This systematic review and meta-analysis evaluated the efficacy of oral corticosteroids for acute wheezing episodes in asthmatic preschoolers. The analysis included 11 randomized controlled trials involving oral corticosteroid treatment compared to placebo. The results showed no significant differences overall between corticosteroids and placebo for hospital admissions, need for additional corticosteroid treatment, or unscheduled visits. However, corticosteroids may reduce hospital admissions and additional corticosteroid need for more severe cases presenting to the emergency department or requiring hospitalization. The evidence was deemed inadequate to form clinical recommendations due to limitations in the studies.

1. EFFICACY OF ORAL CORTICOSTEROIDS IN THE
TREATMENT OF ACUTE WHEEZING EPISODES IN
ASTHMATIC PRESCHOOLERS: SYSTEMATIC REVIEW WITH
META-ANALYSIS
Jose A. Castro-Rodriguez,Andrea A. Beckhaus and Erick Forno
Pediatric Pulmonology · April 2016
Presented by : Surg Lt Cdr Manas R Mishra
Moderator : Lt Col Deepak Joshi

2. THE WHEEZING CHILD
 Common paediatric presenting problem
 End point of variety of pathological
processes
 Large burden of disease
 Frequent diagnostic uncertainty
 Wide variations in management protocols
and guidelines
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3. THE WHEEZING CHILD
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Bronchiolitis
Asthma
Virus-
induced
wheeze
Pneumonia
Chronic
cough

4. AGE OF PRESENTATION
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5. VIRUS-INDUCED WHEEZE
 Between one quarter and one half of all pre-school
children have symptoms of wheeze with a respiratory
infection
 Most do not go on to develop asthma
 Under-5s with episodic wheeze but without interval
symptoms do not have asthma-type airway
inflammation, and are not helped by steroids
 Episodes of wheeze and a history of atopy are strongly
predictive of those who will develop asthma
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6. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

7. EPISODIC VIRAL WHEEZING
 Wheezing during discrete time periods in an otherwise
healthy child who is without symptoms between these
episodes.
 Wheezing episodes are generally associated with a clinical
diagnosis of viral upper respiratory tract infection (URTI).
 Rhinovirus, respiratory syncytial virus (RSV), coronavirus,
human metapneumovirus, parainfluenza virus, and
adenovirus
12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

8. ASTHMA
 Asthma is a chronic inflammatory condition of lung
airway resulting in episodic airway obstruction.
 Annual rate of emergency department (ED) visits is 23–42
per 1,000 for preschoolers versus less than 15 per 1,000
for those aged 6–70 years.
 48% of preschoolers with asthma have an exacerbation
in the preceding year
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9. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

10. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

11. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

12. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

13. OBJECTIVES OF THE STUDY
 Evaluate the efficacy of oral corticosteroids use in children up
to 6 years of age (including infants, toddlers, and
preschoolers) presenting with recurrent wheezing
exacerbations or acute asthma.
 Reason : In recent trials efficacy of oral corticosteroids in
preschoolers does not support their efficacy
12-May-16

14. METHODS
 This study was
 Registered with International Prospective Register of
Systematic Reviews (PROSPERO)
 PRISMA (Preferred Reporting Items for Systematic
Reviews and Meta-Analyses) guidelines followed
 Search and Selection Criteria:
 Studies published in MEDLINE, EMBASE, CINAHL,
SCOPUS,and the Cochrane Controlled Trials Register
(CENTRAL) databases and ClinicalTrials.gov until May
2015 included.
12-May-16

15. INCLUSION CRITERIA
Studies which met the following :
 Children < 6 years of age with recurrent wheezing/asthma
exacerbations of any severity presenting to the ED, receiving
t/t at home (“outpatient studies”) or hospitalized (“inpatient
studies”)
 Randomized clinical trials (RCTs; parallel group or cross-
over design) of any duration
 Comparison of oral Corticosteroids (any type) versus
placebo.
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16. TECHNICAL ASSESSMENT
 According to recommendations outlined in the Cochrane
Handbook
 Adequacy of sequence generation;
 Allocation concealment;
 Blinding of participants and investigators;
 Blinding of outcome assessment;
 Incomplete outcome data;
 Selective outcome reporting, and other bias.
12-May-16

17. EXCLUSION CRITERIA
 Studies involving: Abstracts, letters, reviews, pooled
analysis, Unregistered RCT.
 Studies Failing Technical assessment
 Studies not meeting inclusion criteria
 Sample duplication: Studies including the same
population as another study
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18. OUTCOMES
PRIMARY :
 Hospital Admission,
 Need for additional courses of SCS
 Unscheduled visits to the ED in the 4weeks period
following the trial
 Length of hospital stay,
SECONDARY
Improvement of lung function measured (FEV1) or
(PEF), symptom scores, withdrawals (total and due to
adverse effects [AEs]), and safety (AEs and serious AEs)
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19. DATA EXTRACTION AND ASSESSMENT OF RISK
OF BIAS:
 Independently analyzed by the two authors
 Risk of bias assessment according to the
Recommendations outlined in the Cochrane Handbook
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20. DATA ANALYSIS
 Analysis was performed by intention to treat and
included all participants to minimize bias.
 Outcomes were pooled using mean differences (MD)
(inverse variance method) or Mantel–Haenszel risk
ratios (RR).
 Heterogeneity was measured by the I2 test
 ≤25% absence of bias;
 26–39% unimportant;
 40–60% moderate; and
 60–100% substantial bias).
12-May-16

21.  Subgroup analyses :
 Type of oral Corticosteroids
 Age (<2 vs. >2 years old)
 Severity of exacerbation (mild vs. moderate to
severe)
 Trials sponsored by pharmaceutical industry versus
independent trials.
 The meta-analysis was performed with the Review
Manager 5.3.5 software
12-May-16

22.  Snap shot pg 3
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23. 12-May-16

24.  Total 11 RCTs-
 UK- 6, USA- 3, Israel- 1, Finland- 1
 OPD-4, IPD-5, ED-2
 Steroids Used:
 Prednisolone-07 ,
 Prednisone-02 ,
 Methylprednisolone -01
 Hydrocortisone followed by prednisolone- 01
(Most studies maintained the treatment for 3–5 days)
 Single dose of OCS- 02
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25. RESULTS : PRIMARY OUTCOME
Hospital Admissions:
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26. OVERALL HOSPITAL ADMISSIONS
 Fig 2 a
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27. OUTPATIENT STUDIES AND HOSPITAL
ADMISSIONS
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28. ED STUDIES AND HOSPITAL ADMISSIONS.
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29. HOSPITAL ADMISSIONS
12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC
OCS placebo
Overall No difference
(RR-1.0, CI: 0.49-2.05)
ED/Inpatient Low risk
RR-0.58CI-
0.37-0.92
Out patient Higher risk
RR-2.15
Subgroup <2 yrs
older
No differencce

30. ADDITIONAL COURSE OF SYSTEMIC
CORTICOSTEROIDS
 Inpatient studies : significant difference favoring OCS group
(RR: 0.57;95%CI: 0.40–0.81; I2=0%, P=0.34)
 Outpatient studies reported the need for additional courses
of SCS showing no significant difference between OCS and
placebo(RR: 0.74; 95%CI: 0.40–1.34)
 Over 4 years of age there was no significant difference in
OCS and placebo group.
 Subgroup analysis was not performed due to insufficient
data.
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31. 12-May-16

32.  Fig 3a
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33. UNSCHEDULED VISITS
 Three inpatient studies reported there was no significant
statistical difference between OCS and placebo (RR:
0.73; 95%CI: 0.35–1.52)
 One out patient study reported more ED consults in
OCS group than placebo during treatment period
 Subgroup analysis was not performed due to insufficient
data.
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34.  Fig 4
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35. HOSPITAL LENGTH OF STAY
 No difference in hospital length of stay in both groups.
 Only one study reported the OCS group had a shorter
stay.
12-May-16

36. SECONDARY OUTCOMES
 Outpatient and ED studies did not give any data on pulmonary
function.
 Two inpatient studies found an improvement in PEF
measurements in the OCS
 Outpatient and in patient studies found no differences between
OCS and placebo on symptom scores but ED studies found better
symptom improvement in the OCS group
 No relevant AEs reported.
 Insufficient data to perform meta analysis of AE
12-May-16

37. PATHOPHYSIOLOGY AND DRUG RESPONSE
 Asthma in pre school children is mostly triggered by
episodic viral infection with different virus producing
different immune response.
 Other factors affecting OCS response
 Dosage of OCS
 Timing of administration
 Vitamin D deficiency
 Genetic predisposition
12-May-16

38. 12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC
Prednisolone reduces wheezing relapse in children with acute
rhinovirus infection, this effect was not observed in children with
acute respiratory syncytial virus infection.

39. DISCUSSION
 In studies conducted in ED, OCS treatment was associated
with a lower hospitalization rates
 In the inpatient settings, OCS treatment was associated with
a lower need for additional courses of SCS
 In the outpatient studies, however, OCS administration was
associated with more hospital admissions
 It was stated that, the dosage (single or multiple) of OCS
used in these eleven RCTs was adequate.
12-May-16

40.  Considering the overall group there is no evidence that OCS
administration is effective compared to placebo in any
primary or secondary outcomes.
 Largest study in this group had a high rate of treatment
noncompliance
 Behavioral changes have been reported in children during
OCS therapy, and this factor might affect the clinical decision
to admit to the hospital
12-May-16

41.  The use of OCS in the treatment of recurrent wheezing
in infants, toddlers, and preschoolers remains
controversial.
12-May-16 Dr Manas R Mishra, Department of Pediatrics, AFMC

42. PITFALLS OF THE STUDY
 Allocation concealment in most were unclear
 Different protocols were used in each study
 One study was post hoc analysis
 Mean age was preschool age group but some studies
included older children.
 Not enough data to measure lung function or symptom
score or adverse effect. (secondary outcomes)
12-May-16

43. SUMMARY
 Current evidence is inadequate to formulate any broad
clinical recommendations regarding the use of OCS in
infants, toddlers, and preschoolers with recurrent
episodes of acute wheezing.
 OCS might potentially be beneficial (lower hospital
admission rates and less need for additional courses of
systemic steroids) in children with more severe
asthma/wheezing exacerbations that present to the ED or
require hospitalization
 Future studies should have standardized case definition,
larger sample size, and more homogeneous
methodological quality
12-May-16

44. THANK YOU…..