Data from epidemiological studies suggesting a link between paracetamol use and increased risk of asthma have been conflicting. Researchers conducted a systematic review and meta-analysis to quantify this association. They searched the literature published between 1966 to 2008 for all clinical trials and observational studies, and identified 13 cross-sectional studies, four cohort studies, and two case-control studies comprising 425,140 patients. The following findings were reported:

• The pooled odds ratio for asthma among subjects using paracetamol was 1.63 (95% CI, 1.46 to 1.77).

• The risk of asthma in children among users of paracetamol in the year prior to asthma diagnosis and within the first year of life was elevated (1.60; 1.48 to 1.74 and 1.47; 1.36 to 1.56, respectively).

• Only one study reported the association between high paracetamol dose and asthma in children (3.23; 2.9 to 3.6).

• There was an increase in the risk of asthma and wheezing with prenatal use of paracetamol (1.28; 1.16 to 41 and 1.50; 1.10 to 2.05, respectively).

The researchers conclude that their findings indicate an increase in the risk of asthma with paracetamol use in both adults and children, as well as an increase in risk in children with a history of prenatal exposure to paracetamol. They note that confounding bias has been deemed to be one of the reasons for the positive association with paracetamol and asthma observed in observational studies, and accept that although they cannot disregard this possibility as a potential explanation for their results, they consider it unlikely that bias alone may be the sole explanation. They discuss several mechanisms that may explain the link with asthma, whether ibuprofen would have any advantages over paracetamol with respect to asthma, and note that a well-designed cohort study with adequate information on paracetamol dose, potentially confounding variables, and a long follow-up period, would be more appropriate that a RCT in researching drug-related adverse events. They acknowledge several limitations of their systematic review: all the studies included in the review were observational studies, ascertainment of exposure was heterogeneous among the different studies, and asthma diagnosis in most of the studies was through self-reporting, but state “the results of our review are consistent with an increase in the risk of asthma in both children and adults who have been exposed to paracetamol. Future studies are needed to confirm these findings.”

In November 2008, the UK Commission on Human Medicines reviewed data published in the Lancet from a study (part of international collaborative research effort ‘Asthma and Allergies in Childhood’) that had found a link between asthma and paracetamol use in the first year of life or during the previous 12 months, or both. The Commission expressed concerns about data interpretation, and concluded that the study did not provide strong evidence that paracetamol use in infancy can cause asthma. The MHRA advised healthcare professionals, parents, and carers that the study findings did not necessitate any change to the current guidance for use in children.