SPECIAL ISSUE ARTICLE

Bronchiolitis: Safely Doing Less Is the

Next Big Thing
Amy Weis, MD; and Claire Hailey, MD

ABSTRACT colonization of the nasopharynx with

Bronchiolitis is a viral lower respiratory tract infection primarily affecting children viruses as well as prolonged postinfec-
younger than 2 years; a common cause of health care encounters, including hospitaliza- tion viral shedding, making determi-
tion; and a considerable economic burden for health care systems in the United States nation of causative virus difficult.2
and worldwide. The American Academy of Pediatrics (AAP) most recently updated its Before the coronavirus disease 2019
bronchiolitis guideline in 2014 and reaffirmed supportive care as the mainstay of treat- (COVID-19) pandemic, the seasonal-
ment. Despite these recommendations, there is still significant variability in care pro- ity for RSV was consistent, with onset
vided for these children, especially in bronchodilator usage, radiography, and high-flow typically in mid-September and peak-
nasal cannula. Since the 2014 AAP guideline, many pediatric hospitalists have under- ing from December to mid-February.
taken quality initiatives to improve the adherence to published guidelines, yet a large Owing to COVID-19 mitigation mea-
gap remains between what is recommended and what is practiced. This article presents sures, there was a noticeable decrease
research on the efficacy of common interventions as well as an introduction to diagnos- in both RSV and influenza cases in
tics and treatments potentially on the horizon. [Pediatr Ann. 2024;53(6):e223–e228.] many countries for the typical 2020
and 2021 seasons. However, RSV cir-

B
ronchiolitis is a clinical syn- into the lower respiratory tract, with culation increased in spring of 2021,
drome of viral upper and low- significant mucus production causing peaking in November, followed by a
er respiratory tract infection obstruction of the airways, leading to gradual reduction in December 2022.
(LRTI), and the American Academy wheezing, increased work of breathing, Interestingly, the epidemiology of
of Pediatrics (AAP) defines bronchi- and often, hypoxia. Distal air trapping other viruses was also affected. Hu-
olitis as a “constellation of signs and causes hyperinflation and localized at- man rhinovirus-enterovirus peaked
symptoms including a viral upper electasis. The most common causative in autumn and spring during the 2021
respiratory tract prodrome followed organism is respiratory syncytial virus and 2022 seasons, whereas previous
by increased respiratory effort and (RSV), followed by rhinovirus. Influ- peaks had been noted in winter. A
wheezing in children under the age of enza, human metapneumovirus, en- cross-sectional study by Remien et al.3
two.”1 Transmission between people terovirus, coronavirus, parainfluenza examining 41 large children’s hospitals
by direct inoculation or via inhalation virus, and adenovirus are also com- demonstrated 75% more inpatient ad-
of large droplets triggers a robust im- mon causes. Coinfection is common, missions for bronchiolitis during the
mune response with an influx of natu- and up to 30% of hospitalized children 2022 and 2023 seasons compared with
ral killer cells, lymphocytes, and gran- with bronchiolitis have evidence of median hospitalizations during the
ulocytes. Upper respiratory symptoms several viruses in their nasopharynx at 2010 and 2019 seasons. The patients
are followed by spreading of infection time of illness. However, there can be were often older and had more severe
disease, requiring more intensive care
Amy Weis, MD, is the Section Chief, Pediatric Hospital Medicine, Inova L. J. Murphy Children’s Hospi- unit (ICU) admissions, and were more
tal; and the Medical Director, Pediatric Unit, August Iliff Nursing and Rehabilitation. Claire Hailey, MD, likely to require noninvasive ventila-
is a Clinical Associate Professor, Pediatric Hospital Medicine, Department of Pediatrics, The University tion.3 Peak admissions were noted in
of Chicago. November 2022, suggesting bronchiol-
Address correspondence to Claire Hailey, MD, The University of Chicago, 5841 S. Maryland Avenue, itis admissions had not yet returned to
MC6082, Chicago, IL 60637; email: [email protected]. prepandemic patterns.3
Disclosure: The authors have no relevant financial relationships to disclose. There is considerable economic
doi:10.3928/19382359-20240407-07
burden associated with bronchiolitis,

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 SPECIAL ISSUE ARTICLE

including primary care visits, emer- radiation, and leads to unnecessary anti- no benefit of inhaled bronchodilators;
gency department (ED) use, and hospi- biotic use. Yet studies have demonstrated however, some researchers8-10 have
talization, as well as substantive indirect viral respiratory infections can stimulate shown that a subset of patients demon-
costs such as lost wages from work for an increase in bacterial load;6 17.5% to strate bronchodilator-responsive phe-
caregivers. Despite the recommenda- 44% of patients with severe bronchiolitis notypes and argue that bronchodilators
tions for supportive care in the most requiring ICU admission demonstrate should be used in these phenotypes. In-
recent AAP guideline, there is substan- bacterial growth in lower airway sam- fants with recurrent wheezing illnesses
tial use of bronchodilators, hypertonic ples.7 One study by the AAP Subcom- may demonstrate a “pro-asthmatic im-
saline, racemic epinephrine, inhaled and mittee on Diagnosis and Management mune response,” describing a TH2 cell–
systemic glucocorticoids, and oxygen of Bronchiolitis7 determined the overall mediated immune response causing
delivery, including low-flow and high- incidence of pneumonia (both commu- increased inflammatory interleukins
flow nasal cannula (HFNC). An analysis nity-acquired and hospital-acquired) known for remodeling the airway. This
by Sander et al.4 demonstrated that in was 15.7%. The most common organ- response may be a risk factor in subse-
the United States, bronchiolitis-related ism isolated was Haemophilus influen- quent wheezing development.8-10 Possi-
annual hospitalization expenses exceed zae, followed by Moraxella catarrhalis, bly, this subset of patients would benefit
$500 billion. Staphylococcus aureus, Streptococcus from a trial of bronchodilators, yet evi-
This article will focus on the current pneumoniae, and Klebsiella spp.6 Grow- dence is insufficient to support broncho-
literature regarding the comprehensive ing evidence supports the association dilator use in bronchiolitis at this time.
recommendations in the 2014 AAP between increased disease severity and
bronchiolitis guideline. The concept of polymicrobial infection, leading to in- RACEMIC EPINEPHRINE
“safely doing less” is ideal for bronchi- creased length of hospitalization and a Studies have suggested racemic epi-
olitis, especially for common interven- higher degree of disease severity.7 Thus, nephrine administered in the outpatient
tions such as chest X-rays, bronchodi- current evidence supports the AAP rec- setting could decrease the need for inpa-
lators and other breathing treatments, ommendations to reserve chest X-rays tient care, but at this time, no evidence
HFNC, and continuous pulse oximetry. for patients with severe respiratory dis- supports the use of racemic epinephrine
The most recent review of bronchiolitis tress requiring admission to the ICU, in the inpatient setting, as shown by a
diagnosis and management in Pediatric those with possible underlying cardiac 2011 Cochrane review demonstrating no
Annals (2017) presented and answered or chronic lung disease, or those with clinically relevant improvement in clini-
several questions to help guide general a high clinical suspicion of bacterial cal status or reduction in hospital stay
pediatricians and pediatric hospitalists pneumonia.1 for infants younger than 12 months.11
in the care of patients with suspected
bronchiolitis.5 This article will discuss BRONCHODILATORS NEBULIZED HYPERTONIC SALINE
evidence published since that review, The 2014 AAP1 guideline strongly Ongoing evidence for hypertonic
focusing on ED and inpatient manage- recommends against the routine use of saline in bronchiolitis is mixed. A 2023
ment and highlighting new preventive albuterol or salbutamol in bronchiolitis, Cochrane review concluded hypertonic
and treatment modalities such as the a change from the prior AAP guide- saline use in outpatient and ED settings
new vaccine and monoclonal antibody line from 2006, which included an op- may decrease the risk for hospitaliza-
against RSV. tion for a carefully monitored trial of tion and may modestly reduce length
alpha-adrenergic or beta-adrenergic of hospital stay for bronchiolitis, but the
CHEST X-RAYS AND BACTERIAL medication. Because of the robust evi- certainty of evidence for the reviewed
SUPERINFECTIONS dence demonstrating no benefit and no studies was “low to very low for all out-
Because the radiographic findings in well-established objective method to comes.”12 A meta-analysis concluded hy-
bronchiolitis do not correlate with ill- determine clinical response to broncho- pertonic saline provided limited benefit
ness severity, the 2014 AAP guideline dilators in bronchiolitis, this monitored in patients with bronchiolitis.13
recommends against the routine use of trial was no longer included in the 2014
chest X-ray in children presenting with guideline.1 STEROIDS
clinical bronchiolitis. Routine radiogra- Most publications since the 2014 Several studies that have been re-
phy increases cost, exposes children to AAP guideline continue to demonstrate viewed by Cochrane have examined

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 SPECIAL ISSUE ARTICLE

the role of systemic steroids in the HFNC was not addressed in the 2014 CONTINUOUS PULSE OXIMETRY
management of acute bronchiolitis AAP guideline for bronchiolitis. Based on extrapolations from stud-
to reduce acute symptoms and post- Studies have safely demonstrated ies demonstrating that transient in-
bronchiolitis wheezing.14,15 To date, the usage of HFNC in settings outside termittent hypoxia does not cause
as described in a review by Fernandes of the pediatric ICU. A multicenter adverse consequences such as intel-
et al.,14 evidence does not support the randomized controlled trial (RCT) by lectual disability or behavioral distur-
use of either systemic or inhaled glu- Franklin et al.21 demonstrated infants bances, the 2014 AAP guideline states
cocorticoids in the treatment of acute with bronchiolitis treated outside the that clinicians may choose not to use
bronchiolitis or for the prevention of ICU with high-flow oxygen therapy continuous pulse oximetry in children
postbronchiolitis wheezing. had lower rates of escalation of care with bronchiolitis. However, this is
compared with those receiving stan- classified as a weak recommendation.
CHEST PHYSIOTHERAPY dard oxygen therapy; however, there The use of continuous Spo2 monitor-
Chest physiotherapy (CPT) refers were no observed significant differ- ing is common and highly variable
to therapeutic techniques designed for ences in duration of hospital stay or even in children with bronchiolitis
facilitation of clearance of secretions, the duration of oxygen therapy. Kepre- not requiring supplemental oxygen.
resolution of atelectasis, and optimi- otes et al.22 published a study demon- A cross-sectional study by Stoeck et
zation of air exchange. Cochrane has strating HFNC did not significantly al.25 found a correlation between high
published articles16,17 on the efficacy of decrease the time on oxygen therapy bronchiolitis admission burden and
CPT in bronchiolitis, most recently in in comparison with standard oxygen lower rates of unnecessary pulse ox-
April 2023,18 and the reviewed litera- therapy, overall length of stay, or pe- imetry monitoring in bronchiolitis.
ture demonstrates with high-certainty diatric ICU transfer rate, ultimately Research such as that by Mendlowitz
evidence that CPT does not confer any questioning whether HFNC has a role et al.26 has demonstrated that reliance
significant benefits in bronchiolitis. In in modifying the disease process and on oximetry as a major determinant in
fact, high-certainty evidence shows postulating that HFNC may be better the decision to hospitalize infants with
forced expiratory CPT techniques can served as rescue therapy to decrease mild to moderate bronchiolitis is asso-
lead to severe adverse effects, includ- the number of patients requiring in- ciated with significantly greater costs.
ing increased risk of vomiting and tensive care. A multicenter retrospec-
worsening of clinical severity scores.19 tive study by Coon et al.23 demonstrat- HYDRATION
ed a paradoxical increase in ICU use The AAP guideline recommends
HIGH-FLOW NASAL CANNULA after implementation of non–ICU- nasogastric or intravenous fluids for
Severe bronchiolitis leads to hy- based HFNC protocols; additionally, infants who cannot maintain hydra-
poxia, hypercarbia, and increased there was no change in overall length tion orally. A 2021 Cochrane review
work of breathing, which may require of stay or need for mechanical venti- found 615 unique records of children
treatment with positive-pressure ven- lation. Small studies demonstrated a up to age 2 years who were hospital-
tilation. HFNC delivers humidified decrease in intubation rates after the ized with bronchiolitis and required
and heated air blended with oxygen. initiation of HFNC; however, this de- fluid therapy. Included were two RCTs
There are different theories regard- crease was not noted in other RCTs that demonstrated both enteral tube
ing the mechanism of reduction of comparing HFNC with standard oxy- feeding and intravenous fluid hydra-
work of breathing in HFNC, includ- gen therapy, as reported by Kalburgi tion resulted in similar lengths of hos-
ing washout of nasopharyngeal dead and Halley.24 The optimal role for pital stay.27
space, unidirectional gas flow in the HFNC in bronchiolitis remains un-
upper airway, positive end-expirato- clear, but at this time, the available re- ROLE OF VIRAL TESTING
ry pressure (PEEP) generation, and search supports that its usage should One of the implicit assumptions
aid in secretion clearance. However, be reserved as rescue therapy for pa- in the idea of “safely doing less” in
the amount of PEEP generated is un- tients with severely increased work of clinical bronchiolitis is that all viruses
clear and depends on multiple fac- breathing and that protocols should cause the same illness phenotype. New
tors, including flow rate, cannula size, reflect weight-based dosing with flows research such as that by Rodríguez-
and degree of air leak.20 The usage of that could promote PEEP generation. Martínez et al.10 is challenging this

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 SPECIAL ISSUE ARTICLE

assumption and examining both infants, especially those at high risk, Preliminary data conflict on whether
patient-specific characteristics such receive nirsevimab. As of September this combination will decrease need
as family history of atopy and virus- 2023, the Centers for Disease Control for admission or improve length of
specific clinical presentations. An ar- and Prevention (CDC) recommends stay in patients after admission. Oth-
ticle by Rodríguez-Martínez et al.10 nirsevimab for infants younger than er current studies are also looking at
concluded that in comparison with 8 months shortly before or during combining racemic epinephrine and
patients who have RSV, patients who their first RSV season if the mother hypertonic saline.38 The hypothesis
have bronchiolitis caused by rhino- did not receive an RSV vaccine during is that these two medications may act
virus tend to have a shorter hospital pregnancy, the mother’s RSV vaccina- synergistically on bronchodilation,
length of stay, are more likely to be tion status is unknown, or the infant vasoconstriction, and airway edema.
treated with steroids, and have an in- was born within 14 days of maternal There is some low-quality evidence
creased subsequent risk of asthma. In RSV vaccination.31 Nirsevimab is also that this combination may decrease
fact, according to Cai et al.,28 stud- recommended for children age 8 to length of stay in inpatients. However,
ies have demonstrated patients with 19 months if they are American In- the recent network meta-analysis by
bronchiolitis during rhinovirus-pre- dian or Alaska Native, have chronic Elliott et al.38 ranked confidence in
dominant months have an estimated lung disease of prematurity requiring this evidence as very low, given the
25% increased risk of early childhood medical support during the 6 months heterogeneity of studies and the im-
asthma compared with risk during before the start of their second RSV precision in estimate of effect. Com-
RSV-predominant months. However, season, are severely immunocompro- bination therapy with oral steroids
not all studies support this conclu- mised, or have severe cystic fibrosis.31 and beta-agonists—specifically, dexa-
sion. For example, Hunderi et al.29 Nirsevimab has been in short supply; methasone and salbutamol—is being
found recurrent wheezing at age 2 currently, it is recommended that pa- studied.36 Current trials are studying
years was not significantly associated tients who qualify for palivizumab the effects of 5% and 7% hypertonic
with rhinovirus or RSV. At this time, should receive it when nirsevimab is saline as well as hypertonic saline in
there is not enough evidence to rec- not available.32 combination with salbutamol.39,40 As
ommend the routine use of viral test- of now, there is no consistent evidence
ing in bronchiolitis. Maternal RSV Vaccination for a clinically significant improve-
Pfizer’s bivalent RSVpreF vaccine ment in length of stay or illness dura-
PREVENTION (ABRYSVO) was approved by the FDA tion for patients treated with combina-
Nirsevimab in August 2023 for active immuniza- tion therapy, but there will be new data
Nirsevimab is a monoclonal anti- tion of pregnant individuals at 32 to on the horizon. Other areas of ongoing
body the US Food and Drug Admin- 36 weeks’ gestation for prevention of research are examining how to best dis-
istration30 (FDA) recently approved to LRTI caused by RSV in infants from tinguish between viral illness and bac-
prevent serious illness caused by RSV birth through age 6 months.33 The terial superinfection, including the role
in infants younger than age 1 year who CDC34 recommends the RSVpreF vac- of lung ultrasound in diagnosing bacte-
are born during or shortly before RSV cine for pregnant people, to be given rial pneumonia; usage of inflammatory
season and in children up to age 24 as a single dose during weeks 32 to markers such as fever, procalcitonin, and
months who are at risk of severe ill- 36 of pregnancy during September CRP; and usage of novel inflammatory
ness from RSV through their second through January, to protect their ba- markers such as MxA1 and HMGB1.
RSV season. Phase 2 and 3 clinical tri- bies from severe RSV illness. Stay tuned!
als of nirsevimab demonstrated 79%
efficacy in preventing medically at- On the Horizon CONCLUSIONS
tended RSV-associated LRTI, 80.6% Many studies are currently looking The standards for diagnosis and
efficacy in preventing hospitalization at the efficacy of combining modali- management of bronchiolitis have not
for RSV-associated LRTI, and 90% ef- ties for managing bronchiolitis.11,35-37 changed since the most recent AAP
ficacy in preventing ICU admission Combinations of racemic epineph- guideline was published in 2014, yet
for RSV-associated LRTI.31 In August rine and dexamethasone in the out- physicians and providers do not always
2023, the AAP32 recommended that all patient setting are being studied.35 follow the AAP recommendations.

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 SPECIAL ISSUE ARTICLE

Overuse of X-rays, bronchodilators, and trial basis?. Allergol Immunopathol (Madr). tients between 0 and 24 months old. Cochrane
2021;49(1):153-158. https://doi.org/10.15586/ Database Syst Rev. 2023;4(4):CD004873.
steroids remains. Quality improvement aei.v49i1.12 https://doi.org/10.1002/14651858.CD004873.
initiatives have aligned the care by many 9. Rodriguez-Martinez CE, Nino G, Castro- pub6
Rodriguez JA, Perez GF, Sossa-Briceño MP, 20. Ejiofor BD, Carroll RW, Bortcosh W, Kac-
providers with the standard recommen- Buendia JA. Cost-effectiveness analysis of marek RM. PEEP generated by high-flow
dations, yet additional research and on- phenotypic-guided versus guidelines-guided nasal cannula in a pediatric model. Respir
bronchodilator therapy in viral bronchiolitis. Care. 2019;64(10):1240-1249. https://doi.
going quality improvement efforts could Pediatr Pulmonol. 2021;56(1):187-195. https:// org/10.4187/respcare.06470 PMID:31088986
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JA, Nino G, Midulla F. The impact of vi- gen therapy in infants with bronchiolitis.
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