Sections

Bronchiolitis

Treatment

Approach Considerations

Since no definitive antiviral therapy exists for most causes of bronchiolitis, management of these infants should be directed toward symptomatic relief and maintenance of hydration and oxygenation. Although numerous medications and interventions have been studied for the treatment of bronchiolitis, at present, only oxygen appreciably improves the condition of young children with bronchiolitis and many other medical therapies remain controversial.^[7]

Bronchodilator therapy to relax bronchial smooth muscle, though commonly used, is not supported as routine practice by convincing evidence. If bronchodilator therapy is started, it may be continued in selected patients who demonstrate clinical improvement.

Despite the prominent role that inflammation plays in the pathogenesis of airway obstruction, large multicenter trials of corticosteroids have clearly failed to show a significant benefit in improving the clinical status of patients with bronchiolitis.^[126]However, in some countries they are used routinely.

Beta-agonists and ipratropium bromide, an aerosolized anticholinergic agent, have not shown effectiveness in the management of infants with RSV and wheezing.^{[127, 128, 129, 130, 131]}Epinephrine trials have not shown benefit among outpatients with bronchiolitis or the hospitalized child. Nasal phenylephrine is not effective for treatment of infants hospitalized for bronchiolitis.^[132]

The efficacy of pharmacotherapy in infants is difficult to determine because it can be a function of the pharmacologic agent, the route of administration, the clinical status of the patient, or the adequacy of the outcome measure used to demonstrate an effect. Recombinant human DNAse also had no clinical effects in infants who were not receiving ventilation.^[133]Various immunotherapies are being introduced both to treat the acute disease and to prevent sequelae.^{[134, 135, 136, 137]}

In a network meta-analysis, Elliott et al compared the effectiveness of various therapies for bronchiolitis, including bronchodilators, corticosteroids, hypertonic saline, antibiotics, helium-oxygen, and high-flow oxygen. Nebulized epinephrine and nebulized hypertonic saline plus salbutamol appeared to reduce admission rates during the index emergency department (ED) presentation, and hypertonic saline, alone or in combination with epinephrine, seemed to reduce hospital stays; however, these treatments had no effect on admissions within 7 days of initial presentation.^{[138, 139]}The authors' confidence in the effects of these treatments was low due to imprecisions of the contributing studies, and they concluded that no changes to current clinical practice guidelines are needed based on the current knowledge. In an accompanying editorial, Lipshaw and Florin commented that the strength of evidence for all bronchiolitis treatments is low and agreed that more rigorous, well-designed research on bronchiolitis treatments is needed.^[140]

Guidelines for treatment

As a consequence of the lack of evidence-based support for medicinal interventions to treat bronchiolitis, admission rates and treatment approaches vary widely, particularly in the ED.^{[141, 142]}In a Canadian study, children evaluated in general EDs were admitted twice as often as those observed in pediatric EDs, even when age, gender, estimated family income, medical comorbidity, and clinical severity were controlled for.^[143]

A survey of members of the Emergency Medicine section of the American Academy of Pediatrics (AAP) found that 96% recommended bronchodilators and 8% recommended steroids.^[3]Twice as many pediatric emergency physicians would admit a child with an oxygen saturation of 92% on pulse oximetry than would admit a child with a saturation of 94%, though a respiratory rate of 50 breaths/min as opposed to 65 breaths/min made little difference in the admission rate.

A study of 30 large children’s hospitals in the United States found that 45% of patients received steroids and 25% received systemic antibiotics. Factors that contributed to longer stays included use of antibiotics, steroids, and bronchodilators. Undergoing chest radiography was a significant predictor of antibiotic administration.^[144]

These differences from recommendations and between practices have led to a call for national guidelines for the management of bronchiolitis. In 2006, the AAP, in conjunction with the American Academy of Family Physicians (AAFP), the American College of Chest Physicians (ACCP), and the American Thoracic Society (ATS), published guidelines for the diagnosis and management of bronchiolitis in children 1 through 23 months of age.^[3]These guidelines were updated in 2014 and include the following recommendations^[110]:

Diagnosis and severity should be based on history and physical findings and not on laboratory and radiologic findings; risk factors should be assessed when decisions about evaluation and management are made
Bronchodilators should not be routinely used; routine use of a trial of bronchodilator therapy was de-emphasized in the updated guidelines due to the lack of supportive evidence of benefit exceeding potential harm
Corticosteroids should not routinely be used
Ribavirin should not be used
Risk of serious bacterial infection, especially in infants 30-90 days old with bronchiolitis is low. Antibacterials should be used only upon proven coexistence of bacterial infection
Nutrition and hydration should be assessed. The ability of an infant with respiratory distress due to bronchiolitis to take oral fluids should be evaluated and nasogastric or intravenous hydration may be used as needed
Supplemental oxygen should not be routinely used for patients with saturations above 90% on pulse oximetry; continuous pulse oximetry monitoring may not be necessary
Chest physiotherapy has not shown to benefit infants with bronchiolitis
Deep suctioning may provide temporary relief but has been associated with longer hospitalization
Nebulized hypertonic (3%) saline may improve symptoms of bronchiolitis when length of stay is expected to exceed 3 days
Palivizumab prophylaxis should only be administered to selected children (se below)
Hand decontamination is indicated to prevent nosocomial spread
Infants should not be exposed to passive smoking, and clinicians should inquire about parental smoking and encourage cessation.
Breastfeeding is recommended
Clinicians should inquire about use of complementary and alternative medicine therapies

A recent report from the Value in Inpatient Pediatrics Network, formed out of the AAP section on hospital medicine, found that using the AAP guidelines in a peer-to-peer collaborative manner among the participating hospitals in 14 states reduced the use of bronchodilators to treat pediatric bronchiolitis from 70% in 2007 to 58% in 2010. Bronchodilator doses per patient fell by 45% and inappropriate use of chest physiotherapy also declined from 14% to 4.2% from 2007 to 2010 at the participating hospitals.^[145]

Researchers at Cincinnati Children’s Hospital found that bronchiolitis admissions were increasing so that patients could receive bronchodilator therapy. In 1997, the hospital instituted evidence-based point-of-care algorithms and rules based on guideline recommendations on the overuse of therapies for bronchiolitis and reviewed them in 2001, 2005, and 2006.

The hospital’s guidelines discouraged etiologic testing (because the treatment is directed at the syndrome rather than at its cause), reduced the use of chest radiography (because opacities [atelectasis] are unlikely to change for 7-9 days and are not influenced by antibiotics or chest physiotherapy), and discouraged the use of steroids and bronchodilators unless clear and sustained improvement was noted 20 minutes after aerosol administration.^[146]

After introduction of the guidelines, decreases were seen in admissions (29%), length of stay (17%), nasopharyngeal washings for RSV antigen (52%), chest radiography (20%), all respiratory therapies (30%), beta-agonist administrations (51%), cost of all services (37%), and cost of respiratory therapy services (77%).^[147]These changes continued in the 3-year and 4-year follow-up investigations.^[148]

Initial Management

Patients should be made as comfortable as possible (held in a parent’s arms or sitting in the position of comfort). Administer saline nose drops and perform nasal and oral suctioning. Deep oral and nasal suctioning is not routinely needed. Carefully monitor the patient for apnea. Pay attention to temperature regulation in small infants.^[8]

Cardiorespiratory monitoring is essential. Pulse oximetry is a helpful tool; hypoxia is common. It is vital to have a clear picture of the patient’s clinical respiratory status and the severity of disease. The ability to maintain adequate hydration should be assessed by observing the patient's oral intake. Many dyspneic infants have difficulty taking a bottle.

Although young infants have the unique ability to breathe and swallow simultaneously, the risk of aspiration is significant when the respiratory rate is higher than 60 breaths/min. Fever and hyperpnea may contribute to excessive fluid losses. For these reasons, infants who are hospitalized with bronchiolitis require careful fluid monitoring and provision of nasogastric or intravenous (IV) fluids when hyperpnea precludes safe oral feeding.

An early effort should be made to isolate or cohort patients who are confirmed or likely to have RSV infection, especially from other patients at risk for severe disease. Institute standard and contact isolation precautions to prevent nosocomial transmission.

Antibiotics are not indicated unless bacterial infection is highly suspected (eg, by a toxic appearance, hyperpyrexia, consolidation or focal lobar infiltrates on chest radiography, leukocytosis, or positive bacterial cultures).^[3]Concomitant otitis media is common and may be treated with oral antibiotics.

Admission Criteria

A decision must be made as to whether the patient should be treated in an inpatient or an outpatient setting. For hospitalized patients, the length of stay averages 2-3 days, with a readmission rate of 1-4%. Considerations for hospital admission may include the following^{[38, 40, 149]}:

Persistent resting oxygen saturation below 90% in room air
Markedly elevated respiratory rate (>70-80 breaths/min)
Dyspnea, intercostal retractions and cyanosis (indicating respiratory distress)
Chronic lung disease, especially if the patient is already receiving supplemental oxygen
Congenital heart disease, especially if hemodynamically significant (associated with cyanosis or pulmonary hypertension)
Prematurity
Age younger than 3 months, when severe disease is most common
Inability to maintain oral hydration in patients younger than 6 months and difficulty feeding as a consequence of respiratory distress
Parent unable to care for child at home

A decision must also be made regarding admission to an intensive care unit (ICU). Criteria for ICU admission vary greatly. In general, ICU admission is uncommon for previously healthy infants who present with bronchiolitis. Severely ill children should be admitted to an adequately equipped intensive care unit (ICU). If this requires transfer to another hospital, transport personnel and vehicles specifically intended for pediatric transport are desirable.

Patients with the following conditions should be evaluated for ICU admission:

Worsening hypoxemia or hypercapnia
Worsening respiratory distress
Persistent oxygen desaturation and/or severe cyanosis in spite of adequate oxygen delivery
Apnea
Acidosis
Extrapulmonary symptoms
Worsening mental status
Unclear etiology of symptoms

Supportive Therapy

Management is primarily supportive and should focus on therapies that improve oxygenation and hydration.

Oxygen supplementation

Administer supplemental humidified oxygen, if necessary, to maintain a transcutaneous oxygen saturation higher than 90%. Unger and Cunningham found that oxygen supplementation is the prime determinant of length of hospitalization.^[7]The use of high-flow nasal cannulas may reduce intubation rates in infants with bronchiolitis.^[150]

A multicenter, randomized, controlled trial conducted in Australia that included 1472 patients reported that among infants with bronchiolitis and hypoxemia who were treated outside an ICU (in an emergency department or general floor setting), those who received high-flow oxygen therapy early in their course of management had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy (12% in the high-flow group compared to 23% in the standard-therapy group).^[151]

In selected children with acute bronchiolitis, home oxygen therapy may be a feasible alternative to traditional hospital oxygen therapy. In one study, 44 children aged 3-24 months who still required oxygen supplementation 24 hours after admission were randomly assigned either to receive oxygen therapy at home or to continue inpatient oxygen therapy.^[152]Children in the home oxygen group spent almost 2 days less in a hospital bed than those managed as traditional inpatients. No difference in clinical outcome was noted.

A study by Kepreotes et al did not report a significant reduction in time on oxygen with the use of high-flow warm humidified oxygen (24 hours with standard therapy vs 20 hours using high-flow warm humidified oxygen). However, high-flow warm humidified oxygen could be used in rescue therapy.^[153]

Maintenance of hydration

Infants with bronchiolitis are mildly dehydrated because of decreased fluid intake and increased fluid losses from fever and tachypnea. Accordingly, it is vital to maintain adequate hydration. The goal of fluid therapy is to replace deficits and to provide maintenance requirements. Avoid excessive fluid administration, because this may promote interstitial edema formation, particularly if a component of inappropriate antidiuretic hormone release is present.^[98]

Oral therapy is preferred. Parenteral therapy may be necessary in those patients who are unable to take fluids by mouth or who have a respiratory rate higher than 70 breaths/min. Patients with apneic episodes should have access to IV hydration.

Mechanical ventilation

Infants with bronchiolitis and recurrent apnea or increased work of breathing with respiratory failure occasionally require mechanical ventilation. Treat these patients supportively, providing adequate oxygen, ventilation, and hydration. Continuous positive airway pressure (CPAP) and intermittent mandatory ventilation (IMV) with positive end-expiratory pressure (PEEP) have been successfully used to treat these infants.^{[154, 155, 156, 157]}Negative-pressure ventilation has been used successfully in infants with bronchiolitis, with a reduced need for endotracheal intubation and shortened lengths of stay.

The typical approach in patients who require ventilation using IMV and PEEP is to ventilate at rates slow enough to allow adequate emptying during exhalation. In addition, a short inspiratory time optimizes ventilation to more compliant lung units without overdistending more obstructed ones. Aggressive weaning over the first 2-3 days is not warranted and is usually unsuccessful. Once the illness subsides, weaning can proceed quickly. Infants with progressive hypoxemia that does not respond to conventional ventilation may respond to high-frequency ventilation or extracorporeal membrane oxygenation (ECMO).^{[127, 158]}

Several studies have looked into use of surfactant and nitric oxide in cases of severe respiratory distress; however, the results were not sufficiently conclusive to support routine use in bronchiolitis.^{[142, 159, 160]}A meta-analysis of several small studies suggests that surfactant therapy may shorten the duration of ICU stay in children undergoing ventilation for severe bronchiolitis.^[161]

Heliox is a mixture of oxygen (20-30%) and helium (70-80%) that has lower viscosity than air. It has been used successfully in cases of airway obstruction, croup, airway surgery, and asthma to reduce respiratory effort during the period of airway compromise. Several studies have shown improved respiratory distress scores in patients breathing heliox and have suggested that combining heliox with nasal CPAP may render intubation unnecessary.^{[162, 163, 164, 165, 166, 167, 168]}

Pharmacologic Therapy

Medications have a limited role in the management of bronchiolitis. Several drugs are commonly used (eg, bronchodilators), but there is little in the way of conclusive evidence to support routine use of any drug in the management of bronchiolitis.

In patients who are febrile, have bronchiolitis, and are at high risk, including those who have nosocomial RSV infection or who appear toxic at presentation, the risk of secondary bacterial infection is increased but remains small. The decision to start antibiotics should be made on a case-by-case basis.

Bronchodilators

Although the use of bronchodilators in patients with bronchiolitis remains widespread, the data are insufficient to support this approach as routine practice. One practical approach is to continue the use of bronchodilators only in patients who demonstrate clinical improvement after initial use of these agents.

A meta-analysis reviewed 15 randomized placebo-controlled trials of inhaled albuterol treatment in bronchiolitis.^[127]It concluded that albuterol produces only modest short-term improvement in clinical features of mild or moderately severe bronchiolitis, primarily by making the child more alert.

A meta-analysis of 9 clinical trials noted that conclusive evidence of the efficacy of beta₂ -agonist therapy for bronchiolitis is unavailable and that routine use of such therapy for bronchiolitis is unsupported.^[128]A 2000 Cochrane review of the use of bronchodilators for bronchiolitis further confirmed the lack of direct evidence of a sustained benefit.^[169]A 2010 Cochrane review found that bronchodilators do not improve oxygen saturation, shorten hospital stay, decrease the need for hospitalization, or reduce the length of illness at home.^[170]

One study compared nebulized albuterol with normal saline in an age-matched and severity-matched trial of 52 infants over 72 hours of treatment.^[129]Nebulized albuterol did not improve recovery or attenuate severity, as indicated by improvement in oxygen saturation, length of stay, or clinical score.

Two randomized studies evaluating albuterol, ipratropium, and both medications combined against normal saline found no improvement with medications.^{[130, 171]}In a prospective, nonrandomized study, inhaled albuterol did not yield a significant improvement in the respiratory status of infants with RSV-induced respiratory failure, regardless of whether they had an obstructive or restrictive pulmonary dysfunction.^[172]

Only a single nonrandomized study of 25 ventilated young infants (13 of whom were premature or had preexisting cardiopulmonary disease) with RSV bronchiolitis demonstrated a statistically significant increase in maximum volume functional residual capacity (Vmax FRC) with aerosolized albuterol; however, in 3 of these infants, respiratory function worsened.^[173]

Although initial evidence suggested that nebulized racemic epinephrine reduced symptoms and length of hospital stay,^{[174, 175, 176]}subsequent studies did not support the use of epinephrine.^{[177, 178, 179]}

A randomized, double-blind, placebo-controlled study of 62 somewhat older children (age, 6 weeks to 2 years; mean age, 6.4 months) compared aerosolized racemic epinephrine with albuterol. Racemic epinephrine resulted in significant improvement in wheezing and respiratory distress score on day 2 but did not shorten hospitalization or total duration of illness.^[174]

However, in a randomized placebo-controlled trial of albuterol and epinephrine in equipotent doses, neither drug reduced the need for oxygen or reduced length of stay.^[180]Moreover, neither drug reduced the quantity of oxygen required or reduced clinical respiratory scores.^{[180, 181]}

In an editorial, Wohl and Chernick, both highly respected experts on bronchiolitis, speculated that inhaled epinephrine may relieve symptoms by acting as a nasal decongestant and that similar nose drops may help to relieve symptoms^[182]; a follow-up letter to the editor asked for a controlled study to end the speculation.

In a systematic review and meta-analysis of the use of steroids and bronchodilators for acute bronchiolitis in the first 2 years of life, Harling et al found the majority (83%) of the 48 studies reviewed to have either high or unclear bias.^[183]The evidence only shows effectiveness and superiority of epinephrine for most clinically relevant outcomes among outpatients with acute bronchiolitis.

This conclusion is largely based on a multicenter, double-blind, placebo-controlled trial that randomized 800 infants (age, 6 weeks to 12 months) to 1 of 4 treatment arms (nebulized epinephrine plus oral dexamethasone, nebulized epinephrine plus oral placebo, nebulized placebo plus oral dexamethasone, and nebulized placebo plus oral placebo).^[184]In this large trial, the combination of nebulized epinephrine and oral dexamethasone may reduce the risk of admission within 7 days of a visit to the ED.

In a double-blind study, Livni et al found no significant differences between inhaled epinephrine and nasal decongestant in hospitalized infants with acute bronchiolitis in terms of length of hospitalization, need for oxygen supplementation, or IV fluids and clinical score. They concluded that nasal decongestant is as effective as inhaled epinephrine for treatment of acute bronchiolitis.^[185]

Multiple authors have recommended instillation of saline nose drops before feeding. Instillation of the lowest concentration of nasal decongestant drops 2-3 times a day for no more than 3 days in hospitalized infants could be evaluated for its benefits.

Because bronchodilators lack demonstrable efficacy in bronchiolitis, it may be reasonable to administer a beta-agonist on a trial basis only to older patients with a personal or family history of asthma and then to assess the clinical response in 10-15 minutes. If retractions, respiratory rate, and wheezing improve, scheduled aerosol treatments may be continued, with additional treatments given as needed. If little or no sustained response is noted, bronchodilator therapy should cease, because it contributes to agitation and ventilation-perfusion ratio mismatching.

Antivirals and antibiotics

Antiviral therapy is not routinely recommended for cases of bronchiolitis. Although ribavirin has the potential to reduce days of mechanical ventilation and hospitalization, these effects have been inconsistent and are insufficient to support its routine use to treat RSV infections,^{[3, 82, 186, 187, 188]}and the AAP recommends against such use.^{[110, 3]}However, the AAP suggests that ribavirin aerosol therapy may be considered in selected groups of infants and young children at high risk for potentially life-threatening RSV disease:

Those with complicated congenital heart disease (including pulmonary hypertension) and those with bronchopulmonary dysplasia, cystic fibrosis, and other chronic lung disease
Those with underlying immunosuppressive disease and those who are severely ill with or without mechanical ventilation
Hospitalized patients who are younger than 6 weeks or who have underlying conditions (eg, multiple congenital anomalies or certain neurologic metabolic diseases)

Placebo-controlled studies have not found ribavirin to be clinically effective in children with bronchiolitis. Long-term follow-up studies of ribavirin have not consistently shown a beneficial effect on pulmonary function. Furthermore, this therapy is very expensive. Use of aerosolized ribavirin in mechanically ventilated patients requires administration by physicians and support staff familiar with this mode of administration and the specific ventilator. Given the high cost and the lack of proven benefit, ribavirin therapy is difficult to justify in this setting.

Viruses are the primary etiologic agents in bronchiolitis; therefore, routine administration of antibiotics has not been shown to influence the course of this disease. In young, acutely ill infants, excluding the presence of secondary bacterial infection on clinical grounds may be difficult. Thus, administration of broad-spectrum antibiotics in such critically ill infants may be justified until bacterial culture results prove negative. Studies have shown that the risk of concurrent serious bacterial infections in nontoxic-appearing infants with bronchiolitis is low.^{[85, 86]}

It should be kept in mind that a positive test result for RSV does not exclude coinfection with other respiratory pathogens. Co-infection with parainfluenza, influenza, measles, adenovirus, hMPV, pertussis, Legionella, and Pneumocystis are all possible. Severe cases and those that do not follow typical courses for RSV bronchiolitis may benefit from investigation for co-infections.

Anti-inflammatory agents

The belief that corticosteroids can prevent or reduce the major pathology of inflammation and edema of the bronchiolar mucosa is tempting. However, the data indicate that these agents should not be used routinely in this setting. Numerous studies have failed to conclusively define a beneficial role for routine use of glucocorticoids in the treatment of infants with bronchiolitis.^{[126, 189, 190, 191, 192, 193, 194, 195]}

Additionally, a Cochrane Review that included 13 trials of 1198 children aged 0-30 months failed to demonstrate improvements in length of stay, clinical score, hospital admission rates, or readmission rates for either systemic or inhaled corticosteroids administered either in the hospital or in the ED.^[196]Nevertheless, Weinberger cited several small studies suggesting that high-dose systemic steroids early in the course of bronchiolitis may be effective in preventing the progression of inflammation or, at least, in modifying its course.^[197]

Plint et al found that combining dexamethasone and epinephrine may reduce hospital admissions for infants with bronchiolitis treated in the ED.^[184]In this trial, 800 infants were assigned to 1 of 4 treatment groups (nebulized epinephrine and oral dexamethasone, nebulized epinephrine and oral placebo, nebulized placebo and oral dexamethasone, or nebulized placebo and oral placebo). Only the infants in the epinephrine-dexamethasone group were significantly less likely to be admitted to the hospital within 7 days of treatment.

Sumner et al, using data from the Canadian Bronchiolitis Epinephrine Steroid Trial, found epinephrine and dexamethasone to be the most cost-effective treatment for bronchiolitis in infants aged 6 weeks to 12 months.^[198]

Corticosteroids may be useful in patients with history of reactive airway disease. Steroid treatment has not been shown to decrease the long-term incidence of wheezing or asthma after RSV infection. Nebulized steroid treatment has not been proven efficacious.

In a study by Croe et al, the mast cell inhibitor cromoglycate had no beneficial effects.^[199]One study suggested that montelukast, a Cys-LT receptor antagonist, may reduce postbronchiolitis reactive airway disease, but this intervention cannot be recommended at this time.^[200]

Hypertonic saline

While nebulized hypertonic saline have been used for treating hospitalized, as well as ambulatory, children with viral bronchiolitis with varying degrees of success, there is accumulating convincing evidence that does not support hypertonic saline's effect in reducing length of hospital stay for acute viral bronchiolitis in a typical US population (where the length of stay is 2.4 days on average).^{[201, 202, 203, 204]}

In a prospective, double-blinded, multicenter trial, the use of nebulized 3% hypertonic saline was a safe, inexpensive, and effective treatment for moderately ill hospitalized infants with viral bronchiolitis.^[205]In a randomized, double-blind trial of 187 infants younger than 18 months with acute bronchiolitis, Al-Ansari et al found that nebulization with 5% hypertonic saline was safe and superior to 0.9% saline, and possibly superior to 3% hypertonic saline, for early ambulatory treatment of bronchiolitis.^[206]A multicenter trial with a larger sample size may help establish the clinical benefits of this therapy.

Brooks et al reanalyzed the existing data on the benefit of nebulized hypertonic saline for infants. The study concluded that prior analyses were driven by an outlier population and unbalanced treatment groups in positive trials and that once heterogeneity was accounted for, the data did not support the use of hypertonic saline to decrease hospital length of stay in infants hospitalized with bronchiolitis.^{[203, 204]}

Chest Physiotherapy

Medical therapy for bronchiolitis seems to be disappointing, but chest physiotherapy cannot be recommended either. In 3 clinical trials of unventilated hospitalized infants that compared vibration and percussion techniques in postural drainage positions with no intervention, no differences were reported with respect to length of hospital stay, oxygen requirements, or severity of clinical score in infants with bronchiolitis.^[207]

A 2012 Cochrane review, which included 9 studies of children younger than 2 years with acute bronchiolitis, confirmed that chest physiotherapy does not decrease the severity of the disease, improve respiratory parameters, shorten the hospital stay, or reduce oxygen requirements in nonventilated hospitalized patients. Various chest physiotherapy modalities (vibration and percussion or forced expiratory techniques) have shown equally negative results.^[208]

Complications of Therapy

Complications of therapy include the following:

Ventilator-induced barotrauma
Nosocomial infection
Beta-agonist–induced arrhythmias
Nutritional and metabolic abnormalities

Strict attention to fluid and nutritional therapy, avoidance of unnecessary invasive monitoring, infection control, and judicious ventilator management (including the use of high-frequency oscillatory ventilation to avoid volutrauma, barotrauma, or both), may preclude many of these complications.

Discharge Criteria

Once the relevant criteria are met, the patient may be discharged. Specific discharge criteria for bronchiolitis patients vary considerably from one institution to another, as reported by Weiss and Annamalai.^[209]The fundamental considerations in formulating such criteria are as follows^{[209, 210]}:

The ability of the caretaker to manage the infant’s nasal congestion
Improvement in respiratory distress, as evidenced by a respiratory rate lower than 60-70 breaths/min and a resting oxygen saturation above 90% without supplemental oxygen
Adequate oral intake
The education and confidence of the caretaker

Various criteria for discharge have been proposed, including the following:

Clinical improvement
Oral intake adequate to maintain hydration status
Age older than 2 months without a history of prematurity
No apnea in the preceding 24 hours (in infants younger than 6 months) or the preceding 48 hours (in patients older than 6 months)
Acceptable oxygen saturation for more than 1 day, either on room air or on stable oxygen therapy of less than 0.5 L/min via nasal cannula if discharged on home oxygen
Respiratory rate lower than 60-70 breaths/min
Minimal retractions at rest (not crying)
No underlying cardiopulmonary disease
When appropriate, home oxygen therapy arranged and parents educated in its use
Reliable caregivers with transportation available
Follow-up arranged with primary care physician

For patients who are hospitalized, a follow-up appointment with a primary care physician 1-2 days after discharge is indicated to recheck room air saturation and to reassure parents. No further laboratory testing is necessary unless the patient must test RSV-negative for return to an environment where high-risk patients are present (eg, a medical childcare center or group home). It may be important to note that secretions may remain positive for RSV for as long as 21 days after the onset of symptoms.^[22]

Children who required inpatient antibiotics for concurrent bacterial infection should continue to receive the same antibiotics so as to complete the prescribed course. An older child with reactive airway disease may require continued treatment with bronchodilators.

When discharging infants younger than 2 months, keep in mind that prior hospitalization and male gender may predispose these patients to unscheduled return visits to the ED. Provision of targeted discharge information and arrangement of follow-up care with a primary care physician would be particularly helpful for this group of infants.^[211]

Prevention

RSV is transmitted via direct contact with secretions of infected patients. Droplets and fomites play a less important role. Meticulous attention to handwashing between patient contacts should reduce the likelihood of hospital staff acquiring RSV infection from patients and of spreading infection by carrying RSV on their hands.^{[60, 61, 212, 213, 214]}

Attempts to develop a safe and effective RSV vaccine have thus far been unsuccessful. A 1967 study of a formalin-inactivated RSV vaccine resulted in a 15-fold increase in hospitalization and mortality when immunized patients were subsequently reinfected; an adequate explanation for this exaggerated pulmonary response has not been elucidated.^[215]Efforts to develop an RSV vaccine continue.^[216]A live-attenuated intranasally administered RSV vaccine is being developed. Another approach being studied involves maternal immunization against RSV during pregnancy, with the hope of providing neutralizing antibodies that cross the placenta to protect the infant.^[217]

Active prophylaxis using RSV immunoglobulin intravenously (RSV-IGIV) at high doses was shown to prevent RSV in high-risk patients.^[218]However, a more convenient RSV-specific humanized mouse IgG1 monoclonal antibody preparation, palivizumab, was subsequently developed and FDA-approved in 1998 for prophylaxis for infants at high risk for RSV infection. Palivizumab is administered intramuscularly (IM) at a dose of 15 mg/kg every month for a maximum of 5 doses during the RSV season (ie, from October through February in most U.S. regions).^[219]

In a multi-institutional, randomized, placebo-controlled study of 1502 high-risk preterm infants in 139 centers in the United States and Canada during the 1996-1997 RSV season, rate of hospitalization was reduced by 5.8% (10.6% in placebo vs. 4.8% in palivizumab group, P< 0.001).^[220]Infants receiving palivizumab had reduced hospital length of stay, days on oxygen, and ICU admissions. Adverse effects were uncommon. Romero summarized 4 outcome studies encompassing over 16,000 children after the use of palivizumab; all showed high effectiveness in reducing RSV admissions.^[221]

A 2005 study of PICU admissions for bronchiolitis did not demonstrate a decrease in admissions or need for ventilation before and after palivizumab was licensed. In this study, 83% of the infants admitted to the ICU did not meet AAP criteria for RSV prophylaxis.^[222]Stevens and Hall summarized the controversies regarding the use of palivizumab for children born at 32-35 weeks’ gestation. They concluding that if these infants do not have chronic lung disease and are younger than 6 months at the start of the RSV season, they may benefit from RSV prophylaxis if at least 2 of the following are observed: daycare attendance, school-aged siblings, passive smoke exposure, airway abnormalities or neuromuscular disease.^[223]

Since palivizumab was licensed for RSV immunoprophylaxis, the recommendations for its use have become more restrictive as additional information became available regarding the epidemiology of RSV hospitalizations and the limited benefit of prophylaxis in selected patient populations. AAP guidance regarding palivizumab use^[219]is stratified according to risk and can be summarized as follows:

Preterm infants born before 29 weeks of gestation, without chronic lung disease of prematurity or congenital heart disease and less than 12 months of age at the start of RSV season; those born on or after 29 weeks of gestation should NOT receive prophylaxis as their rate of hospitalization for bronchiolitis is not different from full0term infants.
Preterm infants born before completing 32 weeks of gestation with chronic lung disease of prematurity and requirement for supplemental oxygen for the first 28 days of life.
Infants born with acyanotic congenital heart disease. Palivizumab is NOT recommended routinely for infants with cyanotic congenital heart diseases there is no significant reduction in rate of hospitalization for RSV.
For children older than 12 months of age, palivizumab is recommended only for when there is chronic lung disease requiring supplemental oxygen or diuretic or glucocorticoid therapy.

Prevention of serious RSV infection by giving palivizumab may reduce the incidence of subsequent wheezing.^{[224, 225]}

Unfortunately, although the use of palivizumab is possibly cost-effective, the cost per individual patient is still high (approximately $5000), which means that the availability of this agent is limited to high-risk patients.^{[4, 226, 227]}

In a randomized, double-blind, multinational, phase 3 noninferiority trial comparing motavizumab (a monoclonal antibody with enhanced anti-RSV activity in preclinical studies) with palivizumab, motavizumab recipients had a 26% relative reduction in RSV hospitalization.^[228]This result established that motavizumab was not inferior to palivizumab, but it did not meet the researchers’ criteria for establishing superiority. The data also revealed that motavizumab significantly reduced outpatient RSV-specific, medically attended lower respiratory tract infection.^[228]Consequently, the researchers concluded that motavizumab may offer an improved alternative for preventing serious RSV disease in high-risk infants and children.^[228]However, in 2010, the FDA voted against licensing motavizumab due to concerns that it did not offer significant improvement and cause higher adverse hypersensitivity skin reactions when compared to palivizumab.

Several studies have demonstrated a beneficial effect of breastfeeding, particularly prolonged nursing, for preventing or lessening the severity of RSV bronchiolitis.^{[10, 11]}

Consultations

When a healthy infant presents with a history, physical examination findings, and course consistent with uncomplicated bronchiolitis, no consultations are necessary.

However, refer infants with comorbidities, atypical histories, or critical conditions should be referred to a pediatrician, preferably at a center that can provide a spectrum of pediatric subspecialists in critical care, pulmonology, and infectious diseases.

Long-Term Monitoring

Most previously healthy children with bronchiolitis recover with few complications, but the resolution of symptoms may take weeks. Follow-up should be arranged with the primary care physician.

Among those with severe disease, a few may develop respiratory failure and experience a protracted hospital course. Some patients will require supplemental home oxygen therapy at the time of discharge. On follow-up, these patients should be evaluated to document resolution of the need for oxygen therapy. An association between RSV bronchiolitis and subsequent wheezing and asthma has been noted, but proof of causality is lacking at present. Parental education is an important part of discharge planning.

Electronic cardiac and respiratory monitoring is required for some patients (persons who are very sick, are very young, or are having apneic episodes). This monitoring should be discontinued in a timely manner when it is no longer necessary.

Bronchiectasis after bronchiolitis

Long-term pulmonary sequelae after RSV bronchiolitis are uncommon and may include subsequent wheezing. However, with adenoviral infection, severe lung damage, bronchiectasis, and hyperlucent lungs may result.

Bronchiectasis after bronchiolitis is uncommon but has been described, with many reports implicating adenovirus. Adenovirus is a known cause of bronchiectasis after several childhood infections, especially adenovirus types 3, 7, and 21. Bronchiectasis has also been noted after bronchiolitis in patients co-infected with RSV and adenovirus. In this setting, adenovirus is believed to be the causative factor, given its propensity to cause bronchiectasis.

Long-term outcomes after infections with these pathogens may vary as a result of differences in immune response. Higher levels of interferon gamma and soluble CD 25 and lower levels of soluble tumor necrosis factor receptor II are observed with primary adenoviral infection in infants than with RSV infection. An imbalance in the ratio of T helper cell type 1 (Th1) to Th2 has been observed, favoring Th1 in adenoviral infections and Th2 in RSV infections. Symptoms and treatment of bronchiectasis after bronchiolitis are similar to those in other settings.

Beta agonists, administered by inhaler or nebulizer, may be continued on an outpatient basis if the child responds to them while in the ED. If inhalers are prescribed, a mask and spacer should be provided and the patient’s caregiver instructed in their use before discharge.

Immunoglobulin deficiency and recurrent bronchiolitis

Recurrent respiratory infections, including bronchiolitis, have been reported in children with immunoglobulin A (IgA) or immunoglobulin G (IgG) subclass deficiency. In a report of 225 children aged 6 months to 6 years with recurrent sinopulmonary infections, the overall frequency of antibody defects was 19.1%.^[229]IgA or IgG subclass deficiency was found in 25% of patients with recurrent upper respiratory tract infections, 22% of patients with recurrent pulmonary infections, and 12.3% of patients with recurrent bronchiolitis.

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Media Gallery

A chest radiography revealing lung hyperinflation with a flattened diaphragm and bilateral atelectasis in the right apical and left basal regions in a 16-day-old infant with severe bronchiolitis. Image courtesy of Wikipedia Commons.
Electron micrograph of respiratory syncytial virus (RSV). Image courtesy of Wikipedia Commons.
Airway anatomy showing bronchioles. Image courtesy of Wikipedia Commons.

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Author

Nizar F Maraqa, MD, FAAP, FPIDS Associate Professor of Pediatric Infectious Diseases, Fellowship Program Director for Pediatric Infectious Diseases, Residency Associate Program Director for Pediatrics, Chief Information Officer, Division of Infectious Diseases, Department of Pediatrics, University of Florida College of Medicine-Jacksonville; Medical Director, University of Florida Center for HIV/AIDS Research, Education, and Service (UF CARES); Medical Director of Pediatric Informatics, Wolfson Children’s Hospital, Baptist Health of Northeast Florida

Nizar F Maraqa, MD, FAAP, FPIDS is a member of the following medical societies: American Academy of Pediatrics, Jordan Medical Association, Pediatric Infectious Diseases Society, Pediatric Society - Palestine

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Lucian Kenneth DeNicola, MD, MS, FAAP, FCCM Professor, Department of Pediatrics, University of Florida Health Science Center at Jacksonville

Lucian Kenneth DeNicola, MD, MS, FAAP, FCCM is a member of the following medical societies: American Academy of Pediatrics, American College of Critical Care Medicine, Florida Medical Association, Society of Critical Care Medicine, Florida Chapter of The American Academy of Pediatrics, Florida Pediatric Society

Disclosure: Nothing to disclose.

John Udeani, MD, FAAEM Assistant Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science, University of California, Los Angeles, David Geffen School of Medicine

John Udeani, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Haidee T Custodio, MD Associate Professor, Department of Pediatrics, Division of Pediatric Infectious Diseases, University of South Alabama College of Medicine

Haidee T Custodio, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Local Principal Investigator for a clinical trial for: Allergan.

Acknowledgements

Kirsten A Bechtel, MD Associate Professor, Department of Pediatrics, Yale University School of Medicine; Attending Physician, Department of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital

Kirsten A Bechtel, MD is a member of the following medical societies: American Academy of Pediatrics