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ARTICLE
Predicting Escalated Care in 
Infants With Bronchiolitis
Gabrielle Freire, MD, FRCP(C), a Nathan Kuppermann, MD, MPH, b Roger Zemek, MD, FRCP(C), c Amy C. Plint, MD, FRCP(C), MSc, c 
Franz E. Babl, MD, MPH, d, e Stuart R. Dalziel, MBChB, FRACP, PhD, f Stephen B. Freedman, MDCM, MSc, FRCP(C), g Eshetu G. 
Atenafu, MSc, h Derek Stephens, MSc, i Dale W. Steele, MD, MSc, j Ricardo M. Fernandes, MD, PhD, k Todd A. Florin, MD, MSCE, l 
Anupam Kharbanda, MD, MSc, m Mark D. Lyttle, MBChB, n David W. Johnson, MD, o David Schnadower, MD, p Charles G. Macias, MD, q 
Javier Benito, MD, PhD, r Suzanne Schuh, MD, FRCP(C), a, i for the Pediatric Emergency Research Networks (PERN)
BACKGROUND AND OBJECTIVES: Early risk stratification of infants with bronchiolitis receiving 
airway support is critical for focusing appropriate therapies, yet the tools to risk categorize 
this subpopulation do not exist. Our objective was to identify predictors of “escalated 
care” in bronchiolitis. We hypothesized there would be a significant association between 
escalated care and predictors in the emergency department. We subsequently developed a 
risk score for escalated care.
METHODS: We conducted a retrospective cohort study of previously healthy infants agedDepartments International 
Collaborative (PREDICT) in 
Australia and New Zealand, Pediatric 
Emergency Research United 
Kingdom and Ireland (PERUKI), 
and Research in European Pediatric 
Emergency Medicine (REPEM).33 
The original study was approved 
by the PERN Executive Committee 
and the research ethics boards of all 
participating hospitals.
Included children were younger 
than 12 months and diagnosed 
in a participating ED between 
January and December 2013 with 
bronchiolitis, defined as a viral 
respiratory infection with respiratory 
distress.1, 7 The first bronchiolitis was 
defined by no previous visits to a 
health care provider for bronchiolitis. 
Infants with comorbidities including 
chronic lung, cardiac, neuro-muscular 
disease, immune deficiencies, and 
renal or hepatic insufficiency were 
excluded.
Study Protocol
At each hospital, we identified 
consecutive infants who presented 
to the ED within the study period 
and had a discharge diagnosis 
of bronchiolitis or respiratory 
syncytial virus (RSV) bronchiolitis 
from the International Classification 
of Diseases, Ninth Revision or 
International Classification of 
Diseases, 10th Revision (codes J 
21.0, 21.8, 21.9/466.1). By using a 
random number generator, each 
site was used to identify a random 
sample of records for review. Trained 
abstractors identified eligible 
records and entered the data on 
standardized case report forms and 
into a secure web-based electronic 
database. Targeted information 
included demographics, presenting 
symptoms and physical examination 
in the ED, vital signs, transcutaneous 
oxygen saturation measured in 
triage in room air, disposition from 
the ED (discharge from the hospital, 
admission to inpatient ward or ICU), 
and airway support interventions 
constituting escalated care as defined 
below.
We defined all study variables a 
priori and described them in a 
manual of operations with data 
source hierarchy for all data points. 
Trained site investigators ensured 
data extractors reviewed the 
manual. The manual of operations 
assisted with interpretation and 
standardized data extraction of 
variables somewhat subjective in 
nature. Before the study initiation, 
all coinvestigators reviewed the case 
report forms to assess feasibility of 
collecting the required information 
locally and to ensure information 
clarity.
FREIRE et al2
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Outcome Measures
The primary outcome measure 
was escalated care during the 
ED or inpatient stay, defined as 
hospitalization plus any of the 
following: HFNC, noninvasive 
ventilation (eg, continuous or 
biphasic positive airway pressure), 
intubation and ventilation, or 
management in the ICU without 
airway support. Although the criteria 
for ICU admission are variable16, 34 
and those for HFNC have not yet 
been established, 35 these escalated 
care interventions are generally 
limited to children with hypoxia 
and concern respiratory distress.30 
We did not include isolated use of 
intravenous or nasogastric hydration 
or supplemental oxygen in this 
definition because some institutions 
use intravenous or nasogastric 
hydration routinely on admission, 18 
and the criteria for supplemental 
oxygen are disparate.36 The 
secondary outcome consisted of the 
diagnostic accuracy of the derived 
clinical risk score model for escalated 
care.
Predictor Considerations
We evaluated the following potential 
predictors of escalated care: age 
in months, duration of respiratory 
distress in days, documented 
prematurity, reported poor feeding, 
observed dehydration, observed 
nasal flaring and/or grunting, 
reported or observed apnea, 
respiratory rate in triage, chest 
retractions, and oxygen saturation 
measured in triage on room 
air.14, 16, 17, 19, 24 To develop the risk 
score, the continuous variables were 
dichotomized according to published 
evidence for severe bronchiolitis 
and recommendation for oxygen 
therapy.1, 16
Analyses
The study sample size was estimated 
to provide 80% power to answer the 
primary association, on the basis of 
the multivariable logistic regression 
analysis with escalated care as 
the binary dependent variable. On 
the basis of previous literature, 
we estimated that 5% of infants 
presenting for ED care would be 
admitted to an ICU and that ∼5% 
of the remaining population would 
be managed with HFNC16 for a total 
proportion receiving escalated care 
of ∼10%. Targeting evaluation of 
10 independent variables, with the 
requirement of at least 10 patients 
with the outcome per predictor 
variable and allowing for colinearity, 
we aimed to enroll at least 200 
participants receiving escalated 
care. We thus required at least 2000 
patients presenting to the ED with 
bronchiolitis.
The patient characteristics were 
analyzed with descriptive statistics 
by using proportions for categorical 
data, means with SDs for normally 
distributed continuous data, and 
medians with ranges for continuous 
data lacking normal distributions. 
Relevant 95% confidence intervals 
(CIs) were calculated around 
targeted parameter estimates.
We used bivariable analyses to 
determine the association between 
escalated care as a binary outcome 
and the independent variables 
explored, including an age of ≤2 
months, 16 respiratory rate of ≥60 
breaths per minute, 37 and oxygen 
saturation ofsites. Of these, 1580 visits fulfilled 
exclusion criteria, leaving 3725 
eligible participants, of which 
802 were managed at 8 Canadian 
pediatric EDs (PERC), 978 at 10 EDs 
in the United States (PEM-CRC and 
PECARN), 805 at 8 EDs in Australia 
and New Zealand (PREDICT), 841 
at 9 EDs in the United Kingdom and 
Ireland (PERUKI), and 299 infants at 
3 EDs in Europe (REPEM).
The mean age of included 
participants was 4.5 ± 3.0 months, 
2274 (61.1%) were boys, and the 
mean symptom duration was 
2.9 ± 2.0 days.
Escalated Care
Of the 3725 eligible patients, 2722 
(73.1%) had complete data for all 
variables. A total of 261 of 2722 
(9.6%) study infants received 
escalated care, of which 164 (63%) 
were treated with HFNC, 47 (18%) 
received noninvasive ventilation, 
12 (5%) were mechanically 
ventilated, and 38 (15%) received 
ICU care without airway support. 
Of the 164 HFNC treatments, 114 
(70%) were delivered on inpatient 
wards. The characteristics of the 
infants who did and did not receive 
escalated care appear in Table 1. 
The rates of escalated care ranged 
from 3.6% in the United Kingdom 
and Ireland to 15.7% in Spain and 
Portugal.
With Table 2, we summarize the 
bivariable associations between 
postulated predictors and escalated 
care.
Multivariable Analysis
The variables included in 
multivariable analysis included 
age, poor feeding, oxygen 
saturation, apnea, nasal flaring and/
or grunting, dehydration, retractions, 
and respiratory rate (Table 3). 
FREIRE et al4
TABLE 1 Characteristics of Infants With and Without Escalated Care
Characteristic Escalated Care No Escalated Care P
n = 261 n = 2461
Age, moa 2.9 ± 2.8 4.5 ± 2.9 2 0 Reference 2 months with oxygen 
saturations ≥90% and without 
nasal flaring and/or grunting, 
retractions, or hydration issues have 
a low probability of this outcome. 
The clinical risk score derived in a 
large and diverse infant population 
is used to quantify estimated risk 
for escalated care in bronchiolitis 
during the hospital stay, with a 
demonstrated high stability and 
discrimination ability.
Most studies in which authors 
characterize infants with severe 
bronchiolitis have been focused on 
hospitalization, 9, 14, 17 –19, 25, 43 safe 
discharges from the ED, and ED 
length of stay.15, 20 However, clinical 
severity is only 1 factor involving 
the decision to hospitalize a child 
with bronchiolitis. Other factors 
include social, geographic, and 
cultural considerations. Past studies 
in which authors quantify the risk 
of hospitalization in bronchiolitis 
are also limited by the need for 
complex calculations14 and single-
center design.19 In contrast, we 
have focused our outcome on 
receipt of escalated care because 
this subpopulation either suffers 
from or is at risk for developing 
respiratory decompensation and 
needs timely identification for 
optimal management. Although the 
clinical use of the risk score will 
need to be prospectively validated, 
it has the potentialto individualize 
bronchiolitis care by identifying 
infants who can be discharged 
from the hospital or observed in 
community hospitals versus those 
at risk for requiring care by teams 
skilled in airway support because of 
risk of escalated care.
Research of infants with bronchiolitis 
receiving airway support has 
generally been focused on the 
inpatients, 21 – 23 especially infants 
admitted to ICUs.16, 24 –29 These 
studies had relatively small numbers 
of ICU patients, 16, 22 used single-
center designs, 22, 26, 27 were focused 
on RSV bronchiolitis, 22, 25 – 27 or 
took place before the use of RSV 
immunoprophylaxis.25, 26 HFNC 
therapy has recently become a 
common airway support strategy in 
severe bronchiolitis.30, 44 –46 Although 
some physiological benefits of HFNC 
have been confirmed, 47 – 50 and the 
increasing use of HFNC may have 
contributed to a corresponding 
drop in intubation rates, 30, 50 – 53 
we currently do not know which 
infants with bronchiolitis are the 
best candidates for this intervention. 
Although HFNC may have a role as a 
rescue treatment to prevent the need 
for ICU care in bronchiolitis, it does 
not appear to modify the underlying 
disease course.54 Furthermore, not all 
infants requiring airway support are 
admitted to the ICU. Many patients 
on HFNC appear to be candidates for 
ward therapy, 31, 55 – 57 as was the case 
in this study.
The strongest predictor of escalated 
care was a triage oxygen saturation 
60 breaths per 
minute, and retractions between 
these subgroups were both clinically 
and statistically significant (PNational 
Health Service Foundation Trust, 
Sunderland, UK); Sian Copley, 
MBBS (City Hospitals Sunderland 
National Health Service Foundation 
Trust, Sunderland, UK); Kathryn 
Ferris, MB BCh BAO (Royal Belfast 
Hospital for Sick Children, Belfast, 
UK); Stuart Hartshorn, MB BChir 
(Birmingham Children’s Hospital, 
Birmingham, UK); Christopher Hine, 
MBChB (Birmingham Children’s 
Hospital, Birmingham, UK); Julie-
Ann Maney, MB BCh BAO (Royal 
Belfast Hospital for Sick Children, 
Belfast, UK); Fintan McErlean (Royal 
Belfast Hospital for Sick Children, 
Belfast, UK); Niall Mullen, MB BCh 
(City Hospitals Sunderland National 
Health Service Foundation Trust, 
Sunderland, UK); Katherine Potier 
de la Morandiere, MBChB (Royal 
Manchester Children’s Hospital, 
Manchester, UK); Stephen Mullen, MB 
BCh BAO (Royal Belfast Hospital for 
Sick Children, Belfast, UK); Juliette 
Oakley, MB BCh (The Noah’s Ark 
Children’s Hospital for Wales, Cardiff, 
UK); Nicola Oliver, MBBS (Bristol 
Royal Hospital for Children, Bristol, 
UK); Colin Powell, MD (The Noah’s 
Ark Children’s Hospital for Wales, 
Cardiff, UK); Vandana Rajagopal, 
MBBS (The Noah’s Ark Children’s 
Hospital for Wales, Cardiff, UK); 
Shammi Ramlakhan, MBBS (Sheffield 
Children’s Hospital, Sheffield, UK); 
John Rayner, MBChB (Sheffield 
Children’s Hospital, Sheffield, UK); 
Sarah Raywood, MB BCh (Royal 
Manchester Children’s Hospital, 
Manchester, UK); Damian Roland, 
MBBS, (Leicester Royal Infirmary 
Children’s Emergency Department, 
Leicester, UK); Siobhan Skirka, 
MBChB (Our Lady’s Children’s 
Hospital, Crumlin, Dublin, UK); 
Joanne Stone, MBChB (Sheffield 
Children’s Hospital, Sheffield, UK).
PREDICT: Meredith Borland, MBBS, 
FRACGP, FACEM (Princess Margaret 
Hospital for Children, Perth, WA, 
Australia); Simon Craig, MBBS 
(Monash Medical Centre, Melbourne, 
VIC, Australia); Amit Kochar, MD 
(Women’s and Children’s Hospital, 
Adelaide, SA, Australia); David 
Krieser, MBBS (Sunshine Hospital, St 
Albans, VIC, Australia); Cara Lacey, 
MBBS (Sunshine Hospital, St Albans, 
VIC, Australia); Jocelyn Neutze, 
MBChB (Middlemore Hospital, 
Auckland, New Zealand); Karthikeyan 
Velusamy, MD (Townsville Hospital, 
Douglas, QLD, Australia).
REPEM: Javier Benito, MD, PHD 
(Pediatric Emergency Department, 
Cruces University Hospital, 
Barakaldo, Bizkaia, Spain); Ana 
Sofia Fernandes, MD (Santa Maria 
Hospital, Lisbon, Portugal); Joana 
Gil, MD (Santa Maria Hospital, 
Lisbon, Portugal); Natalia Paniagua, 
MD (Cruces University Hospital, 
Barakaldo, Bizkaia, Spain); Gemma 
Claret Teruel, MD (Hospital Sant Joan 
de Déu, Barcelona, Spain); Yehezkel 
Waisman, MD (Schneider Children’s 
Medical Center of Israel, Petah Tiqva, 
Israel).
Research Network and Development 
of Pediatric Emergency Medicine 
in Latin America: Pedro Bonifacio 
Rino, MD (Hospital de Pediatria Prof. 
Dr Juan P. Garrahan, Buenos Aires, 
Argentina).
PERN Executive Committee: 
Nathan Kuppermann (Chair), 
Stuart R. Dalziel (Vice Chair), James 
Chamberlain (PECARN), Santiago 
Mintegi (REPEM), Rakesh Mistry 
(PEM-CRC), Lise Nigrovic (PEM-CRC), 
Amy C. Plint (PERC), Damien Roland 
(PERUKI), Patrick Van de Voorde 
(REPEM).
PERN Networks: Participating 
networks include the following: 
PECARN, PEM-CRC of the American 
Academy of Pediatrics, PERC, 
PERUKI, PREDICT, REPEM, and the 
Red de Investigacion y Desarrollo 
de la Emergencia Pediatrica 
Latinoamericana, which means 
Research Network and Development 
of Pediatric Emergency Medicine in 
Latin America (Argentine-Uruguayan 
network).
We thank Judy Sweeney and 
Maggie Rumantir for their generous 
contribution to coordinating this 
study and Henna Mian for her 
administrative assistance with the 
study.
ABBREVIATIONS
AUC:  area under the curve
CI:  confidence interval
ED:  emergency department
HFNC:  high-flow nasal cannula
OR:  odds ratio
PECARN:  Pediatric Emergency 
Care Applied Research 
Network
PEM-CRC:  Pediatric Emergency 
Medicine 
Collaborative 
Research Committee
PERC:  Pediatric Emergency 
Research Canada
PERN:  Pediatric Emergency 
Research Networks
PERUKI:  Pediatric Emergency 
Research United 
Kingdom and Ireland
PREDICT:  Pediatric Research in 
Emergency 
Departments 
International 
Collaborative
REPEM:  Research in European 
Pediatric Emergency 
Medicine
RSV:  respiratory syncytial virus
FREIRE et al8
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PEDIATRICS Volume 142, number 3, September 2018 9
Lisbon, Portugal; lDivision of Emergency Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; mDepartment of Pediatric Emergency Medicine, Children’s Hospital 
of Minnesota, Minneapolis, Minnesota; nEmergency Department, Bristol Royal Hospital for Children and Faculty of Health andApplied Life Sciences, University of the West of England, 
Bristol, United Kingdom; pDepartment of Pediatric Emergency Medicine, School of Medicine, Washington University in St Louis, St Louis, Missouri; qDepartment of Pediatric Emergency 
Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas; and rPediatric Emergency Department, Cruces University Hospital, Barakaldo, Spain
Dr Freire conceived the study, cowrote the study protocol, and wrote the manuscript; Dr Kuppermann designed the study and provided major input into the 
concept and analysis of the study and drafting and revision of the manuscript; Dr Zemek designed the study and provided major input into the concept and 
analysis of the study and drafting and revision of the manuscript; Drs Freedman, Plint, Babl, Dalziel, Steele, Fernandes, Florin, Kharbanda, Lyttle, Johnson, 
Schnadower, and Benito designed the study, drafted the manuscript, and revised it for intellectual content; Mr Atenafu conducted the statistical analysis and 
revised the manuscript for intellectual content; Mr Stephens conducted the analysis and revised the manuscript for intellectual content; Dr Macias designed 
the study, provided extensive database support, drafted the manuscript, and revised it for intellectual content; Dr Schuh conceived the study, cowrote the study 
protocol, wrote the manuscript, and revised it critically for intellectual content; and all authors approved the final manuscript as submitted.
DOI: https:// doi. org/ 10. 1542/ peds. 2017- 4253
Accepted for publication May 21, 2018
Address correspondence to Suzanne Schuh, MD, FRCP(C), Division of Pediatric Emergency Medicine, Research Institute, The Hospital for Sick Children, University 
of Toronto, 555 University Ave, Toronto, ON, Canada M5G 1X8. E-mail: suzanne.schuh@sickkids.ca
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2018 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www. pediatrics. org/ cgi/ doi/ 10. 1542/ peds. 2018- 1982.
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DOI: 10.1542/peds.2017-4253 originally published online August 20, 2018; 
2018;142;Pediatrics 
Schuh and for the Pediatric Emergency Research Networks (PERN)
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Steele, Ricardo M. Fernandes, Todd A. Florin, Anupam Kharbanda, Mark D. Lyttle,
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Gabrielle Freire, Nathan Kuppermann, Roger Zemek, Amy C. Plint, Franz E. Babl,
Predicting Escalated Care in Infants With Bronchiolitis
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DOI: 10.1542/peds.2017-4253 originally published online August 20, 2018; 
2018;142;Pediatrics 
Schuh and for the Pediatric Emergency Research Networks (PERN)
David W. Johnson, David Schnadower, Charles G. Macias, Javier Benito, Suzanne 
Steele, Ricardo M. Fernandes, Todd A. Florin, Anupam Kharbanda, Mark D. Lyttle,
Stuart R. Dalziel, Stephen B. Freedman, Eshetu G. Atenafu, Derek Stephens, Dale W. 
Gabrielle Freire, Nathan Kuppermann, Roger Zemek, Amy C. Plint, Franz E. Babl,
Predicting Escalated Care in Infants With Bronchiolitis
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