In Praise of Aspirin
Jacob Schor, ND
February 10, 2007
Subject: Aspirin may reduce risk of developing asthma
Several of my recent newsletters have focused on the downside of particular prescription medications. These side effects, such as the tendency of tumor necrosis factor suppression to cause cancer or proton pump inhibitors to cause pneumonia, gastritis and osteoporosis, are under-reported in the media and I felt an obligation to mention them. An article that brings to light a positive effect of taking aspirin was published in the January 27th edition of Science News and for the sake of balanced reporting, I will take a few moments to sing the praises to the new benefit of aspirin. The article, written by Ben Harder, reviews a series of articles suggesting aspirin may provide protection against developing asthma.
Asthma affects about 5 percent of men and more than 8 percent of women and children. Asthma usually starts in childhood. Some kids outgrow it. In recent years, we have seen a surge in the number of newly diagnosed cases of asthma in both children and in adults. The concurrent decline in aspirin use may be partly to blame.
In a study published January 15, Tobias Kurth and his colleagues in Boston analyzed data on 22,000 male doctors who, once upon a time, had volunteered for a study about heart disease and aspirin. Although the data was collected years ago, between 1982 and 1988, and the study wasn't initially about asthma, the records contained adequate data to analyze and be useful.
None of the doctors in the heart study had asthma at the start of the study. Half received placebos for the duration, the other half took 325 milligrams of aspirin daily. Five years into the study, 145 men in the placebo group had developed asthma, but only 113 aspirin takers had. These numbers suggest that regular aspirin use cut asthma incidence by 22 percent. [i]
Was it the aspirin that protected these doctors from getting asthma or the ‘alternatives to aspirin' that the placebo group from time to time swallowed instead of aspirin? This question needs to be asked as acetaminophen usage has been linked to increased asthma.
Acetaminophen decreases glutathione levels in the lung. Glutathione protects the lungs from oxidative injury and bronchospasm. A 2004 paper looked at newly diagnosed adult-onset asthma in the Nurses' Health Study, a prospective cohort study of 121,700 women. Participants were asked about frequency of acetaminophen use in 1990. During 352,719 person-years of follow-up, 346 participants reported a new diagnosis of asthma. There was a clear statistical trend seen. The more acetaminophen used, the more likely the nurse was to be diagnosed with asthma in subsequent years. Using acetaminophen for more than 14 days a month increased one's chance of getting asthma by 63%. [ii] Women who took aspirin often, developed asthma 40% less often than women who never took aspirin.
There is another piece to this puzzle. During the last thirty years, most doctors have stopped giving aspirin to children because of the increased risk of Reye's syndrome. No more baby aspirin, say hello children's Tylenol. This decrease in aspirin usage provides an explanation for the increase in childhood asthma seen during this same period. On the other hand it may be the increase in acetaminophen use. [iii]
Acetaminophen doesn't reduce inflammation the way aspirin, ibuprofen, and naproxen do. These other drugs, often referred to as non-steroidal-anti-inflammatory-drugs or NSAIDs, may reduce the chance that viral respiratory infections will cause asthma in susceptible children and adults.
A 2005 study linked acetaminophen, but not the NSAIDs aspirin or ibuprofen, to increased risk of adult-onset asthma. [iv]
This is interesting because in the last few years I have seen a growing number of patients complaining of breathing problems following either a cold or bout with the flu. The diagnosis is Reactive Airway Disease, a euphemism for asthma. Though the symptoms often improve with time, they rarely disappear completely. This seems to be a new and rather common phenomenon. I don't recall seeing it or reading about it years ago. One can't help but wonder how many of these patients took acetaminophen rather than aspirin when sick, thinking they were making a healthier and safer choice.
Although aspirin may be protective against developing asthma, do not think of aspirin as a treatment for asthma. In fact, aspirin actually triggers asthma attacks in about 10% of adult onset asthmatics. [v]
With this information in mind, we should consider several changes in the treatment of any respiratory infection. First, if using some over the counter medication for fever or discomfort, skip the acetaminophen. Plain old-fashioned aspirin appears to be the best choice, followed by other NSAIDs. If the patient insists on using acetaminophen, insist back that they also use NAC to increase glutathione production and protect the lungs from oxidative damage. Besides treating the symptoms of the infection, treat both the inflammation in the lungs and the oxidative damage that accompanies it.
[i] Am J Respir Crit Care Med. 2007 Jan 15;175(2):120-5. Epub 2006 Oct 26. Links
Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.
• Barr RG,
• Kurth T,
• Stampfer MJ,
• Buring JE,
• Hennekens CH,
• Gaziano JM.
Sc.D., Brigham and Women's Hospital, Division of Aging, 1620 Tremont Street , Boston , MA 02120-1613 . firstname.lastname@example.org.
RATIONALE: In an observational cohort study, women who self-selected for frequent aspirin use developed less newly diagnosed asthma than women who did not take aspirin. OBJECTIVE: To explore whether low-dose aspirin decreased the risk of newly diagnosed asthma in a randomized, double-blind, placebo-controlled trial. METHODS: The Physicians' Health Study randomized 22,071 apparently healthy male physicians, aged 40-84 yr at baseline and tolerant of aspirin, over an 18-wk run-in period, to 325 mg aspirin or placebo on alternate days. The aspirin component was terminated after 4.9 yr due principally to the emergence of a statistically extreme 44% reduction in risk of first myocardial infarction among those randomly assigned to aspirin. MEASUREMENTS: Physicians could self-report an asthma diagnosis on questionnaires at baseline, 6 mo, and annually thereafter. Asthma was not an a priori endpoint of the trial. RESULTS: Among 22,040 physicians without reported asthma at randomization, there were 113 new asthma diagnoses in the aspirin group and 145 in the placebo group. The hazard ratio was 0.78 (95% confidence interval, 0.61-1.00; p = 0.045). This apparent 22% lower risk of newly diagnosed asthma among those assigned to aspirin was not modified by baseline characteristics including smoking, body mass index, or age. CONCLUSIONS: Aspirin reduced the risk of newly diagnosed adult-onset asthma in a large, randomized clinical trial of apparently healthy, aspirin-tolerant men. This result requires replication in randomized trials designed a priori to test this hypothesis; it does not imply that aspirin improves symptoms in patients with asthma.
PMID: 17068328 [PubMed - in process]
[ii] Am J Respir Crit Care Med. 2004 Apr 1;169(7):836-41. Epub 2004 Jan 7.
Prospective study of acetaminophen use and newly diagnosed asthma among women. Barr RG, Wentowski CC, Curhan GC, Somers SC, Stampfer MJ, Schwartz J, Speizer FE, Camargo CA Jr.
Division of General Medicine, Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. email@example.com
Acetaminophen decreases glutathione levels in the lung, which may predispose to oxidative injury and bronchospasm. Acetaminophen use has been associated with asthma in cross-sectional studies and a birth cohort. We hypothesized that acetaminophen use would be associated with newly diagnosed adult-onset asthma in the Nurses' Health Study, a prospective cohort study of 121,700 women. Participants were first asked about frequency of acetaminophen use in 1990. Cases with asthma were defined as those with a new physician diagnosis of asthma between 1990 and 1996 plus reiteration of the diagnosis and controller medication use. Proportional hazard models included age, race, socioeconomic status, body mass index, smoking, other analgesic use, and postmenopausal hormone use. During 352,719 person-years of follow-up, 346 participants reported a new physician diagnosis of asthma meeting diagnostic criteria. Increasing frequency of acetaminophen use was positively associated with newly diagnosed asthma (p for trend = 0.006). The multivariate rate ratio for asthma for participants who received acetaminophen for more than 14 days per month was 1.63 (95% confidence interval, 1.11-2.39) compared with nonusers. It would be premature to recommend acetaminophen avoidance for patients with asthma, but further research on pulmonary responses to acetaminophen is necessary to confirm or refute these findings and to identify subgroups whose asthma may be modified by acetaminophen.
PMID: 14711794 [PubMed - indexed for MEDLINE]
[iii] Ann Allergy Asthma Immunol. 1998 Oct;81(4):347-51. Links
Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma.
• Varner AE,
• Busse WW,
• Lemanske RF Jr.
Allergy Diagnostic, Beachwood , Ohio 44122 , USA .
BACKGROUND: The prevalence of asthma, atopic eczema, and allergic rhinitis has increased over the last three decades in Western countries. Speculation on the causes of this trend have focused on changes in environmental factors. We hypothesize that the decreased use of aspirin in favor of acetaminophen, due to the association of aspirin with Reye's syndrome during febrile respiratory infections, may be contributing to these trends in the United States . DATA SOURCES: A detailed literature search was conducted utilizing Medline. Studies considered relevant and important involving both humans and animals in English language were used. HYPOTHESIS: In the United States , the documented prevalence of childhood asthma has increased since 1970, but the rate of this increase accelerated upward beginning in the early 1980s when the use of pediatric aspirin decreased. During the resolution of common respiratory viral infections, prostaglandin E2 (PGE2) is produced through the actions of cyclooxygenase-2 (COX-2). Aspirin, but not acetaminophen, inhibits COX-2 activity. As PGE2 promotes TH2 and inhibits THI type cytokine generation, we hypothesize that the decreased use of aspirin may be a factor in facilitating allergic sensitization and asthma by augmenting the relative TH1/TH2 cytokine imbalance in genetically predisposed children. CONCLUSION: We have presented an hypothesis based upon epidemiologic trends, known biologic effects of cytokines and PGE2 on allergic sensitization, and a potentially relevant pharmacologic effect of aspirin to explain a component of the increasing prevalence of childhood asthma in the United States . We suggest this theory be examined further in animal models as well as in other countries where the prevalence of childhood asthma is increasing.
PMID: 9809499 [PubMed - indexed for MEDLINE]
[iv] Am J Respir Crit Care Med. 2005 May 1;171(9):966-71. Epub 2005 Feb 25. Links
The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.
McKeever TM, Lewis SA, Smit HA, Burney P, Britton JR, Cassano PA.
Division of Epidemiology and Public Health, Clinical Science Building , City Hospital , Hucknall Road, Nottingham NG5 1PB , UK . firstname.lastname@example.org
RATIONALE: Oxidative stress may increase the risk of asthma, contribute to asthma progression, and decrease lung function. Previous research suggests that use of acetaminophen, which is hypothesized to reduce antioxidant capacity in the lung, is associated with an increased risk of asthma. We hypothesized that acetaminophen use may also be associated with chronic obstructive pulmonary disease (COPD) and decreased lung function. OBJECTIVES: To investigate the associations between use of pain medication, particularly acetaminophen, and asthma, COPD, and FEV1 in adults. METHODS: A cross-sectional analysis using the Third National Health and Nutrition Examination Survey. MEASUREMENT AND MAIN RESULTS: Increased use of acetaminophen had a positive, dose-dependent association with COPD (adjusted odds ratio for increasing category of intake, 1.16; 95% confidence interval [CI], 1.09-1.24; p value for trend < 0.001) and an inverse association with lung function (daily user compared with never users, -54.0 ml; 95% CI, -90.3 to -17.7, adjusted). Neither of these associations was explained by overlap between COPD and asthma occurrence. We confirmed a dose-response association of acetaminophen use and asthma (adjusted odds ratio, 1.20; 95% CI, 1.12-1.28; p value for trend < 0.001). CONCLUSIONS: This study provides further evidence that use of acetaminophen is associated with an increased risk of asthma and COPD, and with decreased lung function.
PMID: 15735054 [PubMed - indexed for MEDLINE]
[v] Clin Exp Allergy. 1997 May;27(5):574-7.
Aspirin-induced asthma and HLA-DRB1 and HLA-DPB1 genotypes.
Dekker JW, Nizankowska E, Schmitz-Schumann M, Pile K, Bochenek G, Dyczek A, Cookson WO, Szczeklik A.
Nuffield Department of Medicine, John Radcliffe Hospital , Oxford , UK .
BACKGROUND: Aspirin-induced asthma (AIA) affects one in 10 individuals with adult-onset asthma. It is not known if aspirin sensitivity is due to immune mechanisms or to interference with biochemical pathways. OBJECTIVE: The study aimed to test for possible involvement of the genes of the Major Histocompatibility Complex (MHC) in AIA. METHODS: HLA-DPB1 and HLA-DRB1 genotyping was carried out by DNA methods in 59 patients with positive challenge tests for AIA and in 48 normal and 57 asthmatic controls. RESULTS: The DPB1*0301 frequency was increased in AIA patients when compared with normal controls (19.5% vs 5.2%, Odds Ratio = 4.4, 95% Confidence Interval (CI) 1.6-12.1, P = 0.002), and compared with asthmatic controls (4.4%, OR = 5.3, 95% CI = 1.9-14.4, P = 0.0001). The frequency of DPB1*0401 in AIA subjects was decreased when compared with normal controls (28.8% vs 49.0%, OR = 0.42, 95% CI = 0.24-0.74, P = 0.003) and asthmatic controls (45.6%, OR = 0.48, 95% CI = 0.28-0.83, P = 0.008). The results remained significant when corrected for multiple comparisons. There were no significant HLA-DRB1 associations with AIA. CONCLUSION: The presence of an HLA association suggests that immune recognition of an unknown antigen may be part of the aetiology of AIA.
PMID: 9179433 [PubMed - indexed for MEDLINE]