medigraphic.com
ISSN 1561-3119 (Electronic)

2021, Number 4

<< Back Next >>

Rev Cubana Pediatr 2021; 93 (4)

Randomized trial: inflammatory response to corticoids versus placebo in moderate and severe bronchiolitis. COTHEB study

Felipe VA, Balaguer GM, Alejandre GC, Esteban TE, Manrique LLA, Muñoz-Almagro C, Esteban TME, Cambra LFJ, Jordan GI

Language: English
References: 34
Page: 1-18
PDF size: 1157.82 Kb.


ABSTRACT

Introduction: The use of corticosteroids has been shown not to improve the prognosis of patients with bronchiolitis, but it could be assumed that steroids will reduce inflammation.
Objective: This study aimed to assess whether corticoid therapy influenced the inflammatory and clinical response of critically ill infants.
Methods: Prospective, randomized, double blind placebo-controlled trial of glucocorticoids (GCT) in infants of less than 12 months with severe or moderate bronchiolitis. Patients were randomized to receive systemic corticoid therapy (low dose for 7 days) or placebo. The main outcomes were: a) levels of lymphocyte subsets; b) levels of IL-2, IL-12, and IFNγ as pro-inflammatory factors, and c) levels of IL-4 and IL-10 as anti-inflammatory response. Secondary outcomes related with the clinical response were also analyzed.
Results: 97 patients were randomized. Evolution of lymphocyte subsets was similar in both groups. Pro-inflammatory interleukins and interferon decreased, but without differences. Anti-inflammatory interleukins showed a significant decrease from baseline to the end of the study, and IL-10 values were significantly lower (p = 0.046) in the GCT group [1.82 pg/ml (1.2-3.5)] vs non-GCT [4 pg/ml (1.5-6.3)]. GCT group showed a lower time of mechanical ventilation and of hospitalization, but without statistically significant differences. No cases of severe adverse reaction to steroids were detected.
Conclusions: Administration of systemic GCT did not modify the inflammatory nor the clinical response of patients with severe bronchiolitis, except for IL-10 levels that were significantly lower in the GCT group. This can open a line of investigation about the relation of IL-10 and response to bronchiolitis.


REFERENCES

  1. Schaller A, Galloway CS. Bronchiolitis in Infants and Children. S D Med. 2017; 70(6):274-277.

  2. Fretzayas A, Moustaki M. Etiology and clinical features of viral bronchiolitis in infancy. World J Pediatr. 2017;13(4):293-299. doi: 10.1007/s12519-017-0031-8.

  3. Burns JJ, Evans R, Pham C, Nayak V, Amin R. Risk Factors Predicting Readmission to the Hospital in Children With Bronchiolitis. Clin Pediatr (Phila). 2018;57(14):1699-1702. doi: 10.1177/0009922818795904.

  4. Bozzola E, Ciarlitto C, Guolo S, Brusco C, Cerone G, Antilici L, et al. Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost. Front Pediatr. 2021; 8:594898. doi: 10.3389/fped.2020.594898.

  5. Fujiogi M, Goto T, Yasunaga H, Fujishiro J, Mansbach JM, Camargo CA Jr, et al. Trends in Bronchiolitis Hospitalizations in the United States: 2000-2016. Pediatrics. 2019;144(6):e20192614. doi: 10.1542/peds.2019-2614.

  6. Bréver A, Tomat AM, Seghaye MC. Update on the management of bronchiolitis. Rev Med Liege. 2019;74(4):175-8.

  7. Jartti T, Smits HH, Bønnelykke K, Bircan O, Elenius V, Konradsen JR, et al. Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments. Allergy. 2019;74(1):40-52. doi: 10.1111/all.13624.

  8. House SA, Ralston SL. Diagnosis, prevention, and management of bronchiolitis in children: review of current controversies. Minerva Pediatr. 2017;69(2):141-55. doi: 10.23736/S0026-4946.16.04865-9.

  9. Sebina I, Phipps S. The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis. Viruses. 2020;12(8):808. doi: 10.3390/v12080808.

  10. Kikkert M. Innate Immune Evasion by Human Respiratory RNA Viruses. J InnateImmun. 2020;12(1):4-20. doi: 10.1159/000503030.

  11. Bueno SM, González PA, Pacheco R, Leiva ED, Cautivo KM, Tobar HE, et al. Host immunity during RSV pathogenesis. Int Immunopharmacol. 2008;8:1320-9.

  12. Griffiths C, Drews SJ, Marchant DJ. Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment. Clin Microbiol Rev. 2017;30(1):277-319. doi: 10.1128/CMR.00010-16.

  13. Norlander AE, Peebles RS Jr. Innate Type 2 Responses to Respiratory Syncytial Virus Infection. Viruses. 2020;12(5):521. doi: 10.3390/v12050521.

  14. Russell CD, Unger SA, Walton M, Schwarze J. The Human Immune Response to Respiratory Syncytial Virus Infection. Clin Microbiol Rev. 2017;30(2):481-502. doi: 10.1128/CMR.00090-16.

  15. Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. 2003;168:633-9.

  16. Pinto RA, Arredondo SM, Bono MR, Gaggero AA, Díaz PV. T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increasedendogenous plasma cortisol. Pediatrics. 2006;117:e878-86.

  17. Moreno-Solís G, Torres-Borrego J, de la Torre-Aguilar MJ, Fernández-Gutiérrez F, Llorente-Cantarero FJ, Pérez-Navero JL. Analysis of the local and systemic inflammatory response in hospitalized infants with respiratory syncytial virus bronchiolitis. Allergol Immunopathol. 2015;43(3):264-71.

  18. Thompson BT. Corticosteroids for ARDS. Minerva Anestesiol. 2010;76:441-7.

  19. Fernandes RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC, Patel H, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2013;6:CD004878.

  20. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomskiet AM, et al. Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134:e1474-e1502.

  21. Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2014;6:CD001266.

  22. Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, et al. Pediatric Emergency Research Canada (PERC). Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360:2079-89.

  23. Balaguer M, Alejandre C, Vila D, Esteban E, Carrasco JL, Cambra FJ, et al. Bronchiolitis Score of Sant Joan de Déu: BROSJOD Score, validation and usefulness. Pediatr Pulmonol. 2017;52:533-9.

  24. Alansari K, Sakran M, Davidson BL, Ibrahim K, Alrefai M, Zakaria I. Oral dexamethasone for bronchiolitis: a randomized trial. Pediatrics. 2013;132:e810-6.

  25. Tagarro A, Pérez L, Quintero VM, Cañete A. Dexamethasone does not reduce length of hospitalization or recurrent wheezing 1 year after early bronchiolitis. Minerva Pediatr. 2014;66:131-40.

  26. Fernandes RM, Hartling L. Glucocorticoids for acute viral bronchiolitis in infants and young children. JAMA. 2014;311:87-8.

  27. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, et al. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J. 1999;14:144-9.

  28. Holt PG. Postnatal maturation of immune competence during infancy and childhood. Pediatr Allergy Immunol. 1995;6:59-70.

  29. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, et al. Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study. Am J Respir Crit Care Med. 2000;161:1518-23.

  30. Somers CC, Ahmad N, Mejias A, Buckingham SC, Carubelli C, Katz K, et al. Effect of dexamethasone on respiratory syncytial virus-induced lung inflammation in children: results of a randomized, placebo controlled clinical trial. Pediatr Allergy Immunol. 2009;20:477-85.

  31. Van Woensel JB, Wolfs TF, van Aalderen WM, Brand PL, Kimpen JL. Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis. Thorax. 1997;52:595-7.

  32. Hasegawa K, Mansbach JM, Camargo CA Jr. Infectious pathogens and bronchiolitis outcomes. Expert Rev Anti Infect Ther. 2014;12:817-28.

  33. Melendi GA, Laham FR, Monsalvo AC, Casellas JM, Israele V, Polack NR, et al. Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus, or influenza virus in infants. Pediatrics. 2007;120:e410-5.

  34. Jartti T, Lehtinen P, Vanto T, Hartiala J, Vuorinen T, Mäkelä MJ, et al. Evaluation of the efficacy ofprednisolone in early wheezing induced by rhinovirus or respiratory syncytialvirus. Pediatr Infect Dis J. 2006;25:482-8




2020     |     www.medigraphic.com