Paracetamol use in infancy may up asthma risk of in teens

Children who take paracetamol during the first two years of life may be at a higher risk of developing asthma by the age of 18, scientists have found.

The link between paracetamol use and asthma seemed strongest in those who had a particular variant of the glutathione S-transferase (GST) gene, GSTP1, researchers said.

However, the research showed only that there was an association between paracetamol and asthma, not that paracetamol caused the condition.

Further research was needed to confirm the findings. Another GST gene variant, GSTM1, was linked with reduced lung function, researchers found.

GST genes contain the instructions for making enzymes that use an antioxidant called glutathione to mop up the effects of exposure to toxins in the body and the lungs.

This mechanism helps to prevent damage to cells and inflammation.

"Paracetamol, on the other hand, consumes glutathione, reducing the body's capacity to deal with toxic exposure," said Xin Dai, a PhD candidate at the University of Melbourne in Australia.

"We hypothesised that people who did not have full GST enzyme activity because of common genetic variations or deletions may be more susceptible to adverse effects on the lungs from paracetamol use," said Dai.

Researchers investigated their hypothesis in 620 children who had been followed from birth to 18 years old.

The children had been recruited to the study before they were born because they were considered to be potentially at high risk of developing an allergy-related disease.

They had at least one family member with a self-reported allergic disease (asthma, eczema, hay fever or a severe food allergy).

After their birth, a research nurse rang the family every four weeks for the first 15 months, and then at 18 months and at two years old to ask how many days in the previous weeks had the child taken paracetamol.

When the children were 18 years old, they gave a blood or saliva sample, which was tested for variants of the GST genes: GSTT1, GSTM1 and GSTP1.

They were also assessed for asthma, and a spirometry test was performed to measure the amount of air inhaled and exhaled when breathing through a mouthpiece.

One variant of the GSTP1 gene, GSTP1 Ile/Ile (in which the amino acid Isoleucine (Ile) is inherited from both parents), was associated with a higher risk of developing asthma.

"We found that children with the GSTP1 Ile/Ile variant had 1.8 times higher risk of developing asthma by the age of 18 years for each doubling of the days of paracetamol exposure when compared to children who were less exposed," said Dai.

"In contrast, increasing paracetamol exposure in children who had other types of GSTP1 did not alter the risk of asthma," she said.

The findings provide more evidence that paracetamol use in infancy may have an adverse effect on respiratory health for children with particular genetic profiles and could be a possible cause of asthma.

However, these findings would need to be confirmed by other studies and the degree of adverse effect better understood before this evidence could be used to influence practice and before guidelines on paracetamol use are altered, researchers said.