PAEDIATRICS JOURNAL CLUB

Rekha (Rekz)
Intern
 ORAL PREDNISOLONE IN PRESCHOOL CHILDREN
WITH VIRUS-ASSOCIATED WHEEZE: A PROSPECTIVE,
RANDOMISED, DOUBLE-BLIND, PLACEBO-
CONTROLLED TRIAL
BRONCHIOLITIS VS. VIRAL INDUCED
WHEEZE VS. ASTHMA
INTRODUCTION
❖ One in three children generally have an episode
of Viral Induced Wheeze (VIW) before their 3rd
birthday.

❖ Prevalence of wheeze almost 50% at 6 years.

❖ 88% of preschool age kids have detectable virus

as causative agent.
INTRODUCTION
❖ Beneficial role of corticosteroids in adult asthma
has been proven, however minimal evidence in
corticosteroid use in paediatric wheeze.

❖ Current guidelines no longer recommend

corticosteroids as first-line therapy in treating
wheeze
EXISTING EVIDENCE
❖ Most recent study in 2009 concluded that oral
prednisolone was not superior to placebo in pre-
school aged children
❖ Previous studies prior to this proved that oral
prednisolone effectively reduced disease
severity, length of hospital stay and the
duration of symptoms between ages 6-35
months with virally induced respiratory
distress.
❖ Both studies received criticism that they
included patients with bronchiolitis rather than
VIW alone
AIM
❖ To assess the efficacy of oral prednisolone in
children presenting to a paediatric emergency
department with suspected virus-associated
wheeze.
STUDY DESIGN
❖ Prospective, randomised, double-blind, placebo-
controlled trial

❖ Paediatric emergency department of Princess

Margaret Hospital in Perth, WA

❖ Patients randomly assigned to 3 day course of

oral prednisolone or placebo
METHOD
❖ A total of 605 patients selected between June 11
2012 to June 10th 2015, aged between 24-72
months, that presented to ED
➢ 300 patients placebo, 305 patients prednisolone
❖ Clinical diagnosis of wheeze plus
symptoms/signs of viral URTI
❖ Given 3 days of oral prednisolone
❖ Inpatient length if stay calculated from time of
admission to time of discharge.
❖ Follow-up via completion of 7-day symptom
diary and 10 day and 3 month phone call
EXCLUSION CRITERIA
❖ O2 Saturations <92% on RA
❖ Features of critical wheeze
➢ Silent chest on auscultation
➢ Exhaustion with/without cyanosis
❖ Shock/Bacterial sepsis
❖ Active varicella infection
❖ Inhaled foreign body
❖ Previous ICU admission with wheeze or asthma
❖ Premature birth <34 weeks gestation
❖ Known cardiac or respiratory disease
❖ Ongoing immunosuppression therapy or immuno-
deficiency
❖ Upper respiratory tract abnormality
❖ Oral corticosteroid therapy within the preceding 14 days
❖ Known allergy to prednisolone
DISCHARGE CRITERIA
❖ Respiratory status improvement
❖ Nil wheeze
❖ Good air entry bilaterally
❖ Tolerating 3 hourly bronchodilator therapy
❖ Clinical parameters within normal age
appropriate range
OUTCOMES MEASURED
❖ Primary Outcomes
➢ Total length of stay within the hospital until ready
for discharge, calculated as the difference in time
between the time of drug administration and the
clinical state ready for discharge.
❖ Secondary Outcomes
➢ Re-admission/re-attendance to hospital or GP post
7 days after hospital discharge
➢ Mean number of salbutamol Tx given in hospital +
during first 7 days post-discharge
➢ Mean duration of residual symptoms after D/C
➢ Incidence of additional therapies introduced
RESULTS
SELECTION CRITERIA
BASELINE CHARACTERISTICS OF COHORT
LENGTH OF STAY UNTIL READY FOR
DISCHARGE
CHILDREN REMAINING IN HOSPITAL OVER
TIME
VIRUS DETECTION
RESULTS SUMMARISED
❖ Median length of stay until ready for D/C was
longer in placebo group (540 mins [IQR 124-
971]) than in the prednisolone group (370 mins
[IQR 121-709])
❖ Placebo inferior to prednisolone
➢ Prednisolone - 95% Confidence interval 0.71 -1.52,
thus proving it is not inferior
❖ Prednisolone was more efficient compared to
placebo as length of stay in hospital increased -
at approx 200 mins
RESULTS SUMMARISED
❖ Analysis by severity based on pulmonary score
➢ Mild subgroup - prednisolone reduced length of
stay exceeding 12 hours after admission (p=0.0329)
➢ Severe subgroup - prednisolone reduced length of
stay exceeding 7 hours after admission (p=0.0428)
❖ Within the group who had received inhaled
salbutamol before attending ED, prednisolone
had an overall reduced length of stay and
reduced risk of exceeding 7h or 12h, but NOT in
patients who did not receive prior salbutamol
RESULTS SUMMARISED
❖ Follow-up data
➢ Re-admission into ED - 26 patients
■ 15 from prednisolone group
■ 13 from placebo group
➢ Of these, 15 patients were discharged directly from
ED
■ 9 from prednisolone group
■ 6 from placebo group
➢ Re-prescribed steroids at re-presentation
■ 3 from prednisolone group
■ 2 from placebo group
➢ 34 patients (6%) did not complete the 3 day course
of study drug after discharge
RESULTS SUMMARISED
❖ No serious adverse events reported from follow-
up period
❖ One child in placebo developed non-specific
maculopapular rash 5h after receiving drug,
which resolved spontaneously - (withdrawn from
study)
❖ Two kids (one from each group) were reported to
be hyperactive
LIMITATIONS
❖ Single hospital centre
❖ Difficulties to recruit as ED busy with staff
working shift work
❖ Rotational staff required repeated training,
resulting in high non-participation rates
❖ 5% of patients had protocol deviation - received
prednisolone after receiving study drug
❖ Pulmonary score used to assess severity not
fully validated in children aged <5
CONCLUSION

❖ Oral prednisolone had a clear benefit compared

with the placebo in reducing the length of stay
in children with viral-induced wheeze

❖ Greatest efficacy seen in:

➢ Greatest severity at presentation
➢ Receiving salbutamol prior to presentation
CLINICAL SIGNIFICANCE
❖ Further research should be undertaken to
further evaluate the benefits of steroids in VIW,
as this has shown to aid in recovery and
decreased hospital stay, benefiting the patient
and the economy

❖ Given the ambiguity between bronchiolitis, VIW

and asthma, it makes it difficult for definitive
answers
REFERENCES
 Foster SJ, Cooper MN, Oosterhof S and Borland
ML (2018) “Oral Prednisolone in Preschool
Children with Virus-Associated Wheeze: A
Prospective, Randomised, Double-Blind,
Placebo-Controlled Trial,” The Lancet.
Respiratory medicine, 6(2), pp. 97–106. doi:
10.1016/S2213-2600(18)30008-0.
 Steroids in wheeze,
https://dontforgetthebubbles.com/steroids_in_w
heeze_meredith_borland_at_dftb18/