COMMENTARY

Acetaminophen and Asthma

Elizabeth Herman, MD, MPH

Disclosures

March 26, 2012

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Hello, I am Dr. Elizabeth Herman, with the Centers for Disease Control's (CDC's) National Asthma Control Program. I am speaking to you as part of the CDC Expert Commentary Series on Medscape.

Today, I am going to comment on a subject that has received a great deal of press recently: the possible relationship between use of acetaminophen and either the development of asthma or the severity of asthma symptoms.

As you know, the prevalence of asthma has greatly increased since the 1980s for reasons that are not understood. Many possible explanations have been proposed, but none have been proven. The cause of the increase is probably multifactorial and complex, but it is important to determine whether anything can be done to reverse that trend.

As you may recall, in the early 1980s there was a dramatic change in the treatment of fever. Parents were strongly advised to use acetaminophen rather than aspirin because of the association of aspirin use with the development of Reye syndrome. This change paralleled the increase in asthma rates and led researchers to ask 3 questions:

  • Does exposure to acetaminophen at an early age increase the risk for developing asthma?

  • Does acetaminophen use by pregnant women increase the risk for their children developing asthma?

  • Does the use of acetaminophen by children or adults with asthma lead to more frequent or severe asthma symptoms?

The analysis[1] of large, cross-sectional studies across 72 countries showed an association between the use of acetaminophen and asthma, but association does not necessarily mean that one causes the other. A prospective study[2] that followed children with a family history of allergic disease from birth to age 7 years found a weak association between frequency of acetaminophen use and the development of childhood asthma, but that association disappeared when adjusted for the frequency of respiratory infections. This was an example of confounding by indication. In other words, it was likely that early viral infections, rather than the acetaminophen used to treat them, were the cause of the development of asthma. But there is no indication that the frequency of viral infections has increased, so why the increase in the prevalence of asthma?

A prospective study[3] questioned pregnant women during their third trimester about their use of analgesics (including acetaminophen, ibuprofen, and aspirin) during the pregnancy. After controlling for other variables that might affect the development of asthma in their children (eg, maternal asthma, exposure to environmental tobacco smoke, race/ethnicity, birth weight, and the report of environmental triggers), it was reported that acetaminophen use during pregnancy increased the risk for children having current wheeze at age 5 years, but not at earlier ages. That risk however, was greater with increasing days of reported exposure; that is, there seemed to be a dose response that supports the argument of a causal link.

An interesting part of this study is that the risk is only present in those with a minor variant in a gene that regulates glutathione. Glutathione has antioxidant and other metabolic effects that may influence asthma development, suggesting a mechanism for acetaminophen's effect and strengthening the case for a causal link.

A study[4] originally designed to determine the safety of using ibuprofen for children with fever provided a further piece to this puzzle. A randomized, blinded comparison of ibuprofen to acetaminophen for short-term treatment of common childhood ailments showed that children with asthma who received acetaminophen had significantly more outpatient visits for asthma. There were also more hospitalizations, although the numbers were too small to be significant. The study authors state that it is not clear whether the ibuprofen, with its anti-inflammatory effects, was helpful, or the acetaminophen was harmful.

So, the studies are complicated and the evidence is mixed. No official recommendations promote a change from acetaminophen to other analgesics for pregnant women, infants, or children with asthma at the present time. Of course, prudence dictates the cautious and limited use of medications -- even something considered "safe," such as acetaminophen -- particularly during pregnancy and the first 2 years of life. Nonpharmacologic therapies should be used as much as possible. Medications should be reserved for more serious or troublesome symptoms rather than minor complaints.

Given that many medications have multiple effects on the body in addition to those for which they are intended, any medication can have unwanted side effects or consequences. It is important to communicate that to parents. Before advising parents not to use acetaminophen, the potential risks and benefits of alternative antipyretics and analgesics must be taken into account.

Web Resources

CDC: Asthma

CDC: Asthma: A Presentation of Asthma Management and Prevention (Slide Presentation and Speaker Notes)

National Heart, Lung, and Blood Institute: Guidelines for the Diagnosis and Management of Asthma (EPR-3)

National Heart, Lung, and Blood Institute: National Asthma Education and Prevention Program

National Center for Environmental Health

EnviroFlash: Air Quality Notifications

Asthma and Allergy Foundation of America

American Lung Association

American Academy of Allergy Asthma & Immunology

Allergy & Asthma Network/Mothers of Asthmatics

American College of Allergy, Asthma & Immunology

American College of Chest Physicians

American Thoracic Society

Elizabeth Herman, MD, MPH, currently works for the Air Pollution and Respiratory Health Branch of the National Center for Environmental Health, CDC. This branch coordinates the CDC's National Asthma Control Program. Dr. Herman served as the director of the branch's "Controlling Asthma in American Cities" (CAAC) project from 2005 through its end in 2008. This was a 7-site project to address asthma among inner-city children through community-based interventions. She was editor of a special journal supplement on the CAAC project.

Dr. Herman earned her medical degree at the University of Connecticut School of Medicine in 1979. She completed a family practice residency at Duke-Watts Family Medicine Program. After her residency, Dr. Herman worked as a primary care physician in India. When she returned to the United States, she served as a medical officer and clinical director of the ACL Indian Hospital in San Fidel, New Mexico. She later obtained a master's degree in public health and completed a preventive medicine residency at the Johns Hopkins School of Hygiene and Public Health. Dr. Herman began her career with CDC in 1998 as a medical officer in the Malaria Branch; she joined the Air Pollution and Respiratory Health Branch in 2002.

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