Mask side-effects are related to gender in long-term CPAP: results from the InterfaceVent real-life study.

BACKGROUND: Over the past three decades, our understanding of sleep apnea in women has advanced, revealing disparities in pathophysiology, diagnosis, and treatment compared to men. However, no real-life study to date has explored the relationship between mask-related side effects (MRSEs) and gender in the context of long-term CPAP. METHODS: The InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks, no gender specific mask series). MRSE were assessed by the patient using visual analog scales (VAS). CPAP-non-adherence was defined as a mean CPAP-usage of less than 4 h per day. The primary objective of this ancillary study was to investigate the impact of gender on the prevalence of MRSEs reported by the patient. Secondary analyses assessed the impact of MRSEs on CPAP-usage and CPAP-non-adherence depending on the gender. RESULTS: A total of 1484 patients treated for a median duration of 4.4 years (IQ25-75: 2.0-9.7) were included in the cohort, with women accounting for 27.8%. The prevalence of patient-reported mask injury, defined as a VAS score ≥ 5 (p = 0.021), was higher in women than in men (9.6% versus 5.3%). For nasal pillow masks, the median MRSE VAS score for dry mouth was higher in women (p = 0.039). For oronasal masks, the median MRSE VAS score for runny nose was higher in men (p = 0.039). Multivariable regression analyses revealed that, for both women and men, dry mouth was independently and negatively associated with CPAP-usage, and positively associated with CPAP-non-adherence. CONCLUSION: In real-life patients treated with long-term CPAP, there are gender differences in patient reported MRSEs. In the context of personalized medicine, these results suggest that the design of future masks should consider these gender differences if masks specifically for women are developed. However, only dry mouth, a side effect not related to mask design, impacts CPAP-usage and non-adherence. TRIAL REGISTRATION: INTERFACEVENT IS REGISTERED WITH CLINICALTRIALS.GOV (NCT03013283).FIRST REGISTRATION DATE IS 2016-12-23.

Erectile dysfunction in patient with obstructive sleep apnea: effects of continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to various health complications, including erectile dysfunction (ED), which is more prevalent in individuals with OSA. This study explored ED in Korean OSA patients and assessed the impact of continuous positive airway pressure (CPAP) therapy on ED. METHODS: A total of 87 male patients with OSA from four different sleep centers underwent physical measurements and completed sleep and mental health (MH) questionnaires, including the Korean version of the International index of erectile function (IIEF), before and three months after initiating CPAP therapy. RESULTS: After three months of CPAP therapy, the patients demonstrated a significant improvement in ED as measured on the IIEF. However, the study found no significant correlation between the duration of CPAP use and the improvement in IIEF score. It did identify the SF36 quality of life assessment as a significant factor influencing ED improvement after CPAP. CONCLUSIONS: ED is a prevalent issue that escalates with age and is associated with OSA. CPAP therapy has shown potential in alleviating ED symptoms, particularly in those with underlying psychological conditions, although further research is required to confirm these findings and understand the underlying mechanisms.

Continuous positive airway pressure versus high-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

Self-reported oral moistening disorders in obstructive sleep apnoea: A scoping review.

BACKGROUND: Obstructive sleep apnoea (OSA) is a highly prevalent problem with significant consequences. Continuous positive airway pressure (CPAP) and oral mandibular advancement device (MAD) are considered the standard treatments for OSA. Patients may experience self-reported oral moistening disorders (OMDs) (i.e. xerostomia or drooling) at the beginning, throughout and after treatment. This affects oral health, quality of life and treatment effectiveness. The exact nature of the associations between OSA and self-reported OMD is still unknown. We aimed to provide an overview of the associations between self-reported OMD on the one hand and OSA and its treatment (namely CPAP and MAD) on the other hand. In addition, we sought to determine whether OMD affects treatment adherence. MATERIALS AND METHODS: A literature search in PubMed was performed up to 27 September 2022. Two researchers independently assessed studies for eligibility. RESULTS: In total, 48 studies were included. Thirteen papers investigated the association between OSA and self-reported OMD. They all suggested an association between OSA and xerostomia but not between OSA and drooling. The association between CPAP and OMD was addressed in 20 articles. The majority of studies have indicated xerostomia as a CPAP side effect; however, some have observed that xerostomia diminishes with CPAP therapy. In 15 papers, the association between MAD and OMD was investigated. In most publications, both xerostomia and drooling have been described as common side effects of MADs. These side effects are often mild and transient, and they improve as patients continue to use their appliance. Most studies found that these OMDs do not cause or are not a strong predictor of non-compliance. CONCLUSION: Xerostomia is a common side effect of CPAP and MAD, as well as a significant symptom of OSA. It may be regarded as one of the indicators of sleep apnoea. Moreover, MAD therapy can be associated with OMD. However, it seems that OMD may be mitigated by being adherent to the therapy.

Preterm Infants off Positive Pressure Respiratory Support Have a Higher Incidence of Occult Cerebral Hypoxia.

OBJECTIVE: To use cerebral near-infrared spectroscopy (NIRS) to quantify occult cerebral hypoxia across respiratory support modes in preterm infants. STUDY DESIGN: In this prospective, longitudinal, observational study, infants ≤32 weeks gestation underwent serial pulse oximetry (oxygen saturation [SpO2]) and cerebral NIRS monitoring (4-6 hours per session) following a standardized recording schedule (daily for 2 weeks, every other day for 2 weeks, then weekly until 35 weeks corrected gestational age). Four calculations were made: median cerebral saturation, median cerebral hypoxia burden (proportion of NIRS samples below the hypoxia threshold [<67%]), median systemic saturation, and median systemic hypoxia burden (proportion of SpO2 samples below the desaturation threshold [<85%]). During each recording session, respiratory support mode was noted (room air, low-flow nasal cannula, high-flow nasal cannula, noninvasive positive pressure ventilation, continuous positive airway pressure, and invasive ventilation). RESULTS: There were 1013 recording sessions made from 174 infants with a median length of 6.9 hours. Although the systemic (SpO2) hypoxia burden was significantly greater for infants on the highest respiratory support (invasive and noninvasive positive pressure ventilation), the cerebral hypoxia burden was significantly greater during recording sessions made on the lowest respiratory support (8% for room air; 29% for low-flow nasal cannula). CONCLUSIONS: Premature infants on the highest levels of respiratory support have less cerebral hypoxia than those on lower respiratory support. These results raise concern about unrecognized cerebral hypoxia during lower acuity periods of neonatal intensive care unit hospitalization and adverse outcomes.

Obstructive sleep apnea in the patient with atrial fibrillation: current knowledge and remaining uncertainties.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with atrial fibrillation and plays a causal role for OSA in the pathogenesis of atrial fibrillation. The presence of OSA in atrial fibrillation is associated with increased symptom burden and increased risk of hospitalizations. Furthermore, untreated OSA is associated with an increased risk of atrial fibrillation recurrence post ablation or cardioversion, and observational studies suggest that continuous positive airway pressure (CPAP) therapy can attenuate this risk. This review describes our current understanding of the relationship between OSA and atrial fibrillation with an emphasis on emerging evidence. RECENT FINDINGS: Recent studies have identified novel screening questionnaires, which may be superior to traditional questionnaires in identifying OSA in atrial fibrillation populations. Significant night-to-night variability in OSA severity has been shown in atrial fibrillation patients, which has implications for diagnostic testing. While several small, randomized control trials (RCTs) have not shown CPAP therapy to be effective in reducing atrial fibrillation burden, one RCT did show CPAP can attenuate the atrial substrate with implications for long-term outcomes. SUMMARY: Further RCTs, appropriately powered, and focused on well defined cohorts, are required to guide management decisions regarding screening and treatment of OSA in atrial fibrillation populations.

Systematic rotation versus continuous application of 'nasal prongs' or 'nasal mask' in preterm infants on nCPAP: a randomized controlled trial.

To compare whether alternate rotation of nasal mask with nasal prongs every 8 h as compared to continuous use of either interface alone decreases the incidence of nasal injury in preterm infants receiving nasal Continuous Positive Airway Pressure (nCPAP). This was an open-label, three-arm, stratified randomized controlled trial where infants < 35 weeks receiving nCPAP were randomized into three groups using two different nasal interfaces (continuous prongs group, continuous mask group, and rotation group). All infants were assessed for nasal injury six hours post-removal of nCPAP using grading suggested by Fischer et al. The nursing care was uniform across all three groups. Intention-to-treat analysis was done. Fifty-seven infants were enrolled, with nineteen in each group. The incidence of nasal injury was 42.1% vs. 47.4% vs. 68.4% in the rotation group, continuous mask, and continuous prongs groups, respectively (P = 0.228). On adjusted analysis (gestational age, birth weight, and duration of nCPAP therapy), the incidence of nasal injury was significantly less in the rotation group as compared to continuous prongs group (Adjusted Odds Ratio [AOR], 95% confidence interval [CI]; 0.10 [0.01-0.69], P = 0.02) and a trend towards lesser nasal injury as compared to continuous mask group (AOR, 95% CI; 0.15 [0.02-1.08], P = 0.06). However, there was no significant difference in incidence of nasal injuries between continuous prongs versus continuous mask group (P = 0.60). The need for surfactant, nCPAP failure rate, duration of nCPAP, and common neonatal co-morbidities were similar across all three groups.   Conclusion: Systematic rotation of nasal mask with nasal prongs significantly reduced nasal injury among preterm infants on nCPAP as compared to continuous use of nasal prongs alone without affecting nCPAP failure rate.   Trial registration: CTRI/2019/01/017320, registered on 31/01/2019. What is Known: • Use of nasal mask as an interface for nasal Continuous Positive Airway Pressure decreases nasal injury as compared to nasal prongs. What is New: • Rotation of nasal prongs and nasal mask interfaces alternately every 8 h may reduce the nasal injury even further as compared to either interface alone.

The effect of non-invasive high-frequency oscillatory ventilation on the duration of non-invasive respiratory support in late preterm and term infants with transient tachypnea of the newborn: a randomized controlled trial.

Nasal continuous positive airway pressure (nCPAP) is one of the most commonly used non-invasive respiratory support modes in neonates with transient tachypnea of the newborn (TTN). Non-invasive high-frequency oscillatory ventilation (nHFOV) is a non-invasive respiratory support mode that has been increasingly used in neonatal respiratory disorders. This prospective randomized controlled study compared the efficacy of nHFOV and nCPAP in reducing the duration of non-invasive respiratory support. Late preterm and term infants > 34 weeks' gestation were included in the study. The infants were randomly assigned to receive either nHFOV or nCPAP. Treatment was started with standard settings in both groups. Infants who met treatment failure criteria were switched to nasal intermittent mandatory ventilation for further positive-pressure support. A total of 60 infants were included in the study. Thirty of these infants were included in the nHFOV group and 30 were included in the nCPAP group. The median duration of non-invasive respiratory support was not significantly different between the two groups (21 h [IQR: 16-68] for nHFOV vs 15 h [IQR: 11-33] for nCPAP; p = 0.09). However, after adjusting for potential confounders, nHFOV was associated with a shorter duration of non-invasive respiratory support than nCPAP (adjusted mean difference: 16.3 h; 95% CI: 0.7 to 31.9; p = 0.04). nHFOV was well tolerated and did not increase the risk of complications.    Conclusion: Our findings suggest that nHFOV is an effective and safe ventilation mode for late preterm and term neonates with TTN.   Trial registry: Clinicaltrials.gov (NCT03006354). Date of registration: December 30, 2016. What is Known: • nHFOV is a ventilation model that has been increasingly used for the management of RDS. • TTN is one of the most common causes of neonatal respiratory distress. What is New: • nHFOV is associated with shorter duration of non-invasive respiratory support and duration of oxygen support. • nHFOV may be a safe and effective alternative to nCPAP for neonates with TTN.

High flow nasal cannula for respiratory support in term infants.

BACKGROUND: Respiratory failure or respiratory distress in infants is the most common reason for non-elective admission to hospitals and neonatal intensive care units. Non-invasive methods of respiratory support have become the preferred mode of treating respiratory problems as they avoid some of the complications associated with intubation and mechanical ventilation. High flow nasal cannula (HFNC) therapy is increasingly being used as a method of non-invasive respiratory support. However, the evidence pertaining to its use in term infants (defined as infants ≥ 37 weeks gestational age to the end of the neonatal period (up to one month postnatal age)) is limited and there is no consensus of opinion regarding the safety and efficacy HFNC in this population. OBJECTIVES: To assess the safety and efficacy of high flow nasal cannula oxygen therapy for respiratory support in term infants when compared with other forms of non-invasive respiratory support. SEARCH METHODS: We searched the following databases in December 2022: Cochrane CENTRAL; PubMed; Embase; CINAHL; LILACS; Web of Science; Scopus. We also searched the reference lists of retrieved studies and performed a supplementary search of Google Scholar. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the use of high flow nasal cannula oxygen therapy in infants ≥ 37 weeks gestational age up to one month postnatal age (the end of the neonatal period). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, performed data extraction, and assessed risk of bias in the included studies. Where studies were sufficiently similar, we performed a meta-analysis using mean differences (MD) for continuous data and risk ratios (RR) for dichotomous data, with their respective 95% confidence intervals (CIs). For statistically significant RRs, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to evaluate the certainty of the evidence for clinically important outcomes. MAIN RESULTS: We included eight studies (654 participants) in this review. Six of these studies (625 participants) contributed data to our primary analyses. Four studies contributed to our comparison of high flow nasal cannula (HFNC) oxygen therapy versus continuous positive airway pressure (CPAP) for respiratory support in term infants. The outcome of death was reported in two studies (439 infants) but there were no events in either group. HFNC may have little to no effect on treatment failure, but the evidence is very uncertain (RR 0.98, 95% CI 0.47 to 2.04; 3 trials, 452 infants; very low-certainty evidence). The outcome of chronic lung disease (need for supplemental oxygen at 28 days of life) was reported in one study (375 participants) but there were no events in either group. HFNC may have little to no effect on the duration of respiratory support (any form of non-invasive respiratory support with or without supplemental oxygen), but the evidence is very uncertain (MD 0.17 days, 95% CI -0.28 to 0.61; 4 trials, 530 infants; very low-certainty evidence). HFNC likely results in little to no difference in the length of stay at the intensive care unit (ICU) (MD 0.90 days, 95% CI -0.31 to 2.12; 3 trials, 452 infants; moderate-certainty evidence). HFNC may reduce the incidence of nasal trauma (RR 0.16, 95% CI 0.04 to 0.66; 1 trial, 78 infants; very low-certainty evidence) and abdominal overdistension (RR 0.22, 95% CI 0.07 to 0.71; 1 trial, 78 infants; very low-certainty evidence), but the evidence is very uncertain. Two studies contributed to our analysis of HFNC versus low flow nasal cannula oxygen therapy (LFNC) (supplemental oxygen up to a maximum flow rate of 2 L/min). The outcome of death was reported in both studies (95 infants) but there were no events in either group. The evidence suggests that HFNC may reduce treatment failure slightly (RR 0.44, 95% CI 0.21 to 0.92; 2 trials, 95 infants; low-certainty evidence). Neither study reported results for the outcome of chronic lung disease (need for supplemental oxygen at 28 days of life). HFNC may have little to no effect on the duration of respiratory support (MD -0.07 days, 95% CI -0.83 to 0.69; 1 trial, 74 infants; very low-certainty evidence), length of stay at the ICU (MD 0.49 days, 95% CI -0.83 to 1.81; 1 trial, 74 infants; very low-certainty evidence), or hospital length of stay (MD -0.60 days, 95% CI -2.07 to 0.86; 2 trials, 95 infants; very low-certainty evidence), but the evidence is very uncertain. Adverse events was an outcome reported in both studies (95 infants) but there were no events in either group. The risk of bias across outcomes was generally low, although there were some concerns of bias. The certainty of evidence across outcomes ranged from moderate to very low, downgraded due to risk of bias, imprecision, indirectness, and inconsistency. AUTHORS' CONCLUSIONS: When compared with CPAP, HFNC may result in little to no difference in treatment failure. HFNC may have little to no effect on the duration of respiratory support, but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit. HFNC may reduce the incidence of nasal trauma and abdominal overdistension, but the evidence is very uncertain. When compared with LFNC, HFNC may reduce treatment failure slightly. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain. There is insufficient evidence to enable the formulation of evidence-based guidelines on the use of HFNC for respiratory support in term infants. Larger, methodologically robust trials are required to further evaluate the possible health benefits or harms of HFNC in this patient population.

Bubble devices versus other pressure sources for nasal continuous positive airway pressure in preterm infants.

BACKGROUND: Several types of pressure sources, including underwater bubble devices, mechanical ventilators, and the Infant Flow Driver, are used for providing continuous positive airway pressure (CPAP) to preterm infants with respiratory distress. It is unclear whether the use of bubble CPAP versus other pressure sources is associated with lower rates of CPAP treatment failure, or mortality and other morbidity.  OBJECTIVES: To assess the benefits and harms of bubble CPAP versus other pressure sources (mechanical ventilators or Infant Flow Driver) for reducing treatment failure and associated morbidity and mortality in newborn preterm infants with or at risk of respiratory distress. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 1); MEDLINE (1946 to 6 January 2023), Embase (1974 to 6 January 2023), Maternity & Infant Care Database (1971 to 6 January 2023), and the Cumulative Index to Nursing and Allied Health Literature (1982 to 6 January 2023). We searched clinical trials databases and the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials comparing bubble CPAP with other pressure sources (mechanical ventilators or Infant Flow Driver) for the delivery of nasal CPAP to preterm infants. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of the evidence for effects on treatment failure, all-cause mortality, neurodevelopmental impairment, pneumothorax, moderate-severe nasal trauma, and bronchopulmonary dysplasia. MAIN RESULTS: We included 15 trials involving a total of 1437 infants. All trials were small (median number of participants 88). The methods used to generate the randomisation sequence and ensure allocation concealment were unclear in about half of the trial reports. Lack of measures to blind caregivers or investigators was a potential source of bias in all of the included trials. The trials took place during the past 25 years in care facilities internationally, predominantly in India (five trials) and Iran (four trials). The studied pressure sources were commercially available bubble CPAP devices versus a variety of mechanical ventilator (11 trials) or Infant Flow Driver (4 trials) devices.  Meta-analyses suggest that the use of bubble CPAP compared with mechanical ventilator or Infant Flow Driver CPAP may reduce the rate of treatment failure (RR 0.76, 95% confidence interval (CI) 0.60 to 0.95; (I² = 31%); RD -0.05, 95% CI -0.10 to -0.01; number needed to treat for an additional beneficial outcome 20, 95% CI 10 to 100; 13 trials, 1230 infants; low certainty evidence). The type of pressure source may not affect mortality prior to hospital discharge (RR 0.93, 95% CI 0.64 to 1.36 (I² = 0%); RD -0.01, 95% CI -0.04 to 0.02; 10 trials, 1189 infants; low certainty evidence). No data were available on neurodevelopmental impairment. Meta-analysis suggests that the pressure source may not affect the risk of pneumothorax (RR 0.73, 95% CI 0.40 to 1.34 (I² = 0%); RD -0.01, 95% CI -0.03 to 0.01; 14 trials, 1340 infants; low certainty evidence). Bubble CPAP likely increases the risk of moderate-severe nasal injury (RR 2.29, 95% CI 1.37 to 3.82 (I² = 17%); RD 0.07, 95% CI 0.03 to 0.11; number needed to treat for an additional harmful outcome 14, 95% CI 9 to 33; 8 trials, 753 infants; moderate certainty evidence). The pressure source may not affect the risk of bronchopulmonary dysplasia (RR 0.76, 95% CI 0.53 to 1.10 (I² = 0%); RD -0.04, 95% CI -0.09 to 0.01; 7 trials, 603 infants; low certainty evidence).  AUTHORS' CONCLUSIONS: Given the low level of certainty about the effects of bubble CPAP versus other pressure sources on the risk of treatment failure and most associated morbidity and mortality for preterm infants, further large, high-quality trials are needed to provide evidence of sufficient validity and applicability to inform context- and setting-relevant policy and practice.

Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs. OBJECTIVES: Primary objective To determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation. Secondary objectives To compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP. To compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was January 2023. SELECTION CRITERIA: We included randomised and quasi-randomised trials of ventilated preterm infants (less than 37 weeks' gestational age (GA)) ready for extubation to non-invasive respiratory support. Interventions were NIPPV and NCPAP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. respiratory failure. Our secondary outcomes were 2. endotracheal reintubation, 3. abdominal distension, 4. gastrointestinal perforation, 5. necrotising enterocolitis (NEC), 6. chronic lung disease, 7. pulmonary air leak, 8. mortality, 9. hospitalisation, 10. apnoea and bradycardia, and 11. neurodevelopmental status. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 19 trials (2738 infants). Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure postextubation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.67 to 0.84; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 8 to 17; 19 trials, 2738 infants; moderate-certainty evidence) and endotracheal reintubation (RR 0.78, 95% CI 0.70 to 0.87; NNTB 12, 95% CI 9 to 25; 17 trials, 2608 infants, moderate-certainty evidence), and may reduce pulmonary air leaks (RR 0.57, 95% CI 0.37 to 0.87; NNTB 50, 95% CI 33 to infinite; 13 trials, 2404 infants; low-certainty evidence). NIPPV likely results in little to no difference in gastrointestinal perforation (RR 0.89, 95% CI 0.58 to 1.38; 8 trials, 1478 infants, low-certainty evidence), NEC (RR 0.86, 95% CI 0.65 to 1.15; 10 trials, 2069 infants; moderate-certainty evidence), chronic lung disease defined as oxygen requirement at 36 weeks (RR 0.93, 95% CI 0.84 to 1.05; 9 trials, 2001 infants; moderate-certainty evidence) and mortality prior to discharge (RR 0.81, 95% CI 0.61 to 1.07; 11 trials, 2258 infants; low-certainty evidence). When considering subgroup analysis, ventilator-generated NIPPV likely reduces respiratory failure postextubation (RR 0.49, 95% CI 0.40 to 0.62; 1057 infants; I2 = 47%; moderate-certainty evidence), while bilevel devices (RR 0.95, 95% CI 0.77 to 1.17; 716 infants) or a mix of both ventilator-generated and bilevel devices likely results in little to no difference (RR 0.87, 95% CI 0.73 to 1.02; 965 infants). AUTHORS' CONCLUSIONS: NIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one-week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator-generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions. Future trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end-expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials.

Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might reduce chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation delivered through the same nasal interface during which patients are exposed to short inflations, along with background end-expiratory pressure. OBJECTIVES: To examine the risks and benefits of early (within the first six hours after birth) NIPPV versus early NCPAP for preterm infants at risk of or with respiratory distress syndrome (RDS). Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include the incidence of mortality, chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), pneumothorax, duration of respiratory support, duration of oxygen therapy, and intraventricular hemorrhage (IVH). SEARCH METHODS: Searches were conducted in January 2023 in CENTRAL, MEDLINE, Embase, Web of Science, and Dissertation Abstracts. The reference lists of related systematic reviews and of studies selected for inclusion were also searched. SELECTION CRITERIA: We considered all randomized and quasi-randomized controlled trials. Eligible studies compared NIPPV versus NCPAP treatment, starting within six hours after birth in preterm infants (< 37 weeks' gestational age (GA)). DATA COLLECTION AND ANALYSIS: We collected and analyzed data using the recommendations of the Cochrane Neonatal Review Group. MAIN RESULTS: We included 17 trials, enrolling 1958 infants in this review. NIPPV likely reduces the rate of respiratory failure (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.78; risk difference (RD) -0.08, 95% CI -0.12 to -0.05; 17 RCTs, 1958 infants; moderate-certainty evidence) and needing endotracheal tube ventilation (RR 0.67, 95% CI 0.56 to 0.81; RD -0.07, 95% CI -0.11 to -0.04; 16 RCTs; 1848 infants; moderate-certainty evidence) amongst infants treated with early NIPPV compared with early NCPAP. The meta-analysis demonstrated that NIPPV may reduce the risk of developing CLD compared to CPAP (RR 0.70, 95% CI 0.52 to 0.92; 12 RCTs, 1284 infants; low-certainty evidence) slightly. NIPPV may result in little to no difference in mortality (RR 0.82, 95% CI 0.62 to 1.10; 17 RCTs; 1958 infants; I2 of 0%; low-certainty evidence), the incidence of pneumothorax (RR 0.92, 95% CI 0.60 to 1.41; 16 RCTs; 1674 infants; I2 of 0%; low-certainty evidence), and rates of severe IVH (RR 0.98, 95% CI 0.53 to 1.79; 8 RCTs; 977 infants; I2 of 0%; low-certainty evidence). AUTHORS' CONCLUSIONS: When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (GA 28 weeks and above) with respiratory distress syndrome or at risk for RDS. It may also decrease the rate of CLD slightly. However, most trials enrolled infants with a gestational age of approximately 28 to 32 weeks with an overall mean gestational age of around 30 weeks. As such, the results of this review may not apply to extremely preterm infants that are most at risk of needing mechanical ventilation or developing CLD. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population.

Effect of Weight Loss and Continuous Positive Airway Pressure on Obstructive Sleep Apnea and Metabolic Profile Stratified by Craniofacial Phenotype: A Randomized Clinical Trial.

Rationale: Craniofacial structure is believed to modulate the effect of weight loss on obstructive sleep apnea (OSA), but whether this affects metabolic profile after weight loss compared with continuous positive airway pressure (CPAP) is unknown among obese Chinese patients with OSA. Objectives: To compare the change in metabolic profile between a lifestyle modification program (LMP), stratified by craniofacial phenotype, and CPAP therapy for 6 months. Methods: We randomly assigned 194 patients with body mass index ⩾ 25 kg/m2 and moderate to severe OSA to participate in the LMP or receive CPAP therapy for 6 months in a 2:1 ratio. Assessments included computed tomography for assessing maxillomandibular volume (MMV), hsCRP (high-sensitivity C-reactive protein), and insulin sensitivity. Measurements and Main Results: Among 128 and 66 subjects in the LMP and CPAP groups, respectively, hsCRP was reduced more in the LMP group than the CPAP group (median [interquartile range], -0.7 [-1.4 to -0.0] vs. -0.3 [-0.9 to 0.4] mg/L; P = 0.012). More patients in the LMP group achieved low hsCRP (<1 mg/L) than the CPAP group (21.1% vs. 9.1%; P = 0.04). Insulin sensitivity improved only in the LMP group, with 3.1 (95% confidence interval, 1.5-6.6) times more patients with normal glucose regulation after intervention. The LMP group was stratified into LMP-small MMV (n = 64) and LMP-large MMV (n = 64) groups according to the median MMV value of 233.2 cm3. There was no significant difference in hsCRP (median [interquartile range], -0.7 [-1.3 to 0.1] vs. -0.7 [-1.5 to -0.2] mg/L; P = 0.884) and insulin sensitivity (median [interquartile range], 0.5 [-0.2 to 1.9] vs. 0.6 [0.1 to 2.0]; P = 0.4860) between the LMP-small MMV and LMP-large MMV groups. Conclusions: Weight reduction alleviated subclinical inflammation and improved insulin sensitivity more than CPAP among obese Chinese patients with moderate to severe OSA, and this effect was not influenced by craniofacial structure. Clinical trial registered with www.clinicaltrials.gov (NCT03287973).

Meta-analysis of the effects of CPAP therapy on estimated glomerular filtration rate in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease and may lead to a loss of kidney function. However, it remains unclear whether or not continuous positive airway pressure (CPAP) treatment improves the estimated glomerular filtration rate (eGFR) in patients with OSA. This meta-analysis was designed to investigate the effect of CPAP therapy on eGFR in patients with OSA. METHODS: We searched the electronic databases Web of Science, Cochrane Library, PubMed, and Embase through June 1, 2022. Information about patients, CPAP duration, gender distribution, pre- and post-CPAP treatment eGFR, and age of patients were collected for further analysis. We applied the standardized mean difference (SMD) with a 95%confidence interval (CI) to analyze the pooled effects. Both Stata 12.0 software and Review Manager 5.2 software were employed for all statistical analyses. RESULTS: A sample of 13 studies with 519 patients was included in the meta-analysis. There was no significant change of eGFR levels before and after CPAP usage for patients with OSA (SMD = - 0.05, 95%CI: - 0.30 to 0.19, Z = 0.43, p = 0.67). However, subgroup analysis revealed that the level of eGFR was obviously decreased after CPAP therapy in patients with OSA and CPAP use duration > 6 months (SMD = - 0.30, 95% CI = - 0.49 to - 0.12, z = 3.20, p = 0.001), and elderly patients (> 60 years) (SMD = - 0.32, 95% CI = - 0.52 to - 0.11, z = 3.02, p = 0.002). CONCLUSIONS: Meta-analysis confirmed that OSA treatment with CPAP has no clinically significant effect on eGFR.

The effect of continuous positive airway pressure on total antioxidant capacity in obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA), a sleep-related disorder with high prevalence, is associated with an imbalance in oxidative stress and is linked to cardiovascular disease. There are conflicting reports regarding the effectiveness of continuous positive airway pressure (CPAP) therapy on oxidative stress/antioxidant markers in patients with OSA. This review was performed to evaluate the influence of therapy with CPAP on serum/plasma total antioxidant capacity (TAC) in patients with OSA. METHODS: The Cochrane Library, Web of Science, Scopus, Embase, and PubMed were searched through June 2022 to obtain studies evaluating CPAP treatment on TAC in patients with OSA. Overall results were tested using standardized mean difference (SMD) with a 95% confidence interval (CI). Comprehensive Meta-Analysis V2 software was employed to perform analyses. RESULTS: Ten studies with 12 effect sizes were eligible for inclusion in this analysis. The overall SMD revealed that CPAP therapy significantly increased TAC [SMD 0.497; 95% CI: 0.21 to 0.77; p: 0.00] in OSA. Analyses based on subgroups showed that the effect of CPAP therapy was significant in all subgroups according to therapy duration, age, BMI, and AHI. Whereas the meta-regression results indicated that the impact of therapy with CPAP on TAC is associated with AHI, BMI, and age in patients with OSA. CONCLUSIONS: The finding of this meta-analysis demonstrated a favorable impact of CPAP therapy on TAC levels in patients suffering from OSA.

Association between brain-derived neurotrophic factor levels and obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Chronic intermittent hypoxia associated with obstructive sleep apnea (OSA) can affect neurons and glial cells, leading to cell stress and damage, and changes in brain-derived neurotrophic factor (BDNF) levels. This study investigated the relation between BDNF, OSA, and continuous positive airway pressure (CPAP) - the standard of care in patients with OSA. METHODS: Five databases were searched for studies that evaluated BDNF serum and/or plasma levels in patients with OSA and controls or publications assessing the effect of CPAP treatment on BDNF levels. We used standardized mean difference (SMD) with its 95% confidence interval (CI) comparison between patients with OSA and controls. RESULTS: Ten studies were included in our study assessing the relation between BDNF levels, OSA, and CPAP treatment. Five studies of BDNF levels in OSA compared to controls showed no significant difference (SMD = - 0.52, 95% CI [- 1.93; 0.89], p-value = 0.47). No statistically significant difference was found between CPAP treatment in patients with OSA and BDNF levels (SMD = - 0.78, 95% CI [- 1.77; 0.21], p-value = 0.12). CONCLUSION: BDNF peripheral levels are not significantly altered in OSA or by its related treatment, preventing its use as a biomarker.

Nasal pillow vs. standard nasal mask for treatment of OSA: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to compare the effectiveness of nasal pillows with standard nasal masks in the treatment of patients with obstructive sleep apnea (OSA). METHODS: A digitalized search was carried out in four different databases including PubMed, Scopus, EMBASE, and CENTRAL using relevant keywords along with a manual search in relevant journals. All comparative studies comparing outcomes of using a nasal pillow with the use of standard nasal masks for continuous positive airway pressure (CPAP) treatment in patients with OSA were included. The qualitative analysis was carried out by tabulating the demographic data. The quantitative data were subjected to meta-analysis. The quality of comparative studies (both retrospective and prospective cohorts) was evaluated using New-castle Ottawa scale (NOS). RESULTS: A total of 14 studies (eight prospective and six retrospective) were included in the review. Of them, five studies were randomized and were of cross-over study design. No significant differences were observed in achieved CPAP and residual apnea-hypopnea index (AHI) levels between the nasal pillow and nasal mask with SMD - 0.05 95% CI [- 0.18, 0.09], p = 0.50 and SMD - 0.13 95% CI [- 0.28, 0.03], p = 0.12, respectively. However, nasal pillow usage was associated with better CPAP adherence with a difference of only + 0.29 min/night as compared to a standard nasal mask, with SMD 0.29 95% CI [0.07, 0.50], p = 0.009. CONCLUSION: Nasal pillow and standard nasal mask were equally effective in terms of residual AHI level and achieved similar therapeutic CPAP pressures. However, the difference in CPAP adherence between groups, though statistically significant, is of questionable clinical significance.

Evaluation of obstructive sleep apnea: an analysis based on aberrant genes.

BACKGROUND: Obstructive sleep apnea (OSA) is an upstream disorder that frequently causes multisystem disorders. Much research has revealed the pathogenesis of OSA, but there is still a lack of research on the complications caused by OSA. METHODS: The mRNA expression and methylation dataset based on peripheral blood mononuclear cells (PBMCs) were downloaded from the Gene Expression Omnibus (GEO) database. All differential expressed genes (DEGs) were ranked using the Robust Rank Aggregation (RRA) algorithm. A weighted gene co-expression network analysis (WGCNA) was constructed. Subsequently, we used immune infiltration, enrichment analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis for apnea and hypopnea index (AHI) and hypertension and excessive daytime sleepiness (EDS) and constructed diagnostic model using random forest algorithm. RESULTS: In the present study, we identified 318 DEGs in PBMCs involved in pathogenesis or continuous positive airway pressure (CPAP) therapy. Pathway enrichment identified DEGs associated with protein regulation and metabolism. Notably, through intra group analysis, we found that the immune disorder was more significant for OSA in males, non-daytime sleepy, or non-hypertensive OSA. The area under the ROC curve of model for EDS prediction is 0.889 and 0.852 for hypertension. Notably, we found that the diagnostic model had a high linear predictive value for AHI. CONCLUSIONS: Our results indicate that PBMCs are a significant component of alterations in OSA and are expected to explain the mechanism of multisystem diseases caused by OSA. The present study provides new insights for symptom evaluation, classification and treatment of OSA from the molecular level.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

Comparing the effects of continuous positive airway pressure via mask or helmet interface on oxygenation and pulmonary complications after major abdominal surgery: a randomized trial.

The risk of pulmonary complications is high after major abdominal surgery but may be reduced by prophylactic postoperative noninvasive ventilation using continuous positive airway pressure (CPAP). This study compared the effects of intermittent mask CPAP (ICPAP) and continuous helmet CPAP (HCPAP) on oxygenation and the risk of pulmonary complications following major abdominal surgery. Patients undergoing open abdominal aortic aneurysm repair or pancreaticoduodenectomy were randomized (1:1) to either postoperative ICPAP or HCPAP. Oxygenation was evaluated as the partial pressure of oxygen in arterial blood fraction of inspired oxygen ratio (PaO2/FIO2) at 6 h, 12 h, and 18 h postoperatively. Pulmonary complications were defined as X-ray verified pneumonia/atelectasis, clinical signs of pneumonia, or supplementary oxygen beyond postoperative day 3. Patient-reported comfort during CPAP treatment was also evaluated. In total, 96 patients (ICPAP, n = 48; HCPAP, n = 48) were included, and the type of surgical procedure were evenly distributed between the groups. Oxygenation did not differ between the groups by 6 h, 12 h, or 18 h postoperatively (p = 0.1, 0.08, and 0.67, respectively). Nor was there any difference in X-ray verified pneumonia/atelectasis (p = 0.40) or supplementary oxygen beyond postoperative day 3 (p = 0.53). Clinical signs of pneumonia tended to be more frequent in the ICPAP group (p = 0.06), yet the difference was not statistically significant. Comfort scores were similar in both groups (p = 0.43), although a sensation of claustrophobia during treatment was only experienced in the HCPAP group (11% vs. 0%, p = 0.03). Compared with ICPAP, using HCPAP was associated with similar oxygenation (i.e., PaO2/FIO2 ratio) and a similar risk of pulmonary complications. However, HCPAP treatment was associated with a higher sensation of claustrophobia.