Blood thinners and acetaminophen
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ACETAMINOPHEN AND ASTHMA

Acetaminophen associated with the epidemic rise in asthma.  Asthma risk up 323% for those in the top 25% versus bottom 25%.  Paracetamol is the name used in all countries but for US, Canada, Japan, South Korea, Hong Kong and Iran.  It stands for acetyl-para-aminophenol abbreviated APAP, which is the way it is listed on prescription pill bottles.

The Lancet, Volume 372, Issue 9643, Pages 1039 - 1048, 20 September 2008, doi:10.1016/S0140-6736(08)61445-2

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961445-2/fulltext

Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6—7 years: analysis from Phase Three of the ISAAC programme

Summary

Background

Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6—7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma.

Methods

As part of Phase Three of ISAAC, parents or guardians of children aged 6—7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression.

Findings

205,487 children aged 6—7 years from 73 centres in 31 countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6—7 years (OR 146 [95% CI 136—156]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (161 [146—177] and 323 [291—360] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6—7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema.

Interpretation

Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood.  {Other studies show that prenatal usage is also associated with asthma.} 

Funding

The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, Astra Zeneca New Zealand, and Glaxo Wellcome International Medical Affairs.

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Thorax, an International Journal of Respiratory Medicine

Thorax 2010;65:99-100 doi:10.1136/thx.2009.127977  http://thorax.bmj.com/content/65/2/99.extract

Editorial

Acetaminophen and Asthma

1.     Victoria W Persky

1.     Correspondence toDr Victoria W Persky, Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago IL 60612, USA; vwpersky@uic.edu

 

The article by Perzanowski et al in this issue of Thorax (see page 118) adds one more piece of evidence supporting a possible role for acetaminophen in the development of asthma in children.1 Five previous studies, including three prenatal prospective cohorts,2–5 have suggested that in utero ingestion of acetaminophen may increase the risk of asthma and respiratory symptoms in children.2–7 Increased risk of asthma from postnatal use of acetaminophen is also suggested by reports of children8–12 and adults.8 13–17 The possibility that acetaminophen may contribute to the development of asthma is supported by parallel time trends in dramatic increases in use of the medication in response to reports of associations of aspirin use with Reye syndrome18–20 and increases in asthma prevalence between the mid 1970s and mid 1990s.21

There is also biological plausibility. Acetaminophen,22–24 as well as one of its metabolites, the highly reactive N-acetyl-p-benzoquinoneimine,23 has been associated with decreased glutathione. There is substantial literature documenting the antioxidant capacity of glutathione25 as well as the role of reactive oxygen species in asthma morbidity.26 In addition, decreased glutathione may affect the development of asthma by altering antigen recognition towards favouring T helper 2 (Th2) over Th1 cytokines.23 27 Other, less likely, possibilities relate to decreased suppression of cyclo-oxygenase or direct antigenicity of acetaminophen.23

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Greater than 4 tablets of acetaminophen in the last month associated with a .725% increased risk at 1 year versus never.   

American Journal of Respiratory and Critical Care Medicine Jan 15, 2011 Vol 183 No 2 165-170, http://ajrccm.atsjournals.org/content/183/2/165.abstract

The Role of Acetaminophen and Geohelminth Infection on the Incidence of Wheeze and Eczema A Longitudinal Birth-cohort Study

Abstract

Rationale: Acetaminophen has been hypothesized to increase the risk of asthma and allergic disease, and geohelminth infection to reduce the risk, but evidence from longitudinal cohort studies is lacking.

Objectives: To investigate the independent effects of these exposures on the incidence of wheeze and eczema in a birth cohort.

Methods: In 2005–2006 a population-based cohort of 1,065 pregnant women from Butajira, Ethiopia, was established, to whom 1,006 live singleton babies were born. At ages 1 and 3, questionnaire data were collected on wheeze, eczema, child's use of acetaminophen, and various potential confounders, along with a stool sample for geohelminth analysis. Those without wheeze (n = 756) or eczema (n = 780) at age 1 were analyzed to determine the independent effects of geohelminth infection and acetaminophen use in the first year of life on the incidence of wheeze and eczema by age 3.

Measurements and Main Results: Wheeze and eczema incidence between the ages of 1 and 3 were reported in 7.7% (58 of 756) and 7.3% (57 of 780) of children, respectively. Acetaminophen use was significantly associated with a dose-dependent increased risk of incident wheeze (adjusted odds ratio = 1.88 and 95% confidence interval 1.03–3.44 for one to three tablets and 7.25 and 2.02–25.95 for ≥4 tablets in the past month at age 1 vs. never), but not eczema. Geohelminth infection was insufficiently prevalent (<4%) to compute estimates of effect.

Conclusions: These findings suggest frequent acetaminophen use early in life increases the risk of new-onset wheeze, whereas the role of geohelminth infection on allergic disease incidence remains to be seen as the cohort matures.

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Similar to the top study, also from New Zealand.   Increases asthma risk 251% for the medium and high usage groups combined versus the no use group.  (The next article in the same journal as above.}

American Journal of Respiratory and Critical Care Medicine Jan 15, 2011 Vol 183 No 2 1, 171-178 http://171.66.122.149/content/183/2/171.abstract

Acetaminophen Use and Risk of Asthma, Rhinoconjunctivitis, and Eczema in Adolescents International Study of Asthma and Allergies in Childhood Phase Three

Abstract

Rationale: There is epidemiological evidence that the use of acetaminophen may increase the risk of developing asthma.

Objectives: To investigate the risk of asthma and other allergic disorders associated with the current use of acetaminophen in 13- to 14-year-old children in different populations worldwide.

Methods: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, 13- to 14-year-old children completed written and video questionnaires obtaining data on current symptoms of asthma, rhinoconjunctivitis, and eczema, and a written environmental questionnaire obtaining data on putative risk factors, including acetaminophen use in the past 12 months.

Measurements and Main Results: The primary outcome measure was the odds ratio (OR) of current asthma symptoms associated with acetaminophen use calculated by logistic regression. A total of 322,959 adolescent children from 113 centers in 50 countries participated. In the multivariate analyses the recent use of acetaminophen was associated with an exposure-dependent increased risk of current asthma symptoms (OR, 1.43 [95% confidence interval, 1.33–1.53] and 2.51 [95% confidence interval, 2.33–2.70] for medium and high versus no use, respectively). Acetaminophen use was also associated with an exposure-dependent increased risk of current symptoms of rhinoconjunctivitis and eczema.

Conclusions: Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis, and eczema in adolescent children.

 

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It's not at all clear exactly how acetaminophen might trigger asthma and other allergies.   One theory is that the drug affects lung levels of glutathione, an antioxidant important in protecting the lung from damage by free radicals formed by oxygen.  http://www.rxlist.com/script/main/art.asp?articlekey=118919