(also see Synagis)
- acute, infectious,
inflammatory disease of the upper and lower respiratory tract
- results in obstruction of the
- may occur in all age groups,
but the larger airways of older children and adults better accommodate mucosal
edema; severe respiratory symptoms usually are limited to young infants.
- two respiratory syncytial
virus (RSV) subtypes, A and B, with subtype A causing most severe infections.
- one subtype usually
predominates during a given season; thus, “good” years and “bad” years occur
for RSV disease.
- the disease is highly
contagious. Viral shedding in nasal secretions continues for 6-21 days after
development of symptoms. The incubation period is 2-5 days.
- Human rhinoviruses are a major pathogen among children under age 2 and may be responsible for a significant proportion of wheezing in this population and may trigger asthma. These researchers write that hospitalization rates may be similar to RSV. (1)
- Necrosis of the respiratory
- proliferation of goblet cells
results in excessive mucus production
- epithelial regeneration with
nonciliated cells impairs elimination of secretions.
- lymphocytic infiltration may
result in submucosal edema.
- the pathology results in
obstruction of bronchioles by inflammation, edema, and debris, leading to
hyperinflation, increased airway resistance, atelectasis, and
Infants have small airways, high
closing volumes, and insufficient collateral ventilation; thus, they are
affected most often. Recovery begins with regeneration of bronchiolar epithelium
after 3-4 days, but cilia do not appear for up to 2 weeks. Mucus plugs are
removed by macrophages. Risk factors include the following:
- Low birth weight, particularly
- Lower socioeconomic group
- Crowded living conditions and/or
- Parental smoking
- Chronic lung disease, particularly
- Severe congenital or acquired
- Congenital heart disease with
- Congenital or acquired immune
- In the US: Twenty-five
percent of children younger than 12 months and 13% of children aged 1-2 years
have respiratory infections.
- Of these 25%, one half have a
wheezing-associated respiratory disease.
- RSV can be cultured from one third
of these outpatients and from 80% of hospitalized children younger than 6
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 due to transplacental transfer
of maternal antibody.
- In temperate climates, RSV
epidemics generally develop yearly in winter and late spring, while
Parainfluenzae outbreaks usually occur in the fall.
- Evidence indicates that, in the
subtropical areas of the southeastern US, RSV is endemic throughout the year,
with peaks from October to February and subsidence only from March through
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.
- Infection is spread by fomites via
environmental surfaces. Hand washing and the use of disposable gloves and
gowns may reduce nosocomial spread.
Bronchiolitis is a significant cause of respiratory disease worldwide. Its
incidence in developed countries appears similar to the US. Epidemiologic data
from underdeveloped countries are incomplete.
RSV bronchiolitis accounts for
more than 90,000 pediatric hospitalizations and up to 4,500 deaths annually.
Overall, the mortality for
children hospitalized for bronchiolitis in different series is 0.2-7%. This
large variability is based on investigations of different cohorts with
different risk factors and different points in time relative to modern
Very recent studies in
pediatric intensive care units of children with RSV bronchiolitis and without
comorbidities show a 2-3% death rate regardless of whether the children had
congenital heart disease with pulmonary hypertension.
affected 1.7 times more than girls; the male-to-female ratio of
hospitalization among these children is 1.5:1.
Although RSV bronchiolitis clearly is a significant disease of the young
child, no lifelong immunity occurs; mildly symptomatic or asymptomatic adults
can be infected and act as carriers.
- RSV infection may be life
threatening to older children and adults undergoing organ and bone marrow
transplantation because of the increasing use of treatment modalities that
compromise cellular immunity.
As this disease primarily
affects young infants, the clinical manifestations initially are subtle.
Infants may become
increasingly fussy and have
difficulty feeding during the
2- to 5-day incubation period. A
low-grade fever, usually less than 101.5°F, and increasing
congestion usually follow the
Sixty percent of primary RSV
infections are confined to the upper airway.
During a period of 2-5 days,
this may progress to lower respiratory
tract involvement with the development of cough, dyspnea, wheezing, and
By the time the patient is
brought to medical attention, the fever usually has resolved.
Infants younger than 1 month
may present as hypothermic.
Severe cases progress to
respiratory distress with tachypnea, nasal flaring, retractions and
irritability, and, possibly, cyanosis.
- Examination often reveals the
- Otitis media
- Fever (38-39°C)
- Fine rales
- Diffuse, fine wheezing
- Diagnosis is based on the age and
seasonal occurrence, tachypnea, and the presence of profuse coryza and fine
rales and/or wheezes on auscultation of the lungs.
- Hypoxia is the best predictor of
severe illness and correlates best with the degree of tachypnea. The degree
of wheezing or retractions correlates poorly with hypoxia.
First-time infections usually are
most severe. Subsequent attacks generally are milder, particularly in older
manifestations of RSV infections include
- otitis media
- supraventricular and ventricular dysrhythmias
- inappropriate secretion of antidiuretic hormone.
Of infants hospitalized with RSV
18-20% develop apnea. Frequency of apnea increases among premature
infants whose gestation was less than 32 weeks, infants who have not yet
reached the age of 44 weeks from conception, and especially among those who
have neonatal apnea.
- Apnea occurs early in the course
of the disease and may be the
- Nonobstructive central apnea
occurs during quiet sleep and is associated with increases in the apnea
index (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 while in a given sleep state).
Apnea rarely lasts longer than a few
days; however, about 10% of these patients require
and mechanical ventilation to get through this period.
RSV is the most commonly isolated agent in 75% of
children younger than 2 years and who are hospitalized for bronchiolitis.
- Agents that cause
wheezing-associated respiratory infections include the following:
- Mnemonic: PM AIR
Parainfluenza virus causes
10-30% of all bronchiolitis cases.
accounts for 5-15% of cases of bronchiolitis, particularly among older
children and adults.
Adenovirus accounts for 5-10%
of cases of bronchiolitis.
Influenza virus accounts for
10-20% of cases of bronchiolitis.
RSV causes 20-40% of all
cases and 44% of cases involving children younger than 2 years.
- Abundant evidence reveals that
complex immunologic mechanisms play a role in the pathogenesis of RSV
bronchiolitis. Type I allergic reactions mediated by the immunoglobulin E (IgE)
antibody may account for clinically significant bronchiolitis.
are nursed with colostrum rich in immunoglobulin A (IgA) appear relatively
protected from bronchiolitis.
Foreign body aspiration
Congenital structural anomaly
Congenital lobar emphysema
Bronchial cleft cyst
Congenital heart disease
Shown not to work in the
management of the infant with RSV and wheezing. :
corticosteroids , Ipratropium
bromide (atrovent), an aerosolized anticholinergic agent
- Indications for hospital admission
include the following:
- Oxygen saturation monitored by
pulse oximetry below 92% in room air
Younger than 6 months and unable to
maintain oral hydration
elevated respiratory rate
- History of chronic
in 40% oxygen (3-4 L/min oxygen), cyanosis
- Extra pulmonary symptoms
Apnea and acidosis are indicators for
pediatric intensive care referral.
- Administer supplemental
humidified oxygen to maintain
saturation above 92%.
Fluid replacement: These
infants are mildly dehydrated because of decreased fluid intake and increased
fluid losses from fever and tachypnea. The goal of fluid therapy is to replace
deficits and provide maintenance requirements. Avoid excessive fluid
administration because this may promote interstitial edema formation,
particularly if a component of inappropriate antidiuretic hormone release
- Perform nasal and oral
- Monitor patient carefully in order
to detect apnea.
- Pay attention to temperature
regulation in the very small infant.
Mechanical ventilation: Infants
with bronchiolitis occasionally require mechanical ventilation in cases of
recurrent apnea or increased work of
breathing with respiratory failure. The treatment of these patients is
supportive, with provision of adequate oxygen, ventilation, and hydration.
Continuous positive airway pressure (CPAP)
and intermittent mandatory ventilation (IMV)
with positive end-distending pressure (PEEP)
have been used successfully in the treatment of these infants.
- in patients requiring ventilation using IMV and PEEP
- ventilate at rates slow enough to allow adequate emptying during
- short inspiratory time is used to optimize ventilation to more compliant
lung units without overdistending more obstructed ones.
- Aggressive weaning over the first 2 or 3 days is not warranted and
usually is unsuccessful.
- Once the illness subsides, weaning can proceed quickly.
- Infants with progressive hypoxemia unresponsive to conventional
ventilation may respond to high-frequency ventilation or extracorporeal
membrane oxygenation. Current experimental therapies for infants with
pulmonary insufficiency from bronchiolitis include surfactant and nitric
When a healthy infant presents with a history,
physical examination, and course that is consistent with uncomplicated
bronchiolitis, no consultations are necessary; however, refer infants with
comorbidities, atypical histories, or critical conditions to a pediatrician,
preferably at a center that can provide a spectrum of pediatric subspecialists
in critical care, pulmonology, and infectious disease.
Although young infants have the unique ability to
breathe and swallow simultaneously, risk
of aspiration when the respiratory rate is above 60 breaths per minute is
significant. 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 intravenous fluids when
hyperpnea precludes safe oral feeding.
Although a number of medications and interventions have been used to treat
bronchiolitis, at present, only
oxygen and racemic
epinephrine have been shown to affect the condition of the young child with
appreciably. Neither of these appreciably shortens the duration of the
disease; however, each may prevent complications and improve comfort.
Therapeutic use to treat bronchiolitis in infants and young children has been
controversial. Efficacy in infants is complex 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.
A meta-analysis reviewed 15 randomized placebo-controlled trials of
bronchodilator treatment in bronchiolitis. It concluded that bronchodilators
produce modest short-term improvement in clinical features of mild or moderately
A more recent meta-analysis of 8 clinical trials noted that conclusive
analysis for the efficacy of beta2-agonist therapy for bronchiolitis remains
unavailable and that the routine use of
beta2-agonist therapy for
bronchiolitis is not supported.
A recent study compared nebulized
to normal saline in an age-matched and severity-matched trial of 52
infants over 72 hours of treatment.
did not improve recovery or attenuate severity, as indicated by
improvement in oxygen saturation, length of stay, or clinical score.
Although evidence about the efficacy of bronchodilators in bronchiolitis is
conflicting, administering a beta-agonist, such as albuterol (0.15 mg/kg/dose),
on a trial basis to patients with
(particularly if a history of asthma exists) and assessing the clinical response
in 10-15 minutes is reasonable. If improvement in retractions, respiratory rate,
and wheezing is noted, scheduled aerosol treatments may be continued,
with additional treatments administered as needed.
Ribavirin, a nucleotide analog, may have a role in certain unique situations.
Ribavirin treatment for RSV infections has been controversial because of the
aerosol route of administration, the variable course of RSV infection, drug
cost, toxicity, and adverse effects.
The current recommendations of the
Academy of Pediatrics are that
ribavirin aerosol therapy may be
considered in selected infants and young children at high risk for serious RSV
This includes patients with complicated congenital heart disease, including
pulmonary hypertension; patients with bronchopulmonary dysplasia, cystic
fibrosis, and other chronic lung disease; patients with underlying
immunosuppressive disease; patients who are severely ill with or without
mechanical ventilation; and hospitalized patients who are younger than 6 weeks
or who have underlying conditions, such as multiple congenital anomalies or
certain neurological and metabolic diseases.
The academy added, "More definitive answers to the questions of ribavirin
efficacy and effectiveness require multi-institutional prospective randomized
clinical trials. Recommendations may be modified as new information becomes
Subsequent studies have shown that ribavirin does not reduce mortality rate
significantly or lower the probability of respiratory deterioration. Ribavirin
treatment did not reduce the diagnosis of reactive airway disease, and pulmonary
function test results did not show any differences when assessed 5-6 years after
initial RSV infection.
Oxygen -- Decreases the work of breathing, hence, delaying the onset of
respiratory muscle fatigue, allowing other therapies to work.
Bronchodilators -- Act by decreasing muscle tone in both the small and large
airways in the lungs, thereby increasing ventilation.
Immunoglobulins -- Specific immunoglobulin products with anti-RSV activity
have been developed for the prophylaxis of high-risk patients against RSV
infection. Palivizumab (Synagis) -- Humanized monoclonal antibody directed
against the F (fusion) protein of RSV. Given monthly through the RSV season, it
has been demonstrated to decrease the chances of RSV hospitalization in
premature babies who are at increased risk for severe RSV-related illness.
Antibiotics -- 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 often is justified until
culture results prove to be negative.
Nucleoside analogs -- Ribavirin
(1-beta-D-ribafuranosyl-1,2,4-triazole-3-carboxamide) is a synthetic nucleoside
analog that resembles guanosine and inosine. It appears to interfere with the
expression of messenger RNA and inhibit viral protein synthesis. Ribavirin has a
broad spectrum of antiviral activity in vitro, inhibiting replication of RSV,
influenza, parainfluenza, adenovirus, measles, Lassa fever, and Hantaan viruses.
Ribavirin (Virazole) -- Appears to be safe but expensive. Efficiency and
effectiveness have not been demonstrated clearly in large, randomized,
placebo-controlled trials. Routine use at this time cannot be recommended. In
adults, ribavirin can be used for the treatment of other infections, including
Further Inpatient Care:
- 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 for parental reassurance.
- No further laboratory testing is
necessary unless the patient must test RSV negative for return to an
environment where high-risk patients are present, such as at medical daycare
centers or group homes. Secretions may remain positive for RSV for as long as
21 days after the onset of symptoms.
In/Out Patient Meds:
- For children who required inpatient
antibiotics for intercurrent infections, continue the same antibiotics to
complete the suggested course.
- A child with reactive airway
disease may require continued treatment with bronchodilators.
- Transfer to a facility that has an
intensivist-managed critical care unit is indicated for patients with the
- High risk
- Requiring more than 40% oxygen
- Extrapulmonary symptoms
- Unclear etiology of their
- Transmission of RSV probably occurs
via contact with secretions of infected patients. Meticulous attention to
hand washing between patient
contacts should reduce the likelihood of hospital staff acquiring RSV
infection from patients or of spreading infection by carrying RSV on their
hands. Morbidity and death from RSV
occurs predominately 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 with
- Attempts to develop a safe and
effective RSV vaccine thus far have 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. Active
prophylaxis by the use of respiratory
virus immunoglobulin intravenously (RSV-IGIV)
at high doses (500-750 mg/kg) has been shown to prevent RSV in high-risk
- Presently, a number of
disadvantages to the parenteral administration of human polyclonal
RSV-specific immunoglobulin antibodies to infants exist. These include
intravenous administration monthly over 2-4 hours, the need to administer it
in a clinic or hospital, and the potential for excessive fluid load.
A more convenient RSV-specific
monoclonal antibody preparation,
which can be administered as an intramuscular injection, is available. It is
administered at a dose of 15 mg/kg every 30 days from October through February
or according to the local RSV season (ie start in November). See Synagis.
- In a multi-institutional,
randomized, placebo-controlled study of 1502 high-risk, preterm infants in 139
centers in the US and Canada during the 1996-1997 RSV season, hospitalizations
were decreased by 55%. Hospital length of stay, days on oxygen, and intensive
care unit admissions all were reduced. Adverse effects were uncommon.
Unfortunately, while cost effective, per-patient cost is approximately $3000,
thus restricting availability to only high-risk patients.
- As with any disease, complications
of the disease itself and complications of the therapy are present. In most
cases, the disease is mild and self-limiting. In infants who are
immunosuppressed and those with preexisting heart or lung disease, RSV
bronchiolitis can result in any of the following:
- Acute respiratory distress
- Bronchiolitis obliterans
- Congestive heart failure
- Secondary infection
- Chronic lung disease
- Complications of therapy include
- Ventilator-induced barotrauma
- Nosocomial infection
- Beta-agonist–induced arrhythmias
- Nutritional and metabolic
- 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 may
preclude many of these complications.
- RSV does evoke IgE elaboration.
Recent studies suggest that IgE levels can be used as a marker of the severity
of the acute disease. Multiple small
studies suggest that children who have been hospitalized with RSV
have a higher incidence of reactive airway disease and more abnormalities in
their pulmonary function tests than children never hospitalized for RSV.
These abnormalities may persist for as long as 5 years, though
eventually normalizing. Conflicting small studies have failed to prove whether
early treatment of acute RSV bronchiolitis with ribavirin reduces the
persistence of pulmonary dysfunction.
- Importance of RSV prophylaxis for
- Importance of avoiding RSV exposure
in the first 2-3 months of life
- Natural history of bronchiolitis
- Failure to recognize severity based on tachypnea and desaturation
- Failure to recognize apnea in young infants with bronchiolitis
- Failure to recognize myocarditis
- Overtreatment with beta-agonists
Bronchiolitis. Last Updated: July 17, 2003.
(1) Pediatr Inf Dis J. 2009;28:25-29