Asthma: epidemiology, etiology and risk factors

I must congratulate Padmaja Subbarao et al for their elegant review on Asthma: epidemiology, etiology and risk factors. They have missed to cover acetaminophen as an etiological cause of asthma both in adults and children. Several studies have shown a relationship between acetaminophen consumption and presence of asthma.

Newson et al (1) found that acetaminophen sales correlated positively with the prevalence of asthma, rhinitis, atopic eczema, and wheezing in children who participated in ISAAC. Cohet et al(2) studied the association between infections in children aged 0 to 4 years and medications used (antibiotics and acetaminophen) and the subsequent presentation of asthma at age 6 to 7; the authors observed that the use of acetaminophen in the first year of life was weakly associated with wheezing, asthma, rhinitis, and eczema. Shaheen et al(3) conducted a study showing that the increasing use of acetaminophen was strongly associated with presence of asthma and its severity-, before and after adjusting for confounders. In their prospective study, Barr et al(4) found that acetaminophen use was associated with the presence of newly diagnosed asthma among women. In a cohort study of pregnant women, Shaheen et al(5) observed an association between daily or almost-daily use of acetaminophen during late pregnancy (20-32 weeks) and presence of wheezing in their children at age 3. Later, following the same cohort, Shaheen et al(6) reported that the use of acetaminophen during pregnancy was associated with a higher frequency of asthma and wheezing when the children reached 6 to 7 years.

A recent systematic review and meta-analysis by Etminan et al had similar results.The OR for asthma among users of acetaminophen (adult and children) was 1.63 (95% CI, 1.46-1.77). The risk of asthma in children among users of acetaminophen in the year prior to asthma diagnosis and first year of life was elevated by similar magnitude (1.60 [95% CI, 1.48- 1.74], 1.47[95% CI, 1.36-1.56] respectively). There was an increase in the risk of asthma and wheezing with prenatal acetaminophen use (1.28 [95%CI, 1.13-1.39], 1.50 [95% CI, 1.10-2.05] respectively).(7)

Several mechanisms have been postulated that may explain the possible risk of asthma with acetaminophen use. The main mechanism involves glutathione which is a potent antioxidant found in lung tissue(8). Acetaminophen has shown to lower serum glutathione levels in healthy volunteers(9). Glutathione is a potent scavenger of free radicals(10) which are in turn responsible for lung injury and initiation of an inflammatory response leading to bronchoconstriction and asthmatic symptoms.

A second possible mechanism is thought to beacetaminophen’s lack of inhibition of the enzyme cyclooxygeanse (COX)(11). COX is the key enzyme involved in the production of prostaglandins playing a major role in the inflammatory cascade in asthma. Finally, a new emerging hypothesis involves the possible antigenic effect of acetaminophen and subsequent rise in IgE and histamine levels with exposure to acetaminophen(12,13).

References

1. Newson RB, Shaheen SO, Chinn S, Burney PG. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J. 2000;16:817-23.

2. Cohet C, Cheng S, MacDonald C, Baker M, Foliaki S, Huntington N, Douwes J, Pearce N. Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. J Epidemiol Community Health. 2004;58:852-7.

3. Shaheen SO, Sterne JA, Songhurst CE, Burney PG. Frequent paracetamol use and asthma in adults. Thorax. 2000;55:266-70.

4. Barr RG, Wentowski CC, Curhan GC, Somers SC, Stampfer MJ, Schwartz J, Speizer FE, Camargo CA Jr. Prospective study of acetaminophen use and newly diagnosed asthma among women. Am J Respir Crit Care Med. 2004;169:836-41.

5. Shaheen SO, Newson RB, Sherriff A, Henderson AJ, Heron JE, Burney PG, Golding J; ALSPAC Study Team. Paracetamol use in pregnancy and wheezing in early childhood. Thorax. 2002;57:958-63.

6. Shaheen SO, Newson RB, Henderson AJ, Headley JE, Stratton FD, Jones RW, Strachan DP; ALSPAC Study Team. Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood. Clin Exp Allergy. 2005;35:18- 25.

7. Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, Fitzgerald JM. Acetaminophen Use and the Risk of Asthma in Children and Adults: A Systematic Review and Metaanalysis. Chest. 2009 Aug 20.

8. Kelly FJ. Glutathione: in defense of the lung. Food Chem Toxicol 1999;37:963–966.

9. Nuttall SL, Khan, JN, Thorpe, GH, et al The impact of therapeutic doses of acetaminophen on serum total antioxidant capacity. J Clin Pharm Ther 2003;28,289-294.

10. Rahman I, MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J 2000;16,534-554.

11. Varner AE, Busse WW, Lemanske RF Jr. Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma. Ann Allergy Asthma Immunol 1998;81:347–351.

12. De Paramo, BJ, Gancedo, SQ, Cuevas, M, et al Acetaminophen (acetaminophen) hypersensitivity. Ann Allergy Asthma Immunol 2000;85:508

13. Galindo, PA, Borja, J, Mur, P, et al Anaphylaxis to acetaminophen. Allergol Immunopathol (Madr) 1998;26,199-200.

Conflict of Interest:

None declared