Bronchiolitis (See Also: Respiratory Syncytial Virus)

Acute lower respiratory tract infection causing obstruction of the small to medium conducting airways of the lung
GENERAL PREVENTION
The major means of preventing bronchiolitis is strict observance of infection control, with frequent handwashing,
avoidance of known ill contacts and crowded places, and limiting exposure to daycare and secondhand smoke.
EPIDEMIOLOGY

Seen in all geographic areas

In the US, occurs from late fall through the winter and early spring. The Respiratory Syncytial Virus
(RSV) epidemic season begins earlier in the southeastern US, and in some areas (e.g. Florida,
Hawaii) can occur throughout the year. Parainfluenza 3 occurs throughout the year, as does
adenovirus. Influenza virus epidemics usually begin in late fall, peak in January/February, and wane
by April. Human metapneumovirus peaks slightly later in the year (March) than does RSV (January).

RSV infects most children within the 1st 2 years of life; 57% of those hospitalized are younger than 6
months. The infection rate is 68.8/100 in infants <1 year of age; by 2 years of age, 97% of children
have experienced an RSV infection.

RSV reinfection occurs in 5075% of children followed, and reinfection within the same RSV season is
possible.

Approximately 1/2 of all children experience an infection with parainfluenza 3 before 1 year of age.

RSV infection is the leading cause of hospitalization in infants <1 year old and causes >120,000
hospitalizations per year in children <5 years of age in the US. Hospitalization occurs in 2.8 of every
1,000 children with a parainfluenza lower respiratory tract infection.

Mortality associated with primary RSV infection in otherwise healthy children has been estimated to
be 3.1 deaths per 100,000 person-years in infants <1 year of age, and is ~13% among children with
underlying conditions. It is the most common viral cause of death in infants <1 year old.

Risk factors for acquisition of RSV infection:

1. Birth during the months of April through September
2. Day care attendance or older siblings in day care
3. Crowded living condition
4. Lower socioeconomic status
5. Exposure to environmental tobacco smoke or other air pollutants
6. Lower cord serum RSV antibodies
7. Absence of breastfeeding
8. Multiple births

Up to 50% of infants with bronchiolitis develop subsequent wheezing.

Patient groups at high risk of severe RSV disease:

1. Premature infants (<36 weeks gestation)

2. Infants 10 weeks of age at time of RSV infection

3. Congenital heart disease
4. Chronic lung disease (including bronchopulmonary dysplasia [BPD])
5. Low birth weight
6. Cystic fibrosis
7. Compromised immune function (from chemotherapy, transplant, congenital or acquired
immunodeficiencies)
RISK FACTORS
Genetics
Genetic background is unclear, but severity of RSV infection may be determined by:

Single nucleotide polymorphisms close to the IL-8 gene

Single nucleotide polymorphisms close to the IL-10 gene

Overproduction of IL-4

Polymorphisms of the surfactant protein-D gene

Genetic variants in a receptor for chemokines, the CC chemokine receptor 5

PATHOPHYSIOLOGY

RSV is the most common cause of this illness (5090% of those infants hospitalized).

Other agents associated:

1. Rhinovirus
2. Human parainfluenza viruses
3. Influenza virus
4. Adenovirus
5. Human metapneumovirus
6. Mycoplasma pneumoniae (in older children)

RSV is transmitted by:

1. Close contact with infected secretions, large particle aerosols, and fomites
2. Self-inoculation of conjunctivae or nose with infected hands
3. Secretions that remain infectious on countertops and stethoscopes for up to 6 hours, rubber
gloves for 1.5 hours, and on hands or tissue for ~30 minutes

Influenza virus and adenovirus are spread by small droplets that remain airborne and which are then
inhaled.

Viral shedding: Up to 21 days after infection, but can extend to several weeks or months in
immunocompromised patients

Virus proliferates in the nasal epithelium, resulting in coryza with profuse rhinorrhea.

Infected secretions are aspirated into the lower respiratory tract. From there, virus infects bronchiolar
epithelial cells of airways 75300 microns in diameter.

Infection causes necrosis and sloughing of cells into the airway lumen. There is goblet cell
proliferation and mucus hypersecretion. The airway lumen becomes filled with debris consisting of
dead cells and mucus resulting in plugging, which causes partial or complete airway obstruction,
increased airways resistance, hypoxemia, and decreased lung compliance.

Polymorphonuclear leukocytes are the predominant inflammatory cell type recovered from
bronchoalveolar lavage (BAL) fluid of infants with documented RSV bronchiolitis; a subset may also
have an elevated number of eosinophils in BAL fluid.

Mononuclear cells (lymphocytes and macrophages) infiltrate the peribronchial tissue, leading to
airway wall and interstitial edema.

RSV-induced changes in the bronchiolar epithelium can last beyond the acute infection. Regeneration
of bronchiolar epithelium takes weeks to months and lags behind clinical signs of recovery.

Diagnosis
History

Rhinorrhea with clear to white copious nasal secretions?

Coughing? Initially hoarse cough for 35 days; progresses to deep wet cough of increased frequency

Poor feeding? Early sign of respiratory fatigue; may lead to dehydration

Low-grade fever? Characteristic of disease; not a reliable marker of severity of disease, but
contributes to increased insensible fluid loss

Restlessness or lethargy? May indicate impending respiratory failure (hypoxemia and/or

CO2 retention)

Apnea? Can be sole presenting sign in younger infants; if respiratory distress is present, suggests
impending respiratory failure

Cyanosis/color change or increased work of breathing? Impending respiratory failure

Physical Exam

General appearance:
1. Interactive versus ill-appearing
2. Paroxysmal cough (most common sign), not associated with a whoop
3. Poor oral intake

HEENT exam
1. Nasal flaring
2. Nasal congestion with copious secretions

Pulmonary examination
1. Pattern of breathing: Apnea or periodic breathing

2. Tachypnea: >70/min is associated with severe illness

3. Nasal flaring and accessory muscle use
4. Intercostal retractions (increased resistance, decreased compliance); subcostal retractions
(hyperinflation)
5. Thoracoabdominal asynchrony
6. Hyperresonance to percussion
7. Diffuse, high-pitched heterophonous wheezing
8. Prolonged expiratory phase
9. Fine inspiratory crackles (may be heard in both bronchiolitis and pneumonia)
10.Diffuse rhonchi

Other findings:
1. Signs of dehydration
2. Low-grade fever
3. Tachycardia
4. Bradycardia associated with apnea
5. Possible cyanosis of nail beds and oral mucosa
6. Liver and spleen typically caudally displaced by hyperinflated lungs

TESTS
LABORATORY

Pulse oximetry: To assess oxygenation

Arterial blood gas:

1. Degree of hypoxemia (determine A-a gradient)
2. Evidence of respiratory failure and respiratory acidosis with CO 2retention (late finding)

Serum electrolytes: Sickest patients may have Syndrome of Inappropriate Anti-diuretic Hormone
release and hyponatremia; may also see abnormalities in those infants with significant dehydration;
not useful in the majority of infants with milder disease

RSV serology (acute and convalescent serum samples): No practical application for clinical use

Rapid viral identification:

1. Best samples for testing:

Nasopharyngeal aspirate

Nasopharyngeal wash

2. Adequate samples for testing:

Nasal swab

Tracheal aspirate

BAL fluid

Rapid tests:
1. Immunofluorescence assay (direct or indirect):

>85% sensitivity and specificity

Results in 45 minutes

Negative predictive value >87%

2. Enzyme immunoassay (EIA):

6090% sensitivity

7095% specificity

Negative predictive value 7598%

Results in 1530 minutes

Does not require the presence of viable virus

3. Reverse transcriptase polymerase chain reaction (RT-PCR):

93.5100% sensitivity

63.9100% specificity

Results in <1 hour

Viral culture:
1. Culture of nasopharynx
2. Considered gold standard. May take up to 14 days for results
3. Sensitivity and specificity highly dependent on quality of sample, handling of specimen, and
time to delivery to virology laboratory

IMAGING
Chest radiography findings include:

Hyperinflation, flattened diaphragms

Peribronchial thickening

Patchy or more extensive atelectasis

Possible collapse of a segment or a lobe

Diffusely increased interstitial markings commonly seen

DIFFERENTIAL DIAGNOSIS

Pneumonia (viral or bacterial)

Asthma

Gastroesophageal reflux (GER)

Foreign body aspiration

Exposure to noxious agents (chemicals, fumes, toxins)

CHF

Cystic fibrosis

Treatment
GENERAL MEASURES

Most cases are mild and may be treated at home.

Adequate fluid intake

Maintenance of nasal airway patency:

1. Short-term nasal decongestant
2. Suction secretions with suction bulb

OTHER

Careful fluid hydration; deficit plus ~2/3 maintenance fluids

Supplemental oxygen:
1. Given to any patient with hypoxemia
2. Preferably warmed and humidified by nasal cannula, head box, or tent

Management to overcome airway obstruction:

1. Bronchodilators:

Some (but not all) infants with bronchiolitis will improve clinically with
bronchodilator administration. A trial of an aerosolized -adrenergic agent with
critical assessment to see if there is any relief of symptoms is reasonable.

Infants with a prior history of wheezing or familial history of asthma or atopy are
more likely to respond to bronchodilators.

Theophylline is not usually useful as a bronchodilator in bronchiolitis, and may

potentially worsen GER, if present. It may be useful in the infant with impending
respiratory failure or apnea due to its ability to increase diaphragmatic
contractility, respiratory drive, and CO2 responsiveness.

2. Nebulized epinephrine:

Potentially beneficial in infants with moderate to severe bronchiolitis. It is both an

- and -receptor agonist.

Both racemic epinephrine (0.1 mL/kg of 2.25% solution) and L-epinephrine have
been studied separately and showed beneficial results compared with agonists.

3. Anticholinergic agents: Ipratropium bromide has not been shown to be effective in the
treatment of bronchiolitis.

4. Corticosteroids:

In previously healthy infants, corticosteroids are not routinely recommended. Use

of systemic (oral or parenteral) steroids may confer a small benefit in shortening
duration of hospital stay or symptoms (<1/2 day).

Effects of steroids may be greater in infants with more severe disease or

impending respiratory failure.

Use of inhaled corticosteroids does not decrease duration of symptoms or

recurrence of cough and wheezing after acute bronchiolitis resolves.

5. Leukotriene modifiers:

Infants who develop wheezing with RSV infection have high concentrations of
cysteinyl leukotrienes and histamine in respiratory secretions.

One series demonstrated an increase in symptomfree days among infants who

took montelukast in the month after hospitalization for an acute RSV infection.

No studies have evaluated the use of leukotriene modifiers during the acute
phase of bronchiolitis.

6. Mucolytics:

Recombinant human DNase and N-acetyl cysteine are not effective in shortening
the duration of symptoms in infants with bronchiolitis.

Hypertonic saline (3%) aerosolized in combination with epinephrine may shorten

length of hospitalization compared to use of epinephrine alone.

7. Surfactant:

Shown to prevent progression of deterioration in lung mechanics in a small

number of infants with respiratory failure requiring mechanical ventilation
secondary to RSV bronchiolitis

Heliumoxygen mixtures used in place of nitrogenoxygen (air) have been

shown to improve clinical score and shorten ICU stays in small series of infants
with severe bronchiolitis.

The gas does not alter the course of the underlying illness, but because helium is
less dense than nitrogen, resistance in areas of turbulent flow is decreased.

This in turn can decrease breathing effort, respiratory rate, and heart rate.

8. Heliox:

9. Antibiotics:

Not usually indicated

Other than otitis media, the incidence of concurrent serious bacterial infection
(pneumonia, meningitis, sepsis) is <2% in healthy infants with no underlying
disease who have RSV bronchiolitis.

10.Antiviral agents (ribavirin): See Respiratory Syncytial Virus

11.Immunoprophylaxis: See Respiratory Syncytial Virus

OTHER

Historical risk factors for severe disease:

1. <2 months of age
2. Gestational age <36 weeks
3. Underlying cardiopulmonary disease (e.g., hemodynamically significant heart disease,
BPD)

Immunodeficiency or other high-risk group for developing severe disease

Clinical risk factors for severe disease

Presence of apnea, tachypnea (respiratory rate >70/min), retractions, poor feeding, pallor, lethargy, or
agitation (signs of impending respiratory failure)

Pulse oximetry <95% in room air

Atelectasis on chest radiograph

Follow-up Recommendations
EXPECTED COURSE/PROGNOSIS

For most previously healthy infants, the prognosis is good.

Premature infants of 3235 weeks gestation hospitalized for bronchiolitis have been shown to have
an increased number of subsequent hospitalizations for respiratory problems, a greater number of
outpatient visits, and an increased risk of sudden death compared with those who were not
hospitalized for bronchiolitis.

Mortality associated with primary RSV infection in otherwise healthy infants is 0.0050.02%.

Morbidity and mortality are considerable in patients with an underlying chronic disease.

Up to 50% of infants with bronchiolitis develop subsequent episodes of recurrent wheezing until 11
years of age.

Bronchiolitis obliterans may be a sequela in patients infected with adenovirus or Mycoplasma

pneumoniae.

POSSIBLE COMPLICATIONS

Common complications:
1. Otitis media
2. Pneumonia
3. Aspiration syndrome
4. Respiratory failure requiring mechanical ventilation

Apnea, either as a presenting symptom or in association with increasing respiratory distress

Syndrome of inappropriate ADH release (risk for overhydration)

Sepsislike syndrome

PATIENT MONITORING

Most infants with no underlying disease improve within 35 days. In some, nasal congestion and
cough may continue for 13 weeks. Premature infants and those with underlying cardiopulmonary
disease typically experience a protracted illness.

Those who need mechanical ventilation may have difficulties with extubation due to excessive
secretions and atelectasis.

As many as 50% of infants will have recurrent wheezing through the 1st decade of life.

OTHER

Impending respiratory failure (increased breathing effort, retractions, hypoxemia, CO 2 retention,

lethargy)

Sudden deterioration suggesting atelectasis due to mucous plugging

Fatigue may occur in infants who have prolonged and extensive disease.

Fatigue will manifest with increased pCO2and worsening hypoxemia.

CLINICAL:

Hypoxemia is common, so always monitor oxygen saturation.

Be aware of apnea.

In cases of clinical bronchiolitis, causes of false-negative ELISA tests:

1. Poor quality of sample
2. Sample contamination
3. Insufficient sample
4. Non-RSV bronchiolitis

Frequently Asked Questions

Q: How did my child get bronchiolitis?

A: RSV bronchiolitis is a common, seasonal, lower respiratory tract infection that is easily
transmissible.

Q: Can my child become reinfected?

A: Children can become reinfected with RSV bronchiolitis, and infection can occur more than once
during the same respiratory season.

Q: Do patients with bronchiolitis need to be isolated?

A: RSV-positive patients need to be isolated with other RSV-positive patients and from uninfected
patients. Patients receiving ribavirin should be kept in isolation.

Q: Will my child develop asthma?

A: Recurrent wheezing has been described in up to 50% of infants with RSV bronchiolitis. However,
most data are retrospective and observational. Whether RSV per se can contribute to the
development of asthma and allergic sensitization remains unclear.