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Three Part Question

In [febrile children with a past medical history of asthma], is [ibuprofen in antipyretic doses compared to paracetamol], more likely to [cause an acute exacerbation of asthma]?

Clinical Scenario

A 4 year old child presents to the paediatric accident and emergency department with a history of fever for 12 hours and clinical signs of an upper respiratory tract infection. The temperature on assessment is 39.5°C. There is a past medical history of asthma. The attending emergency doctor prescribes ibuprofen. The mother is not willing to give ibuprofen to her child, as she was told in the past that it is contraindicated in children with asthma.

Search Strategy

Cochrane Databases of Systematic Reviews
Pubmed
Pubmed: "Paracetamol" OR "Ibuprofen" AND "Asthma". Limits: All child: 0–18 years, English Language; 30 hits, three relevant.

Search Outcome

Journals@Ovid in Athens (ovid) database: "paracetamol" OR "acetaminophen" AND "Ibuprofen" AND "Asthma"; 218 Hits; three relevant (one, same study as above).
Cochrane - none relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lesko et al, 2002	Total 1879 febrile children 6 mth–12 years receiving asthma medicationGroup1: 632 children receiving paracetamol 12 mg/kg/doseGroup 2: 636 children receiving ibuprofen 5 mg/kg/doseGroup 3: 611 children receiving ibuprofen 10 mg/kg/dose	Randomised controlled trial	Outpatient visits for asthma or hospitalisation for asthma during 4 weeks post-medication	69 (3.4%) documented outpatient visits: 32 in group 1 and 37 in groups 2 and 3	Ibuprofen was found to be less likely to exacerbate asthma when compared to paracetamol. Children with known hypersensitivity to paracetamol or NSAIDs were excluded
McIntyre and Hull, 1996	Febrile inpatient children (2 mth–12 years)Group 1: 76 received ibuprofen (11 had wheeze or asthma, 21 had a history of asthma or wheezing)Group 2: 74 received paracetamol (4 with asthma or wheezing and 12 with a history of asthma or wheezing)	Randomised controlled trial	Change in axillary temperature, palatability, changes in clinical condition, number and nature of adverse effects	10/76 (13%) patients in the ibuprofen group had 16 adverse events, 14/74 (19%) patients in the paracetamol group had 18 events. This was statistically not significant. No patients had an asthma attack, but two became wheezy, both in the paracetamol group	The majority of all adverse events was considered to be either mild or not in relation to the treatment. Children with known hypersensitivity to paracetamol or NSAIDs were excluded

Comment(s)

All three references highlighted by Pubmed using the above search strategy were published by Lesko et al. The data used in all papers were originally derived from the Boston University Fever Study. Therefore, the data described in 2002 and 1999 are overlapping. The original Lesko study (1999) was double blind, randomised, and controlled; patients received either paracetamol in a dose of 12 mg/kg or ibuprofen in a dose of 5 or 10 mg/kg. To establish the asthma morbidity after the short term use of ibuprofen in children (Lesko, 2002) the data were restricted to include only children being treated for asthma, defined as those who had received a ß-agonist, theophylline, or an inhaled steroid on the day before enrolment in the clinical trial. Morbidity from asthma was defined as a report of hospitalisation or outpatient visit for asthma in the month after enrolment. To establish the asthma morbidity after the short term use of ibuprofen in children (2002) the data were restricted to include only children being treated for asthma, defined as those who had received a ß-agonist, theophylline, or an inhaled steroid on the day before enrolment in the clinical trial. Morbidity from asthma was defined as a report of hospitalisation or outpatient visit for asthma in the month after enrolment. The data suggested that there was a significantly lower rate of exacerbations of asthma in children receiving ibuprofen compared to children receiving paracetamol. The authors argue that this could be due to the anti-inflammatory action of ibuprofen. The study by McIntyre and Hull was conducted on an inpatient population, which included children with asthma or wheezing. The results showed that no child receiving ibuprofen (including 32 with asthma or a past medical history of asthma) developed symptoms of asthma or wheezing. In both studies, patients were excluded if there was a known hypersensitivity to paracetamol, ibuprofen, aspirin, or any NSAIDs. Children were also excluded if they had nasal polyps, angioedema, or bronchospastic reactivity to aspirin or other NSAIDs. This small group of children remains potentially vulnerable to ibuprofen or other NSAIDs.

Clinical Bottom Line

Ibuprofen used as an antipyretic in febrile children with a past medical history of asthma is as least as safe as paracetamol and not likely to exacerbate asthma. Ibuprofen should not be used in children with known hypersensitivity to NSAIDs. The possibility of adverse reactions remains in children who have not received NSAIDs at any time in the past.

References

1. Lesko SM. The safety of ibuprofen suspension in children. Int J Clin Pract Suppl 2003;(135):50–3.
2. Lesko SM, Louik C, Vezina RM, et al. Asthma morbidity after short term use of ibuprofen in children. Pediatrics 2002;109:e20.
3. Lesko SM, Mitchell AA. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics 1999;104:e39.
4. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen: a practitioner-based randomized clinical trial. JAMA 1995;273:929–33.
5. McIntyre J , Hull D. Comparing efficacy and tolerability of ibuprofen and paracetamol in fever. Arch Dis Child 1996;72:164–7.