Acetaminophen increases the risk of childhood asthma.
THE INVESTIGATOR
Dr. John T. McBride, Akron
Children’s Hospital.
 
The sharp worldwide increase in childhood asthma over the past 30 years has long perplexed researchers, who have considered explanations as varied as improved hygiene and immunizations. Over the last decade, however, a new idea has emerged.

The asthma epidemic accelerated in the 1980s, some researchers have noted, about the same time that aspirin was linked to Reye’s syndrome in children. Doctors stopped giving aspirin to children with fevers, opting instead for acetaminophen. In a paper published in The Annals of Allergy and Asthma Immunology in 1998, Dr. Arthur Varner, then a fellow in the immunology training program at the University of Wisconsin School of Medicine, argued that the switch to acetaminophen might have fueled the increase in asthma.

Since then, more than 20 studies have produced results in support of his theory, including a large analysis of data on more than 200,000 children that found an increased risk of asthma among children who had taken acetaminophen. In November, Dr. John T. McBride, a pediatrician at Akron Children’s Hospital in Ohio, published a paper in the journal Pediatrics arguing that the evidence for a link between acetaminophen and asthma is now strong enough for doctors to recommend that infants and children who have asthma (or are at risk for the disease) avoid acetaminophen.

Dr. McBride based his assertion on several lines of evidence. In addition to the timing of the asthma epidemic, he said, there is now a plausible explanation for how acetaminophen might provoke or worsen asthma, a chronic inflammatory condition of the lungs. Even a single dose of acetaminophen can reduce the body’s levels of glutathione, a peptide that helps repair oxidative damage that can drive inflammation in the airways, researchers have found.

“Almost every study that’s looked for it has found a dose-response relationship between acetaminophen use and asthma,” Dr. McBride said. “The association is incredibly consistent across age, geography and culture.”

A statistical link between acetaminophen and asthma has turned up in studies of infants, children and adults. Studies have also found an increased risk of asthma in children whose mothers who took acetaminophen during pregnancy.

For instance, a study published in The Lancet in 2008 examined information collected on more than 205,000 children from 31 countries as part of the International Study of Asthma and Allergies in Childhood, known as the Isaac study. The 2008 analysis found that children who had taken acetaminophen for a fever during the first year of life had a 50 percent greater risk of developing asthma symptoms, compared with children who had not taken the drug. The risk rose with increasing use — children who had taken acetaminophen at least once a month had a threefold increase in the risk of asthma symptoms.

A study published by British researchers in 2000 using data from the Isaac study found that the prevalence of asthma increased in lock step with sales of acetaminophen in the 36 countries examined. The more acetaminophen used in a country, the greater that country’s prevalence of asthma.