Bronchiolitis

Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection. Although it may occur in persons of any age, severe symptoms are usually only evident in young infants; the larger airways of older children and adults better accommodate mucosal edema.

Obliterative bronchiolitis (OB) was first described in 1901; in 1985,[9] bronchiolitis obliterans-organizing pneumonia (BOOP) was described as a condition distinct from OB, with different clinical, radiographic, and prognostic features. BOOP is a histopathologic lesion, not a specific diagnosis. Its pathologic hallmark is proliferative bronchiolitis or bronchiolitis obliterans in association with organizing pneumonia. BOOP and OB are beyond the scope of this article and are not discussed further.

Bronchiolitis usually affects children younger than 2 years, with a peak in infants aged 3-6 months. Acute bronchiolitis is the most common cause of lower respiratory tract infection in the first year of life. It is generally a self-limiting condition and is most commonly associated with respiratory syncytial virus (RSV) .

Despite the availability of practice guidelines for bronchiolitis, there is still variation and controversy among healthcare providers regarding the optimal treatment of these patients. It is hoped that with implementation of the updated AAP clinical practice guidelines for bronchiolitis there will be more standardized care, fewer hospitalizations, better management of resources, and shorter length of hospital stays without increasing readmission rates or decreasing family satisfaction.

Bronchioles are small airways (< 2 mm in diameter) and lack cartilage and submucosal glands. The terminal bronchiole, a 16th-generation airway, is the final conducting airway that terminates in the respiratory bronchioles. The acinus (ie, the gas exchange unit of the lung) consists of respiratory bronchioles, the alveolar duct, and alveoli. The bronchiolar lining consists of surfactant-secreting Clara cells and neuroendocrine cells, which are the source of bioactive products such as somatostatin, endothelin, and serotonin.

Bronchiolar injury and the consequent interplay between inflammatory and mesenchymal cells can lead to diverse pathologic and clinical syndromes. The effects of bronchiolar injury may begin 18 to 24 hours after the infection and include the following:

• Increased mucus secretion

• Bronchial obstruction and constriction

• Alveolar cell death, mucus debris, viral invasion

• Air trapping

• Atelectasis

• Reduced ventilation that leads to ventilation-perfusion mismatch

• Labored breathing

Complex immunologic mechanisms play a role in the pathogenesis of bronchiolitis. Type 1 allergic reactions mediated by immunoglobulin E (IgE) may account for some clinically significant bronchiolitis. Infants who are breastfed with colostrum rich in immunoglobulin A (IgA) appear to be relatively protected from bronchiolitis.[10, 11]

Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and occurs within 24 hours of acquisition of infection.[12] Proliferation of goblet cells results in excessive mucus production, whereas epithelial regeneration with nonciliated cells impairs elimination of secretions. Lymphocytic infiltration may result in submucosal edema.

Cytokines and chemokines, released by infected respiratory epithelial cells, amplify the immune response by increasing cellular recruitment into infected airways. Interferon and interleukin (IL)–4, IL-8, and IL-9 are found in high concentrations in respiratory secretions of infected patients.[13, 14]

Johnson et al analyzed autopsy findings from children who died of possible RSV infection between 1925 and 1959 (before modern intensive care) and those from a child with RSV bronchiolitis who died in a motor vehicle accident.[15] They found that small bronchiole epithelium was circumferentially infected but basal cells were spared. Both type 1 and type 2 alveolar pneumocytes were also infected. In this study, airway obstruction was due to epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema fluid but not to bronchial smooth muscle constriction.[15] Other research revealed that neutrophil inflammation, but not eosinophil inflammation, is related to the severity of a first infection in infants.[16]

The inflammation, edema, and debris result in obstruction of bronchioles, leading to hyperinflation, increased airway resistance, atelectasis, and ventilation-perfusion mismatching. Bronchoconstriction has not been described. Infants are affected most often because of their small airways, high closing volumes, and insufficient collateral ventilation. Recovery begins with regeneration of bronchiolar epithelium after 3-4 days; however, cilia do not appear for as long as 2 weeks. Mucus plugs are instead predominantly removed by macrophages.

Infection is spread by direct contact with respiratory secretions. In most temperate regions within the United States, epidemics last 2-4 months, beginning in October/November and peaking in January or February. Whereas 93% of cases occur between November and early April, sporadic cases may occur throughout the year. In tropical/subtropical climates, the season may be more prolonged and seems to correlate with the rainy season.  Attack rates within families are as high as 45% and are higher in childcare centers. Rates of hospital-acquired infection can range from 20-47%.

Virtually all children experience RSV infection within the first 3 years of life, but a previous infection does not convey complete immunity. Reinfection is common; however, significant antibody titers from prior infection ameliorate the severity of symptoms.[17]

Most cases of bronchiolitis result from a viral pathogen, such as RSV, rhinovirus, human metapneumovirus (hMPV), parainfluenza virus, adenovirus, coronavirus, influenza virus or human bocavirus. In one third of hospitalized cases of bronchiolitis, two or more viruses may be detected, especially when using molecular-based testing. Bronchiolitis is highly contagious. The virus that causes it is spread from person to person through direct contact with nasal secretions, airborne droplets, and fomites.

RSV is the most commonly isolated agent in 75% of children younger than 2 years who are hospitalized for bronchiolitis. RSV is an enveloped RNA virus that belongs to the Paramyxoviridae family within the Pneumovirus genus. RSV causes 20-40% of all cases and 44% of cases that involve children younger than 2 years. Two RSV subtypes, A and B, have been identified on the basis of structural variations in the G protein. Subtype A usually causes the most severe infections. One subtype or the other usually predominates during a given season; thus, RSV disease has “good” and “bad” years.[18, 19, 20, 21] Viral shedding in nasal secretions continues for 6-21 days after symptoms develop. The incubation period is 2-5 days.[22]

Rhinoviruses, the cause of the common cold, may cause bronchiolitis or lower respiratory tract infection and are frequently detected in dual infections. Cases tend to occur in the spring and fall seasons. Rhinovirus may lead to a shorter hospitalization than RSV-associated bronchiolitis.[23]

Parainfluenza virus causes 10-30% of all bronchiolitis cases.[5] Parainfluenza type 3 is more likely to cause bronchiolitis than types 1, 2 or 4 which are associated with croup. Epidemics of bronchiolitis due to parainfluenza virus usually begin earlier in the year and tend to occur every other year.

Adenovirus accounts for 5-10% of bronchiolitis cases while influenza virus accounts for 10-20%. Mycoplasma pneumoniae infection accounts for 5-15%, particularly among older children and adults.

The paramyxovirus hMPV, first identified in the Netherlands in 2001,[24] has been increasingly implicated as an etiologic agent in bronchiolitis.[25, 26, 27, 28, 29] Serologic studies indicated that by age 5 years, all Dutch children had seroconverted and that the virus had been prevalent in the population for at least 50 years.[30]  In a retrospective examination of nasal washings obtained between 1976 and 2001 from 2009 children with acute respiratory tract illness, 248 had identifiable viruses.[25] In 20% of these, hMPV was identified, accounting for 12% of all viral lower respiratory illness in children younger than 2 years. The mean age in the hMPV group was 11.6 months, with a male-to-female ratio of 1.8:1. They most often had illnesses between December and April, and 2% were hospitalized. The virus was associated with bronchiolitis in 59% of patients.

Subsequent studies showed that hMPV accounts for 5-50% of bronchiolitis cases, seems to occur later in the bronchiolitis season, occurs with higher fevers, affects somewhat older children, and causes more wheezing but less requirement for oxygen (possibly because the children are older and have less atelectasis).[31, 32, 33] Other studies found that combined hMPV-RSV infections were strongly associated with severe bronchiolitis, with a 10-fold increase in pediatric intensive care unit (PICU) admission.[34, 35, 36]

Human bocavirus (HBoV), discovered in 2005, is known to cause both upper and lower respiratory tract infections and type 1 has been implicated in both bronchiolitis and pertussis-like syndromes. Other HBoV types (2 through 4) are primarily enteric viruses. HBoV is isolated infrequently as a single agent from children hospitalized with bronchiolitis leading to speculation that it may be an innocent bystander rather than a true pathogen. Arnold et al demonstrated that 5.6% of 1474 nasal scrapings collected over a 20-month period at San Diego Children’s Hospital tested positive for HBoV, mostly from March through May.[37]

Risk factors

Risk factors for the development of bronchiolitis include the following[38, 39, 40, 41] :

• Age less than 3 months (two thirds of all infants hospitalized with RSV infection are younger than 5 months of age)

• Low birth weight, particularly premature infants[42]

• Gestational age (infants born at < 29 weeks of gestation are at a particularly higher risk for hospitalization from RSV infection)

• Lower socioeconomic group[43]

• Crowded living conditions, childcare center attendance, presence of an older sibling or a combination of these

• Parental smoking[44]

• Chronic lung disease, particularly bronchopulmonary dysplasia

• Severe congenital or acquired neurologic disease

• Hemodynamically significant congenital heart disease (CHD) e.g, with pulmonary hypertension[45]

• Congenital or acquired immune deficiency diseases

• Airway anomalies

In a study that collected epidemiologic, clinical, and virologic data to determine the incidence and predisposing factors for severe bronchiolitis in 310 previously healthy term infants younger than 12 months who were experiencing their first episode of bronchiolitis,[46] the infants with severe disease were found to present with lower birth weight, younger gestational age, lower postnatal weight, younger postnatal age, and a stronger likelihood of having been born via cesarean delivery. Elevated C-reactive protein (CRP) values (>0.8 mg/dL) and pulmonary consolidation on chest radiographs were more common among infants with severe disease, though no significant differences in epidemiologic variables were found.[46] Although severe bronchiolitis is uncommon in infants with these characteristics (ie, previously healthy term infants younger than 12 months), severity is predicted by young age and RSV carriage. Residency at high altitude (over 2500 meters) may also contribute to severe disease and increased risk of hospitalization.[47] When severe bronchiolitis is present, it typically develops soon after disease onset.

United States statistics

Respiratory infection is observed in 25% of children younger than 12 months and 13% of children aged 1-2 years.[48] Of these 25%, one half have wheezing-associated respiratory disease.[49] RSV can be cultured from one third of these outpatients and from 80% of hospitalized children younger than 6 months of age.[43, 50]

Nearly 100% of children experience an RSV infection within 2 RSV seasons, and 1% are hospitalized.[49] Among healthy full-term infants, 80% of hospitalizations due to bronchiolitis occur in the first year, and 50% of hospitalizations occur in children aged 1-3 months.[43] Fewer than 5% of hospitalizations occur in the first 30 days of life, presumably because of transplacental transfer of maternal antibody.[51]

Descriptive analysis of the US National Hospital Discharge Survey data from 1980 through 1996 showed that admissions associated with bronchiolitis totaled 1.65 million.[52] In a retrospective analysis of data from the same source for 1997-2006, RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million lower respiratory tract infection hospitalizations among children younger than 5 years of age.[53] Between 2-3% of all children younger than 12 months of age are hospitalized with a diagnosis of bronchiolitis, which accounts for between 57,000 and 172,000 hospitalizations annually.[54] The cost of hospitalization for bronchiolitis in children younger than 2 years is estimated to be more than $1.7 billion in 2009.[55]  While bronchiolitis remains a cause of significant mortality among children in the developing world, fewer than 100 annual deaths in the United States among young children are attributable to RSV infection.[56]

In most regions of the United States, the highest RSV activity usually occurs in winter with peaks from October to February and a relative subsidence only from March to July. An exception is the subtropical regions of the southeastern United States (eg, Florida) where RSV is endemic throughout the year.[57, 58, 59]

Secondary RSV infections occur in 46% of family members, 98% of other children attending a childcare center, 42% of hospital staff, and 45% of previously uninfected hospitalized infants.[17, 60, 61] Infection is spread through self-inoculation of nasopharyngeal or ocular mucous membranes after direct contact with respiratory fomites and contaminated environmental surfaces. RSV can survive for several hours on hands and surfaces; therefore, handwashing and using disposable gloves and gowns may reduce nosocomial spread.[62, 63]

International statistics

Bronchiolitis is a significant cause of respiratory disease worldwide. According to the World Health Organization bulletin,[64] an estimated 150 million new cases occur annually; 11-20 million (7-13%) of these cases are severe enough to require hospital admission. Worldwide, 95% of all cases occur in developing countries.

The frequency of bronchiolitis in developed countries appears to be similar to that in the United States. Epidemiologic data for underdeveloped countries are incomplete. Epidemiologic data from underdeveloped countries show that RSV is a predominant viral cause of acute lower respiratory tract infections and accounts for about 65% of hospitalizations attributed to viruses.[65]

Despite incomplete data about RSV-associated mortality from developing countries, in 2005, RSV alone was estimated to cause 66,000 to 199,000 deaths among children younger than 5 years of age.[66, 67] Morbidity and mortality is higher in less-developed countries likely because of poor nutrition and lack of resources for supportive medical care.

In the northern hemisphere, RSV epidemics generally occur annually in winter and late spring, whereas parainfluenza outbreaks usually occur in the fall. Conversely, in the southern hemisphere, wintertime epidemics occur from May to September.

Descriptive epidemiologic data from a population-based cohort (Georgia Air Basin, Canada) reported by Koehoorn et al indicated that from 1999 through 2002, bronchiolitis was associated with 12,474 inpatient and outpatient physician contacts during the first year of life.[68] This equates to 134.2 cases per 1000 person-years. In total, 1588 bronchiolitis cases resulted in hospitalization (17.1 cases per 1000 person-years).

Age-related demographics

Although infection with the agents that cause bronchiolitis may occur at any age, the clinical entity of bronchiolitis includes only infants and young children. About 75% of cases of bronchiolitis occur in children younger than 1 year and 95% in children younger than 2 years. Incidence peaks in those aged 2-8 months.

Age is a significant factor in the severity of infection: The younger the patient is, the more severe the infection tends to be, as measured by the lowest oxygen saturation. Infants younger than 6 months are most severely affected, owing to their smaller, more easily obstructed airways and their decreased ability to clear secretions.

Intrauterine cigarette-smoke exposure may impair in utero airway development or alter the elastic properties of the lung tissue. Exposure to second-hand cigarette smoke (eg, by a parent or family member) in the postnatal period compounds the severity of RSV bronchiolitis in infants.

Although RSV bronchiolitis is clearly a significant disease of the young child, immunity has been shown to wane over time[69] ; susceptible adults may be asymptomatic or mildly symptomatic and act as carriers. With the increasing use of treatment modalities that compromise cellular immunity, RSV infection may be life-threatening to older children and adults undergoing organ and bone marrow transplantation, as well as to the elderly.[70, 71]

Sex-related demographics

Severe bronchiolitis occurs more frequently in males than in females; a pattern similar to other respiratory viral infections. The exact reason for this difference is unknown.[65, 72] Death is 1.5 times more likely in males.[73]

Race-related demographics

Race and low socioeconomic status may adversely affect outcome in patients with acute bronchiolitis. Multiple population-based reports sponsored by the Centers for Disease Control and Prevention (CDC) indicate no disparity in the rates of hospitalization for RSV infection between black and white children.[74]  A study by La Via et al[75] demonstrated that although more minority children than white children were hospitalized with RSV infection, nothing indicated that the infections in minority children were more or less severe than those in white children.

Lower socioeconomic status may increase the likelihood of hospitalization. Hospitalization rates are higher in Native American, Alaskan, and Hispanic populations, but it is not clear if this is due to more severe infection or to a lower threshold for admission.

According to the WHO 2015 Global Health Observatory data repository, acute lower respiratory infection in children younger than 5 years of age remains a leading cause of childhood mortality in the world. In 2015, acute respiratory tract infection accounted for an estimated 1.84 million deaths worldwide; 85% of these deaths occurred in Africa followed by 8% in Southeast Asia.[76]

Bronchiolitis is an infectious, self-limited disease. Therapy is based on supportive care, oxygenation, hydration, and fever control. With early recognition and treatment, prognosis is usually very good. Most children with bronchiolitis, regardless of severity, recover without sequelae. The course of disease is usually 7-10 days, but a few remain ill for weeks. Some infants who recover from acute bronchiolitis have an increased frequency of recurrent wheezing.

Hospitalization is required in 2-3% of bronchiolitis cases among infants younger than 12 months of age.[77]  Annually, RSV bronchiolitis accounts for about 57,000-172,000 hospitalizations.[54] In a prospective, population-based surveillance of acute respiratory infections, RSV accounted for 20% of hospitalizations, 18% of ED visits, and 15% clinic visits in winter.[77] Hospitalization is significantly more likely at altitudes above 2500 meters (8000 ft).

Overall, the mortality in children hospitalized for bronchiolitis in different series ranges from 0.2% to 7%. This large variability is based on investigations of different cohorts with different risk factors and different points in time relative to modern intensive care. Morbidity and mortality from RSV mostly occur in children younger than 2 years. Other high-risk infants and children include premature infants younger than 6 months, infants and children with underlying pulmonary or cardiac disease, and those an immune deficiency.[78]

Studies in pediatric ICUs (PICUs) of children with RSV bronchiolitis without comorbidities show a 2-3% death rate, regardless of whether the children had CHD with pulmonary hypertension.[40] In a cohort study from 1999-2007 in the United Kingdom, RSV bronchiolitis-related mortality was 1.7% with higher risk of death associated with preexisting conditions, especially cardiac anomalies.[79]

Although significant morbidity is unusual, multiple small studies suggest that children who have been hospitalized with RSV bronchiolitis have a higher incidence of reactive airway disease and more abnormalities in pulmonary function than children never hospitalized for RSV.[80, 81] These abnormalities may persist for as long as 5 years, eventually normalizing. Conflicting small studies have failed to prove whether early treatment of acute RSV bronchiolitis with ribavirin reduces the persistence of pulmonary dysfunction.[82]

Although bronchiolitis has been identified as a risk factor for asthma, this does not necessarily imply causation. Children already predisposed to asthma may be more likely to wheeze when exposed to RSV or other respiratory infectious or allergic stimuli. On the other hand, it is postulated that RSV infection may predispose an individual to later bronchospasm by selective promotion of specific subsets of helper T cells.

Multiple studies have shown that children, including febrile infants younger than 8 weeks, with confirmed RSV infection have a lower risk of serious bacterial infections or secondary bacterial superinfection than controls (eg, 0% vs 2.7% for bacteremia, and 2% vs 14% for urinary tract infection).[83] The risk of concurrent bacterial infections is low.[84, 85, 86, 87]

Education should be provided regarding the following:

• Importance of RSV prophylaxis for high-risk patients

• Importance of avoiding RSV exposure in the first 2-3 months of life

• Natural history of bronchiolitis

Instructions to be provided at discharge should include the following:

• Positioning

• Maintenance of oral hydration

• Temperature control

• Use of prescribed medications

• Avoidance of exposure to tobacco smoke or other irritants

• Methods for limiting transmission (eg, handwashing and avoiding childcare centers while ill)

• Criteria for return to the ED

Most cases of bronchiolitis are not readily preventable, because the viruses responsible are ubiquitous. However, careful attention to frequent handwashing, especially around infants, can aid in the prevention of infection or spread of viruses.

The history and the physical examination form the primary basis for the diagnosis of bronchiolitis.

Because bronchiolitis primarily affects young infants, clinical manifestations are initially subtle. Infants may become increasingly fussy and have difficulty feeding during the 2 to 5-day incubation period.[1] A low-grade fever, usually less than 101.5°F, and increasing coryza and congestion usually follow the incubation period. In older children and adults, as well as in up to 60% of infants, respiratory syncytial virus (RSV) infection is generally confined to the upper airway and does not progress further.[88]

Over a period of 2-5 days, RSV infection progresses from the upper to the lower respiratory tract, and this progression leads to the development of cough, dyspnea, wheezing, and feeding difficulties. When the patient is brought to medical attention, the fever has usually resolved. Infants younger than 1 month may present as hypothermic.[2] Severe cases progress to respiratory distress with tachypnea, nasal flaring, retractions, irritability, and, possibly, cyanosis.

Examination often reveals the following:

• Tachypnea

• Tachycardia

• Fever (38-39°C)

• Retractions

• Fine rales (47%)

• Diffuse, fine wheezing

• Otitis media

The diagnosis is made on the basis of age and seasonal occurrence, tachypnea, and the presence of profuse coryza and fine rales, wheezes, or both upon auscultation of the lungs. Some practitioners exclude RSV infection in the absence of coryza.

Hypoxia is the best predictor of severe illness and correlates best with the degree of tachypnea (>50 breaths/min). The degree of wheezing or retractions correlates poorly with hypoxia. First-time infections are usually most severe; subsequent attacks are generally milder, particularly in older children.

Apnea occurs early in the course of the disease and may be the presenting symptom, especially in those younger than 2 months of age or those born prematurely. Nonobstructive central apnea occurs during quiet sleep and is associated with increases in the apnea index (the percentage of time the baby spends apneic), apnea attack rate (the number of episodes of apnea per unit time), and apnea percentage (the distribution of episodes of apnea in a given sleep state).

Apnea rarely lasts longer than a few days; however, approximately 10% of apneic patients require intubation and mechanical ventilation. The observation that very few cases of sudden infant death syndrome are attributable to bronchiolitis suggests that most infants with apnea self-stimulate and recover spontaneously. Mild RSV disease in young infants is not an indication for hospitalization to observe for apnea.[89, 90, 91, 92, 93, 94, 95]

In a systematic review, Ralston et al found that the overall incidence of apnea ranged from 1.2% to 23.8% in infants hospitalized with RSV bronchiolitis.[89] Further analysis showed that apnea occurred more commonly in preterm infants (range, 4.9-37.5%) than in full-term infants (range, 0.5-12.4%).

Kneyber et al found that the strongest independent risk factor for RSV-associated apnea was age younger than 2 years.[96] Apnea at admission was found to increase the risk of recurrent apnea. Additionally, the likelihood of mechanical ventilation significantly increased in children who suffered from recurrent apnea.

Using the criteria of (1) full-term younger than 1 month, (2) preterm (< 37 weeks gestational age) and younger than 48 weeks postconceptional age, and (3) observed apnea, Willwerth et al found the incidence of in-hospital apnea to be only 2.7%.[90]

Nonrespiratory manifestations of RSV infections include otitis media, myocarditis, supraventricular and ventricular dysrhythmias, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH).[97, 98]

With bronchiolitis, as with any disease, various complications are possible, including those caused by therapy. In most cases, the disease is mild and self-limited. However, in infants who are immunosuppressed and those with preexisting heart or lung disease, RSV bronchiolitis can result in any of the following[97, 99, 100] :

• Acute respiratory distress syndrome (ARDS)

• Bronchiolitis obliterans

• Congestive heart failure

• Secondary infection

• Myocarditis

• Arrhythmias

• Chronic lung disease

A possible association with asthma has been reported.[101, 102, 103, 104] RSV infections have been associated with the development of asthma later in life, with an odds ratio of 4.3 in children aged 11 years or younger. However, because virtually all children encounter an RSV infection during the first 2-3 years of life, this association may reflect a multifactorial etiology or a genetic predisposition. A genetic predisposition to wheeze after severe RSV bronchiolitis has been suggested.[13, 80] Other studies suggest that human metapneumovirus (hMPV) or rhinovirus-associated bronchiolitis or coinfection with RSV and hMPV increase the likelihood of developing asthma in later years.[31]

A genetic predisposition to severe bronchiolitis and to subsequent development of asthma is supported by findings of polymorphisms in genes involved in allergy, inflammatory response and innate immunity.[105] In fact, a Danish study of twins found that severe bronchiolitis may be an indicator of a genetic predisposition to asthma and without this disposition, asthma is less likely to develop even if the infant had developed bronchiolitis.[106]

As many as 1% of previously healthy children and 3% of developmentally impaired children with bronchiolitis experience neurologic complications. These include seizures, encephalopathy with hypotonia, irritability, and abnormal tone. The long-term prognosis for these children is still unknown.[107]

The diagnosis of bronchiolitis is based on clinical presentation, the patient’s age, seasonal occurrence, and findings from the physical examination. When all of these are consistent with the expected diagnosis of bronchiolitis, few laboratory studies are necessary.[3] Tests are typically used to exclude other diagnoses (eg, bacterial pneumonia, sepsis, or congestive heart failure) or to confirm a viral etiology and determine required infection control for patients admitted to the hospital. Severely ill children may have dual viral infections.

Although the use of diagnostic tests is common, several investigators argue that these should not be routinely performed, citing concerns about costs, inappropriate use of antibiotics, unnecessary hospitalization, and the lack of proven benefit. In reality, few studies have rigorously evaluated the utility of diagnostic tests for this disease. Some hospitals have developed their own protocols or guidelines for testing and management, whereas others have left the decision entirely to the treating physician.

According to a survey of hospital-based pediatricians, the most common tests are rapid viral antigen testing of nasopharyngeal secretions for respiratory syncytial virus (RSV), arterial blood gas (ABG) analysis (in severely ill patients, especially those requiring mechanical ventilation), white blood cell (WBC) count with differential, C-reactive protein (CRP) level, and chest radiography.

Other common tests are pulse oximetry, blood culture, urine analysis and culture, and cerebrospinal fluid (CSF) analysis and culture. Urine specific gravity may provide useful information regarding fluid balance and possible dehydration. Serum chemistries are not affected directly by the infection but may aid in gauging severity of dehydration.

In previously healthy children with viral bronchiolitis, chest radiography, complete blood count (CBC), or blood culture are usually unnecessary. However, these tests should be carefully considered in persons with severe disease or a very ill appearance, preexisting cardiac or pulmonary disease, a markedly elevated temperature, or other risk factors for more severe disease. A few children at risk for acute respiratory failure may require monitoring of the blood carbon dioxide level.

The WBC count is usually 8,000-15,000/µL and may be left-shifted as a result of stress. Although the WBC count with differential is commonly performed to look for coexisting bacterial infection, few studies have evaluated its utility for this purpose. Elevated WBC counts do not predict serious bacterial infection in children hospitalized with RSV bronchiolitis.[84] However, case reports have described patients with bronchiolitis who had elevated WBC counts that prompted further evaluation and eventual identification of a bacterial pathogen.

In a study of 120 infants with RSV infection, Saijo et al[108] demonstrated a correlation between an elevated WBC count and a radiographic pattern of lobar pneumonia as compared with a pattern of bronchopneumonia or bronchiolitis. CRP levels and erythrocyte sedimentation rate (ESR) followed the same pattern in this study. Veira et al[109] also observed an association between a viral etiology and low WBC counts and CRP levels during initial and follow-up testing.

The WBC count has been decried for its poor test characteristics. Among infants with a febrile illness, WBC values are highly variable. No WBC count threshold has good discriminatory value for the presence of bacterial infection. WBC testing should not be routinely performed in patients with bronchiolitis.[110]

In most patients with RSV bronchiolitis, especially those with mild disease, the risk of serious secondary bacterial infection is low. Kuppermann et al[83] found no evidence of bacteremia in 156 patients with bronchiolitis aged younger than 24 months; patients with lobar consolidation were excluded. Liebelt et al[111] studied infants aged 90 days or younger with bronchiolitis and noted a low risk of serious bacterial infection and wide variability in the use of diagnostic tests in this population.

Multivariate analysis identifies temperature greater than 38°C, oxygen saturation less than 92% at presentation, and a history of apnea as clinical predictors of the use of laboratory studies.

Antonow et al[112] studied 282 hospitalized infants younger than 60 days with bronchiolitis and reported a low rate of serious bacterial infections (5 of 140 tested). A multivariate model identified a higher bronchiolitis score and normal chest radiograph findings as positive predictors of a sepsis workup, whereas an admission diagnosis of bronchiolitis and a chest radiograph with findings typical for bronchiolitis were negative predictors.

Among 1795 children aged 0-14 years who were hospitalized for RSV bronchiolitis, Bloomfield et al[113] reported positive blood culture findings in 11 of 861 children tested. Risk factors for concurrent bacteremia included nosocomial RSV infection, cyanotic congenital heart disease, and admission to the pediatric intensive care unit (PICU). The authors recommended considering antibiotic therapy for children with severe RSV bronchiolitis admitted to the PICU, particularly if needing mechanical ventilation.

In a prospective multicenter study aimed at determining whether infants younger than 60 days with fever and bronchiolitis are at increased risk of serious bacterial infection, 269 (22%) of the 1248 patients enrolled had RSV bronchiolitis. The rate of secondary bacterial infections was 7% in the RSV-positive group and 12.5% in the RSV-negative group. The rate of secondary bacterial infections in the RSV-positive group was smaller but remained appreciable.

When viral testing is performed, RSV is the most commonly isolated organism (26-95%). Such testing is frequently performed in febrile young children who present to the emergency department (ED) with bronchiolitis. It has been argued that rapid identification of a viral cause of a febrile illness obviates the need for a sepsis workup or empiric use of antibiotics, particularly in children who were previously well or do not appear toxic.

Although viral culture for RSV is available and must be considered the standard for making a definitive diagnosis, several commercially available immunologic and molecular-based tests are more rapid, and convenient. The antigen detection tests identify the RSV antigen in epithelial cells from nasopharyngeal secretions, bronchoalveolar lavage fluid, or lung tissue using either direct immunofluorescent antibody (IFA) staining or an enzyme-linked immunosorbent assay (ELISA). The reliability of the tests is highly dependent on sampling techniques.[114] The antigen is attached to mucosal epithelial cells. Simply sampling the mucus from a nasal swab is clearly less traumatic but not nearly as reliable as a swab of the nasopharyngeal area or, preferably, a nasal washing. One third of nasal swab sample results are negative compared with results obtained with more aggressive techniques. With adequate sampling, IFA staining requires 2-6 hours for processing and is 90% sensitive and specific. On the other hand, ELISA requires 30 minutes for processing and is 85-90% sensitive as compared with viral culture. Although ELISA is somewhat quicker and easier to interpret because it yields a more objective endpoint, the IFA technique may be preferable, in that it permits determination of the number of epithelial cells recovered and thereby can verify the adequacy of the sample.

The reliability of rapid antigen detection tests in adults is questionable.[115, 116] RSV samples from adult patients showed 14-39% sensitivity when compared with culture. The decreased performance of rapid test kits with adult samples may be due to numerous factors, including a shorter shedding phase, lower viral titers, and dry mucosa.

Newly available molecular tools such as polymerase chain reaction (PCR) techniques are more commonly being used in diagnosis and epidemiologic surveillance of RSV and other viral infectious agents in infants hospitalized for bronchiolitis. These tests are more sensitive than other diagnostic approaches and now form the backbone of clinical virology laboratory testing. Use of multiplex PCR assays may allow rapid and accurate identification of common and uncommon viral respiratory pathogens.[117]

Although viral detection is commonly practiced and may have good utility, routine testing is not recommended in infants with bronchiolitis.[110] An argument can be made that it has little influence on outcome, however, RSV testing does influence management in that physicians appear to be more likely to withhold antibiotics or to stop them sooner in patients who test RSV-positive. Additionally, despite the fact that infection control procedures are similar for most respiratory viruses, viral testing may be used to isolate hospitalized patients who test positive and to categorize patients for cohort nursing.

Transcutaneous oxygen saturation is reduced in cases of moderate to severe bronchiolitis. However, it is a poor predictor of respiratory distress. It correlates best with tachypnea, but correlates poorly with wheezing and retractions. Patients with persistent resting oxygen saturations below 90% in room air require a period of observation and possible hospitalization. Because of atelectasis, administration of beta-agonist aerosol may increase the heart rate and thus cardiac output without improving ventilation, causing relative desaturation (ie, ventilation-perfusion mismatch).

Recent management guidelines have suggested lower limits of acceptable oxygen saturation levels of 90% for infants with bronchiolitis. The use of pulse oximetry monitoring is not recommended routinely in infants with bronchiolitis who do not require supplemental oxygen or have oxygen saturation >90% on room air.[110, 118]

Increased reliance on the oxygen saturation level may have contributed to the substantial increase (nearly 250%) in the hospitalization rate for children with bronchiolitis since the 1980s.[119, 118] There is some evidence that for previously healthy children admitted with bronchiolitis, hospital discharge may be delayed because of pulse oximetry values when the patients are otherwise stable for discharge, thereby potentially contributing to increased costs. The implications of a particular oxygen saturation level may vary, depending on whether the level is determined upon admission in a child who is sick or upon discharge in a child who is otherwise stable.

A study to determine the effect of intermittent vs continuous pulse oximetry monitoring on hospital length of stay among nonhypoxemic infants and young children hospitalized for bronchiolitis concluded that intermittent pulse oximetry monitoring did not shorten hospital length of stay and was not associated with any difference in rate of escalation of care or use of diagnostic or therapeutic measures. These results suggest that intermittent pulse oximetry monitoring can be routinely considered in the management of infants and children hospitalized for bronchiolitis who show clinical improvement.[120, 121] According to a prospective cohort by Principi et al, pulse oximetry does not effectively predict which infants diagnosed with bronchiolitis will return for unscheduled medical care after an emergency department discharge.[122, 123]

Chest radiographs are not routinely necessary.[4] If clinically indicated, they should include anteroposterior (AP) and lateral views. Chest radiography is most useful in excluding unexpected congenital anomalies or other conditions[5, 6] ; it may also yield positive evidence of alternative diagnoses (eg, lobar pneumonia, congestive heart failure, or foreign body aspiration). Confine neck radiography or contrast studies to children whose diagnosis is unclear or who have histories consistent with structural anomalies.

Findings from chest radiography in individuals with bronchiolitis are variable. Hyperinflation is usually present (see the image below), and 20-30% of chest radiographs show lobar infiltrates, atelectasis, or both.[124] Atelectasis is common and contributes to arterial desaturation. Because ciliated bronchial epithelium does not regenerate for 9-15 days, atelectasis may be persistent and shifting.

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.

Other findings may include bronchial wall thickening, air trapping, flattened diaphragm, increased AP diameter, peribronchial cuffing, tiny nodules, linear opacities, and patchy alveolar opacities. Opacities on radiographs do not suggest bacterial pneumonia and incorrectly lead to inappropriate treatment with antibiotics.

In one study, only 2 of 265 infants were found to have radiographic findings inconsistent with simple bronchiolitis; the risk of airspace disease was particularly low in children with saturation higher than 92% and mild-to-moderate respiratory distress.[125]

In a study of 153 children with acute bronchiolitis, Dawson et al[124] found no correlation between the degree of change on the chest radiograph and a clinical scoring method. However, in Shaw’s study[38] of 213 infants with bronchiolitis, atelectasis was 2.7 times more likely to be found at presentation in the patients with severe disease than in those with mild disease.

Although negative findings from chest radiograph may have some value, children who do not appear ill are unlikely to have a radiograph that shows abnormalities. A practical approach is to obtain a chest radiograph in children who appear ill, are experiencing clinical deterioration, or are at high risk (eg, those with underlying cardiac or pulmonary disease).

Electrocardiography (ECG) or echocardiography should be reserved for those few children who display arrhythmias or cardiomegaly.

In rare situations, such as severe immunodeficiency or a strong history of possible foreign body aspiration, bronchoscopy may be indicated for diagnostic bronchoalveolar lavage or therapeutic foreign body removal.

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]

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.

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

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]

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]

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 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.

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]

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]

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.

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.

AAP releases updated guidelines for pediatric bronchiolitis

The American Academy of Pediatrics has released updated guidelines on the diagnosis, treatment, and prevention of bronchiolitis in children aged 1 to 23 months. The new guidelines emphasize the use of supportive care, including hydration and oxygen.[230, 110] Other recommendations include the following:

• As multiple viruses may cause bronchiolitis, testing for specific viruses is not necessary.

• Routine radiographic or laboratory studies are also not necessary. Diagnosis and assessment of bronchiolitis severity should be based on patient history and physical examination.

• There is no need for a trial dose of a bronchodilator.

• Otherwise healthy infants with gestational age of 29 weeks or more should not receive palivizumab to prevent respiratory syncytial virus infections. Infants under one year of age with hemodynamically significant heart disease or chronic lung disease of prematurity should be treated with palivizumab, up to a maximum of 5 monthly doses, during the respiratory syncytial virus season.

• Risk factors for severe disease include age less than 12 weeks, prematurity, underlying cardiopulmonary disease, and immunodeficiency.

• Epinephrine and chest physiotherapy should not be administered to infants and children with bronchiolitis.

The following guidelines may be helpful:

• American Academy of Pediatrics -Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis.[110]

• American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection.[219]

• American College of Chest Physicians -Chronic cough due to nonbronchiectatic suppurative airway disease (bronchiolitis): ACCP evidence-based clinical practice guidelines[231]

Although numerous medications have been used to treat bronchiolitis (eg, oxygen, bronchodilators, immunoglobulins, antibiotics, antivirals, nasal decongestants, and corticosteroids), only oxygen has demonstrably improved the condition of young children with bronchiolitis.

Oxygen decreases the work of breathing, thus delaying the onset of respiratory muscle fatigue and allowing other therapies to work.

Humidified oxygen is administered via nasal cannula, mask, head box, or tent to maintain transcutaneous oxygen saturations above 92%. A nasal cannula is preferred because it is effective and minimally intrusive and allows full access to the child.

Heliox has been used in patients with acute asthma. It may be a beneficial addition to conventional therapy in critically ill children with respiratory syncytial virus (RSV) bronchiolitis. However, further clinical studies are required to assess its efficacy of this therapy. Heliox may be useful in intubated patients whose condition is not responding to conventional treatment.

Medical therapies used to treat bronchiolitis in pediatric patients are controversial. Healthy children with bronchiolitis usually have limited disease. These patients usually do well with supportive care only.

Class Summary

Bronchodilators are among the most common therapies for bronchiolitis; studies have reported that their use ranges from approximately 50% of cases to more than 90%. They act by decreasing muscle tone in both small and large airways in the lungs, thus increasing ventilation. Most controlled studies have failed to show a benefit in terms of oxygen saturation, rate of hospitalization, or length of hospital stay, but some studies have demonstrated an improvement in short-term surrogate measures.

Epinephrine racemic (Adrenalin, Twinject, EpiPen 2-Pak)

Epinephrine stimulates alpha-adrenergic, beta1-adrenergic, and beta2-adrenergic receptors, resulting in bronchodilatation, increased peripheral vascular resistance, hypertension, increased chronotropic cardiac activity, and positive inotropic effects.

Nebulized epinephrine (0.1 mL/kg) is more efficacious than albuterol in infants with acute bronchiolitis. Randomized controlled trials comparing nebulized racemic epinephrine with placebo found more improvement in the epinephrine-treated group in oxygenation and clinical signs, presumably because of reduction in airway and perhaps nasal mucosal edema. Morbidity and length of stay did not improve.

Albuterol (Proventil, Ventolin)

Albuterol is a beta agonist used to treat bronchospasm refractory to epinephrine. It simulates adenyl cyclase to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and causes bronchodilation. Albuterol relaxes bronchial smooth muscle by acting on beta2 receptors but has little effect on cardiac muscle contractility. It may inhibit airway microvascular leakage.

The frequency may be increased. Institute a regular schedule in patients receiving anticholinergic drugs who remain symptomatic. Albuterol is available as a liquid for nebulizers, metered-dose inhalers (MDIs), and dry-powder inhalers.

Class Summary

Specific immunoglobulin products with anti-RSV activity have been developed for prophylaxis of high-risk patients against RSV infection.

Palivizumab (Synagis)

Palivizumab is a humanized monoclonal antibody directed against the F (fusion) protein of RSV. Given monthly through the RSV season, it has been demonstrated to decrease chances of RSV hospitalization in premature babies who are at increased risk for severe RSV-related illness.

Class Summary

Viruses are the primary etiologic agents in bronchiolitis; therefore, routine administration of antibiotics has not been shown to influence the course of this disease. Although rapid diagnostic techniques are available to identify RSV as a causative agent in bronchiolitis, they are not readily available for other viruses. In small, acutely ill infants, clinically excluding the existence of secondary bacterial invasion may be difficult. Administration of broad-spectrum antibiotics in critically ill infants is often justified until culture results prove to be negative.

Ampicillin

Ampicillin has bactericidal activity against susceptible organisms. It is an alternative to amoxicillin when the patient is unable to take medication orally

Ceftriaxone (Rocephin)

Ceftriaxone is a safe and effective third-generation cephalosporin used for initial antimicrobial coverage of critically ill infants until culture results are known. It covers a wide range of gram-positive and gram-negative organisms but is not a first-line drug for Staphylococcus or Pseudomonas. It does not cover Listeria, an important pathogen in infants younger than 6 weeks; for this age group, add ampicillin.

Cefotaxime (Claforan)

Cefotaxime is a safe and effective third-generation cephalosporin used for initial antimicrobial coverage of critically ill infants until culture results are known. It covers a wide range of gram-positive and gram-negative organisms but is not a first-line drug for Staphylococcus or Pseudomonas. It does not cover Listeria, an important pathogen in infants younger than 6 weeks; for this age group, add ampicillin.

Class Summary

Ribavirin is licensed by the US Food and Drug Administration (FDA) for the management of RSV bronchiolitis and pneumonia. It has a broad spectrum of antiviral activity in vitro, inhibiting replication of RSV as well as influenza, parainfluenza, adenovirus, measles, Lassa fever, and Hantaan viruses. In adults, ribavirin can be used for the treatment of other infections, including hepatitis C.

Ribavirin (Virazole)

Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a synthetic nucleoside analogue that resembles guanosine and inosine. It is believed to act by interfering with expression of messenger RNA and inhibiting viral protein synthesis. Ribavirin appears safe but is expensive. Its efficiency and effectiveness have not been clearly demonstrated in large, randomized, placebo-controlled trials. At present, routine use of ribavirin cannot be recommended.

Class Summary

No controlled studies on the use of nasal decongestants in bronchiolitis have been performed. Aerosolized racemic epinephrine may be primarily beneficial as a nasal decongestant.

Oxymetazoline (Afrin, 12 Hour Nasal Relief)

Oxymetazoline is applied directly to mucous membranes, where it stimulates alpha-adrenergic receptors and causes vasoconstriction. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.

Class Summary

Clinical trials demonstrate that corticosteroids have no benefit in the treatment of bronchiolitis and thus should not be used routinely. However, one study (with a treatment group of 8 patients) showed some clinical improvement with dexamethasone plus albuterol. A subsequent double-blind, placebo-controlled trial of the same agents revealed no difference from placebo. Nebulized steroid treatment has not been proven efficacious. Steroid treatment has not been shown to decrease the long-term incidence of wheezing or asthma after RSV infection.

Prednisone

Prednisone blocks release of inflammatory mediators by inhibiting phospholipase A2. It may be useful in patients who have either asthma or bronchiolitis with asthmatic qualities.

Methylprednisolone (Medrol, Solu-Medrol, A-Methapred)

Methylprednisolone blocks release of inflammatory mediators by inhibiting phospholipase A2. It may be useful in patients who have either asthma or bronchiolitis with asthmatic qualities.