Bubble continuous positive airway pressure for children with pneumonia and hypoxaemia in Ethiopia
Authors: Eric D McCollum, Tisungane Mvalo
Journal: The Lancet Global Health (2024)

In low-income and middle-income countries (LMICs), children with pneumonia and low blood oxygen levels (hypoxaemia) have a more than five times increased risk of death than children with pneumonia without hypoxaemia; approximately 7 million children with hypoxaemic pneumonia were admitted to hospital in 2019.1Wilkes C Bava M Graham HR Duke T What are the risk factors for death among children with pneumonia in low- and middle-income countries? A systematic review.J Glob Health. 2023; 1305003 Crossref PubMed Scopus (3) Google Scholar, 2Rahman AE Hossain AT Nair H et al.Prevalence of hypoxaemia in children with pneumonia in low-income and middle-income countries: a systematic review and meta-analysis.Lancet Glob Health. 2022; 10: e348-e359Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar Aside from antimicrobial drugs and low-flow oxygen, scalable child pneumonia treatments proven to reduce mortality are scarce. In The Lancet Global Health, Meseret Gebre and colleagues3Gebre M Haile K Duke T et al.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.Lancet Glob Health. 2024; (published online March 21.)https://doi.org/10.1016/S2214-109X(24)00032-9Summary Full Text Full Text PDF Scopus (1) Google Scholar share promising results from an open-label, cluster-randomised controlled trial in Ethiopia assessing the risk of treatment failure in children with pneumonia and hypoxaemia at 12 secondary-level hospitals randomly assigned to bubble continuous positive airway pressure (bCPAP) or standard low-flow oxygen therapy. bCPAP provides continuous positive airway pressure and oxygen to improve hypoxaemia and respiratory mechanics in naturally breathing children. The current evidence base for bCPAP treatment of paediatric pneumonia and hypoxaemia in LMICs is mixed.4Sessions KL Smith AG Holmberg PJ et al.Continuous positive airway pressure for children in resource-limited settings, effect on mortality and adverse events: systematic review and meta-analysis.Arch Dis Child. 2022; 107: 543-552Crossref PubMed Scopus (10) Google Scholar In this study, hospitals were randomly assigned to bCPAP or low-flow oxygen as first-line therapy for children aged 1–59 months with WHO-defined severe pneumonia and a peripheral arterial oxyhaemoglobin saturation of less than 90%.3Gebre M Haile K Duke T et al.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.Lancet Glob Health. 2024; (published online March 21.)https://doi.org/10.1016/S2214-109X(24)00032-9Summary Full Text Full Text PDF Scopus (1) Google Scholar The trial enrolled 1240 children between 2021 and 2022. General physicians, paediatricians, and nurses (overall nurse-to-patient ratio of one nurse per six patients) provided care in a paediatric ward per WHO guidelines. 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); in-hospital mortality was a secondary outcome. The investigators reported an impressive 76% lower risk of treatment failure in the bCPAP group than in the low-flow oxygen group (unadjusted relative risk [RR] 0·24, 95% CI 0·09–0·63, p=0·0015), although rates of treatment failure (26 [2%] of 1240 children) and mortality during hospital stay (six [<1%] of 1240) were low overall. All six in-hospital deaths occurred in the low-flow oxygen group and no serious adverse events from bCPAP were identified. These data align with trial results from a well resourced intensive care unit in Bangladesh staffed with paediatricians and high nurse-to-patient ratios, which found a 73% lower risk of treatment failure with bCPAP than with oxygen therapy in children with pneumonia and hypoxaemia (RR 0·27, 99·7% CI 0·07–0·99).5Chisti MJ Salam MA Smith JH et al.Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial.Lancet. 2015; 386: 1057-1065Summary Full Text Full Text PDF PubMed Google Scholar The investigators should be applauded for successfully executing a complex pragmatic trial, providing valuable evidence on the utility of bCPAP in the care of children with pneumonia and hypoxaemia. We agree with the investigators' conclusion that, in the right circumstances, bCPAP "should be available for the care of severe childhood pneumonia" in LMICs. What is less clear are the broader implications of the findings, because crucial questions remain about bCPAP feasibility, and whether similar outcomes can be consistently achieved in other non-tertiary hospitals in LMICs. The investigators used a local bCPAP set-up as a first-line therapy for children with pneumonia and hypoxaemia, requiring only nasal prongs, intravenous tubing, a water bottle, and a 10 L oxygen concentrator. Although practical, it is unclear whether this set-up benefits children from positive end-expiratory pressure, higher oxygen flows and concentration, or both. This is relevant because the set-up relies on an oxygen source to produce flow and availability of oxygen is insufficient in LMICs. Oxygen from concentrators can be effectively shared with as many as five children requiring lower flows, but just one child uses a concentrator in a bCPAP circuit. Thus, implementing this bCPAP set-up to treat all hypoxaemic pneumonia would require vastly higher oxygen supplies. If the pressure is benefiting patients, then redesigning the set-up to conserve oxygen would improve feasibility and reduce costs (the concentrator used in the trial costs US$1000–2000). Alternatively, if higher oxygen flow is benefiting patients, then alternatives such as high-flow oxygen might ease administration. Although bCPAP appears simple, it is deceivingly complex, necessitating monitoring for circuit leaks, heart failure, aspiration, and nasal obstruction and skin breakdown. These issues can largely be avoided, but the workload (and trained personnel) required is substantially higher than that for high-flow or low-flow oxygen.6Sessions KL Mvalo T Kondowe D et al.Bubble CPAP and oxygen for child pneumonia care in Malawi: a CPAP IMPACT time motion study.BMC Health Serv Res. 2019; 19: 533Crossref PubMed Scopus (7) Google Scholar Strategies to overcome these implementation challenges are needed. Ethiopia has the second highest child mortality rate in Africa,7GBD 2019 Under-5 Mortality CollaboratorsGlobal, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019.Lancet. 2021; 398: 870-905Summary Full Text Full Text PDF PubMed Google Scholar yet mortality in this study was rare. One explanation for this could be the high quality of paediatrician-led care and in half of the facilities access to intensive-care-trained personnel and resources, but it might also be explained by a healthier than typical LMIC study population. The fact that participating study hospitals required fee-for-service from patients might have served as a barrier for disadvantaged, high-risk patients. Low socioeconomic conditions are linked with high-risk ailments such as severe acute malnutrition and HIV, both of which are present in most pneumonia deaths in LMICs.1Wilkes C Bava M Graham HR Duke T What are the risk factors for death among children with pneumonia in low- and middle-income countries? A systematic review.J Glob Health. 2023; 1305003 Crossref PubMed Scopus (3) Google Scholar Although regional variation exists in Ethiopia, in this trial, prevalence of severe acute malnutrition was much lower (14%) than that reported in community-based studies (31%).8Mihret ST Biset G Nurye NA Prevalence of acute malnutrition and associated factors among children aged 6-59 months in South Wollo Zone, East Amhara, Northeast Ethiopia: a community-based cross-sectional study.BMJ Open. 2023; 13e062582 Crossref PubMed Scopus (1) Google Scholar Prevalence of HIV infection in pregnant women is also elevated in Ethiopia, but surprisingly none of the participants in the trial had HIV infection or HIV exposure.9Geremew D Tajebe F Ambachew S Endalamaw A Eshetie S Seroprevalence of HIV among pregnant women in Ethiopia: a systematic review and meta-analysis.BMC Res Notes. 2018; 11: 908Crossref PubMed Scopus (12) Google Scholar Data show that bCPAP is less effective in malnourished and HIV-affected paediatric populations, suggesting that wider bCPAP use in LMIC settings with these conditions might fail to produce similar results.10McCollum ED Mvalo T Eckerle M et al.Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial.Lancet Respir Med. 2019; 7: 964-974Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar Careful patient selection for bCPAP application is needed, but the questions of exactly who and how are unresolved. In summary, although key questions remain, this well executed trial provides important results to advance bCPAP closer to realising scalability and meaningful contributions to child pneumonia care in LMICs. EDM declares grants from the National Institutes of Health, Bill & Melinda Gates Foundation, USAID, US Centers for Disease Control and Prevention, Thrasher Research Fund, and Moderna; and participation on an advisory board for the TIMCI Trial. EMD is Co-chair for The Union Child Pneumonia Working Group. TM declares no competing interests. 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 trialIn 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. Full-Text PDF Open Access