- Author: Lucian Kenneth DeNicola, MD, MS, FAAP, FCCM; Chief Editor: Russell W Steele, MD more...
Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection (most commonly respiratory syncytial virus and human metapneumovirus). This condition may occur in persons of any age, but severe symptoms are usually evident only in young infants, as seen in the image below.
Essential update: 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.[1, 2] 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.
Signs and symptoms
Because bronchiolitis primarily affects young infants, clinical manifestations are initially subtle, such as the following:
May become increasingly fussy and have difficulty feeding during the 2 to 5-day incubation period 
Low-grade fever (usually < 101.5°F); possible hypothermia in infants younger than 1 month 
Increasing coryza and congestion
Apnea: May be the presenting symptom in early disease
Severe cases of bronchiolitis may progress over 48 hours to the following signs and symptoms:
Respiratory distress with tachypnea, nasal flaring, retractions
See Clinical Presentation for more detail.
The diagnosis of bronchiolitis is based on clinical presentation, the patient’s age, seasonal occurrence, and findings from the physical examination, which may reveal the following:
Fine rales (47%); diffuse, fine wheezing
When the clinical presentation, patient’s age, seasonal occurrence, and findings from the physical examination are consistent with the expected diagnosis of bronchiolitis, few laboratory studies are necessary. Diagnostic testing is controversial but is 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.
Commonly used tests in the evaluation of patients with bronchiolitis include the following:
Rapid viral antigen testing of nasopharyngeal secretions for respiratory syncytial virus
Arterial blood gas analysis
White blood cell count with differential
C-reactive protein level
Urine analysis, specific gravity, and culture
Cerebrospinal fluid analysis and culture
Electrocardiography or echocardiography should be reserved for those few children who display arrhythmias or cardiomegaly.
Chest radiographs are not routinely necessary. 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).
This imaging modality is most useful in excluding unexpected congenital anomalies or other conditions[7, 8] ; it may also yield positive evidence of alternative diagnoses (eg, lobar pneumonia, congestive heart failure, or foreign body aspiration).
In rare situations (eg, severe immunodeficiency, strong history of possible foreign body aspiration), bronchoscopy may be indicated for diagnostic bronchoalveolar lavage or therapeutic foreign body removal.
See Workup for more detail.
Among numerous medications and interventions used to treat bronchiolitis, thus far, only oxygen appreciably improves the condition of young children. Therefore, therapy is directed toward symptomatic relief and maintenance of hydration and oxygenation.
Supportive care for patients with bronchiolitis may include the following:
Supplemental humidified oxygen
Maintenance of hydration
Nasal and oral suctioning
Apnea and cardiorespiratory monitoring
Temperature regulation in small infants 
Medications have a limited role in the treatment of bronchiolitis. Healthy children with bronchiolitis usually have limited disease and usually do well with supportive care only.
The following medications are used in selected patients with bronchiolitis:
Alpha/beta agonists (eg, racemic epinephrine, albuterol)
Monoclonal antibodies (eg, palivizumab)
Antibiotics (eg, ampicillin, cefotaxime, ceftriaxone)
Antiviral agents (eg, ribavirin)
Intranasal decongestants (eg, oxymetazoline)
Corticosteroids (eg, prednisone, methylprednisolone)
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, 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 increasing hospitalization rate for patients with bronchiolitis, controversy still exists regarding optimal treatment of these patients. As a result, the use of management tools among physicians and between hospitals varies greatly. The use of clinical practice guidelines can standardize care, reduce admissions, manage resources better, and shorten the 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 include the following:
Increased mucus secretion
Bronchial obstruction and constriction
Alveolar cell death, mucus debris, viral invasion
Reduced ventilation that leads to ventilation-perfusion mismatch
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.[12, 13]
Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and occurs within 24 hours of acquisition of infection. 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.[15, 16]
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. 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. Other research revealed that neutrophil inflammation, but not eosinophil inflammation, is related to the severity of a first infection in infants.
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 predominantly removed by macrophages.
Infection is spread by direct contact with respiratory secretions. In the United States, epidemics last 2-4 months, beginning in November and peaking in January or February. Whereas 93% of cases occur between November and early April, sporadic cases may occur throughout the year. Attack rates within families are as high as 45% and are higher in childcare centers. Rates of hospital-acquired infection range from 20-47%.
Virtually all children experience RSV infection within the first 3 years of life, but previous infection does not convey complete immunity. Reinfection is common; however, significant antibody titers from previous infection ameliorate the severity of symptoms.
Most cases of bronchiolitis result from a viral pathogen, such as RSV, human metapneumovirus, parainfluenza virus, influenza virus, or adenovirus. 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 causes the most severe infections. One subtype or the other usually predominates during a given season; thus, RSV disease has “good” and “bad” years.[20, 21, 22, 23] Viral shedding in nasal secretions continues for 6-21 days after symptoms develop. The incubation period is 2-5 days.
Parainfluenza virus causes 10-30% of all bronchiolitis cases. 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. Influenza virus accounts for 10-20%. Mycoplasma pneumoniae infection accounts for 5-15%, particularly among older children and adults.
In a prospective multicenter study of the viral etiology of bronchiolitis in the emergency department (ED), 277 samples were tested, and positive samples were obtained for the following viruses :
RSV - 64%
Human metapneumovirus (hMPV)  - 9-30%
Rhinovirus - 16%
Influenza A virus - 6%
The paramyxovirus hMPV, first identified in the Netherlands in 2001, has been increasingly implicated as an etiologic agent in bronchiolitis.[26, 28, 29, 30, 31] 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.
In a retrospective examination of nasal washings obtained between 1976 and 2001 from 2009 children with acute respiratory tract illness, 248 had identifiable viruses. 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).[33, 34, 35] 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.[36, 37, 38]
Human bocavirus (HBoV), discovered in 2005, is known to cause both upper and lower respiratory tract infections and has been implicated in both pertussis and bronchiolitislike syndromes. 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.
Risk factors for the development of bronchiolitis include the following[40, 41, 42, 43] :
Low birth weight, particularly premature infants 
Gestational age (independently associated with hospital resource use and outcome among infants hospitalized for RSV infection)
Lower socioeconomic group 
Crowded living conditions, daycare, or both
Parental smoking 
Chronic lung disease, particularly bronchopulmonary dysplasia
Severe congenital or acquired neurologic disease
Congenital or acquired immune deficiency diseases
Age less than 3 months
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, 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.
Positive C-reactive protein (CRP) results (>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. 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; 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. Of these 25%, one half have wheezing-associated respiratory disease. RSV can be cultured from one third of these outpatients and from 80% of hospitalized children younger than 6 months.[45, 52]
Nearly 100% of children experience an RSV infection within 2 RSV seasons, and 1% are hospitalized. Among healthy full-term infants, 80% of hospitalizations occur in the first year, and 50% of hospitalizations occur in children aged 1-3 months. Fewer than 5% of hospitalizations occur in the first 30 days of life, presumably because of transplacental transfer of maternal antibody.
Descriptive analysis of the US National Hospital Discharge Survey data from 1980 through 1996 showed that admissions associated with bronchiolitis totaled 1.65 million. During this period, the hospitalization rate for children younger than 1 year increased from 12.9 to 31.2 per 1000 population, and the percentage of hospitalizations for lower respiratory tract illnesses among children younger than 1 year associated with bronchiolitis increased from 22.2% to 47.4%.
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 LRTI hospitalizations among children younger than 5 years. An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in this pediatric population
In this analysis, the RSV-coded hospitalization rate in infants younger than 1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants younger than 3 months (48.9/1000), followed by infants aged 3 to 5 months old (28.4 per 1000), and was substantially lower among those older than 1 year (1.8/1000).
The increase in hospitalizations is attributable not to increased aversion risk on the part of pediatricians but, rather, to physicians’ desire to treat the condition with bronchodilators. The cost of hospitalization for bronchiolitis in children younger than 1 year is estimated to be more than $700 million per year.
In the United States, the highest RSV activity usually occurs in winter, except in the subtropical areas of the southeastern United States (eg, Florida) where RSV is endemic throughout the year, with peaks from October to February and relative subsidence only from March to July.[58, 59, 60]
Secondary infections occur in 46% of family members, 98% of other children in daycare, 42% of hospital staff, and 45% of previously uninfected hospitalized infants.[19, 61, 62] Infection is spread through self-inoculation of fomites via direct contact and environmental surfaces to nasopharyngeal or ocular mucous membranes. RSV can survive for several hours on hands and surfaces; therefore, handwashing and using disposable gloves and gowns may reduce nosocomial spread.[63, 64]
Bronchiolitis is a significant cause of respiratory disease worldwide. According to the World Health Organization bulletin, 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 due to viruses.
However, less is known about RSV-associated mortality in developing countries. Morbidity and mortality may be higher in less-developed countries 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. 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).
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. 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 ; 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.[69, 70]
Race and low socioeconomic status may adversely affect outcome in patients with acute bronchiolitis. In one study, RSV bronchiolitis seemed to be more severe in white children than in black children. The reason for this finding is unknown.
A study by La Via et al 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.
Acute respiratory tract infection in children younger than 5 years is still the leading cause of childhood mortality in the world. In 2000, acute respiratory tract infection accounted for an estimated 1.9 million deaths worldwide; 70% of these deaths occurred in Africa and Southeast Asia.
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. Studies suggest that IgE levels can be used as a marker of acute disease severity. Some infants who recover from acute bronchiolitis have an increased frequency of recurrent wheezing.
Hospitalization is required in as many 2% of cases (mostly patients younger than 6 months). These patients account for as many as 17% of all infant hospitalizations. Annually, RSV bronchiolitis accounts for about 50,000-80,000 hospitalizations. 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. Hospitalization is significantly more likely at altitudes above 2500 meters (8000 ft).
A retrospective study of 740 infants (aged 2 to 12 months) hospitalized with bronchiolitis found that the use of deep suctioning in the first 24 hours after hospital admission was associated with increased mean length of hospital stay (2.35 days for deep suctioning, 1.75 days for noninvasive suctioning), as were lapses longer than 4 hours between suctioning events . There was also a dose-dependent relation between increased number of suctioning lapses and increased length of stay (2.64 days with 3-4 lapses, 1.62 days with 0 lapses).
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.
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. 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.
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.[81, 82] 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.
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). The risk of concurrent bacterial infections is low.[85, 86, 87, 88]
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:
Maintenance of oral hydration
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.
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