ISAAC blows wheezy whistle on APAP

26 January, 2012 by: colinparker

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This 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


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:

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3 Responses to “ISAAC blows wheezy whistle on APAP”
  1. Casey says:

    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.


  2. colinparker says:

    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!



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