Sunday, March 1, 2009

Paracetamol: Pause to reflect

Feb 28, 2009

By Richard Beasley

PARACETAMOL is one of the world's most commonly used drugs. It is popularly sold as Panadol as well as other brands.

Paracetamol is the preferred medication for relieving fever and pain because of its safety profile. Ten years ago, it was hypothesised that its use may increase the risk of developing asthma.

It was suggested that a change from the use of aspirin to paracetamol among children in the US during the 1980s may have contributed to the increasing prevalence of childhood asthma noted during this period. Substitution of paracetamol for aspirin, researchers proposed, may have led to an enhanced allergic immune response, thereby increasing susceptibility to asthma and other allergic disorders.

Since then, a number of epidemiological studies have reported an association between asthma and exposure to paracetamol in the womb, childhood and adulthood. These studies led to the suggestion that the use of paracetamol may represent an important risk factor in the development of asthma.

The latest evidence to support this hypothesis comes from a large international epidemiological study of childhood asthma that was recently published in the medical journal The Lancet. This analysis, from the International Study of Asthma and Allergies in Childhood, involved more than 200,000 six- and seven- year-old children from 73 centres in 31 countries.

The children's parents or guardians completed written questionnaires about current symptoms of asthma, rhinitis (hayfever) and eczema, as well as about several risk factors, including the use of paracetamol for fever in the child's first year of life and frequency of paracetamol use in the past 12 months.

This study found that paracetamol use for fevers in the first year of life was associated with a 46 percent increase in risks of developing asthma in six- and seven-year-old children. Paracetamol use both in the first year of life and in children aged six to seven years was also associated with an increased risk of symptoms of rhinitis and eczema. This suggests that the potential effect of paracetamol is not restricted to the airways and may affect a number of organ systems.

Identifying the potential mechanisms that might underlie this association now noted between paracetamol and asthma (and other allergic disorders) was not part of this study. But other researchers have proposed a number of plausible mechanisms, primarily related to paracetamol's negative effect on the body's ability to withstand oxidant stress and this may lead to an exaggerated allergic immune response.

The authors emphasised that a retrospective study of this design cannot establish causality due to the numerous potential biases that may confound the association. For example, it is known that viral respiratory tract infections in infancy such as respiratory syncytial virus (RSV) are associated with an increased risk of asthma in later childhood and that paracetamol use for such episodes could have caused confounding in the study.

The study has contributed to the debate as to whether it is beneficial to treat fever in children, an issue comprehensively reviewed in a recent World Health Organisation article. The review concludes that the available scientific evidence suggests that fever is a universal, ancient and usually beneficial response to infection, and that its suppression under most circumstances has few if any demonstrable benefits.

On the contrary, it suggests, suppressing fever may occasionally produce harmful effects. Thus the widespread use of drugs to reduce fever should not be encouraged. It recommends that in children their use should be restricted to situations of high fever, obvious discomfort or conditions known to be painful.

What is agreed is the need for randomised controlled trials of the long-term effects of repeated use of paracetamol in children. Only then will it be possible to develop evidence-based guidelines for recommending its use.

Pending the results of such research, paracetamol remains the preferred drug to relieve pain and fever in childhood. Current WHO guidelines recommend that it be reserved for children with a high fever (of 38.5 deg C or above).

Aspirin is not used in young children owing to the risk of Reye's syndrome, a rare but serious complication. So paracetamol still remains the preferred drug of choice to relieve pain or fever in children or adults with asthma, because aspirin (or other medications like it called non-steroidal anti-inflammatory drugs) may also provoke attacks of asthma in susceptible people with this condition too.

The writer is a respiratory physician at Wellington Hospital, director of the Medical Research Institute of New Zealand and a consultant to the World Health Organisation Global Initiative on Asthma.

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