Bronchiolitis

Updated: Aug 21, 2017
  • Author: Nizar F Maraqa, MD, FAAP; Chief Editor: Russell W Steele, MD  more...
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Overview

Practice Essentials

Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection (most commonly respiratory syncytial virus). 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.

A chest radiography revealing lung hyperinflation 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.

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 [1]
  • Low-grade fever (usually < 101.5°F); possible hypothermia in infants younger than 1 month [2]
  • 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
  • Irritability
  • Possibly cyanosis

See Clinical Presentation for more detail.

Diagnosis

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:

  • Tachypnea
  • Tachycardia
  • Fever (38-39°C)
  • Retractions
  • Fine rales (47%); diffuse, fine wheezing
  • Hypoxia
  • Otitis media

Laboratory tests

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. [3] 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 or nucleic acid amplification testing of nasopharyngeal secretions for respiratory syncytial virus
  • Arterial blood gas analysis
  • White blood cell count with differential
  • C-reactive protein level
  • Pulse oximetry
  • Blood cultures
  • Urine analysis, specific gravity, and culture
  • Cerebrospinal fluid analysis and culture
  • Serum chemistries

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

Imaging studies

Chest radiographs are not routinely necessary. [4] 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 [5, 6] ; it may also yield evidence of alternative diagnoses (eg, lobar pneumonia, congestive heart failure, or foreign body aspiration).

Procedures

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.

Management

Among numerous medications and interventions used to treat bronchiolitis, thus far, only oxygen appreciably improves the condition of young children. [7] Therefore, therapy is directed toward symptomatic relief and maintenance of hydration and oxygenation.

Nonpharmacotherapy

Supportive care for patients with bronchiolitis may include the following:

  • Supplemental humidified oxygen
  • Maintenance of hydration
  • Mechanical ventilation
  • Nasal and oral suctioning
  • Apnea and cardiorespiratory monitoring
  • Temperature regulation in small infants [8]

Pharmacotherapy

Medications have a limited role in the treatment of bronchiolitis. Otherwise-healthy children with bronchiolitis usually have limited disease and do well with supportive care only.

The following medications are used in selected patients with bronchiolitis:

  • Alpha/beta agonists (eg, albuterol, racemic epinephrine)
  • Monoclonal antibodies (eg, palivizumab)
  • Antibiotics (eg, ampicillin, cefotaxime, ceftriaxone)
  • Antiviral agents (eg, ribavirin)
  • Intranasal decongestants (eg, oxymetazoline)
  • Corticosteroids (eg, dexamethasone, prednisone, methylprednisolone)

See Treatment and Medication for more detail.

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Background

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.

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Pathophysiology

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]

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Etiology

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.

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Epidemiology

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.

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Prognosis

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]

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Patient Education

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.

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