R E V I E W ARTICLE

Recent Advances in Management of Bronchiolitis

NISHANT VERMA, RAKESH LODHA, S K KABRA
From Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India.
Correspondence to: Dr SK Kabra, Department of Pediatrics, AIIMS, New Delhi. [email protected]

Background: Bronchiolitis is one of the major causes for hospital admissions in infants. Managing bronchiolitis, both in the outpatient and
inpatient setting remains a challenge to the treating pediatrician. The effectiveness of various interventions used for infants with
bronchiolitis remains unclear.
Need and purpose: To evaluate the evidence supporting the use of currently available treatment and preventive strategies for infants
with bronchiolitis and to provide practical guidelines to the practitioners managing children with bronchiolitis.
Methods: A search of articles published on bronchiolitis was performed using PubMed. The areas of focus were diagnosis, treatment
and prevention of bronchiolitis in children. Relevant information was extracted from English language studies published over the last 20
years. In addition, the Cochrane Database of Systematic Reviews was searched.
Results and Conclusions: Supportive care, comprising of taking care of oxygenation and hydration, remains the corner-stone of
therapy in bronchiolitis. Pulse oximetry helps in guiding the need for oxygen administration. Several recent evidence-based reviews
have suggested that bronchodilators or corticosteroids lack efficacy in bronchiolitis and should not be routinely used. A number of other
novel therapies (such as nebulized hypertonic saline, heliox, CPAP, montelukast, surfactant, and inhaled furosemide) have been
evaluated in clinical trials, and although most of them did not show any beneficial results, some like hypertonic saline, surfactant, CPAP
have shown promising results.
Keywords: Bronchiolitis, CPAP, Epinephrine, Hypertonic saline, Surfactant.

A
cute bronchiolitis is an important cause of ETIOLOGY
morbidity in infants and children. It is the
Bronchiolitis is typically caused by a viral infection. With
most common cause of hospitalization due to
improvement in diagnostic ability to identify viruses in
acute lower respiratory tract infection (LRTI)
respiratory secretions (nasopharyngeal aspirates) multiple
in infants. A number of definitions have been proposed for
viral agents have been identified as causative agents of
bronchiolitis: The American Academy of Pediatrics (AAP)
acute bronchiolitis: Respiratory syncytial virus (RSV),
defines bronchiolitis as acute inflammation, edema and
Rhinovirus, Parainfluenza viruses, Influenza virus,
necrosis of epithelial cells lining small airways, increased
Adenovirus, and Coronavirus. RSV is the most common
mucus production, and bronchospasm [1]; but this
cause, accounting for 50-80% cases [3]. In Indian studies,
definition is of little clinical significance. Another useful
RSV infection was diagnosed in 30-70% of children with
definition, which has been used in many clinical studies, is:
bronchiolitis [4-6]. The proportion of disease caused by
the first episode of wheezing in a child younger than 12 to
specific viruses varies depending upon the season and the
24 months who has physical findings of a viral respiratory
year, and there is a wide variation in the reported
infection and has no other explanation for the wheezing,
proportions among various studies. Most of the studies
such as pneumonia or atopy [2].
implicate rhinovirus (which normally causes common
METHODS cold) as the second most common cause of bronchiolitis.
Molecular diagnostic techniques have also revealed a high
A search of articles published on bronchiolitis was
frequency (15-25%) of mixed viral infections among
performed using PubMed. The areas of focus were
children evaluated for bronchiolitis [7-11].
diagnosis, treatment and prevention of bronchiolitis in
children. Relevant information was extracted from Apart from the above mentioned viruses, newer
English language studies published over the last 20 years. respiratory viruses have been described in children,
In addition, the Cochrane Database of Systematic including human metapneumovirus (hMPV) and human
Reviews was searched. We selected relevant articles/ bocavirus (HBoV) [12]. Some of the recent studies have
studies/guidelines in various domains for inclusion in this found hMPV as a common cause of respiratory tract
review. infections in children throughout the world [13] and

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often second only to RSV as a cause of bronchiolitis in Disease Course and Prediction of Severity
infants. In contrast to hMPV, the role of HBoV in causing
Bronchiolitis usually is a self-limited disease. Although
respiratory illnesses is less clear. This is because HBoV
symptoms may persist for several weeks, the majority of
is associated with high coinfection rate (50-60%), and
children who do not require hospital admission may
therefore the role that HBoV alone plays in illness can be
continue to have low grade symptoms upto 4 weeks [16].
questioned. Another problem with HBoV is its lack of
In previously healthy infants, the average length of
cultivability and hence lack of appropriate models for
hospitalization is three to four days [17]. The course may
pathogenesis [12].
be prolonged in younger infants and those with co-
EPIDEMIOLOGY morbid conditions (e.g., chronic lung disease).

Bronchiolitis typically affects children younger than two A number of risk factors and clinical findings have
years with a peak incidence between two and six months been proposed to predict the severity of disease in
of age. In a prospective hospital-based study from children with bronchiolitis (Table I). Various studies and
Southern India, of 114 children with bronchiolitis, 87 treatment trials have also used clinical scores (e.g., the
(76%) were less than 1 year and 107 (94%) were less Respiratory Distress Assessment Instrument) to predict
than 2 years of age [14]. Bronchiolitis occurs in the disease severity in children with bronchiolitis, but
epidemics during winter months. In India, outbreaks none of these scores have been validated for clinical
occur from September to March. predictive value in bronchiolitis. It should be
emphasized that repeated observation over a period of
CLINICAL PRESENTATION time may provide a more valid overall assessment of the
Children with bronchiolitis typically present with a viral disease severity than a single examination [1]. Risk
upper respiratory prodrome comprising of rhinorrhea, factors for mortality include: younger age (<6 months),
cough, and on occasion, a low grade fever. The onset of prematurity, underlying chronic lung disease, cyanotic
these symptoms is acute. Within 1-2 days of these heart disease or immunocompromised state [24].
prodromal symptoms, the cough worsens and child may
also develop rapid respiration, chest retractions, and TABLE I PREDICTORS OF SEVERE BRONCHIOLITIS
wheezing. The infant may show irritability, poor feeding,
and vomiting. Though, in majority of cases, the disease A. Host Related Risk Factors [18-20]
remains mild and recovery starts in 3-5 days, some of Prematurity
these children may continue to worsen. Low birth weight
The importance of a detailed clinical assessment of Age less than 6 to 12 weeks
these children cannot be overemphasized. The Chronic pulmonary disease
components of this assessment include, in-depth review Hemodynamically significant congenital heart disease
of the childs symptoms, impact of these symptoms on (eg, moderate to severe pulmonary hypertension,
his feeding (respiratory distress often prevents adequate cyanotic heart disease, or congenital heart disease that
oral fluid intake and causes dehydration), assessment of requires medication to control heart failure)
the childs responsiveness and alertness, identification of Immunodeficiency
various co-morbidities like underlying chronic
B. Environmental Risk Factors [21]
lung disease, congenital heart disease or immuno-
compromised state, and complete physical examination. Having older siblings
Most of the children with bronchiolitis have tachycardia Passive smoke
and tachypnea. Pulse oximetry helps us in deciding about Household crowding
the need for supplemental oxygen. The chest may appear
Child care attendance
hyper-expanded and may be hyperresonant to
percussion. Wheezes and fine crackles may be heard C. Clinical Predictors [18,22,23]
throughout the lungs. Severely affected patients have Toxic or ill appearance
grunting, marked retractions. They may be cyanosed, Oxygen saturation <95 percent by pulse oximetry
and may have impaired perfusion. Apnea may occur in while breathing room air
those born prematurely and in younger than two months Respiratory rate 70 breaths per minute
of age (15). Other associated problems that may occur in
Moderate/Severe chest retractions
children with bronchiolitis include conjunctivitis, otitis
media and pharyngitis. Atelectasis on chest radiograph

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BASELINE WORK-UP secretions obtained by nasal wash or nasal aspirate. New

techniques such as real-time polymerase chain reaction
The diagnosis of bronchiolitis and the assessment of
(PCR), nested PCR, and multiplex PCR have improved
disease severity should be based on history and physical
the virologic diagnosis of bronchiolitis immensely [5,28,
examination. Laboratory tests and radiographs are not
29]. In a study to detect RSV in children <2 years with
required and do not alter treatment decisions [1].
acute respiratory tract illness using three different
Radiographs techniques: viral culture, direct immunofluorescence,
and nested PCR, it was found that PCR was the most
The radiographic abnormalities of bronchiolitis are sensitive technique (11.1% positivity), followed by
variable and include hyperinflation and peribronchial direct immunofluorescence (7.9% positivity) and viral
thickening. Patchy atelectasis may result from airway culture (6.3% positivity) [30].
narrowing and mucus plugging. In a prospective study
involving 265 children (age 2-23 months) with THERAPY
bronchiolitis, routine radiography identified findings Acute bronchiolitis is, in the majority of cases, a mild and
inconsistent with bronchiolitis in only 2 cases, and in self-limiting illness that can be managed on ambulatory
neither case did these findings affect the acute basis with supportive care alone. Management mainly
management. In fact, radiographic review promoted consists of educating parents or caregivers about
unnecessary use of antibiotics [25]. Results of this study adequate feeding and to report any deterioration (such
highlight that radiographs do not change the as increasing difficulty in breathing, chest indrawing or
management of acute bronchiolitis. A chest X-ray may be problems with feeding) to an appropriate health care
obtained if the diagnosis is in doubt, co-morbidity like facility. Multiple intervention studies have been carried
chronic lung disease or heart disease is suspected, there out to improve treatment of bronchiolitis. Still there is
is no improvement or if the child is severely ill [1]. much controversy, confusion, and lack of evidence over
Laboratory tests
Laboratory tests are not routinely indicated in the TABLE II SUMMARY OF INTERVENTIONS USED FOR
evaluation of infants and young children with suspected MANAGEMENT OF ACUTE BRONCHIOLITIS
bronchiolitis. Abnormalities in total and differential
white blood cell counts do not predict serious bacterial Interventions with clear evidence of effectiveness
infection in infants and young children hospitalized with Supportive care (supplemental oxygen, IV fluids)
lower respiratory tract infection due to RSV [26]. Interventions which are possibly effective
Measurement of lactate dehydrogenase (LDH) Nebulized bronchodilators (epinephrine/salbutamol)
concentration in the nasal-wash fluid has been proposed Nebulized Hypertonic saline
as an objective indicator of bronchiolitis severity; Dexamethasone + Inhaled epinephrine
increased values (suggestive of a robust antiviral
Interventions which are possibly effective for most severe cases
response) have been shown to be associated with
decreased risk of hospitalization [27]. This observation CPAP
needs further validation before nasal wash LDH Surfactant
measurement is used to make decisions regarding Heliox
hospitalization for children with bronchiolitis.
Aerosolized Ribavirin
Virologic testing Interventions which are possibly ineffective
Clinical course, treatment and outcome of acute Oral bronchodilators
bronchiolitis due different viral infections are similar; Montelukast
therefore, identification of viral agents does not affect Inhaled/Systemic corticosteroids
management in the majority of patients. However, in the
Chest physiotherapy
hospital setting, determining the responsible virus may
help to avoid unnecessary antibiotic use and also prevent Antibiotics
nosocomial transmission to other patients. Steam inhalation

The available tools for etiologic diagnosis include RSV polyclonal immunoglobulin / Palivizumab
Antigen detection, Immunofluorescence, Polymerase Inhaled Furosemide/Inhaled interferon alfa-2a / Inhaled
Chain Reaction (PCR), and culture of respiratory recombinant human DNase

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the best treatment for infants hospitalised with moderate carefully performed studies have shown little clear
to severe bronchiolitis [31] (Table II). advantage to one approach over another) are presented:
Supportive Care Supplemental oxygen is indicated if SpO2 falls
persistently below 90% in previously healthy infants.
Supportive care remains the cornerstone of treatment of Oxygen may be discontinued if SpO2 is at or above 90%
children with bronchiolitis. It includes maintenance of and the infant is feeding well and has minimal respiratory
adequate hydration, provision of respiratory support as distress.
necessary, and monitoring for disease progression.
As the childs clinical course improves, continuous
A. Fluid administration measurement of SpO2 is not routinely needed because it
leads to unnecessarily prolonged oxygen supplemen-
Children with bronchiolitis are at an increased risk of tation and hospital stay [34, 35].
dehydration because of their increased needs (related to
fever and tachypnea) and reduced oral acceptance. Continous Positive Airway Pressure
Clinicians should carefully assess hydration and ability In severe bronchiolitis early intervention in form of
to take fluids orally. Children having dehydration or continuous positive airway pressure (CPAP) has been used
difficulty in feeding safely because of respiratory to prevent mechanical ventilation [36]. CPAP helps in
distress should be given intravenous fluids [1]. For recruitment of collapsed alveoli by opening terminal
children who can tolerate enteral feedings, small frequent bronchioles. Airway resistance in terminal airways is
feedings or orogastric or nasogastric feedings may be reduced with CPAP and also there is decreased air
used to prevent dehydration. Children with bronchiolitis trapping, hyperinflation and work of breathing [37]. A
are also at an increased risk of fluid retention (and systematic review in 2011 on use of CPAP in acute
subsequent pulmonary congestion) due to excessive bronchiolitis concluded that the evidence supporting the
antidiuretic hormone production, so urine output should use of CPAP to reduce PCO2 and respiratory distress in
be carefully monitored [1,32]. bronchiolitis was of low methodological quality, and there
B. Nasal Decongestion was no conclusive evidence that CPAP reduced the need
for intubation [36]. However, a recent randomised trial
Saline nose drops and cleaning of nostrils by gentle comparing nasal CPAP and oxygen inhalation concluded
suction may help to relieve nasal block. Instilling saline that CPAP resulted in rapid reduction in work of breathing
drops and cleaning nostrils by gentle suction before and improvement in the respiratory distress score at 6 hour.
feeding may be helpful. Parents should be educated The improvement was proportional to the initial severity,
about instilling saline drops and cleaning secretions suggesting that, early use of CPAP in severe forms of the
from nose before discharge from hospital [33]. disease may be beneficial [38]. CPAP level of 7 cm of
water was associated with greatest improvement [39].
C. Respiratory support Current evidence is inconclusive regarding routine use of
Supplemental oxygen CPAP in children with acute bronchiolitis. More studies
with adequate numbers and better quality are required.
The major consequence of airway obstruction and
Mechanical Ventilation
concomitant poor distribution of ventilation and
perfusion in bronchiolitis is hypoxemia. Humidified The major indications for intubation and mechanical
oxygen should be administered to hypoxemic infants by ventilation are clinical deterioration (worsening
any technique familiar to the nursing personnel (nasal respiratory distress, listlessness, and poor peripheral
cannula, face mask, or head box). Pulse oximetry is the perfusion), apnea and/or bradycardia, and hypercarbia.
most commonly used tool to decide about oxygen Infants do not usually require intubation for oxygenation
supplementation. The cut-off level of oxyhemoglobin alone. In a prospective cohort study done in children
saturation (SpO2), at which supplementation should be admitted with RSV LRTI, approximately 9% of patients
started or stopped varies widely among different required mechanical ventilation [19]. The median
guidelines and different centres. Data are lacking to duration of mechanical ventilation is relatively short,
support the use of a specific SpO2 cut-off value [1, 33]. about 5 days, but protracted courses of ventilation may
In the most recent clinical practice guideline of the be required [40].
American Academy of Pediatrics (AAP) [1], the
Chest Physiotherapy
following options (options define courses that may be
taken when either the quality of evidence is suspect or Chest physiotherapy clears the excessive respiratory

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secretions, and thus helps to reduce airway resistance, associated with adverse effects (increased heart rate)
the work of breathing, and enhances gas exchange. [44].
Inspite of this theoretical advantage, a systematic review
Based on the current evidence it is not easy to decide
of nine randomized trials concluded that chest
about bronchodilator uses. It is also difficult to
physiotherapy using vibration and percussion or passive
distinguish bronchiolitis from viral infection associated
expiratory techniques did not improve respiratory
wheezing or multi-trigger wheeze. In the latter condition,
parameters, reduce supplemental oxygen requirement, or
broncho-dilators may improve clinical outcome.
reduce length of hospital stay [41]. The use of chest
Therefore, we consider a trial of bronchodilator with
physiotherapy is discouraged in children with
careful monitoring. Choice of bronchodilator may be
bronchiolitis, because it may increase the distress and
based on personal or family history of atopy or asthma; if
irritability of ill infants.
present, salbutamol inhalation may be given. In absence
Bronchodilators of it, a trial of epinephrine inhalation may be given.
Further doses of either medications may be continued
Routine use of bronchodilators in the management of only on documentation of improvement.
bronchiolitis is debatable. One of the major problems
with interventional trials evaluating bronchodilators in Steroids
infants and children with bronchiolitis is the difficulty in Systemic corticosteroids
distinguishing bronchiolitis from virus-induced
wheezing and asthma. Children in the latter categories, Initial studies of the treatment of bronchiolitis with
who often respond to bronchodilators (and gluco- corticosteroids suggested that steroids might favourably
corticoids), are invariably included in bronchiolitis influence mortality and morbidity. However, large
trials, making it difficult to determine the effects of these controlled studies have failed to demonstrate any
medications in children with true viral bronchiolitis. significant clinical effect. A meta-analysis evaluating the
use of systemic glucocorticoids (oral, intramuscular, or
In a meta-analysis of 28 trials (1912 participants) intravenous) and inhaled glucocorticoids for acute
comparing bronchodilators other than epinephrine bronchiolitis in children (0 to 24 months of age) included
(included salbutamol, terbutaline, ipratopium) with 17 trials with 2596 patients [45]. In pooled analyses, no
placebo, there were no significant differences in significant differences were found in hospital admission
improvement in oxygenation, hospitalization rate, or rate, length of stay, clinical score after 12 hours, or
duration of hospitalization. A modest improvement in hospital readmission rate. Hence, it is recommended not
clinical scores was noted in the treated outpatients; to use glucocorticoids in healthy infants and young
however, this small improvement in clinical scores must children with a first episode of bronchiolitis. Another
be weighed against the costs and adverse effects of meta-analysis (of 3 studies) studied the role of systemic
bronchodilators [42]. steroids in critically ill children with bronchiolitis [46].
It was found that systemic corticosteroid showed no
Another meta-analysis of 19 trials (2256
overall effect on duration of mechanical ventilation.
participants) compared nebulized epinephrine with
placebo or other bronchodilators [43]. Epinephrine Corticosteroids plus Epinephrine
versus placebo among outpatients showed a significant
A possibility of synergy between epinephrine and
reduction in admissions at Day 1 but not at Day 7 post-
glucocorticoids has also been evaluated. There is one
emergency department visit. Epinephrine versus
trial which suggested that administration of epinephrine
salbutamol showed no differences among outpatients for
and glucocorticoids in the outpatient setting prevents
admissions at Day 1 or 7. Although epinephrine was
hospitalization within seven days [47]. In this
associated with decreased length of stay compared with
multicentre trial, there was a reduction in hospitalization
salbutamol, epinephrine did not decrease length of stay
rates in the group that received dexamethasone and 2
when compared with placebo. This review demonstrated
doses of epinephrine by nebulizer as compared with
the superiority of epinephrine compared to placebo for
those who were treated with placebo (17.1% vs 26.4%).
short-term outcomes for outpatients, particularly in the
Number needed to prevent one admission was 11.
first 24 hours of care, but there was no evidence to
However, the strength of evidence was low and after
support the use of epinephrine for inpatients.
adjustment for multiple comparisons, the difference did
Oral bronchodilators should not be used in the not reach statistical significance. This may have a
management of bronchiolitis. They neither shorten potential role in future treatment algorithms. Till
clinical illness nor improve clinical parameters, but are additional studies shows similar results and safety is

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established, this combination therapy may be review of seven trials involving 581 infants (282
considered under evaluation. inpatients, 65 outpatients and 234 emergency
department patients) with acute bronchiolitis found that
Inhaled Corticosteroids (ICS)
nebulisation with 3% saline results in a significantly
Use of ICS during acute bronchiolitis has been proposed shorter length of hospital stay as well as a lower clinical
to prevent post-bronchiolitic wheezing. A systematic score as compared to nebulisation with 0.9% saline [53].
review of 5 studies involving 374 infants did not The potential side effects, principally acute
demonstrate an effect of ICS, given during the acute bronchospasm, remain a concern with nebulized
phase of bronchiolitis, in the prevention of recurrent hypertonic saline. In six of the seven trials included in
wheezing following bronchiolitis [48]. An additional the above mentioned review, patients received
RCT involving 243 infants with RSV-related LRTI did hypertonic saline inhalation in conjunction with
not find any effect of inhaled corticosteroids on recurrent bronchodilators and no significant adverse events
wheeze [49]. Hence, there is no evidence for use of related to 3% saline inhalation were reported [54].
inhaled corticosteroids to prevent or reduce post-
A recent randomized controlled trial reported that
bronchiolitis wheezing after RSV bronchiolitis.
high volume normal saline was as effective as 3% saline
Antibiotics in children with mild bronchiolitis. It may be inferred
that improved clearance of mucus in airway may be
Unnecessary use of antibiotics is associated with function of total mass of NaCl rather than concentration
increased cost of treatment, adverse reactions and of NaCl [55]. Hypertonic saline inhalation may be
development of bacterial resistance in community/ considered as potential treatment for bronchiolitis.
geographic region. In children with bronchiolitis and However, there are several unanswered questions related
fever, the risk of secondary bacterial infection is low, to its use including optimal volume, concentration of
therefore, routine use of antibiotics is not recommended. saline, frequency of administration and effective device.
It is recommended that antibiotics should be used only in Its use cannot be recommended till all these are
children having specific indications of coexistence of a addressed by further studies.
bacterial infection [1]. Presence of infiltrates or
alelectasis on X-ray film may not indicate bacterial Inhaled Furosemide
infection. Clinical setting, with consolidation on X-ray
Furosemide inhalation in acute bronchiolitis has been
film may indicate a possibility of bacterial pneumonia in
proposed with a hypothesis that it may improve outcome
infants with bronchiolitis [50].
by acting on airway smooth muscle, airway vessels,
A systematic review including five studies (543 electrolytes and fluid transport across respiratory
participants) did not find significant benefits for use of mucosa, and reducing airway inflammation. One RCT
antibiotics in acute bronchiolitis. However, the review (32 participants) studied the effect of inhaled furosemide
indicated a need for research to identify a subgroup of in hospitalized infants with bronchiolitis, and recorded
patients who may benefit from antibiotics [51]. One no significant clinical effects in these infants [56].
small study (21 participants) which was included in this Therefore, there is no evidence for use of inhaled
review, compared clarithromycin for 3 weeks with furosemide in the management of bronchiolitis.
placebo in children with RSV bronchiolitis. Treatment
Steam inhalation
with clarithromycin was associated with reduction in the
length of hospital stay, duration of need for oxygen, and Steam inhalation/ mist inhalation has been proposed to
readmission rates. Clarithromycin was proposed to have improve airway clearance of mucus and outcome of acute
a possible immunomodulatory effect. More well- bronchiolitis. Being less expensive and easily available,
planned studies to clarify role of macrolides in acute steam was considered to be a suitable intervention in low
bronchiolitis are required [52]. income countries. A systematic review could identify
only one RCT (156 participants) that compared role of
Hypertonic Saline
nebulised salbutamol, nebulised saline and mist in a tent
Aerosolized hypertonic saline has been proposed as a in children with acute bronchiolitis. [57,58]. Group of
therapeutic modality for acute bronchiolitis. Hypertonic children receiving salbutamol inhalation showed
saline may reverse some pathophysiological significant improvement in respiratory distress symptom
abnormalities in acute bronchiolitis by decreasing (RDS) score but there was no improvement in children
epithelial edema, improving elasticity and viscosity of receiving mist in a tent or nebulised saline. In view of
mucus and thus improving airway clearance. A Cochrane limited experience with mist/ steam inhalation, more

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studies are required to prove or disapprove role of steam approved for use in bronchiolitis. Numerous other drugs
inhalation in acute bronchiolitis. are undergoing trials for use against RSV, which is the
Leukotriene receptor antagonists (Montelukast) most common cause of bronchiolitis. The immuno-
suppressive agent leflunomide has been shown to exert
Clinical symptoms and post-bronchiolitis cough and potent antiviral and anti-inflammatory activity against
wheeze are attributed to the increased cysteinyl RSV in experimental animal models [66]. Another
leukotrienes in airway secretions of children with promising group of drugs currently under investigation
bronchiolitis during acute phase as well as in short term are the small molecule fusion inhibitors (TMC353121,
follow up. Randomized trials of montelukast as a CL387626, RFI-641, JNJ-2408068 etc) that inhibit viral
treatment for acute bronchiolitis have had conflicting fusion by interacting with the RSV F protein (RSV F
results [59,60]. Randomized trials of montelukast for the protein mediates the fusion of viral envelope with host
prevention of airway reactivity and post-bronchiolitis cell membrane) [67,68]. Fusion inhibitors have also
respiratory symptoms have also had inconsistent results been shown to be effective against hMPV in
[61,62]. However, in the largest trial (979 participants), experimental animals, and some researchers have
use of montelukast for 24 weeks was not associated with suggested a possibility for use of these fusion inhibitors
improvement in post-bronchiolitis respiratory symptoms for early treatment in an epidemic context. However,
[62]. In view of these studies, montelukast is currently more studies are needed to characterize the best delivery
not recommended for treatment of bronchiolitis or for mode, dosage, and schedule of administration for these
prevention of airway reactivity after bronchiolitis. fusion inhibitors [69].
Heliox Surfactant
Heliox (mixture of helium and oxygen) may improve
In severe bronchiolitis there may be secondary surfactant
alveolar ventilation as it flows through airways with less
insufficiency suggesting possible role of administration
turbulence and resistance. This may reduce work of
of exogenous surfactant [64]. A meta-analysis (included
breathing and improve oxygenation in respiratory illness
three RCTs with total 79 participants) evaluated the
with moderate to severe airway obstruction including
effect of exogenous surfactant in infants and children
acute bronchiolitis. A meta-analysis of four clinical trials
with bronchiolitis requiring mechanical ventilation [70].
(84 participants), using heliox demonstrated improved
The duration of mechanical ventilation and duration of
respiratory distress scores in first hour in children with
ICU stay were significantly lower in the surfactant group
moderate to severe acute bronchiolitis. However, heliox
compared to the control group. Use of surfactant had
inhalation did not affect need for intubation and
favourable effects on oxygenation and CO2 elimination.
mechanical ventilation and length of stay in pediatric
No adverse effects and no complications were observed.
intensive care unit. There was significant heterogeneity
Current evidence suggests that surfactant therapy may
in the included studies [63].
have potential use in acute severe bronchiolitis requiring
It is concluded that evidence for beneficial role of mechanical ventilation. However, in view of few studies
Heliox in acute bronchiolitis are inadequate and more including small numbers of participants, reliable
experience is required [64]. estimates of the effects of surfactant cannot be made.
Antivirals There is a need for larger trials with adequate power and
to establish beneficial role of administration of
Ribavirin, a synthetic nucleoside analog resembling surfactant in infants with severe bronchiolitis.
guanosine, acts by inhibiting viral protein synthesis, and
has a broad antiviral effect. It is delivered as a small- PREVENTION OF BRONCHIOLITIS
particle aerosol for 18 to 20 hours per day. The drug is Acute bronchiolitis is a common infection with
relatively expensive and may lead to some risk significant financial burden on society. There is no
(teratogenic effect) to health care personnel effective therapy that can improve outcome if
administering the drug [1]. A systematic review of 10 administered early. There is need to develop preventive
RCTs (320 participants) reported no improvement in strategies. The preventive measures include general
clinical outcome of acute bronchiolitis after ribavirin use measures and specific measures (immunoprophylaxis).
[65]. Ribavirin may be considered in high risk infants
(immunocompromised and/or hemodynamically General measures
significant cardiopulmonary disease) and in infants A careful barrier nursing measures may help in
requiring mechanical ventilation [1, 46]. prevention of nosocomial (cross infection) in hospitals
Apart from ribavarin, no other antiviral is currently and intensive care units.

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Immunoprophylaxis 5. Children who are 24 months of age or younger with

hemodynamically significant cyanotic and acyanotic
Passive immunoprophylaxis using polyclonal or
congenital heart disease. This includes infants who are
monoclonal antibodies to high risk infants before RSV
receiving medication to control congestive heart
season has been documented to reduce admission rates
failure, infants with moderate to severe pulmonary
in these infants with acute bronchiolitis. However, it is
hypertension, and infants with cyanotic heart disease.
important to note that severe bronchiolitis requiring
admission in pediatric intensive care is not restricted to Palivizumab is administered intramuscularly at a
high risk group, rather majority are healthy term infants dose of 15 mg/kg monthly (every 30 days) during the
without risk factors [71]. RSV season. A maximum of 5 doses is generally
sufficient prophylaxis during one season [74]. Once a
Polyclonal antibodies child qualifies for prophylaxis, administration should
Polyclonal antibodies containing RSV IgG is prepared continue throughout the RSV season and not stop at the
from pooled plasma. This is administered by intravenous point he or she reaches any certain age. Palivizumab can
route before RSV season. The potential disadvantages be given with routine immunizations since it does not
associated with polyclonal antibodies include: need for interfere with the immunologic response to vaccines.
intravenous access; risk of transmission of blood-borne Palivizumab is not associated with an increased risk of
infections, possible interference with antibody response localized or systemic adverse events.
to routine immunization specifically live vaccines. [71]. Other monoclonal antibody (mAb) variants, which
It has also been evaluated for treatment of acute are derived from palivizumab are being evaluated in
bronchiolitis without success [72]. clinical trials for immunoprophylaxis. These include
Monoclonal antibodies Motavizumab, a second-generation mAb, and Numax-
YTE, a third-generation mAb. The advantage of Numax-
Palivizumab is a humanized mouse IgG1 monoclonal YTE is its extended half-life, thus obviating the need for
antibody directed against site A and F glycoprotein of monthly treatments [71].
RSV. It blocks the fusion of the virus to the host
epithelial cell. It reduces RSV infection associated CONCLUSIONS
hospitalization in high risk infants but does not reduce Bronchiolitis is a common respiratory tract infection in
mortality rates [1]. Economic analysis of prophylactic infancy; the commonest etiologic agent being the
administration of palivizumab have failed to show respiratory syncytial virus. The diagnosis of
savings in the net cost due to very high cost of bronchiolitis is mostly clinical, and laboratory
palivizumab. The 2006 Report of the Committee on investigations have a limited role in diagnosis and
Infectious Disease (Red Book) includes the following management. The current management primarily
indications for the use of palivizumab [73]: consists of supportive care, including hydration,
1. Children younger than 24 months of age with chronic supplemental oxygen, and mechanical ventilation when
lung disease (CLD) of prematurity who have required. At this point, there is no specific treatment for
required medical therapy for CLD within 6 months bronchiolitis for which there is a strong or convincing
before the start of the RSV season. evidence of effectiveness. It may be appropriate to
administer nebulized epinephrine or salbutamol in a
2. Infants born at 28 weeks of gestation or earlier who given child and continue these if found beneficial and
are younger than 12 months of age at the start of the discontinue if there is no effect. Corticosteroids are
RSV season. judged to be ineffective and not indicated for these
3. Infants born at 29 to 32 weeks of gestation who are infants. In absence of an effective vaccine, Palivizumab,
younger than 6 months of age at the start of the RSV a monoclonal antibody against RSV may be considered
season. for passive immunoprophylaxis in certain high risk
infants before the RSV season.
4. Infants born between 32 and 35 weeks of gestation,
Contribution: All authors were involved in literature search,
who are younger than 6 months of age at the start of manuscript writing and revisions. SKK will act as guarantor.
the RSV season and have 2 or more of the following Funding: None; Conflict of interest: None stated.
risk factors: child care attendance, school-aged
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