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The effect of bethanechol on tracheobronchomalacia in preterm infants with bronchopulmonary dysplasia: a retrospective cohort study

Journal of Perinatology volume 44, pages 288–293 (2024)Cite this article

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Abstract

Objective

Bethanechol has demonstrated improvement in trachealis tone in animal models, but no trials have studied efficacy in infants. This study aimed to examine if bethanechol improves a standardized pulmonary severity score (PSS) in infants with severe bronchopulmonary dysplasia with a diagnosis of tracheobronchomalacia (TBM).

Study design

This retrospective cohort study evaluated cases treated with bethanechol matched with controls who did not receive bethanechol. TBM was diagnosed by dynamic computography. Daily PSS was recorded for each infant from 40 to 55 weeks post-menstrual age.

Results

Cases’ mean PSS change was 21% lower than the controls’ mean PSS change pre- and post-bethanechol (95% CI −40%, −2%) by paired t-test (p = 0.03). Matched differences (controls’ PSS – cases’ PSS) demonstrated greater mean PSS difference post-bethanechol compared to pre-bethanechol 0.17, (95% CI 0.05, 0.29) by paired t-test (p = 0.009).

Conclusion

Infants with TBM treated with bethanechol compared to those not treated had a lower PSS reflecting improved respiratory status.

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Fig. 1: Graphical representation of mean PSS differences of cases (N = 11) pre- and post-bethanechol.
Fig. 2: Graphical representation of daily mean pulmonary severity scores of cases (N = 11) and controls (N = 21) demonstrating a decrease after bethanechol treatment when compared with controls.
Fig. 3: The mean differences of matched controls’ PSS – case’s PSS were compared pre- and post-bethanechol.

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References

  1. Carden KA, Boiselle PM, Waltz DA, Ernst A. Tracheomalacia and tracheobronchomalacia in children and adults. Chest. 2005;127:984–1005.

    Article  PubMed  Google Scholar 

  2. Hysinger E, Friedman N, Jensen E, Zhang H, Piccione J. Bronchoscopy in neonates with severe bronchopulmonary dysplasia in the NICU. J Perinatol. 2019;39:263–8.

    Article  CAS  PubMed  Google Scholar 

  3. Bergeron M, Cohen AP, Cotton RT. The management of cyanotic spells in children with oesophageal atresia. Front Pediatr. 2017;5:106.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wallis C, Alexopoulou E, Antón-Pacheco JL, Bhatt JM, Bush A, Chang AB, et al. ERS statement on tracheomalacia and bronchomalacia in children. Eur Respir J. 2019;54:1900382.

    Article  PubMed  Google Scholar 

  5. Murgu SD, Colt HG. Tracheobronchomalacia and excessive dynamic airway collapse. Respirology. 2006;11:388–406.

    Article  PubMed  Google Scholar 

  6. Boiselle PM, O’Donnell CR, Bankier AA, Ernst A, Millet ME, Potemkin A, et al. Tracheal collapsibility in healthy volunteers during forced expiration: assessment with multidetector CT. Radiology 2009;252:255–62.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gunatilaka CC, Higano NS, Hysinger EB, Gandhi DB, Fleck RJ, Hahn AD, et al. Increased work of breathing due to tracheomalacia in neonates. Ann Am Thorac Soc. 2020;17:1247–56.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hysinger EB, Friedman NL, Padula MA, Shinohara RT, Zhang H, Panitch HB, et al. Tracheobronchomalacia is associated with increased morbidity in bronchopulmonary dysplasia. Ann Am Thorac Soc. 2017;14:1428–35.

  9. Boogaard R, Huijsmans SH, Pijnenburg MWH, Tiddens HAWM, de Jongste JC, Merkus PJFM. Tracheomalacia and bronchomalacia in children. Chest. 2005;128:3391–7.

    Article  PubMed  Google Scholar 

  10. Wagner EM, Jacoby DB. Methacholine causes reflex bronchoconstriction. J Appl Physiol. 1999;86:294–7.

    Article  CAS  PubMed  Google Scholar 

  11. Bass R, Santiago M, Smith L, Quinlan C, Panitch H, Giordano T, et al. Bethanechol in Tracheomalacia: two case series and a review of the literature. Pediatr Allergy Immunol Pulmonol. 2018;31:180–3.

    Article  Google Scholar 

  12. Bhutani VK, Koslo RJ, Shaffer TH. The effect of tracheal smooth muscle tone on neonatal airway collapsibility. Pediatr Res. 1986;20:492–5.

    Article  CAS  PubMed  Google Scholar 

  13. Panitch HB, Keklikian EN, Motley RA, Wolfson MR, Schidlow DV. Effect of altering smooth muscle tone on maximal expiratory flows in patients with tracheomalacia. Pediatr Pulmonol. 1990;9:170–6.

    Article  CAS  PubMed  Google Scholar 

  14. Madan A, Brozanski BS, Cole CH, Oden NL, Cohen G, Phelps DL. A pulmonary score for assessing the severity of neonatal chronic lung disease. Pediatrics 2005;115:e450–7.

    Article  PubMed  Google Scholar 

  15. Ullmann N, Secinaro A, Menchini L, Caggiano S, Verrillo E, Santangelo TP, et al. Dynamic expiratory CT: an effective non-invasive diagnostic exam for fragile children with suspected tracheo-bronchomalacia. Pediatr Pulmonol. 2018;53:73–80.

    Article  PubMed  Google Scholar 

  16. Ngerncham M, Lee EY, Zurakowski D, Tracy DA, Jennings R. Tracheobronchomalacia in pediatric patients with esophageal atresia: Comparison of diagnostic laryngoscopy/bronchoscopy and dynamic airway multidetector computed tomography. J Pediatr Surg. 2015;50:402–7.

    Article  PubMed  Google Scholar 

  17. Goo HW. Free-breathing cine CT for the diagnosis of tracheomalacia in young children. Pediatr Radio. 2013;43:922–8.

    Article  Google Scholar 

  18. Greenberg SB. Dynamic pulmonary CT of children. Am J Roentgenol. 2012;199:435–40.

    Article  Google Scholar 

  19. Lee EY, Boiselle PM. Tracheobronchomalacia in infants and children: multidetector CT evaluation. Radiology. 2009;252:7–22.

    Article  PubMed  Google Scholar 

  20. Lee EY, Zurakowski D, Waltz DA, Mason KP, Riaz F, Ralph A, et al. MDCT evaluation of the prevalence of tracheomalacia in children with mediastinal aortic vascular anomalies. J Thorac Imaging. 2008;23:258–65.

    Article  PubMed  Google Scholar 

  21. Greenberg SB, Dyamenahalli U. Dynamic pulmonary computed tomography angiography: a new standard for evaluation of combined airway and vascular abnormalities in infants. Int J Cardiovasc Imaging. 2014;30:407–14.

    Article  PubMed  Google Scholar 

  22. Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. An evidence-based approach. Am J Respir Crit Care Med. 2019;200:751–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Panitch HB, Talmaciu I, Heckman J, Wolfson MR, Shaffer TH. Quantitative bronchoscopic assessment of airway collapsibility in newborn lamb tracheae. Pediatr Res. 1998;43:832–9.

    Article  CAS  PubMed  Google Scholar 

  24. Davis S, Jones M, Kisling J, Angelicchio C, Tepper RS. Effect of continuous positive airway pressure on forced expiratory flows in infants with tracheomalacia. Am J Respir Crit Care Med. 1998;158:148–52.

    Article  CAS  PubMed  Google Scholar 

  25. Nealon E, Rivera BK, Cua CL, Ball MK, Stiver C, Boe BA, et al. Follow-up after percutaneous patent ductus arteriosus occlusion in lower weight infants. J Pediatr. 2019;212:144–50. e3

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pugh CP, Arkansas Children’s Hospital Research Institute. The effect of bethanechol on work of breathing and expiratory tracheal collapse in infants with tracheobronchomalacia measured by electrical activity of the diaphragm and bronchoscopy. (2022). Available from: https://clinicaltrials.gov/ct2/show/NCT05299008.

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Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    C. Preston Pugh, Sherry E. Courtney, Amit Agarwal, Angela Chandler & David N. Matlock

  2. Biostatistics, Arkansas Children’s Research Institute, Little Rock, AR, USA

    Chary Akmyradov

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  1. C. Preston Pugh
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Correspondence to C. Preston Pugh.

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Pugh, C.P., Akmyradov, C., Courtney, S.E. et al. The effect of bethanechol on tracheobronchomalacia in preterm infants with bronchopulmonary dysplasia: a retrospective cohort study. J Perinatol 44, 288–293 (2024). https://doi.org/10.1038/s41372-023-01799-x

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