Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta-analysis
Wei Tang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorSisi Chen
School of Clinical Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, China
Contribution: Formal analysis (equal), Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorDongmei Shi
Department of Endocrinology, Children's Hospital, Chongqing Medical University, Chongqing, China
Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Validation (equal), Visualization (equal)
Search for more papers by this authorCorresponding Author
Tao Ai
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Correspondence Tao Ai, Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.
Email: [email protected]
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorLei Zhang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (supporting), Formal analysis (equal), Funding acquisition (lead), Methodology (equal), Project administration (equal)
Search for more papers by this authorYijie Huang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (equal), Formal analysis (equal), Resources (equal), Writing - original draft (supporting)
Search for more papers by this authorYinghong Fan
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Formal analysis (equal), Supervision (equal), Writing - review & editing (supporting)
Search for more papers by this authorYiting Du
Department of Emergency, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Formal analysis (equal), Methodology (equal), Resources (equal), Supervision (equal)
Search for more papers by this authorWei Tang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorSisi Chen
School of Clinical Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, China
Contribution: Formal analysis (equal), Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorDongmei Shi
Department of Endocrinology, Children's Hospital, Chongqing Medical University, Chongqing, China
Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Validation (equal), Visualization (equal)
Search for more papers by this authorCorresponding Author
Tao Ai
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Correspondence Tao Ai, Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.
Email: [email protected]
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorLei Zhang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (supporting), Formal analysis (equal), Funding acquisition (lead), Methodology (equal), Project administration (equal)
Search for more papers by this authorYijie Huang
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Conceptualization (equal), Formal analysis (equal), Resources (equal), Writing - original draft (supporting)
Search for more papers by this authorYinghong Fan
Department of Respiratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Formal analysis (equal), Supervision (equal), Writing - review & editing (supporting)
Search for more papers by this authorYiting Du
Department of Emergency, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Contribution: Formal analysis (equal), Methodology (equal), Resources (equal), Supervision (equal)
Search for more papers by this authorAbstract
Objective
To address the effectiveness and safety of early airway combined utilization of budesonide and surfactant for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome (RDS).
Methods
Literature retrieval was carried out in the PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, CQ VIP, and China National Knowledge Infrastructure databases, searching from the inception to September 2021. Stata 16.0 software was used for statistical analysis.
Results
This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway have a superiority on BPD incidence (risk ratio [RR] = 0.62; 95% confidence interval [CI]: 0.54–0.71, p < 0.001], mortality (RR = 0.64; 95%CI: 0.45–0.92, p = 0.016), the composite outcome of BPD or mortality (RR = 0.58; 95%CI: 0.50–0.68, p < 0.001), the additional doses of surfactant (RR = 0.53; 95%CI: 0.44–0.63, p < 0.001), the duration of assisted ventilation (standard mean difference [SMD] = −1.14; 95%CI: −1.58 to −0.70, p < 0.001), duration of invasive ventilation(SMD = −1.77; 95% CI: −2.61 to −0.93, p < 0.001), and hospital stays (SMD = −1.11; 95% CI: −1.73 to −0.49, p = 0.001) in preterm infants with RDS. And these benefits were not associated with increased adverse outcomes. Furthermore, a decreased incidence of patent ducts arterious (PDA) (RR = 0.79; 95% CI: 0.65 to 0.97, p = 0.028) was found in premature infants treated with budesonide and surfactant. Subgroup analysis based on budesonide delivery methods (inhalation or intratracheal instillation) indicated that the decrease of mortality (RR = 0.63; 95% CI: 0.43–0.93, p = 0.019), duration of assisted ventilation (SMD = −0.95; 95% CI: −1.30 to −0.61, p < 0.001), hospital stays (SMD = −1.23; 95% CI: −2.05 to −0.41, p = 0.003) and PDA incidence (RR = 0.80; 95% CI: 0.65 to 0.99, p = 0.044) were mainly in budesonide intratracheal instillation subgroup, rather than in budesonide inhalation subgroup.
Conclusions
This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway might be an effective and safe clinical practice for BPD prevention in premature infants with RDS, especially when budesonide was delivered by intratracheal instillation. However, many of the included studies were small and were from Asian origin. More well-designed randomized controlled trials with larger sample sizes and longer follow-up from all over the world ought to be conducted in the future.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
REFERENCES
- 1Hilgendorff A, Reiss I, Ehrhardt H, Eickelberg O, Alvira CM. Chronic lung disease in the preterm infant. Lessons learned from animal models. Am J Respir Cell Mol Biol. 2014; 50(2): 233-245.
- 2Thébaud B, Goss KN, Laughon M, et al. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019; 5(1): 1-23.
- 3Siffel C, Kistler KD, Lewis JF, Sarda SP. Global incidence of bronchopulmonary dysplasia among extremely preterm infants: a systematic literature review. J Matern-Fetal Neonat Med. 2021; 34(11): 1721-1731.
- 4Gough A, Spence D, Linden M, Halliday HL, McGarvey LP. General and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia: a systematic review. Chest. 2012; 141(6): 1554-1567.
- 5Cummings JJ, D'Eugenio DB, Gross SJ. A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med. 1989; 320(23): 1505-1510.
- 6Baud O, Maury L, Lebail F, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016; 387(10030): 1827-1836.
- 7Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Early (<8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2017; 10:CD001146.
- 8Zeng L, Tian J, Song F, et al. Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis. Arch Dis Child-Fetal Neonatal Ed. 2018; 103(6): F506-F511.
- 9Shah SS, Ohlsson A, Halliday HL, Shah VS. Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev. 2012;(5):CD002058.
- 10O'Callaghan C, Hardy J, Stammers J, Stephenson T, Hull D. Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model. Arch Dis Child. 1992; 67(1 Spec No): 20-24.
- 11Bassler D, Plavka R, Shinwell ES, et al. Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med. 2015; 373(16): 1497-1506.
- 12Shinwell ES, Portnov I, Meerpohl JJ, Karen T, Bassler D. Inhaled corticosteroids for bronchopulmonary dysplasia: a meta-analysis. Pediatrics. 2016; 138(6):e20162511.
- 13Bassler D, Shinwell ES, Hallman M, et al. Long-term effects of inhaled budesonide for bronchopulmonary dysplasia. N Engl J Med. 2018; 378(2): 148-157.
- 14Venkataraman R, Kamaluddeen M, Hasan SU, Robertson HL, Lodha A. Intratracheal administration of budesonide-surfactant in prevention of bronchopulmonary dysplasia in very low birth weight infants: a systematic review and meta-analysis. Pediatr Pulmonol. 2017; 52(7): 968-975.
- 15Shuster JJ. Review: cochrane handbook for systematic reviews for interventions, Version 5.1.0, published 3/2011. Julian P.T. Higgins and Sally Green, Editors. Res Synth Methods. 2011; 2(2): 126-130.
10.1002/jrsm.38 Google Scholar
- 16Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097.
- 17Mander A, Clayton D. Assessing the influence of a single study in meta-analysis. Stata Tech Bull Reprints. 1999; 8: 108-110.
- 18Stata C. Stata statistical software: Release 12. StataCorp LP; 2007.
- 19Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008; 121(5): e1310-e1318.
- 20Kuo HT, Lin HC, Tsai CH, Chouc I, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr. 2010; 156(4): 537-541.
- 21Ke H, Li Z-K, Yu X-P, Guo J-Z. Efficacy of different preparations of budesonide combined with pulmonary surfactant in the treatment of neonatal respiratory distress syndrome: a comparative analysis. Chin J Contemp Pediatr. 2016; 18(5): 400-404.
- 22Yeh TF, Chen CM, Wu SY, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2016; 193(1): 86-95.
- 23Deng L-J, Peng H-B, Gong X-Q. Effect of budesonide combined with pulmonary surfactant on severe respiratory distress syndrome in bronchopulmonary dysplasia. Chin J Neonatol. 2017; 32(5): 361-364.
- 24Pan J, Chen M-W, Ni W-Q, et al. Clinical efficacy of pulmonary surfactant combined with budesonide for preventing bronchopulmonary dysplasia in very low birth weight infants. Chin J Contemp Pediatr. 2017; 19(2): 137-141.
- 25Cao Y-Y, Yao G, Wang Y, Shi B-H, Liu J-L, Li G-F. Aerosol inhalation of budesonide and pulmonary surfactant to prevent bronchopulmonary dysplasia. J Pediatr Pharm. 2018; 24(3): 25-29.
- 26Luo L-Y, Chen K-H, Cao B-B. Observation on the efficacy of budesonide combined with pulmonary surfactant to prevent bronchopulmonary dysplasia in premature infants. Zhejiang Clin Med J. 2018; 5(20): 796-798.
- 27Sadeghnia A, Beheshti BK, Mohammadizadeh M. The effect of inhaled budesonide on the prevention of chronic lung disease in premature neonates with respiratory distress syndrome. Int J Prev Med. 2018; 9: 15.
- 28Kou C, Han D, Li Z-N, et al. Effect of intratracheal administration of pulmonary surfactant plus budesonide on bronchopulmonary dysplasia in premature infant. China Med. 2019; 1(14): 53-57.
- 29Ping L-L, Zhang S-Y, Zhai S-F. Influence of combined drug therapy by intratracheal infusion on clinical prognosis of premature infants with severe RDS. Chin J Postgrad Med. 2019; 2(42): 154-157.
- 30Wang Y-S, Yang M, Han P, Dai Q-M, Cui C-Y. Effect of budesonide suspension oxygenation atomization inhalation on prevention and treatment of bronchopulmonary dysplasia in premature infants. J Clin Exp Med. 2019; 19: 2121-2124.
- 31Zhou X-P, Zhou J, Hu B, Wang X-H. Effects of budesonide combined with pulmonary surfactant on short-term efficacy,blood oxygenation index and risk of bronchopulmonary dysplasia in premature infants with severe respiratory distress syndrome. J Pediatr Pharm. 2019; 11(25): 27-30.
- 32Du FL, Dong WB, Zhang C, et al. Budesonide and Poractant Alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway. Eur Rev Med Pharmacol Sci. 2019; 23(24): 11032-11042.
- 33Heo M, Jeon GW. Intratracheal administration of budesonide with surfactant in very low birth weight infants to prevent bronchopulmonary dysplasia. Turk J Pediatr. 2020; 62(4): 551-559.
- 34Yang B, Lei H-L, Ren Y, et al. Pulmonary surfactant in combination with intratracheal budesonide instillation for treatment of respiratory distress syndrome in preterm infants: a randomized controlled trial. Chin J Neonatol. 2021; 2(36): 33-37.
- 35Gharehbaghi MM, Ganji S, Mahallei M. A randomized clinical trial of intratracheal administration of surfactant and budesonide combination in comparison to surfactant for prevention of bronchopulmonary dysplasia. Oman Med J. 2021; 36(4):e289.
- 36Yi-jiang C, Shui-tang Z, Run-na Y. Intratracheal administration of budesonide within seven days after birth for preventing bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis. Chin J Evidence-Based Pediatr. 2016; 11(4): 259-264.
- 37Moschino L, Nardo D, Bonadies L, et al. Intra-tracheal surfactant/budesonide versus surfactant alone: Comparison of two consecutive cohorts of extremely preterm infants. Pediatr Pulmonol. 2021; 56(7): 2114-2124.
- 38Doyle LW, Victorian Infant Collaborative Study G. Respiratory function at age 8–9 years in extremely low birthweight/very preterm children born in Victoria in 1991–1992. Pediatr Pulmonol. 2006; 41(6): 570-576.
- 39Vom Hove M, Prenzel F, Uhlig HH, Robel-Tillig E. Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age. J Pediatr. 2014; 164(1): 40-45.e44.
- 40Dumpa V, Bhandari V. Surfactant, steroids and non-invasive ventilation in the prevention of BPD. Semin Perinatol. 2018; 42(7): 444-452.
- 41Morrow LA, Wagner BD, Ingram DA, et al. Antenatal determinants of bronchopulmonary dysplasia and late respiratory disease in preterm infants. Am J Respir Crit Care Med. 2017; 196(3): 364-374.
- 42Cole CH. Postnatal glucocorticoid therapy for prevention of bronchopulmonary dysplasia: routes of administration compared. Semin Neonatol. 2001; 6(4): 343-350.
- 43Esmailpour N, Högger P, Rohdewald P. Binding kinetics of budesonide to the human glucocorticoid receptor. Eur J Pharm Sci. 1998; 6(3): 219-223.
- 44Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000; 343(15): 1064-1069.
- 45Szefler SJ. Pharmacodynamics and pharmacokinetics of budesonide: a new nebulized corticosteroid. J Allergy Clin Immunol. 1999; 104(4): S175-S183.
- 46Huang L-T, Yeh T-F, Kuo Y-L, Chen P-C, Chen C-M. Effect of surfactant and budesonide on the pulmonary distribution of fluorescent dye in mice. Pediatr Neonatol. 2015; 56(1): 19-24.
- 47Li L, Yang C, Feng X, Du Y, Zhang Z, Zhang Y. Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits. Pediatr Pulmonol. 2018; 53(1): 28-35.
- 48Kothe TB, Kemp MW, Schmidt A, et al. Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep. Am J Physiol-Lung Cell Mol Physiol. 2019; 316(5): L888-L893.
- 49Hillman NH, Kothe TB, Schmidt AF, et al. Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep. Am J Physiol-Lung Cell Mol Physiol. 2020; 318(1): L41-L48.
- 50Wiedmann T, Bhatia R, Wattenberg L. Drug solubilization in lung surfactant. J Controlled Release. 2000; 65(1-2): 43-47.
- 51Barrette AM, Roberts JK, Chapin C, et al. Antiinflammatory effects of budesonide in human fetal lung. Am J Respir Cell Mol Biol. 2016; 55(5): 623-632.
- 52Moore CD, Roberts JK, Orton CR, et al. Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes. Drug Metab Dispos. 2013; 41(2): 379-389.
Citing Literature
