p=0.850). For mild-moderate OSA (n=17), IH, ITES, and IH&ITES had a significant effect on AHI (p=0.013, p=0.001, p=0.001, respectively) compared with normoxia, but there were no differences in post hoc pairwise comparisons between intervention groups. No serious adverse events were observed. In conclusion, IH, ITES, and IH&ITES significantly reduced OSA severity. IH&ITES showed better efficacy in mild-moderate OSA than IH and was comparable to ITES. Our data do not support recommending IH&ITES over ITES for OSA.

Physiological Effects and Tolerance of Wearing Surgical and N95 Masks during Sleep in Normal Individuals and Patients with Mild-Moderate Obstructive Sleep Apnea: A Randomized Crossover Trial.

BACKGROUND: In certain situations, masks are worn during sleep to prevent respiratory infections. However, the effects of mask wearing on cardiopulmonary function during sleep are unknown. This study aimed to determine whether wearing masks during sleep has an impact on cardiopulmonary function, including in patients with obstructive sleep apnea. METHODS: This was a prospective, randomized crossover-controlled trial. The effects of wearing surgical masks or N95 respirators on cardiopulmonary function were measured in healthy subjects and patients with mild-moderate obstructive sleep apnea. Sleep breathing parameters were monitored during nocturnal sleep using a sleep monitor, and subjective feelings about mask wearing were assessed using a questionnaire. RESULTS: Wearing masks during sleep at night did not significantly impact sleep breathing parameters. Furthermore, there were no significant differences in heart rate, blood oxygenation, and blood pressure before and after wearing masks. However, wearing masks wearing, especially the N95 mask, had an adverse impact on sleep quality, and masks were found to be subjectively uncomfortable. CONCLUSION: Wearing masks during sleep at night does not adversely affect cardiopulmonary function but they can be uncomfortable, especially the N95 mask. Thus, in circumstances where wearing N95 masks during nocturnal sleep proves intolerable, we recommend the use of surgical masks as a more comfortable alternative.

Comparison of the clinical characteristics in parents and their children in a series of family clustered Mycoplasma pneumoniae infections.

BACKGROUND: Mycoplasma pneumoniae infections have increased in China recently, causing some evidence of familial clustering. The purpose of this study was to compare the clinical features of parents and children in cases of familial clustering of Mycoplasma pneumoniae infection. METHODS: A retrospective analysis was performed on the cases of familial clustering of Mycoplasma pneumoniae infection, and the clinical characteristics of parents and children were compared. RESULTS: We identified 63 families, of these, 57 (65.5%) adults and 65 (94.2%) children required hospitalization. Fifty-seven adults (mean age 35.1 ± 4.6 years, 80.7% female) and 55 children (mean age 6.3 ± 3.9 years, 54.5% female) were included in the analysis. The incidence of mycoplasma infection in adults had increased gradually over the past year, while the rate in children had spiked sharply since June 2023. The clinical symptoms were similar in the two groups, mainly fever and cough. The peak temperature of children was higher than that of adults (39.1 ± 0.7℃ vs 38.6 ± 0.7℃, p = 0.004). Elevated lactate dehydrogenase was more common in children than in adults (77.8% vs 11.3%, p < 0.001). Bronchial pneumonia and bilateral involvement were more common in children, while adults usually had unilateral involvement. Three (60%) adults and 21 (52.5%) children were macrolide-resistant Mycoplasma pneumoniae infected. Children were more likely to be co-infected (65.5% vs 22.8%, p < .001). Macrolides were used in most children and quinolones were used in most adults. Ten (18.2%) children were diagnosed with severe Mycoplasma pneumoniae pneumonia, whereas all adults had mild disease. Children had a significantly longer fever duration than adults ((5.6 ± 2.2) days vs (4.1 ± 2.2) days, p = 0.002). No patient required mechanical ventilation or died. CONCLUSIONS: Mycoplasma pneumoniae infection shows a familial clustering epidemic trend at the turn of summer and autumn, with different clinical characteristics between parents and children.

An open-label randomized controlled trial of leflunomide in patients with acute SARS-CoV-2 omicron variant infection.

Objective: To evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19. Methods: A single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone. The primary endpoint was time to sustained clinical recovery. Results: Fifty-seven participants were randomized into two groups: 27 received leflunomide plus symptomatic treatment and 30 were assigned to symptomatic treatment alone. Participants treated with leflunomide had a shorter fever duration [3.0 interquartile range (IQR, 2.0-4.0) days and 4.0 (IQR, 3.0-6.0) days, respectively (p = 0.027)] and reduced viral shedding [7 (IQR, 6-9.5) days and 9.0 (IQR, 7.5-12.0) days, respectively (p = 0.044)] compared with individuals treated with symptomatic treatment alone. However, there were no significant differences in time to sustained clinical recovery between the two groups [hazard ratio, 1.329 (95% confidence interval, 0.878-2.529); p = 0.207]. Conclusion: In acute adult COVID-19 patients presenting within 5 days of symptom onset, leflunomide combined with symptomatic treatment reduced fever duration and viral shedding time. Clinical Trial Registration: https://www.chictr.org.cn/about.html, ChiCTR2100051684.

A randomized controlled crossover trial of acute intermittent and continuous hypoxia exposure in mild-moderate obstructive sleep apnea: A feasibility study.

In a prospective, randomized, controlled crossover study, we explored the effects of acute intermittent hypoxia and acute continuous hypoxia on patients with mild-moderate obstructive sleep apnea. Over three single-night sessions, subjects were alternately exposed to normoxia, acute continuous hypoxia and acute intermittent hypoxia before sleep. The apnea-hypopnea index and oxygen desaturation index were used to diagnose obstructive sleep apnea and evaluate efficacy. A responder was defined as a participant with a ≥ 50% reduction in apnea-hypopnea index between normoxia and hypoxia exposure. Sixteen participants with mild-moderate obstructive sleep apnea completed the study. Compared with normoxia, the mean apnea-hypopnea index decreased by 8.9 events per hr (95% confidence interval, 4.2-13.6, p = 0.001) with acute intermittent hypoxia and by 4.1 events per hr (95% confidence interval, 0.5-8.8, p = 0.082) with acute continuous hypoxia, equating to a mean decrease in apnea-hypopnea index of 4.8 events per hr (95% confidence interval, 0.1-9.5, p = 0.046) with acute intermittent hypoxia compared with acute continuous hypoxia. Compared with normoxia, the mean oxygen desaturation index decreased by 9.8 events per hr (95% confidence interval, 4.4-15.1, p = 0.001) with acute intermittent hypoxia but did not significantly decrease with acute continuous hypoxia; the mean oxygen desaturation index decreased by 7.2 events per hr (95% confidence interval, 1.8-12.6, p = 0.010) with acute intermittent hypoxia compared with acute continuous hypoxia. Of the 16 participants, 11 responded to acute intermittent hypoxia and four responded to acute continuous hypoxia (p = 0.032), of whom eight of 11 cases and all four cases had oxygen desaturation indexes <5 events per hr, respectively (p = 0.273). All participants tolerated acute intermittent hypoxia and there were no obvious adverse events during acute intermittent hypoxia exposure. In conclusion, acute intermittent hypoxia exposure improved apnea-hypopnea index and oxygen desaturation index in patients with mild-moderate obstructive sleep apnea, suggesting that further prospective validation of intermittent hypoxia exposure in patients with obstructive sleep apnea is needed to establish its clinical feasibility as a therapeutic modality.

Effect of obstructive sleep apnea on semen quality.

BACKGROUND: Obstructive sleep apnea (OSA) has several notable complications such as hypertension and diabetes. Studies have also shown that OSA is associated with erectile dysfunction and reduced androgen levels. However, the effect of OSA on semen quality remains poorly studied. METHODS: Men attending a tertiary reproductive center for semen analysis were tested with a portable sleep breathing monitor. Patients were divided into four groups based on their apnea hypopnea index: none, mild, moderate, and severe obstructive sleep apnea. Differences between groups were assessed using χ2, and associations were tested with multiple regression analysis. RESULTS: We included a total of 175 male subjects with a mean age of 32.2 ± 3.6 years. There were significant differences between groups in progressive sperm motility (%) (43 ± 16, 42 ± 17, 36 ± 18, 29 ± 18, respectively; p = 0.002), total motility (%) (59 ± 19, 59 ± 20, 49 ± 21, 42 ± 20, respectively; p = 0.010), and vitality (%) (80 ± 10, 81 ± 11, 79 ± 8, 72 ± 19, respectively; p = 0.039). Asthenospermia (progressive motility < 35%) was significantly more common in subjects with OSA (χ2 = 5.195, p = 0.023). In multiple regression models, after adjusting for age and body mass index, apnea hypopnea index remained negatively and significantly associated with progressive motility, total motility, and vitality. CONCLUSIONS: OSA is an independent risk factor for sperm motility and vitality, and further investigation is now needed to determine if continuous positive pressure ventilation or other therapies can improve semen quality in these patients.

Randomised, controlled crossover trial of intermittent and continuous transcutaneous electrical stimulation of the genioglossus muscle for obstructive sleep apnoea.

PURPOSE: Continuous transcutaneous electrical stimulation (CTES) of the genioglossus muscle may benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of intermittent transcutaneous electrical stimulation (ITES) for OSA is unclear. METHODS: This was a randomised, controlled, crossover study to compare the effects of ITES and CTES of the genioglossus muscle. Over three single-night sessions, participants were alternately subjected to three genioglossus stimulation modalities during sleep (sham, CTES and ITES). The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) were used for OSA diagnosis and to evaluate efficacy. A responder was defined as an individual with a ≥50% reduction in AHI together with <10 AHI events per hour and/or an ODI reduction of ≥25% between sham stimulation and electrical stimulation nights. RESULTS: Fifteen men with OSA completed the study. Compared with sham, the median AHI with ITES decreased by 13.3 events/hour (95% CI 3.1 to 23.5, p=0.030) and by 7.3 events/hour (95% CI -3.9 to 18.5, p=0.825) with CTES. The median ODI was reduced by 9.25 events/hour (95% CI 0.5 to 18.0) with ITES and 3.3 events/hour (95% CI -5.6 to 12.2) with CTES; however, there was no significant difference between groups. Furthermore, ITES outperformed CTES with respect to longest apnoea duration (median (95% CI), 9.5 (0.0 to 19.0), p=0.011)) and the highest sleep efficiency (12.2 (2.7 to 21.7), p=0.009). Of the 15 participants, 8 responded to ITES and 3 responded to CTES (p=0.058), of whom all eight cases and two out of three cases had ODIs <5 events/hour, respectively. All participants tolerated ITES well. CONCLUSIONS: ITES improved upper airway obstruction in patients with OSA, suggesting that further prospective validation of the intermittent approach is warranted. TRIAL REGISTRATION NUMBER: ChiCTR2100050138.

Primary pulmonary nuclear protein of the testis midline carcinoma: case report and systematic review with pooled analysis.

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC.

Combined noradrenergic plus antimuscarinic agents for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Currently, no pharmacotherapy is routinely used for obstructive sleep apnea (OSA). Recently, combined noradrenergic plus antimuscarinic agents have been evaluated for the treatment of OSA in several trials. This systematic review and meta-analysis following PRISMA guidelines investigated the efficacy and safety of this combination drug regimen for the treatment of OSA. Seven databases were systematically screened for randomized controlled trials (RCTs) studying combined noradrenergic plus antimuscarinic agents for OSA to April 2022. Nine RCTs were identified for systematic review and five for meta-analysis. There were significant differences between OSA patients taking noradrenergic plus antimuscarinic agents and placebo with respect to sleep apnea-hypopnea index [mean difference (MD) -11.27 events/h, 95%CI (-21.69, -0.84) events/h; P = 0.03]; nadir oxygen saturation [MD 5.06%, 95% CI (2.57, 7.55)%; P < 0.0001], and arousal index [MD -8.17 events/h, 95% CI (-15.01, -1.33) events/h; P = 0.02] but not sleep efficiency. Our systematic review revealed that drug therapy modestly improved loop gain and upper airway collapsibility but decreased arousal threshold. A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on one night significantly reduced OSA severity and improved OSA upper airway function. The long-term efficacy and safety of drug combinations in OSA patients now require further study.

The Discovery, Validation, and Function of Hypoxia-Related Gene Biomarkers for Obstructive Sleep Apnea.

While there is emerging evidence that hypoxia critically contributes to the pathobiology of obstructive sleep apnea (OSA), the diagnostic value of measuring hypoxia or its surrogates in OSA remains unclear. Here we investigated the diagnostic value of hypoxia-related genes and explored their potential molecular mechanisms of action in OSA. Expression data from OSA and control subjects were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between OSA and control subjects were identified using the limma R package and their biological functions investigated with the clusterProfiler R package. Hypoxia-related DEGs in OSA were obtained by overlapping DEGs with hypoxia-related genes. The diagnostic value of hypoxia-related DEGs in OSA was evaluated by receiver operating curve (ROC) analysis. Random forest (RF) and lasso machine learning algorithms were used to construct diagnostic models to distinguish OSA from control. Geneset enrichment analysis (GSEA) was performed to explore pathways related to key hypoxia-related genes in OSA. Sixty-three genes associated with hypoxia, transcriptional regulation, and inflammation were identified as differentially expressed between OSA and control samples. By intersecting these with known hypoxia-related genes, 17 hypoxia-related DEGs related to OSA were identified. Protein-protein interaction network analysis showed that 16 hypoxia-related genes interacted, and their diagnostic value was further explored. The 16 hypoxia-related genes accurately predicted OSA with AUCs >0.7. A lasso model constructed using AREG, ATF3, ZFP36, and DUSP1 had a better performance and accuracy in classifying OSA and control samples compared with an RF model as assessed by multiple metrics. Moreover, GSEA revealed that AREG, ATF3, ZFP36, and DUSP1 may regulate OSA via inflammation and contribute to OSA-related cancer risk. Here we constructed a reliable diagnostic model for OSA based on hypoxia-related genes. Furthermore, these transcriptional changes may contribute to the etiology, pathogenesis, and sequelae of OSA.

The influence of acute morphine use on obstructive sleep apnea: A systematic review and meta-analysis.

The present study was conducted to systematically evaluate the acute effect of morphine on obstructive sleep apnea (OSA). The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure (CNKI), and Wan-Fang databases were searched for randomised controlled trials studying the influence of morphine on OSA published up to May 24, 2021. The Cochrane risk of bias tool was used to assess study quality and meta-analysis was performed on the included clinical trial results to quantify the impact of morphine on various sleep and respiratory parameters. Three studies (n = 132 patients) were ultimately examined. There were no significant differences between patients with OSA taking morphine and placebo/non-opioids with respect to the sleep Apnea-Hypopnea Index (mean difference [MD] 1.78, 95% confidence interval [CI] -2.41, 5.98; p > 0.05); Oxygen Desaturation Index (MD 1.49, 95% CI -3.21, 6.19; p > 0.05); Obstructive Sleep Apnea Index (MD 0.83, 95% CI -2.08, 3.75; p > 0.05); Hypopnea Index (MD -0.01, 95% CI -2.64, 2.63; p > 0.05); lowest oxygen saturation (MD 0.68, 95% CI -4.50, 5.86; p > 0.05); or sleep oxygen saturation >90% (MD 0.10, 95% CI -1.14, 1.34; p > 0.05). In conclusion, a single dose of 30 or 40 mg morphine does not have a significant effect on sleep or respiratory outcomes compared to placebo in patients with OSA, challenging the orthodoxy that opioids worsen OSA.