Acetaminophen Use in Adolescents May Double Risk for Asthma
News
Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
August 17, 2010 — Acetaminophen use in adolescents is linked to development and/or maintenance of asthma, rhinoconjunctivitis, and eczema, according to the results of a global study reported online August 13 in the American Journal of Respiratory and Critical Care Medicine.
"This study has identified that the reported use of acetaminophen in 13- and 14-year-old adolescent children was associated with an exposure-dependent increased risk of asthma symptoms," said first author Richard W. Beasley, MD, professor of medicine at the Medical Research Institute of New Zealand in Wellington, in a news release, on behalf of the International Study of Asthma and Allergies in Childhood (ISAAC).
At 113 centers throughout 50 countries, 322,959 adolescent children (aged 13 - 14 years) enrolled in ISAAC Phase Three completed written and video questionnaires regarding current symptoms of asthma, rhinoconjunctivitis, and eczema. They also completed a written environmental questionnaire regarding potential risk factors such as acetaminophen exposure in the preceding 12 months. Logistic regression allowed calculation of the odds ratio (OR) of current asthma symptoms associated with acetaminophen use, which was the main study endpoint.
Recent use of acetaminophen was associated with an exposure-dependent greater risk for current asthma symptoms, based on multivariate analyses. For medium use (at least once in the last year) vs no use, the OR was 1.43 (95% confidence interval [CI], 1.33 - 1.53). For high use (at least once in the last month) vs no use, the OR was 2.51 (95% CI, 2.33 - 2.70).
"The overall population attributable risks for current symptoms of severe asthma were around 40 percent, suggesting that if the associations were causal, they would be of major public health significance," Dr. Beasley said. "Randomized controlled trials are now urgently required to investigate this relationship further and to guide the use of antipyretics, not only in children but in pregnancy and adult life."
In multivariate analysis, there was also an acetaminophen exposure–dependent increased risk for current symptoms of rhinoconjunctivitis (OR, 1.38 [95% CI, 1.29 - 1.47] and OR, 2.39 [95% CI, 2.24 - 2.55] for medium and high use, respectively) and eczema (OR, 1.31 [95% CI, 1.21 - 1.42] and OR, 1.99 [95% CI, 1.82 - 2.16] for medium and high use, respectively).
"Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis and eczema in adolescent children," the study authors write.
An accompanying "at a glance commentary" notes that potential mechanisms for these effects of acetaminophen include oxidant-induced airways inflammation and enhanced Th2 responses.
Limitations of this study include cross-sectional design, precluding determination of causality; and potential confounding factors.
Birth-Cohort Study Also Conducted
Also in the same issue of the American Journal of Respiratory and Critical Care Medicine is a small, longitudinal study of the risk for asthma and allergies associated with acetaminophen use in a population in Ethiopia. This birth-cohort study by Alemayehu Amberbir and colleagues from Addis Ababa University, Addis Ababa, Ethiopia, showed a temporal relationship between acetaminophen use and development of asthma and allergy symptoms, supporting a causal role for acetaminophen.
The individual centers and collaborators that undertook ISAAC Phase Three were funded by numerous sources throughout the world. The main source of funding for the ISAAC International Data Centre (IIDC) is The BUPA Foundation, with support from the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Child Health Research Foundation, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the NZ Lottery Board, and AstraZeneca New Zealand. Glaxo Wellcome International Medical Affairs supported the regional coordination for Phase Three, and the IIDC supported this study.
The birth-cohort study was funded by Asthma UK and the Wellcome Trust.
Am J Respir Crit Care Med. Published online August 13, 2010.
Clinical Context
A recent study, published in the current issue of the American Journal of Respiratory and Critical Care Medicine, conducted by Amberbir and colleagues reported that acetaminophen use was associated with increased risk of wheeze, but not eczema, in a small cohort of patients in Ethiopia.
Previously, in 2008, Beasley and colleagues, the current study authors, conducted Phase Three of ISAAC, and in the September 20, 2008, issue of The Lancet, they reported that acetaminophen use (paracetamol) in the first year of life was associated with a greater risk for asthma symptoms in children aged 6 to 7 years.
The current study by Beasley and colleagues uses data from ISAAC Phase Three to evaluate whether acetaminophen use is linked with a greater risk for asthma, allergy, or eczema symptoms in children aged 13 to 14 years.
Study Highlights
- Data were available for 322,959 children aged 13 to 14 years from 113 centers in 50 countries.
- Subjects completed a written environmental questionnaire about protective and risk factors including acetaminophen use in the past 12 months; a written questionnaire about current symptoms of asthma, rhinoconjunctivitis, and eczema; and a video questionnaire about asthma symptoms.
- Exclusion criteria were centers that deleted the acetaminophen use question, centers with less than 70% data for current acetaminophen use, centers with less than 1000 enrolled children, missing data for sex, and missing data for current acetaminophen use.
- Adjusted and multivariate analyses included 180,887 subjects with complete covariate data or subjects who came from centers with at least 70% covariate data.
- Current acetaminophen use was considered medium if taken at least once in the past 12 months and high if taken at least once a month in the past 12 months.
- Current asthma symptoms were defined as reported wheezing or whistling in the chest in the past 12 months.
- Separate assessment of current wheeze was defined as reported symptoms similar to a video showing wheezing at rest.
- Current rhinoconjunctivitis symptoms were defined as sneezing, a runny or blocked nose, or itchy watery eyes in the absence of a cold or the flu in the past 12 months.
- Current eczema symptoms were defined as an itchy rash in the folds of the elbows; behind the knees; in front of the ankles; under the buttocks; or around the neck, ears, or eyes recurring for at least 6 months in the past 12 months.
- Severe asthma was defined as 4 or more wheezing attacks, 1 or more nights per week of disturbed sleep because of wheezing, or wheezing severe enough to limit speech in the past 12 months.
- The primary outcome measure was the OR of current asthma symptoms linked with acetaminophen use.
- Medium acetaminophen use occurred in 73% of participants (range, 41% in China to 92% in Panama).
- High acetaminophen use occurred in 30% of subjects (range, 2% in Taiwan to 68% in Nigeria).
- Analysis adjusting for sex, region of the world,
language, and gross national income showed that an increased risk for
current asthma symptoms was dependent on exposure to acetaminophen use:
- Medium vs no acetaminophen use (OR, 1.38; 95% CI, 1.31 - 1.46)
- High vs no acetaminophen use (OR, 2.36; 95% CI, 2.24 - 2.50)
- Multivariate analysis adjusted for maternal education, current maternal smoking, siblings, and current intake of vegetables and fruit.
- Multivariate analysis showed that an increased risk
for current asthma symptoms was dependent on exposure to acetaminophen
use:
- Medium vs no acetaminophen use (OR, 1.43; 95% CI, 1.33 - 1.53)
- High vs no acetaminophen use (OR, 2.51; 95% CI, 2.33 - 2.70)
- In multivariate analysis, there was also an
acetaminophen exposure–dependent increased risk for current symptoms of
rhinoconjunctivitis:
- Medium vs no acetaminophen use (OR, 1.38; 95% CI, 1.29 - 1.47)
- High vs no acetaminophen use (OR, 2.39; 95% CI, 2.24 - 2.55)
- In multivariate analysis, there was an acetaminophen
exposure–dependent increased risk for current symptoms of eczema:
- Medium vs no acetaminophen use (OR, 1.31; 95% CI, 1.21 - 1.42)
- High vs no acetaminophen use (OR, 1.99; 95% CI, 1.82 - 2.16)
- Current acetaminophen use was linked with an exposure-dependent increased risk for current wheeze determined by video questionnaire, severe asthma, current rhinoconjunctivitis, and eczema.
- After exclusion of subjects with current wheeze, an
increased risk for current rhinoconjunctivitis was linked with current
acetaminophen use:
- Medium vs no acetaminophen use (OR, 1.33; 95% CI, 1.25 - 1.42)
- High vs no acetaminophen use (OR, 2.18; 95% CI, 2.04 - 2.33)
- After exclusion of subjects with current wheeze, an
increased risk for current eczema was linked with current acetaminophen
use:
- Medium vs no acetaminophen use (OR, 1.32; 95% CI, 1.21 - 1.44)
- High vs no acetaminophen use (OR, 1.87; 95% CI, 1.7 - 2.05)
- Study limitations include possible confounding and possible increased use of acetaminophen in persons with asthma.
Clinical Implications
- Recent acetaminophen use is linked with an exposure-dependent increased risk for asthma symptoms in adolescents.
- Recent acetaminophen use is linked with an exposure-dependent increased risk for rhinoconjunctivitis and eczema symptoms in adolescents.
接下來，就是測驗時間了：
CME Test
1.In teenagers, which of the following uses of acetaminophen in the past 12 months is most likely to be associated with the highest risk for asthma symptoms?
1.( )No acetaminophen use
2.( )Acetaminophen use at least once per year
3.( )Acetaminophen use at least once per month
4.( )All of the above
5.( )None of the above
2.A teenager uses acetaminophen approximately once a month for 1 year. Which of the following factors is most likely to be associated with acetaminophen use?
1.( )No link with rhinoconjunctivitis symptoms
2.( )No link with eczema symptoms
3.( )Link with a decreased risk for rhinoconjunctivitis symptoms
4.( )Link with an increased risk for rhinoconjunctivitis symptoms
5.( )None of the above
選好了嗎？
第一提答案是（3）
- In teenagers, which of the following uses of acetaminophen in the past 12 months is most likely to be associated with the highest risk for asthma symptoms?
Answer: Acetaminophen use at least once per month
According to the study by Beasley and colleagues, multivariate analysis showed
that an increased risk for current asthma symptoms was dependent on exposure to
acetaminophen use. For medium vs no use, the OR was 1.43 (95% CI, 1.33 - 1.53).
For high vs no use, the OR was 2.51 (95% CI, 2.33 - 2.70). Asthma symptoms,
defined as 4 or more wheezing attacks, 1 or more nights per week of disturbed sleep
because of wheezing, or wheezing severe enough to limit speech in the past 12
months.
第二提答案是（4）
Answer: Link with an increased risk for
rhinoconjunctivitis symptoms
According to the study by Beasley and colleagues, acetaminophen use was linked
with an increased risk for rhinoconjunctivitis, as well as eczema, symptoms. In
multivariate analysis, there was an exposure-dependent increased risk for
current symptoms of rhinoconjunctivitis (high vs no use: OR, 2.39; 95% CI, 2.24
- 2.55) and eczema (high vs no use: OR, 1.99; 95% CI, 1.82 - 2.16).
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