Frequent use of paracetamol may contribute to asthma morbidity and rhinitis in adults, according to a study published in Thorax (2000;55:266).
In a population based, case-control study, primarily designed to investigate the role of dietary antioxidants in asthma, Dr Seif Shaheen and colleagues, from Guy's, King's and St Thomas's school of medicine, compared the frequency of use of paracetamol and aspirin in 664 individuals with, and 910 without, asthma. The study involved a random sample of adults, aged 16-49 years, who were registered with 40 general practices in Greenwich, south London. Both the association between analgesic use and severity of disease among asthma cases, as well as that between analgesic use and rhinitis were examined.
The researchers found a positive association between increasing (daily or weekly) use of paracetamol and adult asthma. Frequent use of paracetamol was associated with more severe asthma and, in those without asthma, with rhinitis. The frequency of paracetamol use was found to increase with increasing severity of the disease. An association between aspirin use and asthma was found to be inconsistent and aspirin use was not associated with asthma severity.
Discussing possible explanations for their findings, the researchers say that the pulmonary antioxidant glutathione, present in airway epithelial lining fluid in high concentrations, may limit airway inflammation in asthma. They say that animal studies indicate that glutathione plays an important role in preventing oxidative damage to the lung. Glutathione also has a key role in the hepatic detoxification of drug metabolites and stores of it are depleted by the reactive metabolite of paracetamol. In animals, administration of paracetamol depletes the lung of glutathione in a dose dependent fashion. Depletion of glutathione in airway epithelial lining fluid could therefore increase inflammation, the researchers suggest. "This could cause individuals who have subclinical disease to have symptoms, as well as increasing severity of symptoms in those with established asthma," they say.
The researchers emphasise that caution is needed in interpreting their findings. "A study of this kind cannot establish that the association we have observed is causal," they say, adding that they have shown a clear relation only with daily or weekly paracetamol use. They suggest that paracetamol should remain the preferred analgesic and antipyretic because of the potential risks associated with aspirin and NSAIDs. However, they suggest that there may be scope for some individuals who take paracetamol on a daily or weekly basis to reduce their frequency of usage. "We believe that there is a need to clarify whether frequent use, and perhaps overuse, of paracetamol contributes to asthma morbidity in the population, particularly in those who have severe disease. . . . such clarification can only come from a randomised trial," they conclude.
Commenting on the study, Dr Martyn Partridge (chief medical adviser, National Asthma Campaign) said that the best advice would be to reduce paracetamol intake. He said that, generally speaking, paracetamol was safer for people with asthma than aspirin or NSAIDs. "Adverse reactions to aspirin affect approximately 3 per cent of people with asthma so the risk with paracetamol is probably less, especially if only taken in low doses infrequently."
See also MCA statement (PJ, April 1, 2000, p506)