ISAAC blows wheezy whistle on APAP
26 January, 2012 by: colinparkerThis debate is going to be HUGE… Does paracetamol (acetaminophen) cause asthma?
A series of large international studies and reviews dedicated to the question raise some interesting questions. There appears to be an epidemiological association – not the same as a causal association – but something’s going on…
For those of us who have been using APAP (=acetaminophen, =paracetamol) liberally throughout our paediatric careers, this new evidence comes as bit of a shock. You can hear it in the way we talk about these studies – trying not to let evidence get in the way of our own prejudices!
Outline: ISAAC vs APAP
[cp] Welcome, introduction, disclaimer
[cp] Background
Previous PEMcasts on fever and antipyretics
Advantages of antipyretics:
- relieve pain
- improve comfort
- can facilitate clinical assessment
[sf] Disadvantages of antipyretics:
- Do not prevent febrile convulsions
- May increase fever phobia
- Unhelpful in risk stratifying Fever Without Source
- May prolong infective illness
- Impair immune response to vaccination
[RR] APAP = N-Acetyl Para-Amino-Phenol
= acetaminophen = paracetamol
Most widely used drug in pediatrics, increasing use in last 30 years.
Recent market favour towards ibuprofen despite concerns of gastric inflammation, renal damage, wheezing.
[cp] Several papers now added to initial ISAAC 2008 publication; lessons from history include aspirin, phenacetin, thalidomide.
[cp] Beasley 2008 & accompanying editorial (Barr 2008)
[sf] Etminan 2009
[cp] Beasley 2011
[RR] McBride 2011
Often referenced: Lesko 2002
[all] Conclusions, goodbye
References
Beasley R, Clayton T, Crane J, von Mutius E, Lai CK, Montefort S, Stewart A;
ISAAC Phase Three Study Group.
Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme.
Lancet. 2008 Sep 20;372(9643):1039-48. PubMed PMID: 18805332.Barr RG.
Does paracetamol cause asthma in children? Time to remove the guesswork.
Lancet. 2008 Sep 20;372(9643):1011-2. PubMed PMID: 18805311.Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, Fitzgerald JM.
Acetaminophen use and the risk of asthma in children and adults: a systematic
review and metaanalysis.
Chest. 2009 Nov;136(5):1316-23. Epub 2009 Aug 20. Review. PubMed PMID: 19696122.Beasley RW, Clayton TO, Crane J, Lai CK, Montefort SR, Mutius E, Stewart AW;
ISAAC Phase Three Study Group.
Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three.
Am J Respir Crit Care Med. 2011 Jan 15;183(2):171-8. Epub 2010 Aug 13. PubMed PMID: 20709817.McBride JT.
The association of acetaminophen and asthma prevalence and severity.
Pediatrics. 2011 Dec;128(6):1181-5. Epub 2011 Nov 7. PubMed PMID: 22065272.Lesko SM, Louik C, Vezina RM, Mitchell AA.
Asthma morbidity after the short-term use of ibuprofen in children.
Pediatrics. 2002 Feb;109(2):E20. PubMed PMID: 11826230.ISAAC Website: http://isaac.auckland.ac.nz/







Hi Colin
Really fascinating debate. Lots of well held medical memes up for busting. As you conclude – it is hard to know how to apply this data to the patient sitting in front of you – the risk/benefit trade off is tough to quantify.
If you have a good indication for panadol then I think this data doesn’t really mean you should not use it.
However, as an institution – should we be systemically dosing kids with paracetamol at triage for fever, URTI etc – maybe not. Especially in kids with that atopic predilection we just might be doing harm.
I think I will try to change my departmental preferences / practice, but still look at the individual kid before throwing Panadol at them.
Casey
Hey Casey
Thanks for your comment, and the link from your related excellent post on your Broome Docs blog – well worth a read and adds a lot to our PEMcast.
Keep up the webucation!
Cheers
Colin