|Year : 2022 | Volume
| Issue : 4 | Page : 291-295
Managing bronchiolitis in pediatric patients: Current evidence
Subhranshu Sekhar Dhal1, Hiremath Sagar2
1 Department of Paediatrics, Mazumdar Shaw Medical Centre, Paediatric Intensive Care Unit, Narayana Health City, Bengaluru, Karnataka, India
2 Department of Paediatrics, Mazumdar Shaw Medical Centre, Narayana Health City, Bengaluru, Karnataka, India
|Date of Submission||30-Aug-2022|
|Date of Decision||20-Sep-2022|
|Date of Acceptance||24-Sep-2022|
|Date of Web Publication||12-Nov-2022|
Dr. Hiremath Sagar
Room No – C 12, First Floor, Department of Pediatrics, Mazumdar Shaw Medical Centre, Narayana Health City, Bommasandra, Anekal Taluk, Bengaluru - 560 099, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Acute bronchiolitis is an inflammatory process affecting small airways. Although most cases are self-limiting, it is still one of the most common causes of hospitalization below 24 months of age. Treatment is mainly supportive. The purpose of this narrative review was to look for recent evidence in the management of bronchiolitis. Methods: PubMed, EMBASE, Global Health, MEDLINE, SCOPUS, and Cochrane database searches were performed using keywords such as bronchiolitis, management, bronchodilators, nebulized epinephrine, corticosteroids, and hypertonic saline. Systematic reviews, original articles, and clinical practice guidelines with evidence for bronchiolitis management were included during our search. We excluded guidelines and clinical trials which solely focused on high-risk children, articles by a single author, and trials that are not part of a clinical practice guideline. Discussion: The safety and efficacy of various therapies for bronchiolitis such as bronchodilators, epinephrine, hypertonic saline, and corticosteroid were analyzed. Bronchodilators have not shown consistent benefits in bronchiolitis and may be tried in the selected population. Current evidence does not suggest routine use of nebulized epinephrine in bronchiolitis except as rescue therapy in selected cases. Hypertonic saline showed positive results in some studies but questions still remain regarding its effectiveness in all. Recent trials also do not support the use of systemic or inhaled corticosteroids in bronchiolitis. Conclusion: In conclusion, there is no strong evidence to routinely recommend the use of bronchodilator, epinephrine, hypertonic saline, or corticosteroids in acute bronchiolitis. Supportive care still remains the mainstay of therapy for bronchiolitis.
Keywords: Bronchiolitis, bronchodilator, epinephrine, hypertonic saline
|How to cite this article:|
Dhal SS, Sagar H. Managing bronchiolitis in pediatric patients: Current evidence. Indian J Respir Care 2022;11:291-5
| Introduction|| |
Acute bronchiolitis is an inflammatory process affecting small airways of the lungs and predominantly affects children below 24 months of age. Although most cases are self-limiting, it still remains one of the most common causes of hospitalization in this age group. Respiratory syncytial virus (RSV) is the most common etiology of bronchiolitis with other viral etiologies being parainfluenza A and B, influenza A and B, human metapneumovirus, coronavirus, adenovirus, and rhinovirus. RSV is quite common in India accounting for 30%–70% of cases of bronchiolitis as per various Indian studies. RSV mainly peaks between the rainy and winter seasons, that is from September to March.,
The child with bronchiolitis initially develops cough and coryza followed by a fever that lasts for 1–3 days, later on progressing to severe respiratory distress in some cases. The time to peak symptoms is 4 days and is associated with the peak viral load; however, this may vary from infant to infant. Physical findings in severe cases include poor feeding, tachypnea, chest retractions, use of accessory muscles, hyperinflation of the chest, and reduced oxygen saturation. Increased respiratory rate is an important marker of disease severity while apnea is a red flag sign for impending respiratory failure. The disease burden of bronchiolitis and its economic impact is also quite high. In 2019, globally 33 million RSV-associated lower respiratory tract infections were reported among which 3.6 million cases needed hospitalization with 26,300 deaths. Each year, the number of admissions to hospitals is increasing. As per the study which collected data from the Australia and New Zealand Pediatric Intensive Care Registry, bronchiolitis admission rates per 1,00,000 population of <24 months increased from 62.5 in 2002 to 208 in 2014. Every year, managing children with bronchiolitis cost millions of dollars.
Although bronchiolitis remains a cause of high admission rate and high economic burden, still the treatment remains mainly supportive with respiratory support ranging from nasal prong oxygen, high-flow nasal cannula oxygen to mechanical ventilation and maintenance of hydration.
Many other treatment options such as bronchodilators, nebulized epinephrine, nebulized hypertonic saline, and steroids have been studied with varying results. The current review was to look for recent evidence in the treatment of bronchiolitis with these equivocal therapeutic options.
| Methods|| |
Literature databases such as PubMed, EMBASE, Global Health, MEDLINE, and SCOPUS were used during our evidence search. The area of focus was the management of bronchiolitis. Recent evidence was extracted over the past 20 years from the English-published literature. In addition to the Cochrane database of systematic reviews was included during our search.
The following keywords (including specific Medical Subject Headings): bronchiolitis, management, bronchodilators, nebulized epinephrine, hypertonic saline, and corticosteroids were used for searching publication.
Systematic reviews, original articles, and clinical practice guidelines with evidence for bronchiolitis management were included during our search. We excluded guidelines and clinical trial which are solely focusing on high-risk children, articles by a single author, and trials that are not part of a clinical practice guideline. Evidences were extracted by two independent reviewers, and later on, compiled into a single template, and disagreements were resolved with regard to eligibility criteria.
| Discussion|| |
Many patients with bronchiolitis have wheeze and air trapping which has been considered a rationale for therapy with bronchodilators such as salbutamol and ipratropium bromide. Del Vecchio et al. in their retrospective study on the use of albuterol in young infants admitted with RSV bronchiolitis found that albuterol was not useful and in fact may be harmful with regard to increased supplemental oxygen used due to ventilation-perfusion mismatch. Karadag et al. did a prospective double-blind placebo-controlled trial, wherein one group received nebulized salbutamol and ipratropium bromide and the other received a placebo. They concluded that in infants with first-time bronchiolitis severe enough to need admission, bronchodilator therapy improved clinical scores and oxygenation during the first 24 h of disease onset but did not reduce the duration of hospitalization. Patel et al. in their double-blind randomized control trial (RCT) compared oral albuterol with placebo with respect to the resolution of illness as the primary outcome. The study did not reveal any significant difference between the two groups. Levin et al. in their prospective-blinded RCT showed no benefit in the bronchodilators arm rather pointed out significant tachycardia in the intervention group than placebo.
Cochrane database systematic review by Gadomski and Scribani which included 30 trials and 1992 infants compared bronchodilators (other than epinephrine) with placebo. The authors concluded that bronchodilators are neither effective in routine management nor do they reduce the duration of hospitalization. The drawback of this review was the small sample sizes and the lack of a standardized study design. Although many studies have shown no benefit of bronchodilators in bronchiolitis there is a possibility that it may be beneficial in a subgroup of patients with bronchiolitis. These subgroups would be infants with bronchiolitis above 6 months of age, bronchiolitis during nonpeak months, and infants with bronchiolitis and having atopic features or having a family history of asthma in first-degree relatives.,
The reason for variable results and nonresponsiveness of bronchodilators are due to the small sample size, different molecules used, and different causes of wheezing clubbed together and used in differing conditions. Furthermore, the pathophysiology of wheezing in bronchiolitis is complex and involves intraluminal blockage due to mucus plug, debris, and mucosal edema leading to unresponsiveness to bronchodilators. Hence, bronchodilators should not be used routinely in bronchiolitis patients, however, can be considered in the selected population as mentioned above. If there occurs a positive response in the form of improvement in respiratory status, it can be continued. On the other hand, if no response is noted to the bronchodilator, it should be discontinued.
Nebulized epinephrine has been used in bronchiolitis as it is not only a bronchodilator but also reduces mucosal edema. Hartling et al. in their systematic review and meta-analyses found epinephrine nebulization to reduce the admission on day 1 of illness but did not find any benefit in the inpatient group with respect to the length of hospital stay. Wainwright et al. in their RCT of nebulized epinephrine in bronchiolitis did not find any significant reduction in length of hospital stay. Another double-blind RCT conducted by Skjerven et al. which compared inhaled racemic epinephrine with inhaled saline did not show any significant difference in length of hospital stay. The Canadian Bronchiolitis Epinephrine Steroid Trial compared hospitalization rates over 7 days. This study had four arms: nebulized epinephrine plus oral dexamethasone, nebulized epinephrine plus oral placebo, nebulized placebo plus oral dexamethasone, and nebulized placebo plus oral placebo. Infants who received epinephrine with corticosteroids had a lower hospitalization rate by day 7 but the effect was statistically nonsignificant when adjusted for multiple variables. A similar trial called BI-PED study is being carried out across 11 centers in Canada, Australia, and New Zealand with a sample size of around 1616 babies which may give further evidence on the use of nebulized epinephrine and oral steroid in combination.
A recent case report of an otherwise healthy infant who developed unstable ventricular tachycardia after a single dose of nebulized epinephrine highlights the notion that no intervention is benign. Gelbart et al. in a recent study showed oral prednisolone with nebulized epinephrine reduced the duration of positive pressure support (high-flow nasal prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation) as compared with placebo (26 h vs. 40 h, P = 0.001). Current evidence does not support the routine use of nebulized epinephrine in bronchiolitis except as rescue therapy.
Hypertonic saline helps in bronchiolitis by hydrating airway surface liquid, reducing airway edema, and improving mucus clearance by mechanisms such as improving mucus rheology and increasing ciliary beat frequency. Miraglia Del Giudice et al. in a randomized study compared 3% saline with 0.9% saline in addition to epinephrine nebulizations in both groups. The patients in the 3% saline group had a shorter length of stay in the hospital (4.9 ± 1.3 days vs. 5.6 ± 1.6 days, P < 0.05) and also had a better clinical response score. Flores-González et al. compared 3% hypertonic saline with epinephrine and standalone 3% hypertonic saline and found that the combination reduced the length of stay in the hospital and also improved the clinical scores of severity from 3rd day of treatment.
Wu et al. compared 3% saline with 0.9% saline in bronchiolitis patients attending the emergency department. They concluded that 3% saline reduced admission rates but did not significantly reduce the duration of hospital stay or Respiratory Distress Assessment Instrument score. An RCT conducted by Sharma et al. which compared 3% saline versus 0.9% saline did not show any significant difference in duration of hospital stay or clinical severity scores. In a prospective double-blind RCT, Silver et al. compared 3% saline with 0.9% saline in in-Patient bronchiolitis. Results were nonsignificant in terms of length of stay or day 7 readmission rates. While most studies used 3% saline, Jacobs et al. used 7% saline and compared it with 0.9% saline. However, the study did not show any significant difference between bronchiolitis severity score which was the primary outcome, and secondary outcomes such as rate of hospitalization and length of emergency department or hospital stay.
Cochrane review by Zhang et al. which included 28 trials and 4195 infants suggested hypertonic saline nebulizations may modestly reduce the duration of hospital stay and improve clinical severity scores in infants admitted with bronchiolitis. It also suggested a reduction in the risk of hospitalization among outpatient and emergency department patients. However, the review also mentioned that the quality of evidence was low to moderate, thus routine use of hypertonic saline in infants with bronchiolitis could not be recommended. Another recently updated meta-analysis on hypertonic saline in bronchiolitis concluded hypertonic saline should not be used and needs to be further studied in infants with bronchiolitis. Trial sequential analysis was conducted by Harrison et al. to determine whether existing literature was sufficient to prove the effectiveness of hypertonic saline in bronchiolitis. The trial sequential analysis suggested the information or sample size available in the literature is far less than what would be needed to conclude the effectiveness of hypertonic saline in reducing the hospitalization rates and length of hospital stay. The authors concluded that the beneficial effect of hypertonic saline in bronchiolitis potentially represents type 1 error.
Hence, the current evidence for use of hypertonic saline in bronchiolitis seems inconclusive and further studies with adequate sample sizes are needed to evaluate its efficacy.
Bronchiolitis has significant airway inflammation which can be treated by corticosteroids through its anti-inflammatory effect and its ability to reduce airway edema and decrease mucus production. A study by Alansari et al., in which oral dexamethasone was used showed shortened time to readiness for discharge; however, the patient population in this group had eczema and a family history of asthma in a first-degree relative. The Canadian Bronchiolitis Epinephrine Trial mentioned in the epinephrine section suggested a combination of dexamethasone- and nebulized epinephrine-reduced hospitalization rate but the authors in conclusion mentioned that the result should be considered exploratory and need further study with adequate power to confirm the results. One single-center and one large multicenter RCT by Mesquita et al. and Corneli et al. which studied a single dose of oral dexamethasone versus placebo in reducing the rate of hospitalization did not show any benefit with oral dexamethasone.,
The most recent Cochrane review by Fernandes et al. which included 17 RCT and 2596 patients showed no significant reduction in hospitalization rates and length of hospital stay by either inhaled or systemic glucocorticoids Kua and Lee in their systematic review on efficacy and safety of combined epinephrine and corticosteroid therapy concluded that the combination was ineffective in reducing the hospital admission and length of hospital stay. Inhaled corticosteroids have also been used during and after bronchiolitis to study their effectiveness to prevent recurrent wheeze postbronchiolitis. However, none of the studies showed any benefit.,, Summarizing all, current evidence does not support the use of systemic or inhaled corticosteroids in bronchiolitis.
| Conclusion|| |
In conclusion, there is no new strong evidence to routinely recommend the use of bronchodilators, epinephrine, hypertonic saline, or corticosteroids in infants and children with acute bronchiolitis. However, bronchodilators may have a role in a selected population of bronchiolitis such as infants more than 6 months, bronchiolitis during nonpeak months, and infants having atopic features or having a family history of asthma in first-degree relatives. Further large studies are needed to decide the beneficence or nonbeneficence of these interventions in bronchiolitis. Till then supportive care will remain the mainstay of therapy for bronchiolitis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fretzayas A, Moustaki M. Etiology and clinical features of viral bronchiolitis in infancy. World J Pediatr 2017;13:293-9.
Verma N, Lodha R, Kabra SK. Recent advances in management of bronchiolitis. Indian Pediatr 2013;50:939-49.
Panda S, Mohakud NK, Suar M, Kumar S. Etiology, seasonality, and clinical characteristics of respiratory viruses in children with respiratory tract infections in Eastern India (Bhubaneswar, Odisha). J Med Virol 2017;89:553-8.
Skjerven HO, Megremis S, Papadopoulos NG, Mowinckel P, Carlsen KH, Lødrup Carlsen KC, et al.
Virus type and genomic load in acute bronchiolitis: Severity and treatment response with inhaled adrenaline. J Infect Dis 2016;213:915-21.
National Institute for Health and Care Excellence. Bronchiolitis: Diagnosis and Management in Children (Clinical guideline). London UK: National Institute for Health and Care Excellence; 2015. p. 9.
Li Y, Wang X, Blau DM, Caballero MT, Feikin DR, Gill CJ, et al.
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic analysis. Lancet 2022;399:2047-64.
Schlapbach LJ, Straney L, Gelbart B, Alexander J, Franklin D, Beca J, et al.
Burden of disease and change in practice in critically ill infants with bronchiolitis. Eur Respir J 2017;49:1601648.
Heppe Montero M, Gil-Prieto R, Walter S, Aleixandre Blanquer F, Gil De Miguel Á. Burden of severe bronchiolitis in children up to 2 years of age in Spain from 2012 to 2017. Hum Vaccin Immunother 2022;18:1883379.
Oakley E, Borland M, Neutze J, Acworth J, Krieser D, Dalziel S, et al.
Nasogastric hydration versus intravenous hydration for infants with bronchiolitis: A randomised trial. Lancet Respir Med 2013;1:113-20.
Del Vecchio MT, Doerr LE, Gaughan JP. The use of albuterol in young infants hospitalized with acute RSV bronchiolitis. Interdiscip Perspect Infect Dis 2012;2012:585901.
Karadag B, Ceran O, Guven G, Dursun E, Ipek IO, Karakoc F, et al.
Efficacy of salbutamol and ipratropium bromide in the management of acute bronchiolitis – A clinical trial. Respiration 2008;76:283-7.
Patel H, Gouin S, Platt RW. Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. J Pediatr 2003;142:509-14.
Levin DL, Garg A, Hall LJ, Slogic S, Jarvis JD, Leiter JC. A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation. Pediatr Crit Care Med 2008;9:598-604.
Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2014;2014:CD001266.
Nino G, Rodríguez-Martínez CE, Castro-Rodriguez JA. The use of β2
-adrenoreceptor agonists in viral bronchiolitis: Scientific rationale beyond evidence-based guidelines. ERJ Open Res 2020;6:00135-2020.
Bottau P, Liotti L, Laderchi E, Palpacelli A, Calamelli E, Colombo C, et al.
Something is changing in viral infant bronchiolitis approach. Front Pediatr 2022;10:865977.
Hartling L, Fernandes RM, Bialy L, Milne A, Johnson D, Plint A, et al.
Steroids and bronchodilators for acute bronchiolitis in the first two years of life: Systematic review and meta-analysis. BMJ 2011;342:d1714.
Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D, et al.
A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003;349:27-35.
Skjerven HO, Hunderi JO, Brügmann-Pieper SK, Brun AC, Engen H, Eskedal L, et al.
Racemic adrenaline and inhalation strategies in acute bronchiolitis. N Engl J Med 2013;368:2286-93.
Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, et al.
Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009;360:2079-89.
Lan J, Plint AC, Dalziel SR, Klassen TP, Offringa M, Heath A, et al.
Remote, real-time expert elicitation to determine the prior probability distribution for Bayesian sample size determination in international randomised controlled trials: Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone (BIPED) study. Trials 2022;23:279.
Toaimah FH, Al-Ansari K. Life-threatening cardiac arrhythmia after a single dose of nebulized epinephrine in pediatric emergency department. J Trop Pediatr 2011;57:497-9.
Gelbart B, McSharry B, Delzoppo C, Erickson S, Lee K, Butt W, et al.
Pragmatic randomized trial of corticosteroids and inhaled epinephrine for bronchiolitis in children in intensive care. J Pediatr 2022;244:17-23.e1.
Mandelberg A, Amirav I. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale. Pediatr Pulmonol 2010;45:36-40.
Miraglia Del Giudice M, Saitta F, Leonardi S, Capasso M, Niglio B, Chinellato I, et al.
Effectiveness of nebulized hypertonic saline and epinephrine in hospitalized infants with bronchiolitis. Int J Immunopathol Pharmacol 2012;25:485-91.
Flores-González JC, Matamala-Morillo MA, Rodríguez-Campoy P, Pérez-Guerrero JJ, Serrano-Moyano B, Comino-Vazquez P, et al.
Epinephrine improves the efficacy of nebulized hypertonic saline in moderate bronchiolitis: A randomised clinical trial. PLoS One 2015;10:e0142847.
Wu S, Baker C, Lang ME, Schrager SM, Liley FF, Papa C, et al.
Nebulized hypertonic saline for bronchiolitis: A randomized clinical trial. JAMA Pediatr 2014;168:657-63.
Sharma BS, Gupta MK, Rafik SP. Hypertonic (3%) saline vs 0.93% saline nebulization for acute viral bronchiolitis: A randomized controlled trial. Indian Pediatr 2013;50:743-7.
Silver AH, Esteban-Cruciani N, Azzarone G, Douglas LC, Lee DS, Liewehr S, et al.
3% Hypertonic saline versus normal saline in inpatient bronchiolitis: A randomized controlled trial. Pediatrics 2015;136:1036-43.
Jacobs JD, Foster M, Wan J, Pershad J. 7% hypertonic saline in acute bronchiolitis: A randomized controlled trial. Pediatrics 2014;133:e8-13.
Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2008;(4):CD006458.
Heikkilä P, Korppi M. Hypertonic saline in bronchiolitis: An updated meta-analysis. Arch Dis Child 2021;106:102.
Harrison W, Angoulvant F, House S, Gajdos V, Ralston SL. Hypetronic saline in bronchiolitis and type 1 error: A trial sequential analysis. Pedistrics 2018;142:e20181144.
Alansari K, Sakran M, Davidson BL, Ibrahim K, Alrefai M, Zakaria I. Oral dexamethasone for bronchiolitis: A randomized trial. Pediatrics 2013;132:e810-6.
Mesquita M, Castro-Rodríguez JA, Heinichen L, Fariña E, Iramain R. Single oral dose of dexamethasone in outpatients with bronchiolitis: A placebo controlled trial. Allergol Immunopathol (Madr) 2009;37:63-7.
Corneli HM, Zorc JJ, Mahajan P, Shaw KN, Holubkov R, Reeves SD, et al.
A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007;357:331-9.
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;2013:CD004878.
Kua KP, Lee SW. Systematic review and meta-analysis of the efficacy and safety of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. Front Pharmacol 2017;8:396.
Panickar J, Lakhanpaul M, Lambert PC, Kenia P, Stephenson T, Smyth A, et al.
Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med 2009;360:329-38.
Green P, Aronoff SC, DelVecchio M. The Effects of Inhaled Steroids on Recurrent Wheeze After Acute Bronchiolitis: A Systematic Review and Meta-Analysis of 748 Patients. Glob Pediatr Health 2015;2:2333794X15595964. doi: 10.1177/2333794X15595964.
Blom D, Ermers M, Bont L, van Aalderen WM, van Woensel JB. Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing. Cochrane Database Syst Rev 2007;(1):CD004881.