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Three Part Question

In [children with asthma] do [non-steroidal anti-inflammatory drugs] lead to [exacerbation of asthma]?

Clinical Scenario

A 7 year-old asthmatic boy presents to the Emergency Department with a history of fever that has not settled despite paracetamol. You consider prescribing ibuprofen but the staff nurse is concerned that this will cause an exacerbation of his asthma. You wonder whether there is any evidence for this.

Search Strategy

Medline 1966-07/04 using the OVID interface.
[exp Ibuprofen OR ibuprofen.mp OR nurofen.mp OR exp Anti-Inflammatory Agents, Non-Steroidal OR NSAID$.mp] AND [exp Asthma OR exp Asthma, exercise induced OR wheeze.mp OR exp Bronchial Spasm OR exp bronchospasm.mp] LIMIT to human AND English language AND the BestBETs Paediatric Filter.

Search Outcome

Altogether 301 papers were found of which 299 did not answer the study question. The remaining two are summarised in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Short et al 2000 UK	70 children aged 6-15 years with a diagnosis of asthma, recruited from a hospital respiratory clinic or at presentation for day case surgery All patients given 1-1.5mg/kg PO diclofenac after baseline spirometry and after filling a questionnaire detailing the severity of their asthma	Clinical trial	Change in PEFR or FEV1 at 10, 20 & 30 min post-diclofenac	No patient showed fall > 15% in PEFR or FEV1	Uncontrolled, no healthy volunteers to compare with specific population No sample size analysis; sample size of 70 seems small 15% reduction in PEFR or FEV1 considered significant but no explanation offered as to why this figure was chosen
Lesko et al 2002 UK	1879 febrile children (aged 6 months to 12 years) receiving asthma medications randomised to receive either paracetamol 12mg/kg, ibuprofen 5mg/kg or ibuprofen 10mg/kg	Prospective randomised double-blind controlled trial	Hospitalisation rates for asthma over four weeks	Relative risk for hospitilisation in ibuprofen group of 0.63 (95% confidence interval 0.25 - 1.6) 18 admitted	Original study was not designed to look at these outcomes No objective measure of pulmonary function - follow-up by case note review and parental questionnaire Wide confidence intervals for first outcome No power calculations No details of randomisation process
			Outpatient visits for asthma over four weeks	Relative risk in ibuprofen group 0.56 (95% confidence interval 0.34 - 0.95) 69 patients

Comment(s)

Non-steroidal anti-inflammatory medications (NSAIDs) are often withheld from asthmatic children for fear that they may cause an exacerbation of the condition. Although aspirin-induced bronchospasm has been described in the literature, there are no case reports relating to NSAID-induced bronchospasm in children. The two clinical trials that have investigated this problem have not established any link. The paper by Lesko, Louik et al actually demonstrated a statistically significant reduction in outpatient consultations for asthma in the ibuprofen-treated group. This may have been a chance result. Alternatively, it may be that either paracetamol can induce bronchospasm or that NSAIDs lead to an improvement in bronchial tone, perhaps as a result of their anti-inflammatory action. A third paper, by Lesko and Mitchell (1), investigated the safety of ibuprofen and paracetamol in children under two years of age. Although the paper did not answer the three-part question directly, they randomised a total of 27,065 febrile children to receive either paracetamol, ibuprofen 5mg/kg or ibuprofen 10mg/kg. There was no increase in the incidence of hospitalisation with asthma or anaphylaxis in the ibuprofen-treated group. From the available evidence, it would appear that NSAIDs are safe to use in asthmatic children.

Editor Comment

External comment from Christopher Douglas Palmer – 18th April 2004 Re: JA Short, CA Barr, CD Palmer et al. Use of diclofenac in children with asthma. Anaesthesia 2000;55(4):334-337: As one of the authors of this study, I agree with your comments about the limitations of the study. The relatively small size was not intentional and the original intention was to study 200 children. However, it proved more difficult than initially anticipated to recruit suficient subjects for the study. This was due to a combination of a surprisingly small number of children presenting to a hospital respiratory clinic being suitable candidates for the trial and difficulties obtaining consent. Eventually, power calculations were re-examined and it was determined that 70 children would be just sufficient to show that the incidence of bronchospasm after diclofenac was unlikely to be a significant problem.

Clinical Bottom Line

There is no evidence that non-steroidal anti-inflammatory drugs lead to exacerbation of asthma in children.

References

1. JA Short, CA Barr, CD Palmer et al. Use of diclofenac in children with asthma. Anaesthesia 2000;55(4):334-337.
2. Lesko SM, Louik C, Vezina RM, Mitchell AA. Asthma Morbidity After the Short-Term Use of Ibuprofen in Children. Pediatrics 2002;109(2): E20.
3. Lesko SM, Mitchell AA. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics 1999;104(4):e39.