Asthma and obstructive sleep apnea: Unveiling correlations and treatable traits for comprehensive care.

Asthma and obstructive sleep apnea (OSA) are common respiratory disorders. They share characteristics such as airway obstruction, poor sleep quality, and low quality of life. They are often present as comorbidities, along with obesity, gastroesophageal reflux disease (GERD), and allergic rhinitis (AR), which impacts the disease's control. In recent years, there has been discussion about the association between these conditions and their pathophysiological and clinical consequences, resulting in worse health outcomes, increased healthcare resource consumption, prolonged hospital stays, and increased morbidity and mortality. Some studies demonstrate that treatment with continuous positive airway pressure (CPAP) can have a beneficial effect on both pathologies. This review summarizes the existing evidence of the association between asthma and OSA at their pathophysiological, epidemiological, clinical, and therapeutic levels. It intends to raise awareness among healthcare professionals about these conditions and the need for further research.

Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Obstructive Sleep Apnea Effects on Chronic Airway Disease Exacerbations-Missed Opportunities for Improving Outcomes in Chronic Obstructive Pulmonary Disease and Asthma.

In patients with chronic obstructive pulmonary disease (COPD) and asthma, exacerbations determine the natural history of both diseases. Patients with both respiratory diseases who suffer from obstructive sleep apnea (OSA) as a comorbidity (overlap syndromes) have a higher risk of exacerbations and hospitalization. In cases of OSA/COPD and OSA/asthma, continuous positive airway pressure treatment is indicated. Adequate adherence to therapy appears to reduce exacerbations and their severity, especially in OSA/COPD overlap. However, there is a lack of randomized trials that definitively demonstrate this evidence.

Targeting Hypercapnia in Chronic Lung Disease and Obesity Hypoventilation: Benefits and Challenges.

Hypoventilation is a complication that is not uncommon in chronic obstructive pulmonary disease and calls for both medical treatment of the underlying disease and, frequently, noninvasive ventilation either during exacerbations requiring hospitalization or in a chronic state in the patient at home. Obesity hypoventilation syndrome by definition is associated with ventilatory failure and hypercapnia. It may or may not be accompanied by obstructive sleep apnea, which when detected becomes an additional target for positive airway pressure treatment. Intensive research has not completely resolved the best choice of treatment, and the simplest modality, continuous positive airway pressure, may still be entertained.

Chronic Cough and Obstructive Sleep Apnea.

Chronic cough, defined as a cough lasting more than 8 weeks, is a common medical condition occurring in 5% to 10% of the population. Its overlap with another highly prevalent disorder, obstructive sleep apnea (OSA), is therefore not surprising. The relationship between chronic cough and OSA extends beyond this overlap with higher prevalence of OSA in patients with chronic cough than in the general population. The use of continuous positive airway pressure can result in improvement in chronic cough although further studies are needed to understand which patients will experience benefit in their cough from the treatment of comorbid OSA.

Real-world impact of continuous positive airway pressure on sleepiness in patients with obstructive sleep apnea in a national registry.

OBJECTIVE: Excessive daytime sleepiness (EDS) persists in some patients with obstructive sleep apnea (OSA) despite continuous positive airway pressure (CPAP) treatment. This study characterized response to CPAP and factors associated with residual EDS. METHODS: Danish National Patient Registry data were analyzed. Patients with OSA diagnosis (1994-2016), Epworth Sleepiness Scale (ESS) scores and apnea-hypopnea index recorded before beginning CPAP (baseline) and after 1-13 months of CPAP use, and CPAP adherence were included. Odds ratios (OR) for residual EDS after CPAP treatment were estimated using multivariate logistic regression. RESULTS: Of 1174 patients (mean age, 57 years; 75.5% male), 41.1% had baseline EDS (mild, 13.2%; moderate, 14.0%; severe, 13.9%); 58.9% did not. After CPAP treatment, follow-up mean ESS scores were normal (≤10) for all baseline EDS subgroups; however, 15.6% (n = 183) of patients had residual EDS (mild, 6.7%; moderate, 5.5%; severe, 3.4%). Odds of residual EDS were higher for patients with mild (OR, 5.2; 95% confidence interval [CI], 3.2-8.6), moderate (OR, 4.5; 95% CI, 2.7-7.4), and severe (OR, 13.0; 95% CI, 8.0-21.2) EDS at baseline compared with those with normal daytime sleepiness at baseline. Patients adherent with CPAP use were 38.2% less likely to have residual EDS compared with nonadherent patients (OR, 0.62; 95% CI, 0.43-0.88). CONCLUSIONS: EDS was common in this cohort of Danish patients with OSA. Baseline EDS severity predicted higher odds of residual EDS. After CPAP treatment, adherence was associated with reduced odds of residual EDS, but EDS persisted in a subgroup of patients.

Effect of Nasal Continuous Positive Airway Pressure on Retinopathy of Prematurity in Preterm Newborns: A Comparative Analysis with Mechanical Ventilation and High-Flow Nasal Cannula Therapy.

BACKGROUND Retinopathy of prematurity (ROP), originally described as retrolental fibroplasia, represents an abnormal growth of blood vessels in the premature retina that can occur in response to oxygen therapy. The association between ROP and invasive mechanical ventilation has been widely studied in the literature; however, the relationships between different types of ventilation and ROP have not been as well documented. This study aimed to compare the association of ROP incidence with mechanical ventilation (MV), nasal continuous positive airway pressure (nCPAP), and high-flow nasal cannula (HFNC) therapies in 130 pre-term infants with gestational ages <32 weeks. MATERIAL AND METHODS The study includes 130 premature newborns, out of which 54 underwent MV therapy, either alone or in combination with nCPAP or HFNC therapy, 63 underwent nCPAP therapy, either alone or in combination with MV or HFNC therapy, and 23 underwent HFNC therapy, either alone or in combination with MV or nCPAP therapy. The relationships between ROP and the 3 types of ventilation were analyzed by univariate followed by multivariate logistic regression. RESULTS When adjusting for covariates, only nCPAP and birth weight were significantly associated with ROP, the former being a strong risk factor, with an adjusted odds ratio (AOR) of 7.264 (95% CI, 2.622-20.120; P<0.001), and the latter being a weak protective factor, with an AOR of 0.998 (95% CI, 0.996-0.999; P<0.05). CONCLUSIONS The results showed nCPAP was a strong ROP risk factor, birth weight was a weak ROP protective factor, and MV and HFNC were not significantly associated with increased ROP risk.

The effect of compliance with PAP therapy on biochemical parameters in patients with obstructive sleep apnea syndrome: A 6-month follow-up study.

Introduction: The gold standard treatment for obstructive sleep apnea syndrome (OSAS) is positive airway pressure therapy (PAP) treatments. PAP treatments reduce complications by reducing apnea and hypopnea attacks by creating airflow at a determined pressure. In our study, we aimed to examine the effect of treatment compliance on kidney and liver functions, apneahypopnea (AHI) index, and lipid profile of patients diagnosed with OSAS and started PAP treatment. Materials and Methods: Patients who were admitted to the sleep laboratory of our hospital between September 2022 and September 2023 and started PAP treatment after PSG were included in our study. Patients who were called for follow-up six months after the initiation of PAP treatment were divided into two groups according to their compliance with PAP treatment. Patients who used the device for at least four hours per night and more than 70% at night were grouped as PAP-compliant patients, while the other patients were grouped as non-PAP-compliant patients. Result: It was observed that uric acid, BUN, triglyceride, total cholesterol, ALT, GGT, ALP, and AHI levels of the patients who started PAP treatment decreased after six months (p= 0.001, 0.006, <0.001, 0.006, 0.01, <0.001, <0.001, <0.001 with). It was observed that HDL cholesterol levels increased (p≤ 0.001). It was observed that the change in uric acid, AHI, total cholesterol, and GGT levels in group 1 (n= 36) patients who were compliant with PAP treatment was statistically higher than in group 2 (n= 30) patients (p< 0.001, <0.03, <0.001, 0.008, respectively). Conclusions: Uric acid, total cholesterol and GGT are biomarkers that may increase in OSAS due to intermittent hypoxia with the involvement of other systems. Since a decrease in these biomarkers can be observed in the early period depending on treatment compliance, these biomarkers can be used practically in the follow-up of treatment compliance and treatment efficacy.

Non-invasive versus invasive respiratory support in preterm infants.

Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks' gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.

Pulmonary strain and end-expiratory lung volume during apnea test: a comparative analysis using electrical impedance tomography.

The apnea test, employed for brain death assessment, aims to demonstrate the absence of respiratory drive due to hypercapnia. The tracheal oxygen insufflation apnea test mode (I-AT) involves disconnecting the patient from invasive mechanical ventilation (iMV) for approximately 8 minutes while maintaining oxygenation. This test supports the diagnosis of brain death based on a specified increase in PaCO2. Common complications include hypoxemia and hemodynamic instability, and lung collapse-induced reduction in end-expiratory lung volume (EELV). In our case series utilizing electrical impedance tomography (EIT), we observed that continuous positive airway pressure during the apnea test (CPAP-AT) effectively mitigated lung collapse. This resulted in improved pulmonary strain compared to the disconnection of iMV. These findings suggest the potential benefits of routine CPAP-AT, particularly for potential lung donors, emphasizing the relevance of our study in providing quantitative insights into EELV loss and its association with pulmonary strain and potential lung injury.

La prueba de apnea es una técnica diagnóstica ampliamente utilizada para la evaluación de la muerte cerebral, con el objetivo de demostrar la ausencia de impulso respiratorio debido a la hipercapnia. La variante de la prueba de apnea con insuflación de oxígeno traqueal (I-AT) implica desconectar al paciente de la ventilación mecánica invasiva (iVM) durante aproximadamente 8 minutos, manteniendo la oxigenación mediante un catéter de insuflación. Esta prueba respalda el diagnóstico de muerte cerebral cuando se determina un aumento de la PaCO 2 superior a 20 mmHg en comparación con el valor inicial o un nivel de PaCO 2 superior a 60 mmHg al final de la prueba. En nuestra serie de casos, la implementación de la tomografía de impedancia eléctrica (EIT) reveló que la prueba de apnea con presión positiva continua (CPAPAT) mitiga eficazmente el colapso pulmonar. Este enfoque resulta en una mejora en la tensión pulmonar en comparación con la desconexión de iMV, demostrando su relevancia en el contexto de potenciales donantes de pulmones.

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Protecting the non-operative lobe/s of the operative lung can reduce the pneumonia incidence after thoracoscopic lobectomy: a randomised controlled trial.

Lung isolation usually refers to the isolation of the operative from the non-operative lung without isolating the non-operative lobe(s) of the operative lung. We aimed to evaluate whether protecting the non-operative lobe of the operative lung using a double-bronchial blocker (DBB) with continuous positive airway pressure (CPAP) could reduce the incidence of postoperative pneumonia. Eighty patients were randomly divided into two groups (n = 40 each): the DBB with CPAP (Group DBB) and routine bronchial blocker (Group BB) groups. In Group DBB, a 7-Fr BB was placed in the middle bronchus of the right lung for right lung surgery and in the inferior lobar bronchus of the left lung for left lung surgery. Further, a 9-Fr BB was placed in the main bronchus of the operative lung. In Group BB, routine BB placement was performed on the main bronchus on the surgical side. The primary endpoint was the postoperative pneumonia incidence. Compared with Group BB, Group DBB had a significantly lower postoperative pneumonia incidence in the operative (27.5% vs 5%, P = 0.013) and non-operative lung (40% vs 15%) on postoperative day 1. Compared with routine BB use for thoracoscopic lobectomy, using the DBB technique to isolate the operative lobe from the non-operative lobe(s) of the operative lung and providing CPAP to the non-operative lobe(s) through a BB can reduce the incidence of postoperative pneumonia in the operative and non-operative lungs.

Impact of PAP on the gut microbiome in OSA: A pilot study.

OBJECTIVE/BACKGROUND: Microbes within the gastrointestinal tract have emerged as modulators of the host's health. Obstructive sleep apnea (OSA) is characterized by intermittent partial, or complete, airway closure during sleep and is associated with increased risk of non-communicable diseases as well as dysbiosis of the gut microbiome. Thus, we investigated if improving nocturnal airway patency via positive airway pressure (PAP) therapy improves gut microbial diversity in recently diagnosed patients with moderate-to-severe OSA (apnea-hypopnea index ≥15.0 events/hr). PATIENTS/METHODS: Eight subjects (3 F, 56±9yrs, 33.5 ± 7.7 kg/m2, 45.0 ± 38.4 events/hr) provided stool samples before, and two months after, PAP therapy (mean adherence of 95 ± 6%, residual apnea-hypopnea index of 4.7 ± 4.6 events/hr). RESULTS: While the Shannon diversity index tended to increase following PAP (3.96 ± 0.52 to 4.18 ± 0.56, p = 0.08), there were no changes in the Observed (1,088 ± 237 to 1,136 ± 289, p = 0.28) nor Inverse-Simpson (22.4 ± 12.99 to 26.6 ± 18.23, p = 0.28) alpha diversity indices. There were also no changes in beta diversity assessed using the Bray-Curtis (p = 0.98), Jaccard (p = 0.99), WUniFrac (p = 0.98), GUniFrac (p = 0.98), or UniFrac (p = 0.98) methods. No changes in differential abundance taxa were found using a false discovery rate threshold of <0.20. CONCLUSIONS: Our data are the first to report that PAP therapy may not offset, or reverse, gut dysbiosis in patients with OSA. Accordingly, interventions which improve gut microbial health should be explored as potential adjunctive treatment options in patients with OSA to reduce their risk of developing non-communicable diseases.

Airway stability in sleep apnea: Assessing continuous positive airway pressure efficiency.

Obstructive Sleep Apnea Syndrome (OSAS) disrupts millions of lives with its burden of airway obstruction during sleep. Continuous Positive Airway Pressure (CPAP) therapy has been scrutinized for its biomechanical impact on the respiratory tract. This study leverages computational fluid dynamics to investigate CPAP's effects at 9 cm H2O (882.6 Pa) on the computed-tomography-based nasal-to-14-generation full respiratory tract model compared to ambient conditions, focusing on static pressure, airflow velocity, and shear stress. Our findings reveal that CPAP significantly increases static pressure, enhancing airway patency without adverse changes in airflow velocity or harmful shear stress on lung tissue, challenging prior concerns about its safety. Notably, the larynx experiences the highest shear stress due to its narrow anatomy, yet CPAP therapy overall supports airway walls against collapse. This investigation highlights CPAP's critical role in OSAS treatment, offering reassurance about its safety and efficacy. By clarifying CPAP therapy's physiological impacts, our study contributes vital insights for optimizing OSAS management strategies, affirming CPAP's benefit in maintaining open airways with minimal tissue strain.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Impact of posture and CPAP on nasal airflow.

Obstructive sleep apnea (OSA) patients who use continuous positive airway pressure (CPAP) often complain of nasal dryness and nasal obstruction as side effects of CPAP. The physiological mechanisms by which CPAP may cause nasal dryness and nasal obstruction remain poorly understood. It has been hypothesized that CPAP interferes with the nasal cycle, abolishing the resting phase of the cycle and leading to nasal dryness. We performed rhinomanometry measurements in 31 OSA patients sitting, laid supine, and supine after 10 min of CPAP at 10 cmH2O. A posture change from sitting to supine led to more symmetric airflow partitioning between the left and right nostrils in the supine position. CPAP did not have a significant impact on nasal resistance, unilateral airflows, or airflow partitioning. Our results suggest that airflow partitioning becomes more symmetric immediately after changing to a supine position, while CPAP had no effect on nasal airflow, thus preserving the nearly symmetric airflow partitioning achieved after the posture change.

Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. METHODS: Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. RESULTS: We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1-59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial.

BACKGROUND: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. METHODS: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. FINDINGS: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. INTERPRETATION: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. FUNDING: SIDA Sweden and Grand Challenges Ethiopia.