study has shown that the association between paracetamol use and asthma seemed
strongest in those who had a particular variant of the
. They also found that another GST
gene variant, GSTM1 was associated with reduced lung function.
‘Paracetamol use in infancy and increased risk of asthma in adolescents seem to have an association, especially in subjects with certain genetic variants.’
authors, however, ask people to note that the current finding does not
ascertain that paracetamol causes asthma
but only shows an association between the two.
To fully understand the link, they say more research needs to be done.
its action in the body, paracetamol
or acetaminophen gets broken down
(detoxified) by several pathways in the liver to make it more soluble in order
to get excreted.
intermediate formed in one of the breakdown pathways is toxic but is then
quickly, irreversibly conjugated with the sulfhydryl groups of glutathione, an
antioxidant to make it an
inactive, non-toxic conjugate that will eventually be excreted by the kidneys.
Thus, glutathione is involved in
mopping up the effects of toxins in the body and helps prevent damage to cells
This occurs only when paracetamol is taken at the
therapeutic or correct doses as prescribed.
case of a paracetamol overdose, the levels of the toxic intermediate formed
increases and outweigh
the amount of available glutathione; this can lead to liver failure and kidney
and is also detrimental to other organs like the lungs.
isozymes involved in the conjugation of glutathione to the drugs are the
glutathione S-transferases (GST).
shown earlier that mice lacking two of the GST genes, namely glutathione
S-transferase Pi or GSTPi and glutathione S-transferase Mu 1 or GSTM1 genes
show increased resistance to paracetamol-induced liver toxicity indicating the
role of these two genes in the process. GST genes contain the instructions for
making the GST enzymes.
(Daisy) Dai, a nurse and PhD candidate at the Allergy and Lung Health Unit at
the University of Melbourne, Australia explains the reason to conduct the
following study. She says, "Paracetamol consumes glutathione, reducing the body's
capacity to deal with toxic exposure. We 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
Study - Melbourne
Atopy Cohort Study
Dai and her colleagues recruited 620 children to the study even before they
were born. The children were chosen based on the fact of being potentially at
high risk of developing an allergy-related disease - the children had a mother,
father, or sibling with a self-reported allergic disease like asthma, eczema
hay fever or a severe food allergy. The team followed the children from birth
to 18 years.
the children were born, a research nurse called the family at select intervals
- every four weeks for the first 15 months, and then at 18 months and at two
years old, every time to ask how many days in the previous weeks the child had
the children reached 18 years of age, the team took a blood or
from them, to test for variants of the GST genes: GSTT1,
GSTM1, and GSTP1 and for asthma. In addition, a spirometry
taken where the amount of air inhaled and exhaled when breathing through a
mouthpiece is measured.
- Children with one variant of the GSTP1 gene, the GSTP1
Ile/Ile variant (in which the amino acid Isoleucine (Ile) is inherited from
both parents) but not the other types of GSTP1 had a higher risk (1.8 times) of
developing asthma by the age of 18 years each time the number of days of
paracetamol exposure was doubled when compared to children who were less
- Increasing use of paracetamol in children who had a variant
of GSTM1 was associated with a small but significant reduction in lung
function, though this difference might not be clinically important
- Also, regardless of the variants of the GST genes the kids
possess, the authors found a weak association between the use of paracetamol in
the first two years of life and reduced lung function in adolescence
- All these results show that paracetamol
use in infants with particular genetic profiles may have an adverse effect on
their respiratory health and could be a possible cause of asthma
study adds to the body of evidence that the GST superfamily of genes, including
three major classes - GSTM1, GSTT1, and GSTP1 are
associated with various diseases, including cancers, asthma, atherosclerosis
Alzheimer's and Parkinson's disease.
the association could be due to confounding factors - infants could have had
lower respiratory tract infections caused by viruses, which were at the time
treated with paracetamol and this could have caused asthma.
these findings would need to be confirmed by other studies, and the degree of
adverse effect should be better understood before guidelines on paracetamol use
- Eexpert reaction to conference abstract on paracetamol in infants and asthma in teenagers - (http://www.sciencemediacentre.org/expert-reaction-to-conference-abstract-on-paracetamol-in-infants-and-asthma-in-teenagers/)