Chapter 32. Bronchiolitis

Bronchiolitis, a common communicable respiratory illness manifesting with signs of small airways inflammation, primarily affects children younger than 2 years. Over one in five children will have bronchiolitis-associated wheezing in the first year of life.1 Bronchiolitis is the most common cause of hospitalization of children in the United States. Between 1% and 3% of all children are hospitalized as a result of bronchiolitis; one in four infants hospitalized for bronchiolitis are younger than 6 weeks of age, and over half are younger than 6 months of age. The mean length of hospital stay for children is 3 days (interquartile range 2–5 days), and the cost for care is estimated at over a half billion dollars annually.2–4 Despite the high prevalence of the disease and high rates of hospitalization, bronchiolitis is responsible for only about 100 pediatric deaths each year in the United States.5

Respiratory syncytial virus (RSV) causes 50–70% of bronchiolitis-related illness (Table 32–1).6 Recently identified causes of bronchiolitis include human metapneumovirus (hMPV) and human bocavirus (HBoV), a human parvovirus. These viruses have been detected in 20–25% for hMPV7,8 and 5% for HBoV9 of children with bronchiolitis and negative direct fluorescent antibody testing of nasal aspirates for RSV, parainfluenza types 1 to 3, influenza A and B, and adenovirus.

Bronchiolitis is more predominant in the winter months though the timing of disease onset within a particular season and the duration of the respiratory virus season vary by geographic location. For example, RSV season in the southern United States begins earlier and lasts longer than the RSV season in the rest of the nation. Between 1990 and 2000, the median onset of RSV season (defined as the first 2 consecutive weeks where more than 10% of nasal wash specimens tested at a regional reference laboratory were positive for RSV) was late November for the South and late December for the rest of the country.10 The median duration of RSV seasons during this 10-year time period was 16 weeks for states located in the South compared with 13 weeks for states in the Midwest.10 There is also significant season-to-season variation in RSV with the period of peak prevalence varying by as much as 7 weeks (ranging from early January to late February) between seasons.10 While the majority of bronchiolitis seasonality is caused by dramatic annual spikes in RSV prevalence, other viruses exhibit different seasonal outbreak patterns (Figure 32–1).11

Several factors place children at increased risk of severe bronchiolitis. Shortly after recognition of hMPV as a causative agent in bronchiolitis, a group in England noted that 70% of RSV-positive children who required admission to the intensive care unit were coinfected with hMPV, suggesting that coinfection with these two viruses was a risk factor for a more severe disease course.12 In another study, hMPV was detected in 50 (8.5%) of 589 children with respiratory tract infections; 15 (30%) of hMPV-infected children were coinfected with RSV. Coinfected patients had a 3-day longer length of hospitalization than patients infected by either hMPV or RSV alone.13 While hMPV and RSV coinfection may lead to more severe illness, most studies have found very low rates of hMPV coinfection among RSV-infected children.14,15

Infants of Hispanic or Native American descent are at increased risk for severe bronchiolitis.16 Additionally, boys are slightly more likely to develop severe bronchiolitis than girls, a finding that may be associated with sex-related differences in lung volume at the end of tidal expiration.17 Infants who are formula-fed are three times as likely to be hospitalized for bronchiolitis as those who are breastfed, even when adjusting for other risk factors for bronchiolitis such as smoking and socioeconomic status.18 Infants exposed to secondhand smoke are between two and four times as likely to suffer an early wheezing episode.19 Among children with RSV bronchiolitis, disease course is more severe in infants exposed to maternal cigarette use.20

Residence at high altitudes also increases the risk of severe bronchiolitis. The normal physiologic effects of altitude on the respiratory tract are multiple. Baseline oxygen saturation values decrease with increasing altitude, an expected response to the decreased fraction of inspired oxygen. In addition, nasal obstruction and impaired ciliary activity exhibited at high altitude,21 in conjunction with low humidity, can impair the ability to clear respiratory secretions associated with viral lower respiratory tract infections. In Colorado, RSV-specific hospitalization rates increased 25% among infants younger than 1 year and 53% among children 1–4 years of age for every 1000-m increase in altitude; the risk of RSV-associated hospitalization was highest at elevations above 2500 m.22 The stronger effect of altitude on child compared with infant hospitalization is likely because infants decompensate more readily with illness than older children. Thus, clinicians may have a lower threshold for hospital admission at baseline for younger infants, mitigating the additional effect of altitude on the hospitalization decision in younger infants.

Other Factors Predisposing to Severe Bronchiolitis-Related Illness

Underlying conditions such as prematurity, complex congenital heart disease, cystic fibrosis, bone marrow and solid organ transplantation, and human immunodeficiency virus infection contribute to a worsened disease course. Premature infants are at high risk for severe illness as a result of bronchiolitis23,24 because of immune compromise related to immunologic immaturity compounded by incomplete placental transfer of maternal IgG before birth.25 Furthermore, incomplete formation of the alveoli of the lung leads to pulmonary fibrosis and decreased lung compliance. As a consequence, premature infants with bronchiolitis are more likely to require hospitalization and endotracheal intubation than infants born at term gestation. These infants will also have prolonged hospitalization and incur a much higher cost of care.23,25 Children with chronic lung disease, especially those requiring home oxygen therapy, are at highest risk for severe illness, intensive care unit hospitalization, and prolonged length of stay.23,26,27

Children with congenital heart disease have a lower tolerance for increased pulmonary vascular resistance, which accompanies lower respiratory tract infection. They also may not tolerate the higher cardiac output precipitated by the active disease state. One-third of children with congenital heart disease hospitalized with RSV require admission to an intensive care unit and 3.4% die from bronchiolitis-related complications.28,29 Children with cystic fibrosis suffer from thickened mucous secretions and decreased pulmonary ciliary function, placing them at increased risk for a severe illness in the context of any lower respiratory tract infection; RSV is responsible for one-third of hospitalizations in the first year of life in this population.30,31 The median duration of hospitalization for infants with cystic fibrosis and viral respiratory illness is 14 days. Infection with RSV may also precipitate a permanent deterioration in lung function.32 Mortality rates of RSV pneumonia range from 60% to 78% in recipients of both bone marrow and solid organ transplants. Patients with impaired T-cell function, including those with congenital immunodeficiency, those on steroids, and patients undergoing chemotherapy, also have a more severe disease course.32

Multiple etiologic agents have been implicated as causes of bronchiolitis (Table 32–1).6 Following direct inoculation of the eye or nose, or through inhalation of viral particles, the virus directly invades the respiratory epithelium. Progressive infection of the respiratory mucosa leads to lymphocytic infiltration of peribronchial epithelial cells and enhanced goblet cell mucous production. Necrosis and subsequent desquamation of the ciliated respiratory epithelial cells lead to small airway obstruction as intraluminal cellular debris accumulates and mucosal edema worsens. This degraded material, a composite of fibrin and inflammatory debris, may cause plugging of the small airways, further worsening airflow obstruction.33 According to Poiseuille's law, the flow of air through a lumen is proportional to the fourth power of the airway's radius. Thus, even a small deposition of material in the airway will dramatically limit airflow and cause significant obstruction.

The average incubation period for bronchiolitis is 5–7 days, although there is variability of incubation periods between the causal viral pathogens; incubation periods are shorter for parainfluenza and influenza viruses.33 Bronchiolitis in infants usually begins with symptoms of upper respiratory tract infection including rhinorrhea, cough, nasal congestion, and fever. Younger children often exhibit posttussive emesis. Children who are more ill may have anorexia and irritability. Diarrhea is present in a minority of cases. As the disease progresses, however, and as inflammatory material accumulates in the lower airways, infants develop signs of lower airway obstruction. Infants may appear barrel-chested because of air trapping. Tachypnea, flaring of the alae nasi, grunting, and respiratory accessory muscle use are evident on physical examination. On auscultation, most infants have a prolonged expiratory phase, wheezing and rales or rhonchi.8,34,35 The respiratory sounds may be loud enough to obscure auscultation of the heart sounds. Patients with severe disease may develop hypoxia associated with cyanosis.

Approximately one in 30 infants younger than 6 months of age have apnea as their initial manifestation of bronchiolitis. Apnea is more common in younger and premature infants.36 Rarely, bronchiolitis is associated with pneumothorax, subcutaneous emphysema, and subglottic inflammation.37,38 Severe RSV infections may be associated with extrapulmonary complications such as cardiovascular failure, arrhythmias, seizures, focal neurological deficits, hyponatremia, hepatitis, and intussusception.39,40

Approximately half the patients with bronchiolitis also have acute otitis media (AOM).41–43 Among 42 RSV-infected patients followed prospectively, 21 (50%) patients had AOM at study enrollment, an additional five (12%) patients developed AOM within the next 10 days.42 In this study, 10 (24%) additional patients had otitis media with effusion. Bacteria were isolated from the middle ear fluid of all 25 patients with AOM who underwent tympanocentesis; RSV was isolated concurrently from the middle ear fluid in 8 (32%) of these patients.42 Presence of an AOM does not have any impact on the outcome of bronchiolitis.43 Treatment of AOM is discussed in Chapter 28 (Otitis Media).

The diagnosis of bronchiolitis can be made on the basis of history and physical examination. Routine laboratory or radiologic testing in not necessary for the diagnosis or management of bronchiolitis.44

Laboratory Testing

A variety of tests are available for identification of the causative virus in children with bronchiolitis. The most widely used tests are rapid antigen tests (such as direct florescence antibody testing). Additionally, some centers perform polymerase chain reaction (PCR)-based testing to detect viral genome from nasal aspirates or swabs; influenza, parainfluenza, adenovirus, RSV, hMPV, HBoV, and rhinovirus can all be detected by PCR. Multiple studies have demonstrated a high sensitivity and specificity of rapid testing, and a high concordance with viral culture techniques.45 Knowledge of viral pathogen, however, is unlikely to affect clinical management.

Pulse Oximetry

Pulse oximetry is an important tool in the management of infants with bronchiolitis. Infants with hypoxia will have a more serious disease course,11,26,46 and pulse oximetry reliably detects hypoxemia that is not suspected on physical examination. However, appropriate lower limits for oxygen saturation in children with bronchiolitis are not known and transient desaturation occurs in healthy, full-term infants.47 Among outpatients, mild reductions in percutaneous oxygen saturation at initial evaluation are associated with higher return visits for additional care. Among inpatients, the perceived need for supplemental oxygen, based on continuous pulse oximetry measurements, is associated with prolonged hospitalization. Restricting pulse oximetry to intermittent rather than continuous measurements shortens length of stay without adverse consequences.48 Furthermore, clinicians should be wary about using pulse oximetry as the sole surveillance tool for the detection of respiratory failure. Percutaneous oxygen saturation measurements do not accurately predict which infants will become apneic.36 Pulse oximetry measurements do not detect hypoventilation, which, despite the presence of significant hypercapnia, results in only modest decreases in percutaneous oxygenation saturation. Furthermore, small amounts of supplemental oxygen will restore partial pressure of oxygen (PO2), thereby normalizing oxygen saturation; this allows unrecognized inadequate ventilation to progress without further derangements in pulse oximeter readings until the development of significant respiratory acidosis and worsening hypercapnia. Physical examination at this point would reveal somnolence and tachypnea with shallow respirations and apnea or bradypnea.

Arterial Blood Gas Measurements

Arterial blood gases are sometimes used to evaluate severity of respiratory distress in bronchiolitis. A low PaO2 (partial pressure of oxygen, arterial) indicates the need for supplemental oxygen; however, in the setting of bronchiolitis, this can usually be inferred from pulse oximetry in the absence of severe anemia. Partial pressure of carbon dioxide (PCO2) measurements are more valuable in informing mechanical ventilation decisions. Expected derangements in the arterial blood gas values range from hypocapnia associated with tachypnea and hyperventilation to the normal-range PCO2 to hypercapnia and respiratory acidosis. A “normal” PCO2 in the setting of hyperventilation is inappropriate and is an early indication of respiratory insufficiency.

Radiologic Studies

Chest radiography is not routinely required in the diagnosis or management of infants with bronchiolitis. However, radiographs are indicated in the setting of a severe illness, when a patient is not improving as expected or if another diagnosis is suspected.44 Peribronchial cuffing or thickening may be present. Other typical radiographic findings in children with bronchiolitis include hyperinflation with flattening of the diaphragm (Figure 32–2) and scattered areas of consolidation. The consolidation, present in 40% of patients with bronchiolitis undergoing radiography, may represent either atalectasis or true alveolar infiltrates. While most of these alveolar infiltrates are likely related to viral pneumonitis, distinguishing viral from bacterial etiology in an individual patient can be difficult. In a subset of RSV-infected patients with radiographic infiltrates who required intensive care unit admission, 42% had lower airway secretions positive for bacteria.49 The implications of this finding are unclear but it is possible that critically ill patients with RSV are more likely to have bacterial superinfection than other RSV-infected patients. Subcutaneous emphysema and pneumomediastinum are rare complications of bronchiolitis (Figure 32–3). Studies assessing the utility of radiography in predicting disease course have been mixed, with some showing marked increased risk for a severe course among those with infiltrates,11,41 and another showing no predictive value.50

Complete Blood Count

Higher white blood cell counts and absolute neutrophil counts are associated with an increased risk of bacterial disease but the results rarely affect the diagnosis or management of bronchiolitis.45 An ANC above 10,000/mm3 increases the likelihood of bacterial infection (8% vs. 0.8% for those with an ANC <10,000/mm3)51 though the positive predictive value of an elevated ANC is low, particularly in infants who received the heptavalent pneumococcal conjugate vaccine. Routine complete blood counts are not recommended.

Lumbar Puncture

Meningitis is rare in well-appearing infants and children with fever, particularly in the context of bronchiolitis. In older children, the risk of meningitis is quite low and a lumbar puncture is not warranted unless the child has signs or symptoms that suggest meningitis. The decision to perform lumbar puncture routinely in young infants is more controversial. Febrile infants younger than 2 months with bronchiolitis appear to be at lower risk for meningitis than those without bronchiolitis. However, the risk is not zero and clinicians must balance the risk of missing a case of bacterial meningitis against the risk of the procedure in an infant with a respiratory illness. In a prospective, multicenter study of febrile infants younger than 2 months, the prevalence of bacterial meningitis was 0% [95% confidence interval (CI): 0–1.2%] in RSV-positive infants and 0.9% (95% CI: 0.4–1.7%) in RSV-negative infants.52 Other studies addressing the issue were conducted retrospectively and contain important methodologic flaws that limit their generalizability.53–56 It is prudent to consider meningitis in ill-appearing young infants with fever, however care should be taken not to impede respiratory effort during the procedure, and lumbar puncture (but not empiric antibiotic therapy) should be deferred in children with significant respiratory distress and suspected meningitis.

Blood Culture

Blood cultures are performed in one-third of all infants with bronchiolitis.57 However, rates of bacteremia in infants have dramatically decreased since the introduction of the heptavalent pneumococcal vaccine.58 The prevalence of bacteremia in infants with fever is low, particularly in the presence of overt signs of bronchiolitis. In older infants, a blood culture is more likely to reveal a contaminant than a pathogenic organism.58 However, the prevalence is higher among young children with high fever, immunization delay, or ill appearance. In the previously mentioned multicenter study of infants younger than 2 months, the prevalence of bactermia was 1.1% in RSV-positive infants and 2.3% in RSV-negative infants.52 Therefore, infants in these higher risk categories may warrant blood culture as part of their initial evaluation.

Urinalysis and Urine Culture

Rates of urinary tract incontinence (UTI) in infants with bronchiolitis have been reported between 1.9% and 12% with higher rates in the youngest infants.52,55,59–61 Among febrile infants younger than 2 months, rates of UTI were 5.4% in RSV-positive infants and 10.1% in RSV-negative infants.52 Empiric testing of the urine in young febrile children may be indicated, even in the presence of bronchiolitis.62 UTIs are discussed further in Chapter 42.

Guidelines and Pathways

There is a wide variation in the way practitioners and hospitalists manage bronchiolitis.63,64 The American Academy of Pediatrics has published evidence-based guidelines for management of this common disease.44 Institution of evidence-based guidelines or pathways for therapy has reduced unnecessary care, reduced bed occupancy, shortened length of stay, and decreased costs of care at several institutions.65–67 An example of a pathway for the management of infants with bronchiolitis is shown in Figure 32–4. Sustainability of these benefits has been demonstrated.68 Inpatient management strategies are summarized in Table 32–2.

Supplemental Oxygen

Hospitalized children with bronchiolitis often receive supplemental oxygen therapy. While the normal mean percutaneous oxygen saturation exceeds 95%, infants may exhibit transient decreases as a result of periodic breathing, physiologic apnea, and gastroesophageal reflux.47 In the context of bronchiolitis, airway edema and necrosis of respiratory epithelial cells causes ventilation–perfusion mismatch and subsequent hypoxia. Because of longitudinal variation, continuous pulse oximetry measurements may demonstrate a variability that makes distinction between normal physiology and disease pathology difficult. The increased rates of hospitalization for bronchiolitis over the past two decades have been attributed to the improved ability to noninvasively determine oxygen saturation levels rather than to an increased disease burden.69 Continuous pulse oximetry has been shown to prolong length of stay in the hospital unnecessarily, and has been estimated to incur a cost of $1500 per patient as a result.48

From a management standpoint, data support the position that otherwise healthy infants with bronchiolitis with a percutaneous oxygen saturation at or above 90% at sea level while breathing room air gain little benefit from increasing PaO2 with supplemental oxygen.44 As infants recover, improvement of low percutaneous oxygen saturation may lag behind other indicators like accessory muscle use. Though home oxygen therapy requires further assessment of safety, one study found low complication rates and high parental satisfaction with a strategy of 8-hour emergency department observation followed by home oxygen therapy for infants with bronchiolitis.70 This study excluded patients with prior wheezing, corticosteroid receipt, apnea, significant underlying medical conditions, and focal radiographic infiltrates and residence more than 30 minutes from the health care facility.

Hydration

Symptoms of bronchiolitis can be a double-edged sword against an infant's ability to maintain adequate hydration. Patients suffer increased insensible losses via fever and tachypnea. Increased respiratory effort and upper airway mucous obstruction may render feeding difficult. Viral illness may also decrease appetite. Furthermore, in normal infants with increased respiratory effort secondary to bronchiolitis, aspiration of food products is possible, worsening respiratory distress.71 To render the picture more complicated, however, patients with bronchiolitis have increased plasma levels of antidiuretic hormone, placing them at risk for fluid overload. There may be an increased propensity specifically for RSV to generate an inappropriately elevated level of antidiuretic hormone72 Thus, while rapid correction of clinical dehydration is appropriate, clinicians should monitor the infants’ intake and urinary output to ensure that the infant is not retaining fluid, which can lead to hyponatremia. In patients with ongoing poor feeding, intravenous maintenance fluids are indicated, however patients with adequate oral intake do not require parenteral hydration.44 While in many cases of dehydration, the nasogastric route is preferred over the intravenous route, nasogastric tube placement may impede respiratory effort in infants with bronchiolitis.

Beta-Agonists

It is often difficult to clinically distinguish, in advance, children with bronchiolitis who are normal infants with an infectious process causing wheezing, and children who have an underlying predisposition to wheezing, which has been triggered by an infectious process. There is no role for oral albuterol in the management of bronchiolitis.73,74 Many clinicians have argued for use of nebulized or inhaled beta-agonists such as albuterol in the management of bronchiolitis. In the ambulatory setting, Flores and Horwitz75 found no difference in respiratory rate and a statistically significant but clinically unimportant improvement in percutaneous oxygen saturation (by 1.2%) following nebulized albuterol therapy. Kellner et al.76 found a modest short-term reduction in severity of illness among infants with bronchiolitis, however, the benefit was not sustained and respiratory effort returned to pretreatment levels within an hour. Albuterol use in the ambulatory setting does not affect hospitalization rates.75,76

In the hospital setting, albuterol use does not decrease the length of hospital stay or the frequency of bronchiolitis-associated adverse outcomes.77 Although beta-agonists are usually well tolerated, adverse reactions such as tachycardia, flushing, and tremor occur commonly. Albuterol may also cause a ventilation–perfusion mismatch immediately after therapy, leading to transient oxygen desaturation.78 Despite its unproven efficacy, beta-agonist use for RSV bronchiolitis has been estimated to cost over $37 million annually.79

In summary, beta-agonist therapy is not routinely indicated for the treatment of bronchiolitis. While practitioners may use this as a trial therapy, it should only be continued if a significant objective clinical benefit to the patient has been demonstrated.44 While ipratropium bromide has been found to be a useful adjuvant in the treatment of asthma, there is no role for anticholinergic therapy in the management of bronchiolitis, either alone or in combination with beta-agonists.44

Racemic Epinephrine

Inhaled racemic epinephrine caries a theoretical advantage over inhaled beta-agonists in bronchiolitis because the drug not only carries the beta-agonist benefits of bronchodilation, but also the alpha-agonist effect of reducing edema and mucous production through vasoconstriction.34 One randomized trial found a decreased admission rate for children who were administered racemic epinephrine (33%) compared with those administered albuterol (81%) during emergency department evaluation.80 However, most other studies in the ambulatory setting have failed to find any differences.81 Among hospitalized patients, while racemic epinephrine use resulted in minor improvements in respiratory assessment score or respiratory rate compared with either placebo or albuterol, there was no difference in length of hospital stay.81 Racemic epinephrine is not used outside the hospital setting. In hospitalized patients, the American Association of Pediatrics (AAP) currently recommends a carefully monitored trial of racemic epinephrine with continuation of the drug only in those who demonstrate clear and objective improvement.44

Corticosteriods

Despite the high prevalence of corticosteroid usage, there is very little evidence that steroids improve the clinical course of patients with bronchiolitis.82 Most trials and a Cochrane database review have failed to demonstrate an improvement in length of stay in the hospital, clinical breathing scores, oxygenation, readmission rates, or duration of illness regardless of route of corticosteroid administration.82–86 In a meta-analysis that included six studies, infants receiving corticosteroids had a mean length of stay that was 0.43 days less than those who received the placebo treatment (95% confidence interval: –0.81 to –0.05 days); however, this difference was not statistically significant when only studies that excluded children with prior wheezing were included.87

Ribavirin

Ribavirin, a guanosine analog, disrupts the replication of RSV viral RNA, thereby inhibiting replication of the virus. While its efficacy has been demonstrated in vitro, its therapeutic utilization remains controversial. One small study demonstrated decreased length of stay and decreased time of mechanical ventilation in patients, however the authors used nebulized sterile water, a known precipitant of bronchospam, as a control for comparison.88 Another study demonstrated a reduction in rates of future wheezing in patients treated with ribavirin during acute illness but two others failed to replicate this result.44 Because ribavirin is a potential teratogen, administration to patients requires either positive pressure ventilation or a specialized vacuum exhaust hood system.89 The cost of this medicine is estimated at $1100 per day and use of the drug is not cost-effective.90,91 In practice, ribavirin use is limited to small subsets of immunocompromised or critically ill patients.

Helium–Oxygen Mixtures

In diseases where an obstruction of air flow causes increased respiratory effort, helium, an inert gas with no bronchodilatory or anti-inflammatory properties, has been proposed as a possible solution. Mixing oxygen with low-density helium at a helium:oxygen ratio of 80:20 or 70:30 (heliox) results in easier, more laminar flow past obstructions in the airway compared with ambient air, which is comprised of higher density nitrogen.92 While use in asthma is still controversial, it is effective in diseases of upper airway obstruction, such as croup. In bronchiolitis, several small trials have studied its efficacy at relieving respiratory distress. By improving laminar flow in the lungs, it becomes easier for infants to move a larger quantity of air, which in turn reduces respiratory effort. Most of these studies have shown that heliox reduces respiratory effort93–95 and decreases intensive care unit length of stay,94 and one argued that heliox may reduce the likelihood of endotracheal intubation.93

Other Drugs

In animal models, RSV infection has altered the production of endogenous surfactant. In mechanically ventilated infants with bronchiolitis, treatment with surfactant decreased the duration of ventilatory support.96 However, surfactant is still considered an experimental treatment for critically ill children with bronchiolitis. Other therapies including decongestants, antihistamines, and dextromethorphan offer no benefit to children with bronchiolitis.97–99

Other Therapeutic Considerations

The accrual of mucous in the upper airway can contribute to the respiratory distress of infants with bronchiolitis. Nasal bulb suctioning preceded by saline administration is a mainstay of clearing the upper airway for infants; this technique may be taught to parents as a method of managing their children's illness at home. Optimally, patients should be suctioned in this manner prior to feedings and prior to any inhalational therapy that has been demonstrated to be efficacious.62 In the hospital setting, respiratory therapists may be inclined to use vacuum-assisted nasopharyngeal suctioning by catheter. This technique is more traumatic and painful than bulb suction, and may cause bleeding and may worsen gastroesophageal reflux,100 and has been reported as a cause of pneumothorax, apnea, worsened bronchospasm, and even intraventricular hemorrhage of the newborn.101 It may be prudent to limit invasive suctioning to patients with significant respiratory distress, as the efficacy of this modality on moderately ill patients has never been demonstrated.

While patients with bronchiolitis may demonstrate areas of atalectasis on chest radiography and secretions may obstruct airflow, chest physiotherapy is contraindicated. Infantile chest physiotherapy has been associated with adverse events such as rib fractures and does not improve respiratory effort or reduce hospital length-of-stay.102

Ninety percent of infants will acquire RSV in their first two years of life, and almost half of these will develop bronchiolitis.44 Much effort has been spent in trying to prospectively determine which patients with bronchiolitis will have a more severe course of illness. Roughly 0.5% of infants who acquire bronchiolitis will be hospitalized.2 Of these, 14% will require mechanical ventilation for apnea or respiratory failure.41 It is difficult, but important, to be able to predict which patients are likely to deteriorate, and thus warrant observation in the hospital setting. Infants younger than 1 month, who were premature or who have witnessed apnea, require careful observation for apnea or a repeated episode of apnea.36 Children with high fever are more likely to have a more severe and prolonged hospital course.103 Patients who have underlying pulmonary or cardiac conditions, especially cystic fibrosis, pulmonary hypertension, and chronic lung disease of prematurity are also at risk for severe bronchiolitis-related illness. These patients warrant a lower threshold for admission and close monitoring.44

The typical acute bronchiolitis illness lasts 3–7 days. Infants hospitalized early in the course of illness may worsen clinically for several days before improving. Potential complications include cardiac arrhythmia (2%) and electrolyte imbalance (20%).41 Apnea associated with bronchiolitis usually resolves within 48–72 hours, although some infants may require longer periods of hospitalization and monitoring. In general, improvement is gradual. For infants younger than 24 months, the median length of illness is 12 days, but up to 9% of patients will still have persistence of symptoms at 28 days of illness.104

Bronchiolitis in infancy has long-term implications. In mice, infection with either RSV and hMPV in the perinatal period results in asthma in adult mice.105,106 While causality is difficult to determine in humans, RSV exposure in infancy is strongly associated with development of asthma. In one study, 47 children hospitalized for bronchiolitis and 93 age-matched controls were followed prospectively. At 13 years of age, 48% of the children hospitalized with RSV in infancy had suffered wheezing in the past 12 months, compared with 8% of their age-matched controls.107 Additionally, among children who develop persistent wheezing, encountering a first-time wheezing episode early in life is correlated with having more severe disease.108

Infection Control and Patient Safety

During the peak of the bronchiolitis season, there is a high risk of nosocomial transmission of infection. Approximately 5% of RSV-infected children acquire their RSV in a health care setting.109 Transmission rates approach at least 45% of contacts within the hospital in the absence of infection control measures.110 Nosocomially acquired RSV leads to a median 8-day increase in the length-of-hospital stay.111 A program consisting of early recognition of patients with respiratory symptoms, cohorting nursing staff to care for isolated patients, and widespread use of gown and glove barrier precautions has proven cost-effective in reducing nosocomial RSV transmission.111 Isolating patients in private rooms more effectively reduces nosocomial transmission than cohorting patients by type of virus isolated because infants with bronchiolitis (1) do not generate a robust immunoglobulin response to RSV; (2) may be infected by different strains of RSV simultaneously or within the span of the same viral season;112 and (3) shed multiple unrelated respiratory viruses in 20% of cases.113

Alcohol-based hand sanitizers are an easy, effective technique for cleansing after caring for patients with bronchiolitis.114 Family members with viral symptoms should remained confined to their child's room, wear face masks when venturing outside their child's room,115 and refrain from any contact with other patients. Other visitors with viral symptoms should be restricted from visiting hospitalized patients. Clinicians should also educate families about the importance of hand hygiene to prevent spread of disease.44 In the home setting, secondary transmission rates were 0.63 respiratory illnesses per susceptible person-month.116 Alcohol-based hand sanitizers and hand hygiene education can reduce transmission of illness within the home setting.116,117Chapters 5 (Hospital Infection Control) and 4 (Office Infection Control) provide additional guidance on infection control issues.

In addition to risks for nosocomial infection, children hospitalized for bronchiolitis have a high rate of preventable adverse events during hospitalization. One study found that 10% of admitted patients with bronchiolitis suffered a near miss or adverse event. The rate was higher among critically ill patients. These included a range of severity from unwarranted phlebotomy to infection of central catheters and the acquisition of serious nosocomial infection.118

Palivizumab

Palivizumab (Synagis™) is a humanized mouse antibody directed against a glycoprotein specific for the RSV virus. The use of this drug has replaced RSV-IG, which is no longer available. Palivizumab is administered as an intramuscular injection on a monthly basis during the course of the RSV season, usually a 5-month course. Administration is highly effective at preventing RSV infection and also at curtailing severity of disease. Compared with placebo, palivizumab decreases by half an infant's risk for hospitalization (from 10.6% to 4.8%), and reduces length of stay and oxygen utilization in those who are hospitalized.29,119 Among 1287 infants with hemodynamically significant heart disease, hospitalization rates were lower among palivizumab recipients (5.3%) compared with placebo recipients (9.7%; P = 0.003). For a 5-kg child, a 5-month course of therapy costs over $3000. It is estimated that for every 7.4 patients treated, one hospitalization is averted.120 When given to selected patients, palivizumab costs $12,000 per averted hospitalization, however the money saved by administration does not likely cover the cost of the drug across a given population.121 Thus, administration of palivizumab is recommended only in certain patients at increased risk for significant disease (Table 32–3). Among children with hemodynamically significiant heart disease, the estimated cost per year-of-life saved is over $100,000.29,122 Palivizumab is well tolerated and rates of complaints after administration are similar to placebo.119 There is no therapeutic role for Palivizumab in children acutely infected with RSV.123