The acetaminophen and asthma hypothesis 10 years on: A case to answer
2009; Elsevier BV; Volume: 124; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2009.07.037
ISSN1097-6825
AutoresH. G. Farquhar, Julian Crane, Edwin A. Mitchell, Sally Eyers, Richard Beasley,
Tópico(s)Dermatology and Skin Diseases
ResumoAs summarized in Table I,2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 3Shaheen S.O. Newson R.B. Henderson A.J. Headley J.E. Stratton F.D. Jones R.W. et al.Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.Clin Exp Allergy. 2005; 35: 18-25Crossref PubMed Scopus (182) Google Scholar, 4Rebordosa C. Kogevinas M. Sorensen H.T. Olsen J. Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: a birth cohort study.Int J Epidemiol. 2008; 37: 583-590Crossref PubMed Scopus (109) Google Scholar, 5Koniman R. Chan Y.H. Tan T.N. Van Bever H.P. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma.Pediatr Allergy Immunol. 2007; 18: 128-134Crossref PubMed Scopus (32) Google Scholar, 6Garcia-Marcos L. Sanchez-Solis M. Perez-Fernandez V. Pastor-Vivero M.D. Mondejar-Lopez P. Valverde-Molina J. Is the effect of prenatal paracetamol exposure on preschool wheezing modified by asthma in the mother?.Int Arch Allergy Immunol. 2008; 149: 33-37Crossref PubMed Scopus (45) Google Scholar, 7Persky V. Piorkowski J. Hernandez E. Chavez N. Wagner-Cassanova C. Vergara C. et al.Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life.Ann Allergy Asthma Immunol. 2008; 101: 271-278Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 8Perzanowski M.S. Miller R.L. Ali D.B. Garfinkel R.S. Chew G.L. Goldstein I.F. et al.Prenatal acetaminophen use is a risk for wheeze at age 5 years in a low income urban population with a high risk for asthma.J Allergy Clin Immunol. 2008; 121: S231Abstract Full Text Full Text PDF Google Scholar, 9Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.Acetaminophen use in infancy and later childhood and risk of asthma, rhinoconjunctivitis and eczema in 6 to 7 year old children: International Study of Asthma and Allergies in Childhood Phase Three.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar, 10Shaheen S.O. Sterne J.A.C. Songhurst C.E. Burney P.G.J. Frequent paracetamol use and asthma in adults.Thorax. 2000; 55: 266-270Crossref PubMed Scopus (185) Google Scholar, 11Shaheen S. Potts J. Gnatiuc L. Makowska J. Kowalski M.L. Joos G. et al.The relation between paracetamol use and asthma: a GA2LEN European case-control study.Eur Respir J. 2008; 32: 1231-1236Crossref PubMed Scopus (62) Google Scholar, 12Davey G. Berhane Y. Duncan P. Aref-Adib G. Britton J. Venn A. Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia.J Allergy Clin Immunol. 2005; 116: 863-868Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 13McKeever T.M. Lewis S.A. Smith H.A. Burney P. Britton J.R. Cassano P.A. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.Am J Respir Crit Care Med. 2005; 171: 966-971Crossref PubMed Scopus (97) Google Scholar, 14Barr R.G. Wentowski C.C. Curhan G.C. Somers S.C. Stampfer M.J. Schwartz J. et al.Prospective study of acetaminophen use and newly diagnosed asthma among women.Am J Respir Crit Care Med. 2004; 169: 836-841Crossref PubMed Google Scholar, 15Thomsen S.F. Kyvik K.O. Skadhauge L. Steffensen I. Backer V. Intake of paracetamol and risk of asthma in adults.J Asthma. 2008; 45: 675-676Crossref PubMed Scopus (30) Google Scholar, 19Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Paracetamol as a risk factor for allergic disorders.Lancet. 2009; 373: 120-121Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 22Lesko S.M. Louik C. Vezina R.M. Mitchell A.A. Asthma morbidity after the short-term use of ibuprofen in children.Pediatrics. 2002; 109: e20Crossref PubMed Scopus (169) Google Scholar, 25Eder W. Ege M.J. von Mutius E. The asthma epidemic.N Engl J Med. 2006; 355: 2226-2235Crossref PubMed Scopus (1331) Google Scholar, 26Bertolini A. Ferrari A. Ottani A. Guerzoni S. Tacchi R. Leone S. Paracetamol: new vistas of an old drug.CNS Drug Rev. 2006; 12: 250-275Crossref PubMed Scopus (489) Google Scholar, 27Nuttall S.L. Williams J. Kendall M.J. Does paracetamol cause asthma?.J Clin Pharmacy Ther. 2003; 28: 251-257Crossref PubMed Scopus (29) Google Scholar, 28Micheli 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; 102: 63-64Crossref PubMed Scopus (40) Google Scholar, 29Dimova S. Hoet P.H.M. Dinsdale D. Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro.Int J Biochem Cell Biol. 2005; 37: 1727-1737Crossref PubMed Scopus (62) Google Scholar, 30Barnes P.J. Reactive oxygen species and airway inflammation.Free Radic Biol Med. 1990; 9: 235-243Crossref PubMed Scopus (475) Google Scholar, 31Peterson 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; 95: 3071-3076Crossref PubMed Scopus (454) Google Scholar, 34Hill A.B. The environment and disease: association or causation?.Proc R Soc Med. 1965; 58: 295-300PubMed Google Scholar, 35Kurth T. Barr R.G. Gaziano J.M. Buring J.E. Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study.Thorax. 2008; 63: 514-518Crossref PubMed Scopus (24) Google Scholar, 36Barr R.G. Kurth T. Stampfer M.J. Buring J.E. Hennekens C.H. Gaziano J.M. Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.Am J Respir Crit Care Med. 2007; 175: 120-125Crossref PubMed Scopus (27) Google Scholar, 37McConnell R. Berhane K. Gilliland F. London S.J. Islam T. Gauderman W.J. et al.Asthma in exercising children exposed to ozone: a cohort study.Lancet. 2002; 359: 386-391Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar, 38Shaheen S.O. Sterne J.A.C. Thompson R.L. Songhurst C.E. Margetts B.M. Burney P.G.J. Dietary antioxidants and asthma in adults: population-based case-control study.Am J Respir Crit Care Med. 2001; 164: 1823-1828Crossref PubMed Scopus (243) Google Scholar, 39Rubin R.N. Navon L. Cassano P.A. Relationship of serum antioxidants to asthma prevalence in youth.Am J Respir Crit Care Med. 2004; 169: 393-398Crossref PubMed Google Scholar there is evidence to suggest that acetaminophen use might be an important risk factor for the development of asthma and might have contributed to the increasing prevalence of asthma and allergic disorders over recent decades. Although further epidemiologic and laboratory-based studies will undoubtedly be informative, the priority is to undertake randomized controlled trials to explore the association of acetaminophen with both the development and maintenance of asthma. Indeed, it is a concern that no randomized controlled trials have been undertaken of the long-term use of acetaminophen and the development of asthma and its severity. We propose that there is a case to answer and that such randomized controlled trials should now be a high priority for the research community. Only then will it be possible to determine the role of acetaminophen in the pathogenesis of asthma and related disorders and for evidence-based guidelines for the recommended use of acetaminophen to be made.Table ISummary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation34Hill A.B. The environment and disease: association or causation?.Proc R Soc Med. 1965; 58: 295-300PubMed Google ScholarStrength of effectIncreased asthma risk of up to 2.1 (paracetamol exposure in utero),2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 3Shaheen S.O. Newson R.B. Henderson A.J. Headley J.E. Stratton F.D. Jones R.W. et al.Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.Clin Exp Allergy. 2005; 35: 18-25Crossref PubMed Scopus (182) Google Scholar, 4Rebordosa C. Kogevinas M. Sorensen H.T. Olsen J. Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: a birth cohort study.Int J Epidemiol. 2008; 37: 583-590Crossref PubMed Scopus (109) Google Scholar, 5Koniman R. Chan Y.H. Tan T.N. Van Bever H.P. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma.Pediatr Allergy Immunol. 2007; 18: 128-134Crossref PubMed Scopus (32) Google Scholar, 6Garcia-Marcos L. Sanchez-Solis M. Perez-Fernandez V. Pastor-Vivero M.D. Mondejar-Lopez P. Valverde-Molina J. Is the effect of prenatal paracetamol exposure on preschool wheezing modified by asthma in the mother?.Int Arch Allergy Immunol. 2008; 149: 33-37Crossref PubMed Scopus (45) Google Scholar, 7Persky V. Piorkowski J. Hernandez E. Chavez N. Wagner-Cassanova C. Vergara C. et al.Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life.Ann Allergy Asthma Immunol. 2008; 101: 271-278Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 8Perzanowski M.S. Miller R.L. Ali D.B. Garfinkel R.S. Chew G.L. Goldstein I.F. et al.Prenatal acetaminophen use is a risk for wheeze at age 5 years in a low income urban population with a high risk for asthma.J Allergy Clin Immunol. 2008; 121: S231Abstract Full Text Full Text PDF Google Scholar 1.5 to 3.2 (paracetamol use in infancy or childhood),2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 9Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.Acetaminophen use in infancy and later childhood and risk of asthma, rhinoconjunctivitis and eczema in 6 to 7 year old children: International Study of Asthma and Allergies in Childhood Phase Three.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar and up to 2.9 (paracetamol use in adults)10Shaheen S.O. Sterne J.A.C. Songhurst C.E. Burney P.G.J. Frequent paracetamol use and asthma in adults.Thorax. 2000; 55: 266-270Crossref PubMed Scopus (185) Google Scholar, 11Shaheen S. Potts J. Gnatiuc L. Makowska J. Kowalski M.L. Joos G. et al.The relation between paracetamol use and asthma: a GA2LEN European case-control study.Eur Respir J. 2008; 32: 1231-1236Crossref PubMed Scopus (62) Google Scholar, 12Davey G. Berhane Y. Duncan P. Aref-Adib G. Britton J. Venn A. Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia.J Allergy Clin Immunol. 2005; 116: 863-868Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 13McKeever T.M. Lewis S.A. Smith H.A. Burney P. Britton J.R. Cassano P.A. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.Am J Respir Crit Care Med. 2005; 171: 966-971Crossref PubMed Scopus (97) Google Scholar, 14Barr R.G. Wentowski C.C. Curhan G.C. Somers S.C. Stampfer M.J. Schwartz J. et al.Prospective study of acetaminophen use and newly diagnosed asthma among women.Am J Respir Crit Care Med. 2004; 169: 836-841Crossref PubMed Google Scholar, 15Thomsen S.F. Kyvik K.O. Skadhauge L. Steffensen I. Backer V. Intake of paracetamol and risk of asthma in adults.J Asthma. 2008; 45: 675-676Crossref PubMed Scopus (30) Google ScholarDose responsePresent for paracetamol exposure in utero,2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 3Shaheen S.O. Newson R.B. Henderson A.J. Headley J.E. Stratton F.D. Jones R.W. et al.Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.Clin Exp Allergy. 2005; 35: 18-25Crossref PubMed Scopus (182) Google Scholar in childhood,9Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.Acetaminophen use in infancy and later childhood and risk of asthma, rhinoconjunctivitis and eczema in 6 to 7 year old children: International Study of Asthma and Allergies in Childhood Phase Three.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar and in adults10Shaheen S.O. Sterne J.A.C. Songhurst C.E. Burney P.G.J. Frequent paracetamol use and asthma in adults.Thorax. 2000; 55: 266-270Crossref PubMed Scopus (185) Google Scholar, 12Davey G. Berhane Y. Duncan P. Aref-Adib G. Britton J. Venn A. Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia.J Allergy Clin Immunol. 2005; 116: 863-868Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 13McKeever T.M. Lewis S.A. Smith H.A. Burney P. Britton J.R. Cassano P.A. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.Am J Respir Crit Care Med. 2005; 171: 966-971Crossref PubMed Scopus (97) Google Scholar, 14Barr R.G. Wentowski C.C. Curhan G.C. Somers S.C. Stampfer M.J. Schwartz J. et al.Prospective study of acetaminophen use and newly diagnosed asthma among women.Am J Respir Crit Care Med. 2004; 169: 836-841Crossref PubMed Google ScholarConsistency/coherenceConsistency between different studies in different age groups in different populations worldwide2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 3Shaheen S.O. Newson R.B. Henderson A.J. Headley J.E. Stratton F.D. Jones R.W. et al.Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.Clin Exp Allergy. 2005; 35: 18-25Crossref PubMed Scopus (182) Google Scholar, 4Rebordosa C. Kogevinas M. Sorensen H.T. Olsen J. Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: a birth cohort study.Int J Epidemiol. 2008; 37: 583-590Crossref PubMed Scopus (109) Google Scholar, 5Koniman R. Chan Y.H. Tan T.N. Van Bever H.P. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma.Pediatr Allergy Immunol. 2007; 18: 128-134Crossref PubMed Scopus (32) Google Scholar, 6Garcia-Marcos L. Sanchez-Solis M. Perez-Fernandez V. Pastor-Vivero M.D. Mondejar-Lopez P. Valverde-Molina J. Is the effect of prenatal paracetamol exposure on preschool wheezing modified by asthma in the mother?.Int Arch Allergy Immunol. 2008; 149: 33-37Crossref PubMed Scopus (45) Google Scholar, 7Persky V. Piorkowski J. Hernandez E. Chavez N. Wagner-Cassanova C. Vergara C. et al.Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life.Ann Allergy Asthma Immunol. 2008; 101: 271-278Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 8Perzanowski M.S. Miller R.L. Ali D.B. Garfinkel R.S. Chew G.L. Goldstein I.F. et al.Prenatal acetaminophen use is a risk for wheeze at age 5 years in a low income urban population with a high risk for asthma.J Allergy Clin Immunol. 2008; 121: S231Abstract Full Text Full Text PDF Google Scholar, 9Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.Acetaminophen use in infancy and later childhood and risk of asthma, rhinoconjunctivitis and eczema in 6 to 7 year old children: International Study of Asthma and Allergies in Childhood Phase Three.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar, 10Shaheen S.O. Sterne J.A.C. Songhurst C.E. Burney P.G.J. Frequent paracetamol use and asthma in adults.Thorax. 2000; 55: 266-270Crossref PubMed Scopus (185) Google Scholar, 11Shaheen S. Potts J. Gnatiuc L. Makowska J. Kowalski M.L. Joos G. et al.The relation between paracetamol use and asthma: a GA2LEN European case-control study.Eur Respir J. 2008; 32: 1231-1236Crossref PubMed Scopus (62) Google Scholar, 12Davey G. Berhane Y. Duncan P. Aref-Adib G. Britton J. Venn A. Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia.J Allergy Clin Immunol. 2005; 116: 863-868Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 13McKeever T.M. Lewis S.A. Smith H.A. Burney P. Britton J.R. Cassano P.A. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.Am J Respir Crit Care Med. 2005; 171: 966-971Crossref PubMed Scopus (97) Google Scholar, 14Barr R.G. Wentowski C.C. Curhan G.C. Somers S.C. Stampfer M.J. Schwartz J. et al.Prospective study of acetaminophen use and newly diagnosed asthma among women.Am J Respir Crit Care Med. 2004; 169: 836-841Crossref PubMed Google Scholar, 15Thomsen S.F. Kyvik K.O. Skadhauge L. Steffensen I. Backer V. Intake of paracetamol and risk of asthma in adults.J Asthma. 2008; 45: 675-676Crossref PubMed Scopus (30) Google Scholar, 22Lesko S.M. Louik C. Vezina R.M. Mitchell A.A. Asthma morbidity after the short-term use of ibuprofen in children.Pediatrics. 2002; 109: e20Crossref PubMed Scopus (169) Google ScholarExposure before responseObserved in studies of paracetamol exposure in the intrauterine environment,2Shaheen S.O. Newson R.B. Sherriff A. Henderson A.J. Heron J.E. Burney P.G.J. et al.Paracetamol use in pregnancy and wheezing in early childhood.Thorax. 2002; 57: 958-963Crossref PubMed Scopus (177) Google Scholar, 3Shaheen S.O. Newson R.B. Henderson A.J. Headley J.E. Stratton F.D. Jones R.W. et al.Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.Clin Exp Allergy. 2005; 35: 18-25Crossref PubMed Scopus (182) Google Scholar, 4Rebordosa C. Kogevinas M. Sorensen H.T. Olsen J. Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: a birth cohort study.Int J Epidemiol. 2008; 37: 583-590Crossref PubMed Scopus (109) Google Scholar, 5Koniman R. Chan Y.H. Tan T.N. Van Bever H.P. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma.Pediatr Allergy Immunol. 2007; 18: 128-134Crossref PubMed Scopus (32) Google Scholar, 6Garcia-Marcos L. Sanchez-Solis M. Perez-Fernandez V. Pastor-Vivero M.D. Mondejar-Lopez P. Valverde-Molina J. Is the effect of prenatal paracetamol exposure on preschool wheezing modified by asthma in the mother?.Int Arch Allergy Immunol. 2008; 149: 33-37Crossref PubMed Scopus (45) Google Scholar, 7Persky V. Piorkowski J. Hernandez E. Chavez N. Wagner-Cassanova C. Vergara C. et al.Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life.Ann Allergy Asthma Immunol. 2008; 101: 271-278Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 8Perzanowski M.S. Miller R.L. Ali D.B. Garfinkel R.S. Chew G.L. Goldstein I.F. et al.Prenatal acetaminophen use is a risk for wheeze at age 5 years in a low income urban population with a high risk for asthma.J Allergy Clin Immunol. 2008; 121: S231Abstract Full Text Full Text PDF Google Scholar in infancy,9Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.Acetaminophen use in infancy and later childhood and risk of asthma, rhinoconjunctivitis and eczema in 6 to 7 year old children: International Study of Asthma and Allergies in Childhood Phase Three.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar and in adult life14Barr R.G. Wentowski C.C. Curhan G.C. Somers S.C. Stampfer M.J. Schwartz J. et al.Prospective study of acetaminophen use and newly diagnosed asthma among women.Am J Respir Crit Care Med. 2004; 169: 836-841Crossref PubMed Google Scholar, 15Thomsen S.F. Kyvik K.O. Skadhauge L. Steffensen I. Backer V. Intake of paracetamol and risk of asthma in adults.J Asthma. 2008; 45: 675-676Crossref PubMed Scopus (30) Google ScholarBiologic plausibilityThrough increased oxidant-induced inflammation and potentially enhanced TH2 response27Nuttall S.L. Williams J. Kendall M.J. Does paracetamol cause asthma?.J Clin Pharmacy Ther. 2003; 28: 251-257Crossref PubMed Scopus (29) Google Scholar, 28Micheli 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; 102: 63-64Crossref PubMed Scopus (40) Google Scholar, 29Dimova S. Hoet P.H.M. Dinsdale D. Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro.Int J Biochem Cell Biol. 2005; 37: 1727-1737Crossref PubMed Scopus (62) Google Scholar, 30Barnes P.J. Reactive oxygen species and airway inflammation.Free Radic Biol Med. 1990; 9: 235-243Crossref PubMed Scopus (475) Google Scholar, 31Peterson 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; 95: 3071-3076Crossref PubMed Scopus (454) Google ScholarRemoval of exposure prevents diseaseNot yet examinedSpecificityNo increased risk of asthma associated with aspirin or other nonsteroidal anti-inflammatory drugs35Kurth T. Barr R.G. Gaziano J.M. Buring J.E. Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study.Thorax. 2008; 63: 514-518Crossref PubMed Scopus (24) Google Scholar, 36Barr R.G. Kurth T. Stampfer M.J. Buring J.E. Hennekens C.H. Gaziano J.M. Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.Am J Respir Crit Care Med. 2007; 175: 120-125Crossref PubMed Scopus (27) Google ScholarTemporal associationInternational trends of increasing paracetamol use and increasing prevalence of asthma1Varner A.E. Busse W.W. Lemanske Jr., R.F. Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma.Ann Allergy Asthma Immunol. 1998; 81: 347-351Abstract Full Text PDF PubMed Scopus (93) Google Scholar, 25Eder W. Ege M.J. von Mutius E. The asthma epidemic.N Engl J Med. 2006; 355: 2226-2235Crossref PubMed Scopus (1331) Google Scholar, 26Bertolini A. Ferrari A. Ottani A. Guerzoni S. Tacchi R. Leone S. Paracetamol: new vistas of an old drug.CNS Drug Rev. 2006; 12: 250-275Crossref PubMed Scopus (489) Google ScholarAnalogyOxidant-induced airway inflammation in asthma (eg, ozone)37McConnell R. Berhane K. Gilliland F. London S.J. Islam T. Gauderman W.J. et al.Asthma in exercising children exposed to ozone: a cohort study.Lancet. 2002; 359: 386-391Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar; protective effects of antioxidant diet in asthma38Shaheen S.O. Sterne J.A.C. Thompson R.L. Songhurst C.E. Margetts B.M. Burney P.G.J. Dietary antioxidants and asthma in adults: population-based case-control study.Am J Respir Crit Care Med. 2001; 164: 1823-1828Crossref PubMed Scopus (243) Google Scholar, 39Rubin R.N. Navon L. Cassano P.A. Relationship of serum antioxidants to asthma prevalence in youth.Am J Respir Crit Care Med. 2004; 169: 393-398Crossref PubMed Google ScholarDerived with modification from Beasley et al.19Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Paracetamol as a risk factor for allergic disorders.Lancet. 2009; 373: 120-121Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Open table in a new tab
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