Received: 20 November 2022 | Accepted: 7 March 2023

DOI: 10.1002/ppul.26386

ORIGINAL ARTICLE

Dexamethasone versus methylprednisolone for critical

asthma: A single center, open‐label, parallel‐group clinical trial

Meghan R. Roddy PharmD1 | Austin R. Sellers MS2 | Kristina K. Darville ARNP3 |

Beatriz Teppa‐Sanchez MD3 | Scott D. McKinley DO4 | Meghan Martin MD5 |
Neil A. Goldenberg MD, PhD2,6,7 | Thomas A. Nakagawa MD8 |
Anthony A. Sochet MD, MSc2,3,9

1
Departments of Pharmacy, Johns Hopkins All
Children's Hospital, St. Petersburg, Abstract
Florida, USA
Background: Evidence for the use of dexamethasone for pediatric critical asthma is
2
Institute for Clinical and Translational
Research, Johns Hopkins All Children's
limited. We sought to compare the clinical efficacy and safety of dexamethasone
Hospital, St. Petersburg, Florida, USA versus methylprednisolone among children hospitalized in the pediatric intensive
3
Departments of Pediatric Critical Care care unit (PICU) for critical asthma.
Medicine, Johns Hopkins All Children's
Hospital, St. Petersburg, Florida, USA Methods: A prospective, single center, open‐label, two‐arm, parallel‐group,
4
Departments of Pulmonlogy, Johns Hopkins nonrandomized trial among children ages 5−17 years hospitalized within the PICU
All Children's Hospital, St. Petersburg, from April 2019 to December 2021 for critical asthma consented to receive
Florida, USA
5
methylprednisolone (standard care) or dexamethasone (intervention) at a 2:1
Departments of Emergency Medicine, Johns
Hopkins All Children's Hospital, St. allocation ratio, respectively. The intervention arm received intravenous dexameth-
Petersburg, Florida, USA
asone 0.25 mg/kg/dose (max: 15 mg/dose) every 6 h for 48 h and the standard care
6
Departments of Pediatrics, Johns Hopkins
arm intravenous methylprednisolone 1 mg/kg/dose every 6 h (max dose: 60 mg/
University School of Medicine, Baltimore,
Maryland, USA dose) for 5 days. Study endpoints were clinical efficacy (i.e., length of stay [LOS],
7
Departments of Medicine, Johns Hopkins continuous albuterol duration, and a composite of adjunctive asthma interventions)
University School of Medicine, Baltimore,
Maryland, USA
and safety (i.e., corticosteroid‐related adverse events).
8
Department of Pediatrics, Division of Results: Ninety‐two participants were analyzed of whom 31 were allocated to the
Pediatric Critical Care Medicine, University of intervention arm and 61 the standard care arm. No differences in demographics, clinical
Florida‐Jacksonville, Jacksonville, Florida, USA
9
characteristics, or acute/chronic asthma severity indices were observed. Regarding
Departments of Anesthesiology and Critical
Care Medicine, Johns Hopkins University efficacy and safety endpoints, no differences in hospital LOS, continuous albuterol
School of Medicine, Baltimore, Maryland, USA duration, adjunctive asthma intervention rates, or corticosteroid‐related adverse events

Correspondence
were noted. Compared to the intervention arm, participants in the standard care arm
Anthony A. Sochet, MD, MSc, Department of more frequently were prescribed corticosteroids at discharge (72% vs. 13%, p < 0.001).
Medicine, Division of Pediatric Critical Care
Conclusions: Among children hospitalized for critical asthma, dexamethasone
Medicine, Johns Hopkins All Children's
Hospital, 501 6th St S., St. Petersburg, appears safe and warrants further investigation to fully assess clinical efficacy and
FL 33701, USA.
potential advantages over commonly applied agents such as methylprednisolone.
Email: sochet@jhmi.edu

Preliminary findings were presented at the American Academy of Pediatrics National Conference and Exhibition in October 2022 in Anaheim, CA, USA as a oral‐podium presentation as part of
the Section on Critical Care.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.

Pediatric Pulmonology. 2023;58:1719–1727. wileyonlinelibrary.com/journal/ppul | 1719


1720 | RODDY
KEYWORDS
corticosteroids, glucocorticoids, pediatric critical care medicine, pediatric intensive care unit,
status asthmaticus
1 | INTRODUCTION
Childhood asthma has an estimated United States prevalence of 5.1
million and an associated mortality of 2.4 deaths per million.1,2
Annual exacerbations account for approximately 75,000 hospitaliza-
tions and 767,000 emergency department encounters.2–4 Cases
prompting pediatric intensive care unit (PICU) admission, termed
critical asthma, represent an estimated ~10% of pediatric asthma
5,6
hospitalizations. For critical asthma, adjunctive intravenous (IV)
pharmacologic agents (e.g., aminophylline, terbutaline, and ketamine),
and respiratory interventions (e.g., heliox, noninvasive ventilation,
invasive mechanical ventilation, inhaled anesthetic gasses, and
extracorporeal life support) are judiciously applied. Yet, systemic
corticosteroids and nebulized bronchodilators remain fundamental to
acute management by mitigating inflammatory hypersecretion,
reversing bronchospasm, improving pulmonary resistance, and
7,8
relieving expiratory airway obstruction.
Since the 1950s, systemic corticosteroids have been the
cornerstone therapy for critical asthma.9 Several corticosteroid
agents are approved for use in pediatric asthma and vary by
pharmacologic properties such as glucocorticoid potency, volume of
distribution, and elimination half‐life.10,11 In general, mild asthma
exacerbations are managed with enteral prednisolone or prednisone
and severe exacerbations with IV methylprednisolone for those
unable to tolerate enteral formulations due to respiratory failure or
altered mentation.12–14 Yet, an increasing trend toward dexametha-
sone prescribing for severe exacerbations has been observed among
15
PICU encounters. Dexamethasone is a promising agent given its
long elimination half‐life (36−72 h) and potent glucocorticoid
activity.16 In the emergency department and general pediatric wards,
observational data and systematic reviews suggest dexamethasone
as an alternative to methylprednisolone as a result of observed
reductions of inpatient length of stay (LOS), hospital relapse rates,
gastrointestinal side effects, and direct costs.13,17–20 Yet, qualitative
data reveals 96% of pediatric intensivists report prescribing IV
methylprednisolone using clinical experience as the basis for
14
preferred drug and dosage in this context.
To date, few clinical trials have compared IV methylprednisolone
to dexamethasone among children with critical asthma in the PICU
setting. To address this knowledge gap, we conducted a prospective,
single center, open‐label, two‐arm, parallel‐group, nonrandomized
clinical trial comparing IV methylprednisolone and dexamethasone
among children admitted to the PICU for critical asthma assessing
clinical efficacy (i.e., LOS, continuous nebulized albuterol duration,
and a composite exposure rate to critical asthma adjunctive
interventions) and safety (i.e., gastritis, gastrointestinal bleeding,
hypertension, hyperglycemia, altered mentation, and adrenal
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ET AL.
insufficiency rates) endpoints. We hypothesized that children
provided dexamethasone experience a reduced LOS without differ-
ences in corticosteroid‐related adverse events.
2 | M A T E R I A L S AN D M E T H O D S
2.1 | Study design and oversight
The Ideal STeroids for Asthma Treatment in the PICU (iSTAT PICU)
trial (www.Clinicaltrials.gov, NCT03900624) was an investigator‐
initiated, single center, open‐label, non‐randomized, two‐arm,
parallel‐group trial conducted at Johns Hopkins All Children's
Hospital from April 2019 through December 2021. In response to
the COVID‐19 pandemic, enrollment was held from March 2020 until
October 2020 due to an institutionally mandated halt on research
activity. The protocol was approved by the institutional review board
at Johns Hopkins University (IRB#:00187813). Signed informed
consent and assent were required for participants. The trial was
overseen by a Steering Committee. Data and safety monitoring were
performed by the investigators and qualified research staff. A listing
of committee membership, trial protocol, analysis plan, schedule of
assessments, and data sharing agreement are detailed in E‐
Supporting Information: 1.
2.2 | Participants
Study inclusion criteria were children 5 through 17 years of age with
a primary diagnosis of critical asthma admitted to the PICU. Exclusion
criteria included a medical history positive for tracheostomy, cystic
fibrosis, pulmonary hypertension, active malignancy, or transplanta-
tion status. Eligible children less than 5 years of age were excluded to
limit misclassification bias of young children with bronchiolitis or
reactive airway disease that may present with obstructive respiratory
patterns or wheezing difficult to distinguish from critical asthma.
Those with malignancy and transplantation status were excluded to
limit bias from alternative corticosteroid indications.
2.3 | Trial procedures
Participants were screened and sequentially approached for consent
immediately before PICU hospitalization in the local emergency
department or immediately following PICU transfer to facilitate early
enrollment. Enrollment in the intervention arm was prioritized if
participants had yet to be exposed to methylprednisolone,

RODDY ET AL.
prednisolone, or prednisone during the course of local or outlying
facility emergency department management. If the eligible participant
already received systemic corticosteroids other than dexamethasone
or if consent to the intervention arm were not obtained, families and
eligible subjects were approached for consent to the parallel,
standard care arm. After enrollment, study procedures were initiated
(as detailed below).
2.4 | Intervention arm
For the intervention arm, IV dexamethasone was initiated upon PICU
admission dosed at 0.25 mg/kg/dose (maximum dose of 15 mg) every
6 h to complete a 48 h course following enrollment. If participants
were determined by the primary clinical team to tolerate enteral
medications or deemed appropriate for hospital discharge before
48 h, IV dexamethasone was transitioned to enteral dosing of 0.5 mg/
kg (max 16 mg dose) every 24 h to start 6 h after the preceding IV
dose and to complete a total of 48 h of dexamethasone. The IV dose
and duration of exposures were selected based upon approximate
glucocorticoid equivalent dosing and administered every 6 h as a
process control for clinical staff. Enteral and IV dexamethasone
dosing strength and duration of treatment were chosen based on
prior reports.13,17–19,21–24 On the fourth day following enrollment, if
an extended course of corticosteroids was desired by the clinical
team, participants were permitted a tapered regimen in consultation
with the clinical pulmonology service (standard care).
2.5 | Standard care arm
For the standard care arm, IV methylprednisolone was initiated upon
PICU admission using protocolized, standard dosing at 1 mg/kg/dose
(maximum dose of 60 mg) every 6 h to complete a 5‐day course. If
participants were determined by the primary clinical team to tolerate
enteral medications or deemed appropriate for hospital discharge
prior, IV methylprednisolone was transitioned to prednisolone or
prednisone 2 mg/kg/day divided twice daily to complete a 5‐day
course following enrollment. If an extended course of corticosteroids
(beyond 5‐days and assessed on the fourth day following enrollment)
was desired by the clinical team, participants were permitted a
tapered regimen in consultation with the clinical pulmonology service
(standard care).
2.6 | Outcomes
The primary clinical efficacy endpoint was hospital LOS, a secondary
clinical efficacy endpoint was duration of continuous nebulized
albuterol (defined as the time between continuous initiation and first
intermittent albuterol administration), and a tertiary clinical efficacy
endpoint was the composite outcome of exposure to adjunctive
asthma pharmacologic or respiratory‐based interventions including
10990496, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ppul.26386 by Nat Prov Indonesia, Wiley Online Library on [06/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
| 1721
noninvasive ventilation, invasive mechanical ventilation, heliox,
terbutaline, aminophylline, ketamine, inhaled anesthetic gases, or
extracorporeal life support. The safety endpoint was the cumulative
rate of known corticosteroid‐related adverse events including
clinically‐relevant gastrointestinal bleeding, gastritis, ventilator asso-
ciated pneumonia, necrotizing enterocolitis, hypertension, hyper-
glycemia, altered mentation (including hallucinations and delirium),
and adrenal insufficiency before hospital discharge. Delirium was
assessed using Cornell Assessment of Pediatric Delirium scores.
Adrenal insufficiency was signified by clinical symptoms after
corticosteroid discontinuation. All adverse events were assessed
throughout hospitalization up until 30‐days following hospital
discharge. Serious adverse events were reviewed and adjudicated
by research personnel.
Additional descriptive data included demographics, anthropometrics,
acute and chronic asthma severity indices (i.e., admission pediatric asthma
severity scores,25 pediatric risk of mortality‐3 probability of mortality,26
pediatric index of mortality‐3 risk of mortality,27 National Heart Lung and
Blood Institute Chronic Asthma Severity Classification,28 and outpatient
asthma‐severity factors such as history of prior life‐threating asthma,
critical asthma, patient noncompliance, and chronic monoclonal antibody
exposure), acute and chronic comorbidities, discharge mortality, and 30‐
day same‐cause hospitalization (assessed within our institution and
regional affiliated hospitals).
2.7 | Statistical analysis plan
Demographic data and baseline characteristics were summarized
with counts (percentages) for categorical variables, and means ±
standard deviation or medians (interquartile range [IQR]) for
quantitative variables depending on data distribution and normalcy
(assessed via Shapiro−Wilk tests). An a priori power and sample size
estimation was conducted to detect a 1‐day difference in hospital
LOS (primary clinical efficacy endpoint) with 80% power and type I
error set at 0.05, and yielded a minimum sample size of 90
participants allocated at a standard care to intervention arm ratio
of 2:1. To assess for differences in clinical efficacy and safety
endpoints, comparative statistics were employed including students t,
Wilcoxon rank sum, and χ2 tests. Adverse events were descriptively
analyzed in the safety population, defined as all patients who
received at least one dose of intervention or standard care drugs
after enrollment. Testing was two‐sided, type I error was set at 0.05,
and missing data were not imputed. Study analyses were completed
using Stata© v15.1 software (Statacorp.).
3 | RESULTS
3.1 | Sample characteristics
Of the 92 participants enrolled into study, 61 were allocated to the
standard care arm and 31 the intervention arm (see CONSORT

1722 | RODDY
flowchart in Figure 1). Detailed demographic data, anthropometrics,
acute/chronic asthma severity indices, and general hospitalization
characteristics for the overall sample and clinical trial arms are listed
in Table 1. For the overall sample, mean age was 9.6 ± 3.8 years,
weight for age z‐scores were 0.9 ± 1.2, 53.3% were male participants,
and median admission pediatric asthma severity scores were 11 (IQR:
8−12). No differences were observed for demographics, anthropo-
metrics, acute/chronic asthma severity indices, chronic comorbidities,
and acute hospital comorbidities between participants in standard
care and intervention arms.
3.2 | Efficacy endpoint data
A complete listing of clinical efficacy endpoints and applied
adjunctive asthma therapies are provided in Table 2. Overall median
hospital LOS was 2.9 (IQR: 2−4) days and no different between
participants in the standard care and intervention arms (1.8 [IQR:
1.1−3.2] vs. 1.5 [IQR: 1−2.7] days, p = 0.632). Continuous albuterol
FIGURE 1 The CONSORT flow diagram for the clinical trial. IV, intravenous.
10990496, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ppul.26386 by Nat Prov Indonesia, Wiley Online Library on [06/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
ET AL.
was initiated in 97.8% of participants with a median treatment
duration of 24 (IQR: 12−40.8) h and no different among participants
in the standard care and intervention arms (24 [IQR: 12−45.6] vs.
19.2 [IQR: 12−40.8] h, p = 0.725). Overall rate of composite adjunc-
tive therapy exposure was 62% and no different between partici-
pants in the standard care versus intervention arms (67.2% vs. 51.6%,
p = 0.176).
3.3 | Safety endpoint data
During study, no serious adverse events recorded. Corticosteroid‐
related adverse events were uncommon and not detectably different
for participants within standard care and intervention arms including
hyperglycemia (11.5% vs. 6.5%, p = 0.713), hypertension (1.6% vs.
3.2%, p > 0.999), adrenal insufficiency (3.3% vs. 0%, p = 0.538), or
altered mentation (3.3% vs. 0%, p = 0.538). No episodes of gastro-
intestinal bleeding, gastritis, necrotizing enterocolitis, gastric perfora-
tion, or ventilator associated pneumonia were observed.
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RODDY ET AL. | 1723

T A B L E 1 Demographic, anthropometric, acute/chronic asthma severity indices, and general characteristics for overall study sample and trial
arms defined by corticosteroid agents administered after enrollment.

Variables Total sample (n = 92) Methylprednisolone (n = 61) Dexamethasone (n = 31) p

Age in years, mean ± SD 9.6 ± 3.8 9.7 ± 3.9 9.3 ± 3.5 0.642

Gender, n (%) 0.659

Female 43 (46.7) 30 (49.2) 13 (41.9)

Male 49 (53.3) 31 (50.8) 18 (58.1)

Weight in kilograms, mean ± SD 41.7 ± 22.6 41.7 ± 20.4 41.4 ± 26.8 0.934

Weight for age z‐score, mean ± SD 0.9 ± 1.2 0.9 ± 1.2 0.9 ± 1.3 0.609

NHLBI category, n (%)

Intermittent 14 (15.2) 10 (16.4) 4 (12.9) 0.457

Mild persistent 20 (21.7) 13 (21.3) 7 (22.6) >0.999

Moderate persistent 36 (39.1) 26 (42.6) 10 (32.3) 0.374

Severe persistent 23 (25) 12 (19.7) 11 (35.5) 0.128

Severity indices, median (IQR)

Pediatric asthma severity score 11 (8−12) 11 (9−12) 10.5 (8−12) 0.471

PRISM‐3‐POM, % 0.3 (0.3−0.7) 0.3 (0.3−0.9) 0.3 (0.3−0.6) 0.229

PIM‐3‐ROM, % 0.2 (0.1−0.3) 0.2 (0.2−0.5) 0.2 (0.1−0.3) 0.114

Chronic comorbidities, n (%)

Allergic rhinitis 41 (44.6) 28 (45.9) 13 (41.9) 0.825

Atopic dermatitis 16 (17.4) 12 (19.7) 4 (12.9) 0.564

Cardiovascular 0 (0) 0 (0) 0 (0) >0.999

Endocrine 3 (3.3) 2 (3.3) 1 (3.2) >0.999

Food/environmental allergies 29 (31.5) 19 (31.2) 10 (32.3) >0.999

Gastroenterological 3 (3.3) 3 (4.9) 0 (0) 0.548

Hematological/oncological 6 (6.5) 5 (8.2) 1 (3.2) 0.660

Obesity 24 (26.1) 16 (26.2) 8 (25.8) >0.999

Nephrological 4 (4.4) 3 (4.9) 1 (3.2) >0.999

Neurological 7 (7.6) 6 (9.8) 1 (3.3) 0.416

Prematurity 5 (5.4) 3 (4.9) 2 (6.5) >0.999

Acute comorbidities, n (%)

Allergic reaction 0 (0) 0 (0) 0 (0) >0.999

Bacterial upper respiratory illness 5 (5.4) 3 (4.9) 2 (6.5) >0.999

Bacterial pneumonia 25 (27.2) 19 (31.2) 6 (19.4) 0.322

Pneumothoraces 2 (2.2) 1 (1.6) 1 (3.2) >0.999

Prior cardiopulmonary arrest 1 (1.1) 1 (1.6) 0 (0) >0.999

Viral upper respiratory illness 43 (46.7) 31 (50.9) 12 (38.7) 0.377

Immunizations up to date, n (%) 85 (93.4) 56 (93.3) 29 (93.6) >0.999

Pulmonary medical home, n (%) 54 (58.7) 34 (55.7) 20 (64.5) 0.504

Chronic inhaled corticosteroids, n (%) 50 (54.4) 33 (54.1) 17 (54.8) >0.999

IgE monoclonal antibodies, n (%) 3 (3.3) 2 (3.3) 1 (3.2) >0.999

Prior PICU admissions, n (%) 24 (26.1) 15 (24.6) 9 (29) 0.802

(Continues)

1724 | RODDY
TABLE 1 (Continued)
Variables Total sample (n = 92)
Prior intubation for asthma, n (%) 6 (6.5)
History of noncompliance, n (%) 21 (22.8)
Abbreviations: IQR, interquartile range; NHLBI, National Heart Lung and Blood Institute; PICU, pediatric intensive care unit; PIM‐3‐POM, pediatric index
of mortality‐3 risk of mortality; PRISM‐3‐POM, pediatric risk of mortality‐3 probability of mortality; SD, standard deviation.
3.4 | Additional descriptive and clinical data
Sixty‐three percent of study participants including 45.9% of the
standard care arm and 100% of the interventional arm were given
dexamethasone in the emergency department before enrollment
(mean dose, 0.44 ± 0.15 mg/kg). The remaining 54% in the standard
care arm were given methylprednisolone in the emergency depart-
ment (mean dose, 1.65 ± 0.65 mg/kg). Following enrollment, the
intervention arm received IV dexamethasone per protocol (mean
dose, 0.25 ± 0.05 mg/kg/dose) and the standard care arm IV
methylprednisolone (mean dose, 0.9 ± 0.3 mg/kg/dose). Most parti-
cipants in the standard care arm (91.8%) were transitioned to enteral
prednisolone/prednisone and 72.1% required a prescription upon
discharge to complete a 5‐day course. In contrast, 74.2% (p = 0.029)
of participants in the intervention arm were transitioned to enteral
dexamethasone and only 12.9% (p < 0.001) were provided a
prescription at discharge to complete a 48 h course. No difference
in frequency of extended tapers was observed (13.1% in the standard
care arm vs. 6.5% in the intervention arm). Following hospital
discharge, no cases of 30‐day same‐cause hospitalization were
recorded.
4 | DISC US SION
This prospective clinical trial is one of the first to assess clinical
efficacy and safety endpoints among children hospitalized in the
PICU setting for critical asthma comparing groups allocated to
receive 2‐days of dexamethasone at 0.25 mg/kg/dose every 6 h
(intervention group) versus 5‐days of methylprednisolone at
1 mg/kg/dose every 6 h (standard care group). We found no
difference in clinical efficacy measured by hospital LOS, duration
of continuous albuterol, and frequency of adjunctive asthma
interventions. No children suffered serious adverse events and
corticosteroid‐related adverse events were rare, with the most
frequent being transient hyperglycemia (9.8% of participants).
Those receiving dexamethasone more frequently completed
corticosteroid dosing without transition to enteral formulations
and less frequently required a prescription at discharge. These
findings reflect an apparent clinical efficacy and relative safety
for dexamethasone in pediatric critical asthma as compared to
methylprednisolone. Potential advantages in discharge prescrip-
tion compliance and reliance on enteral formulations warrant
further investigation.
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ET AL.
Methylprednisolone (n = 61) Dexamethasone (n = 31) p
6 (9.8) 0 (0) 0.093
16 (26.2) 5 (16.1) 0.308
Systemic corticosteroids are part of the standard immunomo-
dulatory approach for children hospitalized with asthma exacerba-
tion. Glucocorticoid activity modulates genetic expression resulting
in reduced pulmonary inflammation, airway edema, and broncho-
constriction. This is accomplished through pathways including
induction of annexin‐1 inhibiting eicosanoid production, inactivation
of mitogen‐activated protein kinase cascades, suppression of
cyclooxygenase‐2 and prostaglandin production, and promotion of
ventilation and perfusion matching via endothelial nitric oxide
synthesis.29–33 Although both dexamethasone and methylpredniso-
lone are approved for use in children for inflammatory disorders like
asthma, they differ pharmacologically in their elimination half‐life
and body distribution.10,11 Before this report, only one pilot PICU‐
specific trial had been conducted by Doymaz et al. who randomized
61 children aged 1 through 21 years to receive IV methylpredni-
solone (0.5 mg/kg/dose every 6 h for 5 days), hydrocortisone
(1.67 mg/kg/dose every 8 h for 5 days), and dexamethasone
(0.6 mg/kg/dose every 6 h for 3 days) for critical asthma.34
The authors found no detectable differences in continuous
albuterol duration, the primary study endpoint, and no observed
corticosteroid‐related adverse events. This report included a
heterogenous sample (young adults and children under 5 years of
age), was intended as a pilot, and inadequately powered to detect
relationships to offer generalizability.
Although prior survey data of United States pediatric intensivist
respondents suggested a preference for IV methylprednisolone in
cases of critical asthma,14 wide variation in practice has been
reported including a multicenter, registry‐based cohort study by
Sellers et al. who queried an administrative data set, the Pediatric
Health Information System registry.15 In their report including
~27,000 pediatric critical asthma encounters from 49 children's
hospitals, dexamethasone‐only prescribing rates in the PICU ex-
hibited a linear increase of 0.5% per year from 0.6% in 2011 to 4.5%
in 2019. Although the dexamethasone group exhibited a lower
median hospital LOS compared to children receiving methylpredni-
solone (2 [IQR: 1−3] vs. 3 [IQR: 2−4] days), the lack of granularity
regarding clinical severity makes it difficult to draw conclusions or
infer causal relationships. A similar report by Parikh et al. assessed
hospitalized children in the general pediatric ward with acute asthma
exacerbation and observed lower hospital LOS and costs for those
receiving dexamethasone versus alternative enteral corticosteroids.20
Although the primary driver of hospital costs remains LOS,
differences in pharmaceutical costs reported by Parikh may reflect
shorter durations of drug administration and highlight a potential
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RODDY ET AL. | 1725

T A B L E 2 Clinical efficacy endpoints and a complete listing of adjunctive critical asthma pharmacologic and respiratory interventions for the
study sample and by trial groups defined by corticosteroid.

Variables Total sample (n = 92) Methylprednisolone (n = 61) Dexamethasone (n = 31) p

Clinical efficacy endpoints

Length of stay, median days (IQR)

Pediatric intensive care unit 1.7 (1.1−3) 1.8 (1.1−3.2) 1.5 (1−2.7) 0.785

Total hospital 2.9 (2−4) 2.9 (2.1−4) 2.9 (1.8−4.1) 0.632

Continuous albuterol, n (%) 90 (97.8) 59 (96.7) 31 (100) 0.548

Duration, median hours (IQR) 24 (12−40.8) 24 (12−45.6) 19.2 (12−40.8) 0.725

Composite of all adjunctive critical 57 (62) 41 (67.2) 16 (51.6) 0.176

asthma interventions, n (%)

Pharmacologic adjunctive interventions

Intravenous terbutaline, n (%) 13 (14.1) 10 (16.4) 3 (9.7) 0.532

Duration, median days (IQR) 0.6 (0.4−2.1) 0.6 (0.4−2.5) 0.5 (0.3−1.1) 0.446

Intravenous aminophylline, n (%) 3 (2.2) 1 (1.6) 2 (3.2) >0.999

Duration, median days (IQR) 2 (1.6−3.5) 2 2.6 (1.6−3.5) >0.999

Intravenous magnesium, n (%) 74 (80.4) 50 (82) 24 (77.4) 0.592

Nebulized ipratropium, n (%) 60 (65.2) 41 (67.2) 19 (61.3) 0.646

Subcutaneous epinephrine, n (%) 20 (21.7) 13 (21.3) 7 (22.6) >0.999

Enteral montelukast, n (%) 29 (31.5) 19 (31.2) 10 (32.3) >0.999

Intravenous ketamine, n (%) 6 (6.5) 6 (9.8) 0 (0) 0.093

Any pharmacologic adjunct, n (%) 44 (47.8) 30 (49.2) 14 (45.2) 0.826

Respiratory adjunctive interventions

Noninvasive heliox, n (%) 3 (3.3) 2 (3.3) 1 (3.2) >0.999

Duration, median days (IQR) 1.5 (0.9−2.3) 1.6 (0.9−2.3) 1.5 >0.999

Noninvasive ventilation, n (%) 33 (35.9) 24 (39.3) 9 (29) 0.366

Duration, median days (IQR) 1.3 (0.8−1.6) 1.2 (0.8−1.6) 1.3 (1−1.5) 0.632

Noninvasive modality, n (%)

Bilevel positive airway pressure 27 (29.4) 19 (31.2) 8 (25.8) 0.637

Continuous positive airway pressure 4 (4.4) 1 (1.6) 3 (9.7) 0.109

High‐flow nasal cannula 6 (6.5) 5 (8.2) 1 (3.2) 0.660

Invasive ventilation, n (%) 5 (5.4) 5 (8.2) 0 (0) 0.163

Duration, median days (IQR) 1.3 (1.3−4) 1.3 (1.3−4) ‐ ‐

Volatile anesthetic gas, n (%) 0 (0) 0 (0) 0 (0) >0.999

Extracorporeal life support, n (%) 1 (1.1) 1 (1.6) 0 (0) >0.999

Any respiratory adjunct, n (%) 35 (38) 26 (42.6) 9 (29) 0.258

Abbreviation: IQR, interquartile range.

advantage for dexamethasone over methylprednisolone, predni- emergency department relapse rates, same‐cause hospitalizations,
sone, and prednisolone. Observational cohort data suggest two and asthma‐related mortality.35 Our report is the first to
daily doses of dexamethasone may be equivalent to a 5‐day specifically assess same‐cause readmission and rates of prolonged
course of prednisone or methylprednisolone.13,20,24 In the context corticosteroid tapers. While rates of extended corticosteroid
of hospital discharge, this may represent an advantage in the form exposure were not detectably different, no instances were
of postdischarge patient compliance that contributes to observed among children receiving dexamethasone. Yet, these

1726 | RODDY
observations may reflect disease severity rather than drug
superiority.
4.1 | Next steps and future inquiry
While our data did not detect superiority of dexamethasone over
methylprednisolone, there are additional knowledge gaps in the form
of physiologic efficacy endpoints which should prompt further
inquiry. Noninvasive, objective indices of physiologic efficacy could
include spirometry and surrogate minute ventilation markers such as
transcutaneous carbon dioxide measurements. Multicenter collabo-
rations should integrate risk‐stratified sampling (i.e., participants with
severe NHLBI chronic asthma severity classification or life‐
threatening asthma [invasively ventilated children]) and should assess
dexamethasone dosing frequency, routes of administration, and
exposure durations. Molecular efficacy, assessed in the form of
asthma‐specific immunomodulation measured via proteomics, offers
opportunities to identify causal pathways and therapeutic discovery.
Finally, longitudinal clinical efficacy endpoints should incorporate
postdischarge follow‐up to add to our understanding of delayed
asthma exacerbation relapse rates specific to inpatient corticosteroid
exposure.
4.2 | Limitations
The study analytic plan was powered to assess differences in hospital
LOS as the primary clinical endpoint. Other important clinical efficacy
endpoints such as the risk reduction for life‐threatening asthma and
hospital readmission, given their rare incidence, would require larger
study samples. As this study was not designed to detect non‐
inferiority, we cannot comment on drug superiority specific to
primary endpoints assessed herein. Family socioeconomic factors,
outpatient access to healthcare including primary care follow‐up and
prescription medications, and institutional and provider variability
may alter disposition timing from the hospital and PICU. As such,
these features may have influenced our primary clinical endpoints as
described. While no differences in baseline clinical and demographic
characteristics were noted, study allocation was not randomized and
this may have introduced sampling bias. A non‐randomized approach
was chosen to address provider concerns regarding clinical equipoise,
the absence of rigorously conducted prospective cohort studies, and
as a prerequisite to support future phase 3 trials. Research was
conducted at a quaternary referral center and study findings may not
be generalizable across all other healthcare settings.
5 | C ONC LUS I ON S
In this prospective clinical trial, children hospitalized for critical
asthma in the PICU setting receiving protocolized IV dexamethasone
for 48 h were found to have no observable differences in clinical
10990496, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ppul.26386 by Nat Prov Indonesia, Wiley Online Library on [06/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
ET AL.
efficacy and safety endpoints as those treated with IV methylpredni-
solone for 5‐days. Additional prospective trials are needed to further
evaluate physiologic and molecular efficacy endpoints, longitudinal
safety endpoints, and ideal dosing strategies including frequency,
dose, and duration of dexamethasone exposure. Given a shorter
observed duration of corticosteroid exposure and less frequent
reliance on prescribed corticosteroids at the time of hospital
discharge, dexamethasone may have potential advantages over
methylprednisolone for children hospitalized in the PICU for critical
asthma that warrant additional investigation.
A UT H O R C O N T R I B U TI O NS
Meghan R. Roddy: Conceptualization; investigation; supervision;
writing—original draft; writing—review & editing; methodology;
project administration; data curation. Austin R. Sellers: Investigation;
data curation; writing—original draft; writing—review & editing;
conceptualization; project administration. Kristina K. Darville:
Writing—review & editing; investigation; conceptualization; project
administration; writing—original draft. Beatriz Teppa‐Sanchez: Con-
ceptualization; methodology; investigation; writing—review & editing;
project administration. Scott D. McKinley: Writing—original draft;
writing—review & editing; project administration; methodology;
conceptualization; investigation. Meghan Martin: Conceptualization;
methodology; investigation; writing—original draft; writing—review &
editing. Neil A. Goldenberg: Conceptualization; methodology; inves-
tigation; supervision; writing—review & editing; resources. Thomas A.
Nakagawa: Conceptualization; methodology; writing—review & edit-
ing; investigation; supervision. Anthony A. Sochet: Conceptualiza-
tion; methodology; data curation; investigation; formal analysis;
supervision; project administration; writing—original draft; writing—
review & editing.
ACKNOWLEDGME NT S
The authors acknowledge clinical trial research coordination support
through the Clinical and Research Pharmacy at Johns Hopkins All
Children's Hospital and biostatistical support provided through the
Johns Hopkins All Children's Hospital Institute for Clinical and
Translational Research and Data Coordinating Center.
CONFLIC T OF INTEREST STATEM ENT
The authors declare no conflict of interest.
DATA AVAILABILITY STATEMENT
All data collected for the study, including deidentified individual
participant data, as well as a data dictionary defining each field in the
data set, will be made available with investigator support after
approval of an IRB approved proposal with a data access agreement
in place via the Johns Hopkins All Children's Hospital Institute for
Clinical and Translational Research.
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SUPP ORTING INFO RM ATION
Additional supporting information can be found online in the
Supporting Information section at the end of this article.
How to cite this article: Roddy MR, Sellers AR, Darville KK,
et al. Dexamethasone versus methylprednisolone for critical
asthma: a single center, open‐label, parallel‐group clinical trial.
Pediatric Pulmonology. 2023;58:1719‐1727.
doi:10.1002/ppul.26386