Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine) 4th Ed.

CHAPTER

35

Bronchiolitis

Maneesha Agarwal

HIGH-YIELD FACTS

• Bronchiolitis is a self-limited, virally mediated, acute inflammatory disease of the lower respiratory tract, resulting in obstruction of the small airways that occurs almost exclusively in infants.

• It is a clinical diagnosis characterized by rapid respiration, chest retractions and wheezing, and, frequently, hypoxia.

• Respiratory failure may occur secondary to respiratory muscle fatigue or apnea, especially in very young and premature infants.

• Treatment is largely supportive. Routine treatment with bronchodilators or corticosteroids has not been shown to be of benefit.

• Indications for hospital admission include need for supportive care (oxygen or IV fluids), persistent respiratory distress or respiratory failure, adjusted age <6 weeks, or significant underlying disease.

Bronchiolitis is an acute inflammatory disease of the lower respiratory tract that is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, increased mucous production, and bronchospasm.1The term describes a clinical syndrome that occurs in infancy and is characterized by rapid respiration, chest retractions, wheezing, and, frequently, hypoxia. It is a disease that occurs almost exclusively in children younger than 2 years. It is the leading cause of hospitalization in infancy in the United States, accounting for 3% of all hospitalizations. This results in nearly 150,000 hospital admissions per year with an associated annual cost over $500 million.2There is evidence that hospitalization rates are increasing as well. It has a seasonal pattern, being most common in the winter and spring.3

ETIOLOGY

The most common etiologic agent in bronchiolitis is respiratory syncytial virus (RSV) which is responsible for 70% of all bronchiolitis cases and even higher in winter months.4 Nearly all children are RSV seropositive by the age of 2. Infection with RSV does not grant permanent or long-term immunity; reinfections are common throughout life.5 Numerous other viruses have been implicated in bronchiolitis. This includes rhinovirus, human bocavirus, metapneumovirus, enterovirus, coronavirus, parainfluenza, adenovirus, influenza, mumps, picornavirus, and echovirus. Adenovirus causes a severe form of the disease. These viruses may also be associated with varying severity of disease and seasonality from the more typical RSV bronchiolitis.69 Mycoplasma pneumoniae and Chlamydia trachomatis also have been associated with bronchiolitis. The principal agent in school-aged children with bronchiolitis is Mycoplasma.

PATHOPHYSIOLOGY

Infection produces inflammation of the bronchiolar epithelium, causing necrosis, sloughing, and luminal obstruction. Ciliated epithelium that has sloughed is replaced by cuboidal cells without cilia. The absence of ciliated epithelium prevents adequate mobilization of secretions and debris. The bronchioles and small bronchi are obstructed by submucosal edema, peribronchiolar cellular infiltrate, mucous plugging, and intraluminal debris. The obstruction is not uniform throughout the lungs, leading to ventilation/perfusion mismatching, resultant hypoxia, and compensatory hyperventilation. If the obstruction is severe, hypercapnia may occur. Distal to the obstructed bronchiole, air trapping or atelectasis may occur. The epithelium usually regenerates from the basal layer within 3 to 4 days. However, functional regeneration of the ciliated epithelium usually requires approximately 2 weeks.

Adenovirus is associated with a particularly severe reaction termed bronchiolitis obliterans. In this disease, the destruction of the normal ciliated epithelium is extensive. The normal cells are replaced by stratified undifferentiated epithelium with an intense inflammatory response extending to the alveoli. During the reparative phase, extensive fibrosis and scarring lead to obliteration of the small airways.

CLINICAL PRESENTATION

Typically, a child with bronchiolitis will have a prodrome of an upper respiratory tract infection. Parents describe runny nose, low-grade fever, and decreased appetite for 1 to 2 days prior to the development of tachypnea and evidence of increased work of breathing. However, in some children lower-tract symptoms may develop over hours. Often, there will be a family or contact history of upper respiratory tract infection. Increased work of breathing may compromise patients’ abilities to tolerate oral intake; this, combined with increased insensible losses from tachypnea and fever, may result in dehydration (Fig. 35-1).

image

FIGURE 35-1. Management of a child with bronchiolitis.

Hyperventilation occurs as a compensatory response for hypoxia secondary to ventilation–perfusion mismatch. Respiratory rates of 70 to 90 per minute or more are common. Flaring of the nasal alae and use of intercostal muscles may also be present. Respirations are shallow because of persistent distention of the lungs by the trapped air. Wheezing, prolonged expiration, and musical rales are common. The chest is often hyperexpanded and hyperresonant due to the air trapping. The liver and spleen may be displaced downward because of the hyperinflation and flattening of the diaphragm. Thoracoabdominal asynchrony may be present with breathing. Fever is present in two-thirds of children with bronchiolitis. Despite these findings, the patient often has a nontoxic appearance.

Respiratory fatigue may occur as the infant may increase his work of breathing up to sixfold. Apnea generally occurs early in the illness, often prior to the onset of other respiratory symptoms. Rates of apnea range from 1% in healthy, term infants to as high as 24%, in very young and premature infants or those with comorbidities.10

LABORATORY AND RADIOGRAPHIC FINDINGS

Hypoxia is common and the patient should have oxygen saturations assessed with a pulse oximeter. Hypercarbia will be present in those with more severe obstruction. Respiratory rates greater than 60 breaths/min correlate well with carbon dioxide retention noted on blood gas analysis.

In many patients, a chest radiograph will reveal hyperinflation, peribronchial cuffing (thickening of the bronchiole walls), and areas of subsegmental atelectasis that can be difficult to differentiate from pneumonia. Although no study has convincingly demonstrated an association between radiographic findings and severity of disease,11 chest radiography may help rule out other disease processes in the differential diagnosis of bronchiolitis. The American Academy of Pediatrics (AAP) practice guidelines for bronchiolitis state that the current evidence does not support routine radiography in children with bronchiolitis.1

Laboratory studies are generally not helpful and not indicated in the acute management of bronchiolitis.12 Virologic tests for RSV, if obtained during peak RSV season, have a high predictive value. These tests are helpful in hospital cohorting to minimize nosocomial transmission, however, such testing rarely alters management decisions or outcomes for the majority of children with clinically diagnosed bronchiolitis.13 The use of complete blood counts is not useful in diagnosing bronchiolitis or guiding its therapy. Research has demonstrated that young febrile infants with clinical bronchiolitis are less likely to have a serious bacterial illness than febrile infants without bronchiolitis.14 One systematic review estimated the rate of urinary tract infection in patients younger than 90 days to be 3.3%; there were no cases of meningitis identified and few cases of bacteremia.15 Acute otitis media may occur concomitantly with bronchiolitis and warrants standard therapy.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for bronchiolitis is essentially the same as for asthma. Bronchiolitis may be very difficult to differentiate from infantile asthma. Response to bronchodilators does not exclude bronchiolitis, since some children with bronchiolitis may have some degree of bronchospasm. Since bronchiolitis most commonly occurs in infancy, pay particular attention to other processes that may mimic bronchiolitis and present in infancy. Congenital heart disease, cystic fibrosis, vascular rings, and other congenital anomalies may all mimic the findings of bronchiolitis. Infants and toddlers are particularly prone to foreign-body aspiration, and this possibility must be considered.

TREATMENT

Therapy is supportive. No medication appears to be beneficial in patients with bronchiolitis, although this is an area of extensive, ongoing research. Most children with bronchiolitis will have some degree of hypoxia; monitoring of oximetry and provision of oxygen, if needed, is important. The AAP practice guidelines state that supplemental oxygen is indicated if SpO2 falls persistently below 90% in previously healthy infants. Oxygen may be discontinued if SpO2 is at or above 90% and the infant is feeding well and has minimal respiratory distress.1 Patients who are dehydrated and unable to take adequate oral fluids may require intravenous hydration. As discussed above, a chest radiograph often reveals areas of opacity suggestive of pneumonia. However, no significant benefit was demonstrated from routine antibiotic usage in patients with a clinical diagnosis of bronchiolitis.1,16,17

The similarities and association between bronchiolitis and the development of asthma have led some physicians to advocate the use of steroids in bronchiolitis. Although small studies have suggested their benefit,18 more robust studies and large meta-analyses have failed to demonstrate any clinical benefit to support use of oral or inhaled steroids.19,20

The use of inhaled bronchodilators in bronchiolitis remains controversial. Many clinicians believe that bronchodilators produce clinical improvement in some patients with bronchiolitis; some small studies support this.21However, systematic reviews looking at studies of the efficacy of oral or inhaled β-agonists and anticholinergic agents in bronchiolitis have not demonstrated a significant benefit in their routine use.22,23 A systematic review, assessing the use of any bronchodilator therapy in bronchiolitis, demonstrated a modest improvement in clinical scores that was of questionable clinical significance. No difference was found in oxygenation or rates of hospitalization.24 Despite the lack of proven benefit, the most recent AAP practice guidelines on bronchiolitis suggest that a carefully monitored trial of αadrenergic or β-adrenergic medication is an option and should be continued only if there is a documented positive clinical response.1

Some authors have suggested that nebulized epinephrine therapy is superior to nebulized albuterol therapy in patients with bronchiolitis based on the αadrenergic–mediated vasoconstriction ameliorating airway edema. Earlier studies comparing nebulized epinephrine with nebulized albuterol in patients with bronchiolitis did not reveal a significant difference in benefit.24,25 However, a recent meta-analysis suggests that use of nebulized epinephrine may reduce hospital admissions.26 Another high-quality study suggests that combination therapy with nebulized epinephrine and dexamethasone may produce synergistic effects and reduce hospital admissions and result in earlier hospital discharge27; however, additional research is needed.

There has been research on the use of nebulized hypertonic saline in the treatment of bronchiolitis. This therapy is thought to work by enhancing mucociliary clearance via osmotic hydration and disruption of mucous strand cross-linking, decreasing epithelial swelling, and decreasing airway obstruction.28 Although a meta-analysis has demonstrated that this therapy can reduce hospitalization length of stay without any adverse clinical effects, there is no definitive evidence that it reduces hospital admission.29

There has been extensive research into additional therapies for bronchiolitis, including montelukast,30,31 topical nasal phenylephrine,32 chest physiotherapy,33 and inhaled furosemide.34 The use of ribavirin35or surfactant therapy36is best left to the discretion of the intensivist once the child is admitted based on the particular clinical circumstances.

Two to five percent of infants hospitalized for bronchiolitis will go on to develop respiratory failure and require some level of mechanical support. A mixture of helium and oxygen (Heliox) and continuous positive airway pressure may be of benefit as noted by some authors; however, there is a paucity of good evidence documenting decreased rates of intubation.3740 There are no absolute criteria for endotracheal intubation. Suggested indications include PCO2 greater than 60 to 65 mm Hg, recurrent apneic spells, decreasing mental status, and hypoxia despite oxygen therapy. Once intubated, these infants have many of the same problems that intubated asthmatics have and are at risk for air trapping and the development of air leaks, including pneumothorax. There are also reports of successful management of severe bronchiolitis with high-frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional therapy.

DISPOSITION/OUTCOME

The acute phase of bronchiolitis is a short-lived, self-limited process; however, residual symptoms may persist for a few weeks.41 Determining the need for admission can be difficult. In one study, 40% of patients required admission and about 4% of patients initially discharged from the emergency department were subsequently admitted.42 A multicenter trial found that the following factors predicted safe discharge to home: age of ≥2 months, no history of intubation, history of eczema, age-specific respiratory rates (<45 breaths/min for 0–1.9 months, <43 breaths/min for 2–5.9 months, and <40 breaths/min for 6–23.9 months), no/mild retractions, initial oxygen saturation of ≥94%, fewer albuterol or epinephrine treatments in the first hour, and adequate oral intake. The importance of each factor varied slightly according to age.43 Other suggested criteria for admission include age (adjusted for prematurity) less than 6 weeks, hypoxemia, and persistent respiratory distress. Children with a history of prematurity, congenital heart disease, bronchopulmonary dysplasia (BPD), underlying lung disease, and/or compromised immune function are at the highest risk for morbidity and mortality and admission should be considered. Follow-up within 24 hours is recommended for those who are discharged. There is research pertaining to the use of home oxygen therapy for patients with mild hypoxemia, although further studies are needed.44

The overall mortality rate for infants with RSV bronchiolitis is 1% to 3%.5 The mortality rate for infants with congenital heart disease and RSV bronchiolitis is 37% and has been improving with the implementation of RSV prophylaxis with palivizumab in high-risk patients.45 Up to 15% to 30% of infants who are hospitalized with bronchiolitis will require admission to an ICU for ventilatory support. Up to 50% of infants with RSV bronchiolitis will go on to have recurrent wheezing. The only factor shown to increase the likelihood of subsequent wheezing is a family history of asthma, or atopy. Whether the initial infection causes changes that predispose to the development of asthma or patients with a genetic predisposition to reactive airway disease develop wheezing as a response to infection in infancy is controversial. Patients with bronchiolitis obliterans have a much poorer prognosis. They usually develop debilitating chronic lung disease.

REFERENCES

1. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774.

2. Pelletier AJ, Mansbach JM, Camargo CA Jr. Direct medical costs of bronchiolitis hospitalizations in the United States. Pediatrics. 2006;118:2418.

3. Mullins JA, Lamonte AC, Bresee JS, et al. Substantial variability in community respiratory syncytial virus season timing. Pediatr Infect Dis J. 2003;22:857.

4. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med. 2001;344:1917.

5. Shay DK, Holman RC, Roosevelt GE, et al. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979–1997. J Infect Dis. 2001;183:16.

6. Calvo C, Pozo F, Garcia-Garcia ML, et al. Detection of new respiratory viruses in hospitalized infants with bronchiolitis: a three-year prospective study. Acta Paediatr. 2010;99:883.

7. Chawes BL, Poorisrisak P, Johnston SL, et al. Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants. J Allergy Clin Immunol. 2012;130:354.

8. Jacques J, Moret H, Renois F, et al. Human Bocavirus quantitative DNA detection in French children hospitalized for acute bronchiolitis. J Clin Virol. 2008;43:142.

9. Stempel HE, Martin ET, Kuypers J, et al. Multiple viral respiratory pathogens in children with bronchiolitis. Acta Paediatr. 2009;98:123.

10. Ralston S, Hill V. Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr. 2009;155:728.

11. Dawson KP, Long A, Kennedy J, et al. The chest radiograph in acute bronchiolitis. J Paediatr Child Health. 1990;26:209.

12. Bordley WC, Viswanathan M, King VJ, et al. Diagnosis and testing in bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2004;158:119.

13. Agency for Healthcare Research and Quality. Management of Bronchiolitis in Infants and Children. Rockville, MD: Agency for Healthcare Research and Quality. Evidence Report/Technology Assessment No. 69. AHRQ Publication No. 03-E009; 2003.

14. Bilavsky E, Shouval DS, Yarden-Bilavsky H, et al. A prospective study of the risk for serious bacterial infections in hospitalized febrile infants with or without bronchiolitis. Pediatr Infect Dis J. 2008;27:269.

15. Ralston S, Hill V, Waters A. Occult serious bacterial infection in infants younger than 60 to 90 days with bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2011;165:951.

16. Henderson M, Rubin E: Misuse of antimicrobials in children with asthma and bronchiolitis: a review. Pediatr Infect Dis J. 2001; 20:214.

17. Spurling GKP, Doust J, Del Mar CB, et al. Antibiotics for bronchiolitis in children. Cochrane Database Syst Rev. 2011;(6):CD005189. doi:10.1002/14651858.CD005189.pub3.

18. Schuh S, Coates AL, Binnie R, et al. Efficacy of oral dexamethasone in outpatients with acute bronchiolitis [see comment]. J Pediatr. 2002;140:27.

19. Corneli HM, Zorc JJ, Majahan P, et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med. 2007;357:331.

20. Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2010;CD004878.

21. Walsh P, Caldwell J, McQuillan KK, et al. Comparison of nebulized epinephrine to albuterol in bronchiolitis. Acad Emerg Med. 2008; 15:305.

22. 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;14:509.

23. Everard ML, Bara A, Kurian M, et al. Anticholinergic drugs for wheeze in children under the age of 2 years. Cochrane Database Syst Rev. 2005;(3):CD001279.

24. Wainwright C, Altamirano L, Cheney M, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. 2003;349:27.

25. Mull CC, Scarfone RJ, Ferri L, et al. A randomized trial of nebulized epinephrine vs. albuterol in the emergency department treatment of bronchiolitis. Arch Pediatr Adolesc Med. 2005;158:113.

26. Hartling L, Bialy LM, Vandermeer B, et al. Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2011;CD003123.

27. Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360:2079.

28. Luo Z, Fu Z, Liu E, et al. Nebulized hypertonic saline treatment in hospitalized children with moderate to severe viral bronchiolitis. Clin Microbiol Infect. 2011;17:1829.

29. Zhang L, Mendoza-Sassi RA, Wainwright C, et al. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008;CD006458.

30. Amirav I, Luder AS, Kruger N, et al. A double-blind, placebo-controlled, randomized trial of montelukast for acute bronchiolitis. Pediatrics. 2008;122:e1249.

31. Zedan M, Gamil N, El-Assmy M, et al. Montelukast as an episodic modifier for acute viral bronchiolitis: a randomized trial. Allergy Asthma Proc. 2010;31:147.

32. Ralston S, Roohi M. A randomized, controlled trial of nasal phenylephrine in infants hospitalized for bronchiolitis. J Pediatr. 2008;153:795.

33. Figuls M, Gine-Garriga M, Granados RC, et al. Chest physiotherapy for acute bronchiolitis in pediatric patients between 0 and 24 months old. Cochrane Database Syst Rev. 2012;(2):CD004873.

34. Bar A, Srugo I, Amirav I, et al. Inhaled furosemide in hospitalized infants with viral bronchiolitis: a randomized, double-blind, placebo-controlled pilot study. Pediatr Pulmonol. 2008;43:261.

35. Chen CH, Lin YT, Yang YH, et al. Ribavirin for respiratory syncytial virus bronchiolitis reduced the risk of asthma and allergen sensitization. Pediatr Allergy Immunol. 2008;19:166.

36. Jat KR, Chawla D. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev. 2012;(9):CD009194.

37. Martinon-Torres F, Rodríguez-Núñez A, Martinón-Sánchez JM. Heliox therapy in infants with acute bronchiolitis. Pediatrics. 2002;109:68.

38. Cambonie G, Milesi C, Fournier-Favre S, et al. Clinical effects of heliox administration for acute bronchiolitis in young infants. Chest. 2006;129:676.

39. Thia LP, McKenzie SA, Blyth TP, et al. Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis. Arch Dis Child. 2008;93:45.

40. Donlan M, Fontela PS, Puligandla PS. Use of continuous positive airway pressure (CPAP) in acute viral bronchiolitis: a systematic review. Pediatr Pulmonol. 2011;46:736.

41. Petruzella FD, Gorelick MH. Duration of illness in infants with bronchiolitis evaluated in the emergency department. Pediatrics. 2010; 126:285.

42. Corneli HM, Zorc JJ, Holubkov R, et al. Bronchiolitis: clinical characteristics associated with hospitalization and length of stay. Pediatr Emerg Care. 2012;28:99.

43. Mansbach JM, Clark S, Christopher NC, et al. Prospective multicenter study of bronchiolitis: predicting safe discharges from the emergency department. Pediatrics. 2008;121:680.

44. Halstead S, Roosevelt G, Deakyne S, Bajaj L. Discharged on supplemental oxygen from an emergency department in patients with bronchiolitis. Pediatrics. 2012;129:e605.

45. American Academy of Pediatrics. Policy statements–modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124:1694.