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Three Part Question

In [preschool children with viral induced wheeze] do [oral steroids] result in [fewer symptoms, shorter stay in hospital]

Clinical Scenario

An 18month old girl presents to A&E with coryzal symptoms and wheeze. You wonder whether the addition of oral steroids (prednisolone) would lead to a faster resolution of her symptoms than bronchodilators alone.

Search Strategy

Medline on the pubmed interface, accessed 25th April 2005.
Cochrane database of systematic reviews, accessed 25/4/05
[wheeze OR viral wheeze OR viral respiratory infection] AND [orals steroids OR corticosteroids OR prednisolone]. Limited to [all infant (birth-23months) and english language]

Search Outcome

Medline search gave 159 hits, of which only 6 were relevant to the clinical question and are appraised below. 2 further articles were in journals which were not easily accessed and could not be appraised.
No relevant articles from cochrane search.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Webb et al 1986 UK	38 children less than 18 months with at least 2 previous wheezy episodes. Included if 48 hour history of wheeze, cough, tachypnoea, recession and disturbance of sleep or feeding. Excluded those needing inpatient care. Randomised to prednisolone 1mg/kg bd for 5 days or placebo. 18 children with ongoing symptoms or recurrent attack were crossed over to alternative treatment arm. Total 56 treatment courses.	Double blind, randomised controlled trial with partial crossover. CEBM = 1b	Twice daily subjective parent scoring of symptoms (cough, wheeze, shortness of breath) for 8 days from start of treatment. Max daily score 18	Median symptom scores (prednisolone;placebo): day 1 (9;9.5), day 3 (8;9), day 5 (7;5.5), day 7 (5;6). All NS by Mann-whitney test. Also no difference when split into 6 month age groups.	Subjective scoring system. Excluded hospital admissions so may select milder cases. Only started treatment once symptomatic for 48 hours. Final assessment at least 10 days after onset of symptoms.
			Symptom scores in 18 children who had crossover of both treatments.	No significant difference in symptom scores between placebo and prednisolone (no statistics)
			Subjective parental assessment 8 days post start of treatment whether the clinical course varied from previous episodes.	12/29 in prednisolone group said child benefited from treatment, 10/27 benefited with placebo. No significant difference between placebo and prednisolone (no statistics)
Daugbjerg et al 1993 Denmark	123 children aged less than 18 months admitted to hospital with wheezing over 2 winters. Randomly allocated to i) oral prednisolone & terbutaline nebuliser, ii) budesonide & terbutaline nebulisers, iii) terbutaline neb & placebo, iv) all placebo. Treatment arms i & iii relevant to BET. Prednisolone 4-6mg/kg on day 1, 1.6-2.6mg/kg days 2 &3. 9 pts excluded leaving 114 children.	Double blind placebo controlled multicentre study. CEBM = 1b	Symptom scores (0-3) for temperature, wheeze, respiratory rate, heart rate, accesory muscle use, prolonged expiration and general condition	Mean symptom score during admission 2.2 for prednisolone & terbutaline group, 2.4 for placebo and terbutaline. Non-significant (Mann-Whitney)	All children hospitalised. Significant number had RSV (33/107) or bacterial growth on swabs (57/108).
			Time from patient contact to	No difference between groups
			Number of days in hospital	Prednisolone & terbutaline mean 3.5 days, placebo & terbutaline mean 4.3 days. p=0.04 (Mann-whitney)
			No of doses administered	No difference between groups
			Treatment failure - withdrawl from trial due to worsening symptoms	Prednisolone & terbutaline 5/31; placebo & terbutaline 3/27 (NS Chi-squared). Both significantly better than placebo only group (14/27 failures; p<0.05 chi-squared)
Fox et al 1995 UK	62 children aged 3 - 15 months with a wheezing episode lasting over 48 hrs and at least one prevoius episode of wheezing. Excluded those with known cardio-respiratory illnesses and those who improved with salbutamol or ipratropium nebulisers. Inpatients and outpatients. 3 treatment groups i) salbutamol syrup & prednisolone 2mg/kg for 5 days, ii) salbutamol syrup & placebo, iii) placebo	Double blind RCT CEBM=1b	Twice daily parental symptom scores 0-3 for cough, wheeze, shortness of breath (max daily score 18) for 14 days	No significant difference in symptom scores between the three treatment groups eg day 3 median scores salbutamol syrup & prednisolone 9, salbutamol & placebo 7, both placebo 7. p=NS (Kruksal-wallace)	Waited 48 hours before treatment. Oral salbutamol not first line treatment of wheeze Subjective parent scoring
			Proportion of children with minor symptoms (daily score<6)	No significant difference in symptom scores between the three treatment groups eg day 5: salbutamol syrup & prednisolone 11/20, salbutamol & placebo 12/21, both placebo 10/21. p=NS (Kruksal-wallace)
			Number of additional doses of salbutamol syrup required (over tds)	No significant difference in median number of daoses: prednisolone group 5, placebo & salbutamol 12 p=NS (kruksal-wallace)
			No. days in hospital	Median number of days: prednisolone & salbutamol 1 day, placebo & salbutamol 1 day (p=NS)
			Treatment failure (re-admission, persistent symptoms for >14 days)	Prednisolone & salbutamol 4/20 failures, placebo & prednisolone 3/21 failures (p=NS). relative risk of failure without steroids = 0.71
Chavasse et al 2002 UK	Children under 1 year of age admitted to hospital with acute wheeze.	Questionnaire based study of consultant paediatricians. CEBM=5	Reported use of oral steroids for acute wheeze	84% of consultants said they used oral setroids for acute wheeze in under ones.	No specific information on symptoms, no typical case history presented. No information on dose or type of steroid preferred. Outcome measure not directly relevant to BET.
			Vital signs (Pulse and BP) at times as above	No significant change in vital signs seen after any route of administration
Oommen et al 2003 UK	Children aged 1-5 years admitted to hospital with wheeze and co-existing coryzal symptoms. Excluded chronic respiratory problems. Randomised to prednisolone 20mg daily for 5 days or placebo to be taken at home at the onset of next wheezy episode.	Double blind RCT with stratification for systemic eosinophil priming (measure of atopic tendency). CEBM=1b	Parental assessment of symptom scores by day (cough, wheeze, breathlessness and impaired activity) Score 0-3	Mean daytime symptom scores for 7 days: Prednisolone 0.95, placebo 0.96 p=NS, 95% CI for difference in means -0.22 - 0.2	Mild symptom scores and little use of salbutamol - ? enough illness for effect to be seen. Concerns over compliance and parental assessment of need to start steroids.
			night time symptom score (sleep disturbance). 0-3	Mean score: prednisolone 0.92, placebo 0.82, p=NS, 95% CI for means -0.12 - 0.32
			heart rate and BP at 0, 10 and 30mins	No difference between nor within groups
			Use of inhaled salbutamol - geometric mean of number of actuations per day	Prednisolone 1.59, placebo 1.66 (p=NS)
			Need for hospital admission	6/52 children on prednisolone admitted, 2/69 on placebo (p=0.06, chi-squared) Trend towards prednisolone group having more admissions.
			Treatment failure - need to withdraw from trial due to progressive symptoms	Prednisolone 9/52, placebo 8/69 (p=NS, chi-squared)
			Parents opinion on whether treatment was effective	Prednsiolone 17/23, placebo 21/33 (p=NS, chi-squared)
			All above outcomes when cohort divided into high-primed and low-primed based on stratification for systemic eosinophil priming (measure of atopic tendency).	No significant differences between response to steroids between high and low-primed groups.
Csonka et al 2003 Finland	230 children aged 6-35 months presenting to A&E with tachypnoea, wheezing or accessory muscle use in presence of apparent viral illness. Excluded those with more than 2 previous episodes. treatment: 2mg/kg prednisolone bd or placebo	Double-blind RCT, placebo controlled parallel group trial CEBM=1b	Development of severe respiratory symptoms needing further treatment	Prednisolone group 11/61, placebo 23/62 (p=NS, cho-squared) NNT to prevent one child needing rescue medication = 5 children.	Doesn't cover those children with recurrent wheeze. Subjective parental diary cards
			Admission to hospital	Prednisolone 61/113, placebo 62/117 (p=NS, chi=squared)
			Median length of stay	Prednisolone 2.0 days, placebo 3.0 days (p=NS, chi-squared)
			Hospital stay 3 or more days	Prednisolone 29/61, placebo 42/62 (p=NS, chi-squared). NNT to prevent stay >3days = 5 children.
			Duration of symptoms (based on parental diary cards)	Median duration of symptoms: prednisolone 1.0days, placebo 2.0 days (p<0.01, Mann Whitney)
			Children with symptoms lasting 3 or more days (based on parental diary cards)	Prednisolone 21/113, placebo 46/117 (p=0.001, chi-squared). NNT to prevent symptoms >3 days = 5 children.
			Reattendence to medical care after discharge	Prednisolone 15/105, placebo 23/112 (p=NS, chi-squared) data missing from 13 children.

Comment(s)

Wheezing conditions are amongst the commonest causes for hospital admission in infants. There appears to be little consistency in their management as highlighted by this heterogenious group of studies in terms of ages, severity of symptoms, additional medications and when steroids were commenced. 2 studies show shorter hospital stay in those children receiving oral steroids although only 1 shows benefit in terms of duration or severity of symptoms. No significant side effects reported in any study.

Clinical Bottom Line

No clear evidence to recommend the use of oral steroids in preschool viral wheeze, however with no reported side-effects and a majority of consultants using them, oral steroids may be worth a try pending conclusive evidence of their efficacy.

References

1. Webb M, Henry R & Milner A Oral corticosteroids for wheezing attacks under 18 months. Archives of Disease in Childhood 1986 vol 61 p15-19.
2. Daugbjerg P, Brenoe E, Forchhammer H, Frederiksen B, Glazowski M, Kaas Ibsen K, Knabe N, Leth H, Marner B, Karup Pedersen F, Zahle Ostergaard G A comparison between nebulised terbutaline, nebulised corticosteroid and systemic steroid for acute wheezing in children up to 18 months of age Acta Paediatr 1993, vol 82 p547-551
3. Fox G, Marsh M, Milner A Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone. Eur J Pediatr 1996 Vol 155 p512-516.
4. Chavasse R, Bastian-Lee Y, Seddon P How do we treat wheezing infants? Evidence or anecdote Arch Dis Child 2002 Vol 87 p546-7.
5. Oommen A, Lambert P, Grigg J Efficacy of a short course of parent initiated oral prednisolone for viral wheeze in children aged 1-5 years: randomised controlled trial The Lancet 2003 Vol 362(1) p1433-38.
6. Csonka P, Kaila M, Laippala P, Iso-Mustajarvi M, Vesikari T, Ashorn P Oral prednisolone in the acute management of children aged 6 - 35 months with viral respiratory infection-induced lower airway disease: a randomised, placebo-controlled trial Journal of Pediatrics 2003 vol 143 p725-30