Paracetamol use in infancy may lead to asthma in teenage

Children may be at a higher risk of developing asthma by the age of 18 due to the intake of paracetamol during their first two years of life, reports a new research presented at the European Respiratory Society International Congress.

Researchers at the meeting revealed that the link between paracetamol use and asthma seemed strongest in children with a particular genetic constitution who had a particular variant of the glutathione S-transferase (GST) gene, GSTP1. The investigators also found that another GST gene variant, GSTM1, was linked with reduced lung function.

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.

Xin Dai and her associates hypothesized 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.

The 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 (mother, father or sibling) with a self-reported allergic disease (asthma, eczema, hay fever or a severe food allergy).

After their birth, data was collected from their 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.

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

"We also found effects in children who had a variant of GSTM1 in which one part is not functioning. In these children increasing paracetamol use was associated with a small, but significant reduction in the amount of air they could forcibly breathe out in one second at 18 years. It is not known if the relationship we found between paracetamol use and lung function is clinically important. In addition, we found some weak evidence that paracetamol use in the first two years of life may be associated with reduced lung function in adolescence regardless of which variants of the GST genes the children had."

The authors concluded that 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, according to the authors, 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.