Thursday September 18 2008
Asthma and paracetamol have been looked at before
“Regular users of paracetamol are nearly three times more likely to have asthma”, the Daily Mail reported today. It said that a study had analysed the frequency of painkiller use in people with and without asthma in Europe and its findings suggested that using paracetamol at least once a week increases the risk of suffering symptoms. Other painkillers apparently did not have the same effect.
The study behind this report is a case-control study and by virtue of its design, it cannot prove causation (that paracetamol increases asthma). It also cannot rule out reverse causation (that asthma causes people to take more painkillers). However, when considered alongside the findings of other studies, these results suggest that there may be an association between use of paracetamol and asthma that needs further exploration. This is not a new concern, and researchers have been investigating this for some time. As the researchers conclude, “there is now a need to carry out suitable intervention studies to determine whether the link is causal”. Prospective studies, preferably those that randomly allocate healthy participants to having paracetamol or not, would produce more conclusive results.
Where did the story come from?
Dr Seif Shaheen and colleagues from the Imperial College, London, and other medical and academic institutes across Europe carried out this multi-centre study. The study was published in the peer-reviewed medical journal: European Respiratory Journal.
What kind of scientific study was this?
This case-control study assessed whether the frequent use of paracetamol is associated with asthma in European adults. In this type of study, cases (people with a condition or outcome) are compared to controls (people without that condition or outcome) to see whether their likelihood of exposure to some factor is different.
This was a multi-centre study, where the participants were recruited from 12 centres across Europe. In total, 1,028 people were recruited between May 2005 and May 2007. Of these, about half (521) were recruited as cases and a similar number (507) were recruited as controls. Cases were aged between 20 and 45 years and had both a self-reported diagnosis of asthma and either wheezing, or shortness of breath, or waking at night with breathlessness in the previous 12 months. The control group consisted of healthy volunteers with no diagnosis of asthma and no asthmatic symptoms in the previous 12 months. The participants were initially recruited through a population-based survey, mostly through postal questionnaires. However, where this method did not acquire enough cases, more participants were recruited from clinics.
When they had been identified, the participants completed a longer questionnaire and had their height and weight measured. The questionnaire asked them how often they took paracetamol and other painkillers (e.g. aspirin or ibuprofen), and were given the choices of answering: less than once a week, one to two days/week, three to four days/week, five to six days/week or daily. The researchers later collapsed these last four categories into one and classified people as either taking aspirin less than weekly or weekly. Based on their symptoms (lung function, night time and day time symptoms) people with asthma symptoms were classified into two categories: intermittent, mild persistent disease, or moderate/severe persistent disease. Skin tests were carried out to determine presence of atopy (hypersensitivity to allergens) in particular to grass, cat hair, dust mites and various fungi and plants.
Other key information collected through the questionnaire included socio-economic status, smoking status, and whether or not multi-vitamins were taken.
What were the results of the study?
The researchers found significant differences between those who reported having asthma (cases) and the healthy volunteers (controls). Cases were more likely to have atopy (i.e. hypersensitivity to some allergens). In the case group, 82% were atopic compared with 36% of the control group. Cases were also more likely to take paracetamol than controls (13% v 4.5%).
When the researchers took into account other factors that can be responsible for asthma, they found that cases were about 2.5 to 2.9 times more likely to have taken paracetamol regularly (i.e. weekly as opposed to less than weekly) than controls. There was no association found between use of other painkillers and asthma.
What interpretations did the researchers draw from these results?
The researchers conclude that there is a positive association between the frequent use of paracetamol and adult asthma. These findings support those of other studies in the UK and the US.
What does the NHS Knowledge Service make of this study?
This case-control study has some limitations and the researchers acknowledge the following:
- The study did not distinguish between people who never took paracetamol and those who took it less than once a week. As most people took paracetamol less than once a week (over 90%), the researchers collapsed the top four dose categories into one, which then became ‘more than once a week’. These two points mean that they were unable to investigate any dose response, such as whether taking a greater quantity of paracetamol was linked more often to asthma.
- As mentioned above, few people took paracetamol more than once a week (only 9% of participants). This small sample size limits the confidence that can be had in the accuracy of the results.
- The participants were asked if they took other analgesics, but not how often they took them. This limits the value of information about these drugs.
- The researchers cannot rule out that some unmeasured factor may be responsible for the difference between the two groups.
There are two important points to highlight in relation to case-control study designs:
- A case-control study cannot prove causation. Although the researchers say that it is unlikely that having asthma led to an increase in paracetamol use, this cannot be ruled out by this study design. Given that asthma is linked with atopy and that atopy may be linked with headaches, people with allergies may indeed be more likely to take painkillers. However, the researchers say that other studies have suggested that this is not the case.
- Given the large number of people who have asthma, it is surprising that only 521 people in this 20-45 age group volunteered for what was an international study. This raises the possibility that those who put themselves forward for this trial may differ from the usual person with asthma or from the controls in some way other than their asthma. This sort of methodological difficulty with a trial can only be resolved by randomisation, as the authors recommend.
- Reporting bias is also an issue. The researchers relied on participants’ recall of asthma symptoms in the previous 12 months and also relied on their report of how many painkillers were taken each week.
This study suggests that there may be a link between frequent use of paracetamol and symptoms of asthma. This is not a new concern, and researchers from the Imperial College have been investigating this for some time. However, there are problems with this study design that cannot rule out reverse causation, in other words, that having asthma causes people to take more painkillers.
As the researchers conclude, ‘there is now a need to carry out suitable intervention studies to determine whether the link is causal’. Prospective studies, preferably those that randomise healthy participants to paracetamol or not, will produce more conclusive results.