Upper Airway Manifestations and Otolaryngologic Management of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review

ENT Updates

Review

Upper Airway Manifestations and Otolaryngologic Management of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review

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https://doi.org/10.54963/entu.v15i3.1256
Almutairi, M., Alomari, S., Alomari, N., Aldhafeeri, F., Almutairi, A., Alqathanin, W., Aljifri, H., Alsaggaf, S., Halawany, K., Alhunaiti, D., Al-Qahtani, H., Felemban, A., Alshehri, A., Alsubaie, M., & Kanan, M. (2025). Upper Airway Manifestations and Otolaryngologic Management of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review. ENT Updates, 15(3), 1–14. https://doi.org/10.54963/entu.v15i3.1256
Volume 15 Issue 3 (2025)
Copyright (c) 2025 Mohammed Almutairi, Sahar Alomari, Nujood Alomari, Fahdah Aldhafeeri, Abeer Almutairi, Wajan Alqathanin, Hind Aljifri, Sarah Alsaggaf, Khaled Halawany, Dana Alhunaiti, Hadeel Al-Qahtani, Alla Felemban, Amal Alshehri, Mashael Alsubaie, Mohammed Kanan
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This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors

  • Mohammed Almutairi

    Dental Department, Northern Area Armed Forces Hospital, King Khalid Military City, Hafr Al Batin 31991, Saudi Arabia
  • Sahar Alomari

    Department of Doctor of Pharmacy, Al-Baha university, Al-Baha 65779, Saudi Arabia
  • Nujood Alomari

    Department of Doctor of Pharmacy, Al-Baha university, Al-Baha 65779, Saudi Arabia
  • Fahdah Aldhafeeri

    Department of‏ health care & family medicine, Northern Area Armed Forces Hospital, King Khalid Military City, Hafr Al Batin 31991, Saudi Arabia
  • Abeer Almutairi

    Social worker Department, Northern Area Armed Forces Hospital, King Khalid Military City, Hafr Al Batin 31991, Saudi Arabia
  • Wajan Alqathanin

    Department of Doctor of Pharmacy, College of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia
  • Hind Aljifri

    Faculty of Medicine, Fakeeh College of Medical Sciences, Jeddah 23323, Saudi Arabia
  • Sarah Alsaggaf

    Department of Doctor of Pharmacy, King Abdulaziz University, Jeddah 22254, Saudi Arabia
  • Khaled Halawany

    Department of Doctor of Pharmacy, Armed Forces Hospital, Wadi ad-Dawasir 18511, Saudi Arabia
  • Dana Alhunaiti

    Department of Doctor of Pharmacy, College of Pharmacy, Umm-Al-Qura University, Makkah 24382, Saudi Arabia
  • Hadeel Al-Qahtani

    Doctor of Pharmacy, King Faisal University, Al Hofuf 31982, Saudi Arabia
  • Alla Felemban

    Pediatrics Department, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia
  • Amal Alshehri

    Department of Doctor of Pharmacy, College of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia
  • Mashael Alsubaie

    Department of Pharmaceutical Science, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16278, Saudi Arabia
  • Mohammed Kanan

    Department of Pharmacy, Rafha General Hospital, Northern Border Health Cluster, Rafha 76321, Saudi Arabia

Bronchopulmonary dysplasia (BPD) is a complex chronic lung disorder that affects extremely premature infants, particularly those born before 30 weeks of gestation or weighing less than 1500 g at birth. This systematic review aimed to evaluate the effectiveness of pharmacological interventions for BPD and to explore otolaryngologic manifestations and management strategies. A comprehensive literature search was conducted in the PubMed, Scopus, and Web of Science databases, yielding five studies that met the inclusion criteria. The studies investigated the effects of corticosteroids (prednisolone, hydrocortisone, and dexamethasone), erythropoietin, and diuretics on BPD outcomes. Prednisolone showed minimal short-term benefits, whereas hydrocortisone did not significantly reduce the incidence of BPD. However, extended dexamethasone regimens have been shown to improve survival rates without increasing complications. Early erythropoietin treatment reduced the incidence of BPD but did not affect hospital readmission rates. Diuretic use varied widely across centers, without clear survival or discharge benefits. Preterm infants with severe BPD requiring prolonged mechanical ventilation are at a high risk of subglottic stenosis, tracheomalacia, and vocal cord paralysis. Early diagnosis through airway endoscopy and multidisciplinary management, including tracheostomy for severe cases, are crucial for optimizing outcomes. BPD survivors may experience long-term respiratory impairment, exercise intolerance, and developmental delays, necessitating close monitoring and intervention. Future research should focus on developing standardized, evidence-based management protocols and exploring novel therapies to improve long-term respiratory and neurodevelopmental outcomes in this vulnerable population group.

Keywords:

Bronchopulmonary Dysplasia Subglottic Stenosis Airway Obstruction Neonatal Intubation Laryn‑ goscopy Corticosteroids

References

  1. Htun, Z. T.; Schulz, E. V.; Desai, R. K.; et al. Postnatal Steroid Management in Preterm Infants with Evolving Bronchopulmonary Dysplasia. J. Perinatol. 2021, 41, 1783–1796.
  2. O’Reilly, M.; Thébaud, B. Animal Models of Bronchopulmonary Dysplasia. The Term Rat Models. Am. J. Physiol. Lung Cell Mol. Physiol. 2014, 307, L948–L958.
  3. Thekkeveedu, R. K.; Guaman, M. C.; Shivanna, B. Bronchopulmonary Dysplasia: A Review of Pathogenesis and Pathophysiology. Respir. Med. 2017, 132, 170–177.
  4. Baker, C. D.; Abman, S. H. Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia. Neonatology 2015, 107, 344–351.
  5. Salimi, U.; Dummula, K.; Tucker, M. H.; et al. Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD". Am. J. Respir. Cell Mol. Biol. 2022, 66, 137–145.
  6. Malleske, D. T.; Chorna, O.; Maitre, N. L. Pulmonary Sequelae and Functional Limitations in Children and Adults with Bronchopulmonary Dysplasia. Paediatr. Respir. Rev. 2018, 26, 55–59.
  7. Zhang, S.; Mulder, C.; Riddle, S.; et al. Mesenchymal Stromal/Stem Cells and Bronchopulmonary Dysplasia. Front. Cell Dev. Biol. 2023, 11, 1247339.
  8. Ito, M.; Kato, S.; Saito, M.; et al. Bronchopulmonary Dysplasia in Extremely Premature Infants: A Scoping Review for Identifying Risk Factors. Biomedicines 2023, 11, 553.
  9. Klinger, G.; Sokolover, N.; Boyko, V.; et al. Perinatal Risk Factors for Bronchopulmonary Dysplasia in a National Cohort of Very-Low-Birthweight Infants. Am. J. Obstet. Gynecol. 2013, 208, 115.e1–115.e9.
  10. Rutkowska, M.; Hożejowski, R.; Helwich, E.; et al. Severe Bronchopulmonary Dysplasia - Incidence and Predictive Factors in a Prospective, Multicenter Study in Very Preterm Infants with Respiratory Distress Syndrome. J. Matern. Fetal Neonatal Med. 2019, 32, 1958–1964.
  11. Trembath, A.; Laughon, M. M. Predictors of Bronchopulmonary Dysplasia. Clin. Perinatol. 2012, 39, 585–601.
  12. Laughon, M. M.; Langer, J. C.; Bose, C. L.; et al. Prediction of Bronchopulmonary Dysplasia by Postnatal Age in Extremely Premature Infants. Am. J. Respir. Crit. Care Med. 2011, 183, 1715–1722.
  13. Davidson, L. M.; Berkelhamer, S. K. Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes. J. Clin. Med. 2017, 6, 4.
  14. Gibbs, K.; Jensen, E. A.; Alexiou, S.; et al. Ventilation Strategies in Severe Bronchopulmonary Dysplasia. Neo-reviews 2020, 21, e226–e237.
  15. Sammour, I.; Karnati, S. Non-invasive Respiratory Support of the Premature Neonate: From Physics to Bench to Practice. Front. Pediatr. 2020, 8, 214.
  16. Escribá Alepuz, F. J.; Alonso Garcı́a, J.; Cuchillo Sastriques, J. V.; et al. Emergency Ventilation of Infant Subglottic Stenosis Through Small-Gauge Lumen Using the Ventrain: A Case Report. A A Pract. 2018, 10, 136–138.
  17. Dankle, S. K.; Schuller, D. E.; McClead, R. E. Risk Factors for Neonatal Acquired Subglottic Stenosis. Ann. Otol. Rhinol. Laryngol. 1986, 95, 626–630.
  18. Downing, G. J.; Kilbride, H. W. Evaluation of Airway Complications in High-Risk Preterm Infants: Application of Flexible Fiberoptic Airway Endoscopy. Pediatrics 1995, 95, 567–572.
  19. Ehret, J.; Thomas, A.; Penn, D. L.; et al. Delayed Bilateral Vocal Cord Paralysis Following Cervical Spine Trauma. Cureus 2023, 15, e39891.
  20. Miyake, F.; Ito, M.; Minami, H.; et al. Management of Bronchopulmonary Dysplasia in Japan: A 10-Year Nationwide Survey. Pediatr. Neonatol. 2020, 61, 272–278.
  21. Hulscher, J. B.; van Sandick, J. W.; Devriese, P. P.; et al. Vocal Cord Paralysis After Subtotal Oesophagectomy. Br. J. Surg. 1999, 86, 1583–1587.
  22. Bush, D.; Juliano, C.; Bowler, S.; et al. Development and Disorders of the Airway in Bronchopulmonary Dysplasia. Children 2023, 10, 1127.
  23. Pérez-Ramı́rez, R. O.; Lona-Reyes, J. C.; Ochoa-Meza, C. A.; et al. Neonatal Morbidity and Mortality Associated with Low Adherence to Prenatal Corticosteroids. An. Pediatr. (Engl. Ed.) 2019, 91, 105–111.
  24. Linafelter, A.; Cuna, A.; Liu, C.; et al. Extended Course of Prednisolone in Infants with Severe Bronchopulmonary Dysplasia. Early Hum. Dev. 2019, 136, 1–6.
  25. Wilson-Costello, D.; Walsh, M. C.; Langer, J. C.; et al. Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Months’ Adjusted Age: Effects of Dose, Timing, and Risk of Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants. Pediatrics 2009, 123, e430–e437.
  26. Onland, W.; Cools, F.; Kroon, A.; et al. Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA 2019, 321, 354–363.
  27. Doyle, L. W.; Cheong, J. L. Y. Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia - Who Might Beneϐit? Semin. Fetal Neonatal Med. 2017, 22, 290–295.
  28. Bassler, D.; van den Anker, J. Inhaled Drugs and Systemic Corticosteroids for Bronchopulmonary Dysplasia. Pediatr. Clin. North Am. 2017, 64, 1355–1367.
  29. Bui, K. C. T.; Kim, R.; Abbasi, A.; et al. Erythropoietin Treatment Is Associated with a Reduction in Moderate to Severe Bronchopulmonary Dysplasia in Preterm Infants. A Regional Retrospective Study. Early Hum. Dev. 2019, 137, 104831.
  30. Principi, N.; Di Pietro, G. M.; Esposito, S. Bronchopulmonary Dysplasia: Clinical Aspects and Preventive and Therapeutic Strategies. J. Transl. Med. 2018, 16, 36.
  31. Mandell, E. W.; Kratimenos, P.; Abman, S. H.; et al. Drugs for the Prevention and Treatment of Bronchopul monary Dysplasia. Clin. Perinatol. 2019, 46, 291–310.
  32. Bhandari, A.; Panitch, H. An Update on the Post-NICU Discharge Management of Bronchopulmonary Dysplasia. Semin. Perinatol. 2018, 42, 471–477.
  33. Bamat, N. A.; Nelin, T. D.; Eichenwald, E. C.; et al. Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge. J. Pediatr. 2021, 231, 43–49.
  34. Ogawa, R.; Mori, R.; Iida, K.; et al. Effects of the Early Administration of Sivelestat Sodium on Bronchopulmonary Dysplasia in Infants: A Retrospective Cohort Study. Early Hum. Dev. 2017, 115, 71–76.
  35. Papagianis, P. C.; Pillow, J. J.; Moss, T. J. Bronchopulmonary Dysplasia: Pathophysiology and Potential Anti-Inflammatory Therapies. Paediatr. Respir. Rev. 2019, 30, 34–41.
  36. Suzuki, T.; Sato, Y.; Yamamoto, H.; et al. Mesenchymal Stem/Stromal Cells Stably Transduced with an Inhibitor of CC Chemokine Ligand 2 Ameliorate Bronchopulmonary Dysplasia and Pulmonary Hypertension. Cytotherapy 2020, 22, 180–192.
  37. Miller, A. N.; Shepherd, E. G.; Manning, A.; et al. Tracheostomy in Severe Bronchopulmonary Dysplasia-How to Decide in the Absence of Evidence. Biomedicines 2023, 11, 2572.
  38. Isaiah, A.; Moyer, K.; Pereira, K. D. Current Trends in Neonatal Tracheostomy. JAMA Otolaryngol. Head Neck Surg. 2016, 142, 738–742.
  39. Upadhyay, K.; Vallarino, D. A.; Talati, A. J. Outcomes of Neonates with Tracheostomy Secondary to Bronchopulmonary Dysplasia. BMC Pediatr. 2020, 20, 414.
  40. House, M.; Nathan, A.; Bhuiyan, M. A. N.; et al. Morbidity and Respiratory Outcomes in Infants Requiring Tracheostomy for Severe Bronchopulmonary Dysplasia. Pediatr. Pulmonol. 2021, 56, 2589–2596.
  41. Kielt, M. J.; Levin, J. C.; MBI. To Trach or Not To Trach: Long-term Tracheostomy Outcomes in Infants with BPD. Neoreviews 2023, 24, e704–e719.
  42. Gien, J.; Kinsella, J.; Thrasher, J.; et al. Retrospective Analysis of an Interdisciplinary Ventilator Care Program Intervention on Survival of Infants with Ventilator-Dependent Bronchopulmonary Dysplasia. Am. J. Perinatol. 2017, 34, 155–163.
  43. Lemyre, B.; Davis, P. G.; De Paoli, A. G.; Kirpalani H. Nasal Intermittent Positive Pressure Ventilation (NIPPV) Versus Nasal Continuous Positive Airway Pressure (NCPAP) for Preterm Neonates After Extubation. Cochrane Database Syst. Rev. 2017, 2, CD003212.
  44. Duijts, L.; van Meel, E. R.; Moschino, L.; et al. European Respiratory Society Guideline on Long-Term Management of Children with Bronchopulmonary Dysplasia. Eur. Respir. J. 2020, 55, 1900788.
  45. Sehgal, A.; Steenhorst, J. J.; McLennan, D. I.; et al. The Left Heart, Systemic Circulation, and Bronchopulmonary Dysplasia: Relevance to Pathophysiology and Therapeutics. J. Pediatr. 2020, 225, 13–22.
  46. Moher, D.; Shamseer, L.; Clarke, M.; et al. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 Statement. Syst. Rev. 2015, 4, 1–9.
  47. Marr, B. L.; Mettelman, B. B.; Bode, M. M.; et al. Randomized Trial of 42-Day Compared with 9-Day Courses of Dexamethasone for the Treatment of Evolving Bronchopulmonary Dysplasia in Extremely Preterm Infants. J. Pediatr. 2019, 211, 20–26.
  48. Jensen, E. A.; Dysart, K.; Gantz, M. G.; et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-Based Approach. Am. J. Respir. Crit. Care Med. 2019, 200, 751–759.
  49. Thébaud, B.; Goss, K. N.; Laughon, M.; et al. Bronchopulmonary Dysplasia. Nat. Rev. Dis. Primers 2019, 5, 78.
  50. Greenberg, R. G.; Gayam, S.; Savage, D.; et al. Furosemide Exposure and Prevention of Bronchopulmonary Dysplasia in Premature Infants. J. Pediatr. 2019, 208, 134–140.
  51. Lodha, A.; Seshia, M.; McMillan, D. D.; et al. Association of Early Caffeine Administration and Neonatal Outcomes in Very Preterm Neonates. JAMA Pediatr. 2015, 169, 33–38.
  52. Jensen, E. A. What Is Bronchopulmonary Dysplasia and Does Caffeine Prevent It? Semin. Fetal Neonatal Med. 2020, 25, 101176.
  53. Darlow, B. A.; Graham P. J.; Rojas-Reyes M. X. Vitamin A Supplementation to Prevent Mortality and Short- and Long-Term Morbidity in Very Low Birth Weight Infants. Cochrane Database Syst. Rev. 2016, 2016(8), CD000501.
  54. Hysinger, E. B. Central Airway Issues in Bronchopulmonary Dysplasia. Pediatr. Pulmonol. 2021, 56, 3518– 3526.
  55. Wu, K. Y.; Jensen, E. A.; White, A. M.; et al. Characterization of Disease Phenotype in Very Preterm Infants with Severe Bronchopulmonary Dysplasia. Am. J. Respir. Crit. Care Med. 2020, 201, 1398–1406.
  56. Jensen, E. A.; Schmidt, B. Epidemiology of Bronchopulmonary Dysplasia. Birth Defects Res. A Clin. Mol. Teratol. 2014, 100, 145–157.
  57. Duncan, S.; Eid, N. Tracheomalacia and Bronchopulmonary Dysplasia. Ann. Otol. Rhinol. Laryngol. 1991, 100, 856–858.
  58. Donda, K.; Agyemang, C. O.; Adjetey, N. A.; et al. Tracheostomy Trends in Preterm Infants with Bronchopulmonary Dysplasia in the United States: 2008–2017. Pediatr. Pulmonol. 2021, 56, 1008–1017.
  59. Ambalavanan, N.; Mourani, P. Pulmonary Hypertension in Bronchopulmonary Dysplasia. Birth Defects Res. A Clin. Mol. Teratol. 2014, 100, 240–246.
  60. Carraro, S.; Piacentini, G.; Lusiani, M.; et al. Exhaled Air Temperature in Children with Bronchopulmonary Dysplasia. Pediatr. Pulmonol. 2010, 45, 1240–1245.
  61. Thomas, S. R.; Jain, S. K.; Murthy, P.; et al. Neurodevelopmental Outcomes of Preterm Infants Born <29 Weeks with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Multicenter Study. Am. J. Perinatol. 2024, 41, e2505–e2513.

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