REVIEW ARTICLE
The Problematic 2014 American Academy of Pediatrics
Bronchiolitis Guidelines
Larry B. Mellick, MD*† and Juan Gonzalez, DO†
Abstract: The 2014 American Academy of Pediatrics bronchiolitis guide-
lines do not adequately serve the needs and clinical realities of front-line clini-
cians caring for undifferentiated wheezing infants and children. This article
describes the clinical challenges of evaluating and managing a heterogeneous
disease syndrome presenting as undifferentiated patients to the emergency de-
partment. Although the 2014 American Academy of Pediatrics bronchiolitis
guidelines and the multiple international guidelines that they closely mirror
have made a good faith attempt to provide clinicians with the best evidence-
based recommendations possible, they have all failed to address practical,
front-line clinical challenges. The therapeutic nihilism of the guidelines and
the dissonance between many of the recommendations and frontline realities
have had wide-ranging consequences. Nevertheless, newer evidence of thera-
peutic options is emerging and forecasts hope for more therapeutically opti-
mistic recommendations with the next revision of the guidelines.
Key Words: bronchiolitis, RSV, respiratory syncytial virus, rhinovirus,
wheezing, reactive airway disease
(Pediatr Emer Care 2019;00: 00–00)
T he 2014 American Academy of Pediatrics (AAP) bronchiol-
itis guidelines are a revision of the 2006 AAP guidelines and
represents careful analysis of the literature by expert academic
clinicians and researchers.1,2 The AAP guidelines also mirror
closely a number of international guidelines that provide similar
evidence-based recommendations for the evaluation and management
of the bronchiolitis patient.3–6 The stated goal of the guideline is to
provide an evidence-based approach to the diagnosis, management,
and prevention of bronchiolitis in children from 1 month to 23 months
of age. In addition, the guideline was intended for use by the spec-
trum of health care providers who care for these children.1
The definition of bronchiolitis used in the guideline is that of
the Agency for Healthcare Research and Quality.1 Bronchiolitis is
a disorder commonly caused by a viral lower respiratory tract infec-
tion in infants. Bronchiolitis is characterized by acute inflammation,
edema, and necrosis of epithelial cells lining small airways and
increased mucus production. Signs and symptoms typically begin
with rhinitis and cough, which may progress to tachypnea, wheez-
ing, rales, use of accessory muscles, and/or nasal flaring.7
In this article, we intend to provide alternative viewpoints based
on current literature, explain the perspective of many practicing
clinicians, and include the evidence currently available supporting
a number of practices that are not currently accepted by the 2014
practice guidelines.
Not only is it our opinion that the 2014 AAP guidelines are
now outdated in regards to therapeutic options for bronchiolitis,
we believe that they have failed to acknowledge the unique clinical
From the Departments of *Emergency Medicine, and †Pediatrics, Children's &
Women's Hospital, University of South Alabama, Mobile, AL.
Disclosure: The authors declare no conflict of interest.
Reprints: Larry B. Mellick, MD, Department of Emergency Medicine,
Children's & Women's Hospital, University of South Alabama, 2451 USA
Medical Center Dr, 10th Floor, Suite L, Mobile, AL 36617-2293
(e‐mail: lmellick@health.southalabama.edu).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0749-5161
Pediatric Emergency Care • Volume 00, Number 00, Month 2019
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
challenges of the practicing clinician. We also believe that current
evidence now supports some of the therapeutic interventions
rejected by the 2014 guidelines. By presenting an evidence-based
discussion of the clinical challenges unique to practitioners caring
for bronchiolitis syndrome patients, we hope to generate a national
conversation that might influence subsequent iterations of the AAP
bronchiolitis guidelines.
IT'S NOT THAT SIMPLE
A Disease Syndrome
Bronchiolitis is a disease syndrome, not a specific disease,
and more than 1 infectious agent is responsible for this syndromic
presentation.8–12 In addition, when there are multiple responsible
infectious agents, the potential exists for variations in presenta-
tion and therapeutic responses influenced by patient age and
genetic vulnerabilities.9,13–19
Different Clinically Heterogeneous Conditions
Even though bronchiolitis has generally been considered a
single disease, a growing body of literature suggests that it is actu-
ally a syndrome of significant heterogeneity.12,13,17,18 Dumas
et al13 describe 4 heterogeneous profiles, and several profiles were
more commonly treated with bronchodilators and corticosteroids.
Jartti et al9 state that clinically, pathophysiologically, and even ge-
netically 3 main clusters of patients can be identified among chil-
dren suffering from severe bronchiolitis or first wheezing episode.
These 3 clinically heterogeneous conditions are the following: (a)
respiratory syncytial virus (RSV)–induced bronchiolitis, (b) rhi-
novirus (RV)-induced wheezing, and (c) wheeze due to other vi-
ruses, characteristically likely to be less frequent and severe.9,13
The importance of distinguishing between these partially overlap-
ping patient groups is that they are likely to respond to different
treatments.9,13,17–21 Specifically, 2 of the 3 clusters may very well
respond to some of the therapies recommended against by the
2014 AAP guidelines. Whereas the RSV predominates as the
cause of bronchiolitis under 12 months of age, the clinically
and genetically different RV becomes predominate in the second
year of life.9,14,17,22 The other common viruses causing bronchiol-
itis are human bocavirus and human metapneumovirus followed
by parainfluenza virus, adenovirus, coronavirus, and influenza
virus.9,12,23,24 Furthermore, coinfections, usually RSV and RV,
occur in 10% to 40% of the severe cases.9,12
Disease Spectrums
The bronchiolitis syndrome includes a spectrum of disease
severity, clinical signs, and symptoms. Early in the infectious process,
the infant infected with RSV or RV has a different clinical presenta-
tion than later in the disease. The pathophysiology of intraluminal de-
bris and edema of the airways and vasculature with established or
severe disease no doubt effects therapeutic options. In other words,
responsiveness to therapeutic options may significantly change
as a disease progresses. The severe end of the spectrum is the pa-
tients who are not responsive to therapeutic interventions and are
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Mellick and Gonzalez
admitted to the hospital or intensive care unit.13,17,19 Nevertheless,
not every infant infected with RSV or RV will develop severe
lower tract disease or even wheezing early in the course of the dis-
ease.25 It is also not clear whether there is responsiveness to bron-
chodilators or corticosteroids in the early stages of the disease.
Discharged Bronchiolitis Patients Are Different
The evidence suggests that the admitted patient cohort is differ-
ent from the outpatient or emergency department cohort or patient's
discharged home.17 Approximately 3 of 4 bronchiolitis patients
are discharged home, and the percentage of discharged patients
may actually be increasing.26,27 The wheezing infant younger than
2 years admitted to the hospital floor or pediatric intensive care unit
is included in a different cohort of patients from the 2 or 3 other in-
fants treated and discharged from the emergency department.17,28,29
Studies confirm that severity in bronchiolitis is predicted by young
age and RSV carriage.8,29–31 There is general agreement that RSV
bronchiolitis has a more severe clinical course.9,32 The admitted
population will generally be younger and sicker with RSV being
the predominate cause of the bronchiolitis syndrome.8,30,31,33 Older
patients infected with RV and other viruses (metapneumovirus, in-
fluenza, and Boca virus) are less commonly admitted.8 The RV pa-
tients resemble older children with asthma and more frequently are
treated with corticosteroids and appear to respond to such.15–17,20,21
One reason the 2014 guidelines are problematic is that its
recommendations are based heavily on research that does not
consistently represent the spectrum of undifferentiated patients
seen in the emergency department or outpatient setting. Many
of the large-scale bronchiolitis medication trials to date required
that the enrolled children be under 12 months of age and have
no history of wheezing.5,17 Consequently, these inclusion criteria
may have created homogenous study populations of children with
RSV bronchiolitis.17 Moustaki et al34 also recognized this research
characteristic and blamed it on the difficulty and variability in
clinically defining bronchiolitis. Many researchers include only
children younger than 12 months to minimize the possibility of in-
cluding children with early onset virus-induced wheezing instead
of bronchiolitis. However, the AAP guidelines acknowledged pre-
requisite for making the diagnosis of bronchiolitis is first time
wheezing in infants younger than 24 months.1–4 Although the results
of these studies are valid, other researchers suggest that the large-scale
studies should be repeated in children with RV-associated bronchiol-
itis.5,17 The often-omitted spectrum of patients includes bronchiolitis
syndrome patients with less disease severity or who responded to thera-
peutic interventions (simple nasal suctioning, hypertonic saline, nebulized
epinephrine, or albuterol) and were discharged home. Unfortunately, this
creates a research spectrum bias between the inpatient services and
the emergency department or outpatient clinics that inadvertently
influence the guideline's recommendations. In fact, if the AAP
guidelines were specifically written primarily from the perspective
of the inpatient pediatric specialist, they would be less problematic.
A Subset of Bronchiolitis Syndrome Infants
Respond to Asthma Treatments
Asthma and viral bronchiolitis are nearly indistinguishable
clinically in the infant and toddler. Both patients wheeze and have
retractions with cough and nasal congestion.35 Studies by Mansbach
et al12 demonstrated that RV-associated bronchiolitis resembles
older children with asthma, including more frequent treatment
with corticosteroids. Those authors stated that the observed dis-
ease heterogeneity should cause one to question current thinking
that the infectious etiology of severe bronchiolitis does not affect
short-term outcomes.17 Douglas and Feder35 made the observa-
tion that “we must make a choice to treat with the gold standard
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Pediatric Emergency Care • Volume 00, Number 00, Month 2019
for bronchiolitis, which is currently no treatment at all, or commit
to asthma medications of albuterol and steroids.” Other authors
have addressed the AAP guidelines concrete proscription against
the use of bronchodilators. Lin and Madikians stated, “The pro-
scription against a bronchodilator trial in the latest AAP bronchiol-
itis guideline — regardless of history of recurrent wheeze, atopy, or
family history of asthma — will need to be reconciled with both
asthma biology and more long-term efforts to modify the natural
history of childhood asthma.”36 In addition, even more directly
critical of the guidelines, Walsh and Rothenberg37,38 stated their
evidence-based opinion that the conclusion not to recommend a
trial of bronchodilator medications was flawed for multiple reasons.
However, even the 2014 AAP guidelines concede this point by
acknowledging that “…it is true that a small subset of children with
bronchiolitis may have reversible airway obstruction resulting from
smooth muscle constriction, attempts to define a subgroup of re-
sponders have not been successful to date.”1 The 2006 AAP Guide-
lines were even more conciliatory on this therapeutic option.
“Although there is no evidence from RCTs to justify routine use
of bronchodilators, clinical experience suggests that, in selected
infants, there is an improvement in the clinical condition after
bronchodilator administration. It may be reasonable to administer
a nebulized bronchodilator and evaluate clinical response.” As
long as bronchiolitis is broadly defined as the first episode of
wheezing in a child younger than 2 years, there will be some bron-
chiolitis syndrome patients who respond to asthma medications.
Unfortunately, there is no way to know which patient's viral-
associated reactive airway disease will or will not respond without
a trial of therapy. What is clear is that, despite over a decade of na-
tional and international guideline recommendations against the
use of bronchodilators in bronchiolitis syndrome patients, most
emergency physicians believe that a bronchodilator trial of the
bronchiolitis syndrome patient frequently results in degrees of im-
provement in bronchiolitis signs and symptoms.39
Other lines of evidence would suggest that bronchospasm as-
sociated with the viruses causing the bronchiolitis syndrome do
frequently respond to bronchodilator therapy. Merckx et al40 per-
formed a prospective cohort study of children presenting to the
emergency department with moderate or severe wheezing exacer-
bations. These patients underwent viral testing and were evaluated
for treatment failures after a standardized severity-specific treat-
ment.40 Although this was not specifically a study of bronchiolitis
patients, the median age for the 958 patients was 3 years. In addi-
tion, more specifically, the median age for children testing positive
for a virus was 2 years, and the interquartile range was 1 to 5 years.
Consequently, many of the infected wheezing infants and children
were in the age range of the bronchiolitis syndrome.40 Just over
61% (61.7%) were positive for at least 1 pathogen. Rhinovirus
was the most prevalent (29.4%), and 16.9% experienced treatment
failure.40 The majority of the viral-associated wheezing responded
to these treatments with non-RV pathogens being associated with
a higher risk of treatment failure. Absolute risk of treatment failure
for RSV was 8.8%; influenza, 24.9%; and parainfluenza, 34.1%.
Notably, the absolute risk of treatment failure was significantly be-
low 100% for any of the viruses associated with bronchiolitis.
THE UNDIFFERENTIATED WHEEZING PATIENT
It is one thing to make clinical recommendations concerning
the admitted and clinically differentiated bronchiolitis patient, but
it is problematic to apply these same recommendations to the un-
differentiated wheezing infant presenting for the very first time to
the emergency department or outpatient setting.35,40 Many other
conditions can be the etiology of wheezing in infants and must
be considered.41 From the perspective of front-line clinicians seeing
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Pediatric Emergency Care • Volume 00, Number 00, Month 2019
these patients at their initial presentation to the emergency depart-
ment or clinics, these patients must be considered undifferentiated.
In fact, all wheezing patients younger than 2 years presenting to the
emergency department or other outpatient settings are, in reality,
undifferentiated or incompletely differentiated patients. Not only
is it unclear whether or not the wheezing will be responsive to
β2 agonists and steroids, but the etiology of the wheezing must
be differentiated from bronchiolitis look-a-likes or masqueraders.
• Asthma
• Recurrent viral-triggered wheezing
• Pneumonia
• Chronic pulmonary disease
• Foreign body aspiration
• Aspiration pneumonia
• Congenital heart disease
• Congestive heart failure
• Myocarditis
Without further diagnostic testing and/or therapeutic trials, it is
nearly impossible to define which bronchiolitis look-a-like condition
is responsible for the presentation. The AAP guidelines fail to ac-
knowledge the fact that undifferentiated bronchiolitis (RSVor RV
or other viral etiology of wheezing) and undifferentiated wheez-
ing patients are the clinical norm. Instead, the recommendations
encourage making the diagnosis and subsequent therapeutic plan
entirely based on history and physical examination. Although it is
standard practice to start with a history and physical examination,
other steps are commonly required to differentiate the cause of the
wheezing and the source of a fever as well as responsiveness to
therapeutic agents such as β2 agonists, racemic epinephrine, and
3% hypertonic saline. In fact, the failure of clinicians in the outpa-
tient setting to perform this differentiation process will consis-
tently result in missed diagnostic and therapeutic opportunities.
CURRENT EVIDENCE-BASED
THERAPEUTIC OPTIONS
The current evidence suggests that therapeutic options for
bronchiolitis actually do exist, and we hope that these therapeu-
tic options will be included in the 2019 iteration of the AAP
bronchiolitis guidelines.
Hypertonic Saline
The 2017 Cochrane review by Zhang et al42,43 is the latest re-
view of this topic and was previously reviewed and published in
2008, 2010, and 2013. Previous reviews were less optimistic about
the benefits of hypertonic saline. However, the 2017 Cochrane re-
view clearly states that hypertonic may reduce length of stay among
hospitalized infants and improve the clinical severity score as well
as reduces the risk of hospitalization.42 Not only does the 2017
Cochrane review support this therapeutic intervention, there are
other systematic reviews that come to the same conclusion.44–46
The available evidence is sufficient to recommend that this inter-
vention be currently accepted as standard outpatient and inpatient
therapy options for bronchiolitis patients.
Nebulized Epinephrine
First, there are multiple studies confirming that racemic epi-
nephrine is effective in treating wheezing children.47–50 Although
many of these are noninferiority studies that report racemic epi-
nephrine is no better than the newer drug being studied, these stud-
ies provide strong evidence that racemic epinephrine effectively
treats pulmonary bronchospasm.
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Problematic AAP Bronchiolitis Guidelines
Although no new Cochrane guidelines for outpatient benefit
of nebulized epinephrine exist for bronchiolitis, both the 2004 and
the 2011 Cochrane reviews found evidence that epinephrine ap-
peared to be effective in the outpatient setting for treating bronchi-
olitis.51,52 Both the 2006 and 2014 AAP guidelines acknowledged
that the evidence suggested benefit of epinephrine in the outpa-
tient setting. Although acknowledging these benefits, the 2014
guidelines recommended against the use of epinephrine in any set-
ting with specific reasoning.2 Unfortunately, in our opinion, this
recommendation selectively addressed inpatient management
while not adequately addressing the potential benefit in the outpa-
tient setting. A subsequent 2013 systematic review by Tudor and
Hafner53 also concluded that epinephrine was beneficial for bron-
chiolitis in the outpatient setting. Both previous and more current
evidence have consistently demonstrated that in the outpatient set-
ting nebulized epinephrine is more effective than placebo for
treating bronchiolitis patients.51–53
High-Flow Nasal Cannula With Humidified Air
The 2014 AAP guidelines indicated that the evidence available
suggested that the use of high flow nasal cannula with humidified
air was promising. However, the absence of any completed random-
ized trial of the efficacy of high-flow nasal cannula (HFNC) in
bronchiolitis precluded specific recommendations on it use.1 A
Cochrane review also published in 2014 found only 1 study that
met their inclusion criteria.54 This Cochrane review also con-
cluded that there was insufficient evidence to determine the effec-
tiveness of HFNC therapy for treating infants with bronchiolitis.54
Since that time, the evidence base for benefit of HFNC in severe
bronchiolitis has significantly expanded. Multiple studies have
now demonstrated that infants with bronchiolitis receiving high-
flow oxygen therapy had significantly lower rates of escalation
of care owing to treatment failure.55–63 In addition, evidence for
the physiologic benefit of HFNC oxygen or air has also been re-
ported. Increases in end-expiratory lung volume and improved respi-
ratory rate, Fio2, and Spo2 are benefits observed with application of
this treatment modality.64 Current evidence and widespread clini-
cal experience demonstrating clear clinical benefits now seem suf-
ficient to allow the recommendation of HFNC in the management
of severe bronchiolitis.
The HFNC therapy combined with aerosol of medications
such as nebulized albuterol or epinephrine is another consider-
ation for HFNC. Even though technological challenges exist and
data are lacking, it is another area needing urgent study.65–68
SUMMARY
The 2014 AAP bronchiolitis guidelines do not adequately
serve the needs and clinical realities of front-line clinicians caring
for undifferentiated wheezing infants and children. Articles decrying
the lack of compliance with current national and international
bronchiolitis guidelines are common for both outpatients and in-
patients with the bronchiolitis syndrome.39,69–73 However, there
are good reasons why bronchiolitis guidelines are not consistently
followed, and it goes beyond the lag time between publication and
incorporation into clinical practice. Clinicians have long recog-
nized that their undifferentiated patients often need further diag-
nostic testing and therapeutic trials before their evaluation of the
bronchiolitis syndrome patient is complete. They also recognize
that the bronchiolitis syndrome is a heterogeneous disease and under-
stand that some bronchiolitis syndrome patients do respond to thera-
pies that were discouraged by the 2014 AAP bronchiolitis guidelines.
There is now a growing body of evidence that helps explain the
disconnect between the bronchiolitis guidelines and the clinical
practice of front-line health care providers. Valid, evidence-based
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Mellick and Gonzalez
criticisms of the AAP guidelines proscription against the use
of bronchodilators followed shortly after the release of the
guidelines.37,38 In addition, additional evidence of benefit for
the outpatient use of nebulized epinephrine that was inexplicably
set aside by the guidelines has also been published.53 Finally, the
AAP guidelines attempt to give guidance concerning the management
of heterogeneous populations of outpatient bronchiolitis syndrome
patients 2 years and younger based on research biased toward homog-
enous populations of admitted patients 12 months and younger.9,17 In
light of significant problems with the 2014 AAP bronchiolitis guide-
lines, we hope that the next major revision of the guidelines will
acknowledge the growing evidence for therapeutic options previ-
ously discouraged and demonstrate a greater understanding of the
practice realities of front-line clinicians.
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