Abstract
BACKGROUND—The pulmonary antioxidant glutathione may limit airway inflammation in asthma. Since paracetamol (acetaminophen) depletes the lung of glutathione in animals, a study was undertaken to investigate whether frequent use in humans was associated with asthma. METHODS—Information was collected on the use of analgesics as part of a population based case-control study of dietary antioxidants and asthma in adults aged 16-49 years registered with 40 general practices in Greenwich, South London. The frequency of use of paracetamol and aspirin was compared in 664 individuals with asthma and in 910 without asthma. Asthma was defined by positive responses to questions about asthma attacks, asthma medication, or waking at night with shortness of breath. The association between analgesic use and severity of disease amongst asthma cases, as measured by a quality of life score, was also examined. RESULTS—Paracetamol use was positively associated with asthma. After controlling for potential confounding factors the odds ratio for asthma, compared with never users, was 1.06 (95% CI 0.77 to 1.45) in infrequent users (<monthly), 1.22 (0.87 to 1.72) in monthly users, 1.79 (1.21 to 2.65) in weekly users, and 2.38 (1.22 to 4.64) in daily users (p (trend) = 0.0002). This association was present in users and non-users of aspirin and was stronger when cases with more severe disease were compared with controls; amongst cases increasing paracetamol use was associated with more severe disease. Frequency of aspirin use was not associated with asthma when cases as a whole were compared with controls, nor with severity of asthma amongst cases. Frequent paracetamol use was positively associated with rhinitis, but aspirin use was not. CONCLUSIONS—Frequent use of paracetamol may contribute to asthma morbidity and rhinitis in adults.
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Selected References
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- Barnes P. J. Reactive oxygen species and airway inflammation. Free Radic Biol Med. 1990;9(3):235–243. doi: 10.1016/0891-5849(90)90034-g. [DOI] [PubMed] [Google Scholar]
- Blomberg A., Sainsbury C., Rudell B., Frew A. J., Holgate S. T., Sandström T., Kelly F. J. Nasal cavity lining fluid ascorbic acid concentration increases in healthy human volunteers following short term exposure to diesel exhaust. Free Radic Res. 1998 Jan;28(1):59–67. doi: 10.3109/10715769809097876. [DOI] [PubMed] [Google Scholar]
- Burney P. G., Chinn S., Britton J. R., Tattersfield A. E., Papacosta A. O. What symptoms predict the bronchial response to histamine? Evaluation in a community survey of the bronchial symptoms questionnaire (1984) of the International Union Against Tuberculosis and Lung Disease. Int J Epidemiol. 1989 Mar;18(1):165–173. doi: 10.1093/ije/18.1.165. [DOI] [PubMed] [Google Scholar]
- Burney P. G., Luczynska C., Chinn S., Jarvis D. The European Community Respiratory Health Survey. Eur Respir J. 1994 May;7(5):954–960. doi: 10.1183/09031936.94.07050954. [DOI] [PubMed] [Google Scholar]
- Cantin A. M., North S. L., Hubbard R. C., Crystal R. G. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol (1985) 1987 Jul;63(1):152–157. doi: 10.1152/jappl.1987.63.1.152. [DOI] [PubMed] [Google Scholar]
- Chen T. S., Richie J. P., Jr, Lang C. A. Life span profiles of glutathione and acetaminophen detoxification. Drug Metab Dispos. 1990 Nov-Dec;18(6):882–887. [PubMed] [Google Scholar]
- Jenkinson S. G., Black R. D., Lawrence R. A. Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia. J Lab Clin Med. 1988 Sep;112(3):345–351. [PubMed] [Google Scholar]
- Kanazawa H., Kurihara N., Hirata K., Takeda T. The role of free radicals in airway obstruction in asthmatic patients. Chest. 1991 Nov;100(5):1319–1322. doi: 10.1378/chest.100.5.1319. [DOI] [PubMed] [Google Scholar]
- Kelly F. J., Blomberg A., Frew A., Holgate S. T., Sandstrom T. Antioxidant kinetics in lung lavage fluid following exposure of humans to nitrogen dioxide. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1700–1705. doi: 10.1164/ajrccm.154.6.8970358. [DOI] [PubMed] [Google Scholar]
- Kelly F. J., Mudway I., Blomberg A., Frew A., Sandström T. Altered lung antioxidant status in patients with mild asthma. Lancet. 1999 Aug 7;354(9177):482–483. doi: 10.1016/S0140-6736(99)01812-7. [DOI] [PubMed] [Google Scholar]
- Ketterer B., Coles B., Meyer D. J. The role of glutathione in detoxication. Environ Health Perspect. 1983 Mar;49:59–69. doi: 10.1289/ehp.834959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kharitonov S. A., Yates D., Robbins R. A., Logan-Sinclair R., Shinebourne E. A., Barnes P. J. Increased nitric oxide in exhaled air of asthmatic patients. Lancet. 1994 Jan 15;343(8890):133–135. doi: 10.1016/s0140-6736(94)90931-8. [DOI] [PubMed] [Google Scholar]
- Kourounakis A. P., Rekka E. A., Kourounakis P. N. Antioxidant activity of guaiazulene and protection against paracetamol hepatotoxicity in rats. J Pharm Pharmacol. 1997 Sep;49(9):938–942. doi: 10.1111/j.2042-7158.1997.tb06140.x. [DOI] [PubMed] [Google Scholar]
- Marks G. B., Burney P. G., Premaratne U. N., Simpson J., Webb J. Asthma in Greenwich, UK: impact of the disease and current management practices. Eur Respir J. 1997 Jun;10(6):1224–1229. doi: 10.1183/09031936.97.10061224. [DOI] [PubMed] [Google Scholar]
- Marks G. B., Dunn S. M., Woolcock A. J. A scale for the measurement of quality of life in adults with asthma. J Clin Epidemiol. 1992 May;45(5):461–472. doi: 10.1016/0895-4356(92)90095-5. [DOI] [PubMed] [Google Scholar]
- Marks G. B., Dunn S. M., Woolcock A. J. An evaluation of an asthma quality of life questionnaire as a measure of change in adults with asthma. J Clin Epidemiol. 1993 Oct;46(10):1103–1111. doi: 10.1016/0895-4356(93)90109-e. [DOI] [PubMed] [Google Scholar]
- Micheli L., Cerretani D., Fiaschi A. I., Giorgi G., Romeo M. R., Runci F. M. Effect of acetaminophen on glutathione levels in rat testis and lung. Environ Health Perspect. 1994 Nov;102 (Suppl 9):63–64. doi: 10.1289/ehp.94102s963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson H. S. The Bela Schick lecture for 1985. The atopic diseases. Ann Allergy. 1985 Sep;55(3):441–447. [PubMed] [Google Scholar]
- Peterson J. D., Herzenberg L. A., Vasquez K., Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3071–3076. doi: 10.1073/pnas.95.6.3071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Premaratne U. N., Sterne J. A., Marks G. B., Webb J. R., Azima H., Burney P. G. Clustered randomised trial of an intervention to improve the management of asthma: Greenwich asthma study. BMJ. 1999 May 8;318(7193):1251–1255. doi: 10.1136/bmj.318.7193.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rahman I., MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax. 1998 Jul;53(7):601–612. doi: 10.1136/thx.53.7.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Resta O., Foschino-Barbaro M. P., Carnimeo N., Bavoso P., Picca V. Asthma relieved by acetylsalicylic acid and nonsteroid anti-inflammatory drugs. Respiration. 1984;46(1):121–127. doi: 10.1159/000194679. [DOI] [PubMed] [Google Scholar]
- Seaton A., Godden D. J., Brown K. Increase in asthma: a more toxic environment or a more susceptible population? Thorax. 1994 Feb;49(2):171–174. doi: 10.1136/thx.49.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Settipane R. A., Schrank P. J., Simon R. A., Mathison D. A., Christiansen S. C., Stevenson D. D. Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol. 1995 Oct;96(4):480–485. doi: 10.1016/s0091-6749(95)70290-3. [DOI] [PubMed] [Google Scholar]
- Settipane R. A., Stevenson D. D. Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. J Allergy Clin Immunol. 1989 Jul;84(1):26–33. doi: 10.1016/0091-6749(89)90174-7. [DOI] [PubMed] [Google Scholar]
- Slade R., Crissman K., Norwood J., Hatch G. Comparison of antioxidant substances in bronchoalveolar lavage cells and fluid from humans, guinea pigs, and rats. Exp Lung Res. 1993 Jul-Aug;19(4):469–484. doi: 10.3109/01902149309064358. [DOI] [PubMed] [Google Scholar]
- Smith L. J., Anderson J., Shamsuddin M., Hsueh W. Effect of fasting on hyperoxic lung injury in mice. The role of glutathione. Am Rev Respir Dis. 1990 Jan;141(1):141–149. doi: 10.1164/ajrccm/141.1.141. [DOI] [PubMed] [Google Scholar]
- Smith L. J., Houston M., Anderson J. Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1461–1464. doi: 10.1164/ajrccm/147.6_Pt_1.1461. [DOI] [PubMed] [Google Scholar]
- Spielberg S. P. Acetaminophen toxicity in human lymphocytes in vitro. J Pharmacol Exp Ther. 1980 May;213(2):395–398. [PubMed] [Google Scholar]
- Strachan D. P., Butland B. K., Anderson H. R. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ. 1996 May 11;312(7040):1195–1199. doi: 10.1136/bmj.312.7040.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Varner A. E., Busse W. W., Lemanske R. F., Jr Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma. Ann Allergy Asthma Immunol. 1998 Oct;81(4):347–351. doi: 10.1016/S1081-1206(10)63127-4. [DOI] [PubMed] [Google Scholar]