Frequent paracetamol use and asthma in adults
Open accessAbstract
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 (
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Depletion of glutathione in airway epithelial lining fluid by paracetamol metabolites has been suggested as a possible cause of asthma in chronic users.
“Depletion of glutathione in airway epithelial lining fluid by paracetamol metabolites has been suggested as the possible cause (192).”
From Paracetamol: New Vistas of an Old Drug (2006) · cites this paper as [192]
The Discussion proposes that frequent paracetamol use could contribute to asthma morbidity by depleting glutathione in airway epithelial lining fluid. However, the paper attributes depletion by a reactive paracetamol metabolite to the liver; it does not establish that metabolites deplete glutathione in airway lining fluid. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThere is increased evidence of asthma in chronic paracetamol users.
“Finally, it is worth mentioning an increased evidence of asthma in chronic paracetamol users (17,192).”
From Paracetamol: New Vistas of an Old Drug (2006) · cites this paper as [192]
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Cites
The European Community Respiratory Health Survey
Burney, P., Luczynska, C. M., Chinn, S., & Jarvis, D. (1994) · European Respiratory Journal · doi:10.1183/09031936.94.07050954 · Cited by 1,999 · see citing works
Increased nitric oxide in exhaled air of asthmatic patients
Kharitonov, S. A., Yates, D. H., Robbins, R. A., Barnes, P. J., Logan-Sinclair, R., & Shinebourne, E. A. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90931-8 · Cited by 1,432 · see citing works
Standard occupational classification
Surveys (1990) · HMSO eBooks · Cited by 963 · see citing works
Normal alveolar epithelial lining fluid contains high levels of glutathione
Cantin, A. M., North, S. L., Hubbard, R. C., & Crystal, R. G. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.63.1.152 · Cited by 797 · see citing works
Strachan, D. P., Butland, B. K., & ANDERSON, H. R. (1996) · BMJ · doi:10.1136/bmj.312.7040.1195 · Cited by 654 · see citing works
Reactive oxygen species and airway inflammation
Barnes, P. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90034-g · Cited by 528 · see citing works
Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns
Peterson, J. D., Herzenberg, L. A., Vasquez, K. O., & Waltenbaugh, C. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3071 · Cited by 508 · see citing works
Role of transcription factors in inflammatory lung diseases
Rahman, I., & MacNee, W. (1998) · Thorax · doi:10.1136/thx.53.7.601 · Cited by 470 · see citing works
Increase in asthma: a more toxic environment or a more susceptible population?
Seaton, A., Godden, D., & Brown, K. (1994) · Thorax · doi:10.1136/thx.49.2.171 · Cited by 468 · see citing works
A scale for the measurement of quality of life in adults with asthma
Marks, G. B., Dunn, S. M., & Woolcock, A. J. (1992) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(92)90095-5 · Cited by 391 · see citing works
The role of glutathione in detoxication
KETTERER, B., Coles, B., & Meyer, D. J. (1983) · Environmental Health Perspectives · doi:10.1289/ehp.834959 · Cited by 385 · see citing works
Altered lung antioxidant status in patients with mild asthma
Kelly, F. J., Mudway, I., Blomberg, A., Frew, A. J., & Sandström, T. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01812-7 · Cited by 343 · see citing works
Marks, G. B., Dunn, S. M., & Woolcock, A. J. (1993) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(93)90109-e · Cited by 183 · see citing works
Burney, P., Chinn, S. H. F., Britton, J. R., Tattersfield, A. E., & Papacosta, O. (1989) · International Journal of Epidemiology · doi:10.1093/ije/18.1.165 · Cited by 179 · see citing works
Increased Levels of Glutathione in Bronchoalveolar Lavage Fluid from Patients with Asthma
Smith, L. J., Houston, M., & Anderson, J. (1993) · American Review of Respiratory Disease · doi:10.1164/ajrccm/147.6_pt_1.1461 · Cited by 161 · see citing works
Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects
Settipane, R. A., Schrank, P. J., Simon, R. A., Mathison, D. A., Christiansen, S. C., & Stevenson, D. D. (1995) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(95)70290-3 · Cited by 156 · see citing works
Slade, R., Crissman, K. M., Norwood, J., & Hatch, G. E. (1993) · Experimental Lung Research · doi:10.3109/01902149309064358 · Cited by 128 · see citing works
Antioxidant Kinetics in Lung Lavage Fluid Following Exposure of Humans to Nitrogen Dioxide
Kelly, F. J., Blomberg, A., Frew, A. J., Holgate, S. T., & Sandström, T. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.154.6.8970358 · Cited by 118 · see citing works
Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma
Settipane, R. A., & Stevenson, D. D. (1989) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(89)90174-7 · Cited by 117 · see citing works
Varner, A. E., Busse, W. W., & Lemanske, R. F. (1998) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)63127-4 · Cited by 111 · see citing works
Life span profiles of glutathione and acetaminophen detoxification.
Chen, T. S., Richie, J. P., & Lang, C. A. (1990) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08686-6 · Cited by 101 · see citing works
Premaratne, U. N., Sterne, J. A. C., Marks, G. B., Webb, J. R., Azima, H., & Burney, P. (1999) · BMJ · doi:10.1136/bmj.318.7193.1251 · Cited by 94 · see citing works
The Role of Free Radicals in Airway Obstruction in Asthmatic Patients
Kanazawa, H., Kurihara, N., Hirata, K., & Takeda, T. (1991) · CHEST Journal · doi:10.1378/chest.100.5.1319 · Cited by 94 · see citing works
Acetaminophen toxicity in human lymphocytes in vitro.
Spielberg, S. P. (1980) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)32074-4 · Cited by 86 · see citing works
Antioxidant Activity of Guaiazulene and Protection Against Paracetamol Hepatotoxicity in Rats
Kourounakis, A. P., Rekka, E. A., & Kourounakis, P. N. (1997) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1997.tb06140.x · Cited by 69 · see citing works
Dimova, S., Hoet, P., & Nemery, B. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00257-4 · Cited by 58 · see citing works
Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia.
Sg, J., Rd, B., & Ra, L. (1988) · PubMed · Cited by 56 · see citing works
Asthma in Greenwich, UK: impact of the disease and current management practices
Marks, G. B., Burney, P., Premaratne, U. N., Simpson, J. A., & Webb, J. (1997) · European Respiratory Journal · doi:10.1183/09031936.97.10061224 · Cited by 55 · see citing works
Effect of acetaminophen on glutathione levels in rat testis and lung.
Micheli, L., Cerretani, D., Fiaschi, A. I., Giorgi, G., Romeo, M. R., & Runci, F. M. (1994) · Environmental Health Perspectives · doi:10.1289/ehp.94102s963 · Cited by 53 · see citing works
Effect of Fasting on Hyperoxic Lung Injury in Mice: The Role of Glutathione
Smith, L. J., Anderson, J., Shamsuddin, M., & Hsueh, W. (1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/141.1.141 · Cited by 48 · see citing works
Blomberg, A., Sainsbury, C., Rudell, B., Frew, A. J., Holgate, S. T., Sandströw, T., & Kelly, F. (1998) · Free Radical Research · doi:10.3109/10715769809097876 · Cited by 42 · see citing works
The Bela Schick lecture for 1985. The atopic diseases.
Hs, N. (1985) · PubMed · Cited by 34 · see citing works
The Role of Glutathione in Detoxication
KETTERER, B., Coles, B., & Meyer, D. J. (1983) · Environmental Health Perspectives · doi:10.2307/3429581 · Cited by 23 · see citing works
Asthma Relieved by Acetylsalicylic Acid and Nonsteroid Anti-Inflammatory Drugs
Resta, O., Barbaro, M. P. F., Carnimeo, N., Bavoso, P., & Picca, V. (2009) · Respiration · doi:10.1159/000194679 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Glutathione dysregulation and the etiology and progression of human diseases
Ballatori, N., Krance, S. M., Notenboom, S., Shi, S., Tieu, K., & Hammond, C. L. (2009) · Biological Chemistry · doi:10.1515/bc.2009.033 · Cited by 1,118 · see citing works
“Recently, there has been growing interest in reports that associate acetaminophen use (a well-known GSH-depleting agent), with an increased risk of asthma (Shaheen et al., 2000; Barr et al., 2004; Eneli et al., 2005; McKeever et al., 2005).”
BackgroundParacetamol: New Vistas of an Old Drug
Bertolini, A., Ferrari, A., Ottani, A., Guerzoni, S., Tacchi, R., & Leone, S. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2006.00250.x · Cited by 654 · see citing works
“Finally, it is worth mentioning an increased evidence of asthma in chronic paracetamol users (17,192).”
BackgroundBeasley, R. W., Clayton, T., Crane, J., von Mutius, E., Lai, C. K. W., Montefort, S., & Stewart, A. W. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61445-2 · Cited by 429 · see citing works
Long‐term adverse effects of paracetamol – a review
McCrae, J. C., Morrison, E. E., MacIntyre, I. M., Dear, J. W., & Webb, D. J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13656 · Cited by 308 · see citing works
“studies demonstrated a connection between paracetamol use and asthma diagnoses or exacerbations [47-54].”
BackgroundDietary Antioxidants and Asthma in Adults
SHAHEEN, S. O., Sterne, J. A. C., THOMPSON, R. L., SONGHURST, C. E., Margetts, B., & Burney, P. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.10.2104061 · Cited by 306 · see citing works
“After allowing for likely wrong addresses, the overall response rate was 55% ( 14 ).”
BackgroundSelf-citationAre all wheezing disorders in very young (preschool) children increasing in prevalence?
Kuehni, C. E., Davis, A. D., Brooke, A., & Silverman, M. A. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04958-8 · Cited by 259 · see citing works
Paracetamol use in pregnancy and wheezing in early childhood
Shaheen, S. O. (2002) · Thorax · doi:10.1136/thorax.57.11.958 · Cited by 208 · see citing works
“10 Our subsequent ecological study showed that countries with higher paracetamol sales had higher prevalences of wheeze, asthma, rhinitis and BHR in adults, and higher prevalences of wheeze, allergic rhinoconjunctivitis, and atopic eczema in children and teenagers.”
BackgroundSelf-citationAllergic disease and sensitization in Steiner school children
Flöistrup, H., Swartz, J., Bergström, A., Alm, J. S., Scheynius, A., van Hage, M., Waser, M., Braun‐Fahrländer, C., Schram-Bijkerk, D., Huber, M., et al. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.09.039 · Cited by 208 · see citing works
“The association between antipyretics and asthma is supported by a previously reported dose-response relation between paracetamol intake and asthma severity in young adults.(21) Moreover, a strong correlation between paracetamol consumption and the incidence of atopic diseases in children has been reported.”
BackgroundPrenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood
Shaheen, S. O., Newson, R. B., Henderson, A. J., Headley, J. E., Stratton, F. D., Jones, R. W., Strachan, D. P., & the ALSPAC Study Team (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02151.x · Cited by 206 · see citing works
Self-citationAsthma Morbidity After the Short-Term Use of Ibuprofen in Children
Lesko, S. M., Louik, C., Vezina, R. M., & Mitchell, A. A. (2002) · PEDIATRICS · doi:10.1542/peds.109.2.e20 · Cited by 199 · see citing works
Confounding by Indication in Epidemiologic Studies of Commonly Used Analgesics
Signorello, L. B., McLaughlin, J. K., Lipworth, L., Friis, S. R., Sørensen, H. T., & Blot, W. J. (2002) · American Journal of Therapeutics · doi:10.1097/00045391-200205000-00005 · Cited by 178 · see citing works
“At the individual level, the same authors also reported a significant association between acetaminophen use and asthma(30); however, this casecontrol study used prevalent asthma cases and evaluated analgesic usage after the onset of the disease.(30) Thus, it is likely that the indication for taking acetaminophen could…”
BackgroundHudson, V. M. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00530-5 · Cited by 166 · see citing works
Graham, G. G., Scott, K. F., & Day, R. O. (2005) · Drug Safety · doi:10.2165/00002018-200528030-00004 · Cited by 163 · see citing works
̈r, K. S. (2007) · Pediatric Drugs · doi:10.2165/00148581-200709030-00008 · Cited by 158 · see citing works
Paracetamol sales and atopic disease in children and adults: an ecological analysis
Newson, R. B., Shaheen, S. O., Chinn, S., & Burney, P. (2000) · European Respiratory Journal · doi:10.1183/09031936.00.16581700 · Cited by 150 · see citing works
“Paracetamol sales were also positively associated with the prevalence of wheeze, asthma and rhinitis and with mean bronchial responsiveness in young adults across centres participating in the ECRHS, which is in keeping with the recent observation that frequent use of paracetamol was positively associated with asthma a…”
BackgroundResultInfluentialSelf-citationCohet, C., Cheng, S., MacDonald, C., Baker, M., Foliaki, S., Huntington, N., Douwes, J. E., & Pearce, N. E. (2004) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2003.019182 · Cited by 145 · see citing works
Acetaminophen Use and the Risk of Asthma in Children and Adults
Etminan, M., Sadatsafavi, M., Jafari, S., Doyle-Waters, M., Aminzadeh, K. K.-W., & FitzGerald, J. M. (2009) · CHEST Journal · doi:10.1378/chest.09-0865 · Cited by 138 · see citing works
Beasley, R. W., Clayton, T. O., Crane, J., Lai, C. K. W., Montefort, S., von Mutius, E., & Stewart, A. W. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201005-0757oc · Cited by 131 · see citing works
Eyers, S., Weatherall, M., Jefferies, S., & Beasley, R. W. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03691.x · Cited by 130 · see citing works
Prospective Study of Acetaminophen Use and Newly Diagnosed Asthma among Women
Barr, R. G., Wentowski, C. C., Curhan, G. C., Somers, S. C., Stampfer, M. J., Schwartz, J., Speizer, F. E., & Camargo, C. A. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200304-596oc · Cited by 125 · see citing works
“(interquartile range) 24 (11, 42) 22 ( 10 , 39) 23 (11, 40) 25 (12, 41) 28 (14, 47)”
BackgroundInfluentialPre-natal exposure to paracetamol and risk of wheezing and asthma in children: A birth cohort study
Rebordosa, C., Kogevinas, M., Sørensen, H. T., & Olsen, J. H. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dyn070 · Cited by 124 · see citing works
Acetaminophen and the Risk of Asthma
Eneli, I., Sadri, K., Camargo, C. A., & Barr, R. G. (2005) · CHEST Journal · doi:10.1378/chest.127.2.604 · Cited by 123 · see citing works
The Association of Acetaminophen, Aspirin, and Ibuprofen with Respiratory Disease and Lung Function
McKeever, T. M., Lewis, S., Smit, H. A., Burney, P., Britton, J. R., & Cassano, P. A. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200409-1269oc · Cited by 122 · see citing works
“The first study that reported an acetaminophen–asthma association was a case-control study of asthma in adults (adjusted OR for daily users of acetaminophen compared with never users, 2.4; 95% CI, 1.2–4.6) ( 13 ).”
BackgroundInfluentialA clinical and safety review of paracetamol and ibuprofen in children
Kanabar, D. J. (2017) · Inflammopharmacology · doi:10.1007/s10787-016-0302-3 · Cited by 125 · see citing works
“A further study has shown that the incidence of asthma in infrequent users (\monthly) and monthly, weekly and daily users was 1.06, 1.22, 1.79 and 2.38, respectively (p = 0.0002) (Shaheen et al. 2000).”
BackgroundInfluentialSordillo, J. E., Scirica, C. V., Rifas‐Shiman, S. L., Gillman, M. W., Bunyavanich, S., Camargo, C. A., Weiss, S. T., Gold, D. R., & Litonjua, A. A. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.07.065 · Cited by 113 · see citing works
Nassini, R., Materazzi, S., Andrè, E., Sartiani, L., Aldini, G., Trevisani, M., Carnini, C., Massi, D., Pedretti, P., Carini, M., et al. (2010) · The FASEB Journal · doi:10.1096/fj.10-162438 · Cited by 112 · see citing works
Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma
Shaheen, S. O., Newson, R. B., Ring, S. M., Rose-Zerilli, M. J. J., Holloway, J. W., & Henderson, A. J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.08.047 · Cited by 111 · see citing works
Self-citationInternational patterns of the prevalence of pediatric asthma
Beasley, R. W., Ellwood, P., & Asher, I. (2003) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(03)00050-6 · Cited by 111 · see citing works
“It is also consistent with the recent report that frequent (daily or weekly) use of paracetamol is positively associated with asthma including asthma severity [25].”
ResultCheelo, M., Lodge, C. J., Dharmage, S. C., Simpson, J. A., Matheson, M., Heinrich, J., & Lowe, A. J. (2015) · Archives of Disease in Childhood · doi:10.1136/archdischild-2012-303043 · Cited by 110 · see citing works
Asthma Inception: Epidemiologic Risk Factors and Natural History Across the Life Course
Mélen, E., Zar, H., Siroux, V., Shaw, D., Saglani, S., Koppelman, G., Hartert, T., Gern, J., Gaston, B., Bush, A., et al. (2024) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202312-2249so · Cited by 80 · see citing works
“In an adult population 16 – 40 years of age, asthma risk correlated positively with the frequency of acetaminophen use ( P trend=0.0002), which was highest among weekly (OR, 1.79; 95% CI, 1.21 – 2.65), and daily users (OR, 2.38; 95% CI, 1.22 – 4.64) (164).”
InfluentialThe Association of Acetaminophen and Asthma Prevalence and Severity
McBride, J. T. (2011) · PEDIATRICS · doi:10.1542/peds.2011-1106 · Cited by 95 · see citing works
The role of paracetamol in the pathogenesis of asthma
Farquhar, H., Stewart, A. J., Mitchell, E. A., Crane, J., Eyers, S., Weatherall, M., & Beasley, R. W. (2009) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2009.03378.x · Cited by 90 · see citing works
Lauterburg, B. H. (2002) · American Journal of Therapeutics · doi:10.1097/00045391-200205000-00008 · Cited by 87 · see citing works
“GSH is lower than normal in patients with inflammatory lung diseases, such as adult respiratory distress syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, possibly as a result of consumption by detoxification of reactive oxygen species.62 Evidence also exists for an oxidant stress in asthma;63 however, GSH…”
BackgroundInfluentialHenderson, A. J., & Shaheen, S. O. (2012) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2012.04.004 · Cited by 80 · see citing works
Self-citationPrenatal exposure to acetaminophen and respiratory symptoms in the first year of life
Persky, V., Piorkowski, J., Hernández, E., Chávez, N., Wagner-Cassanova, C., Vergara, C., Pelzel, D., Enriquez, R., Gutierrez, S., & Busso, A. (2008) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)60492-9 · Cited by 80 · see citing works
The dental patient with asthma
Steinbacher, D. M., & Glick, M. (2001) · The Journal of the American Dental Association · doi:10.14219/jada.archive.2001.0365 · Cited by 79 · see citing works
End of life care in chronic obstructive pulmonary disease: in search of a good death
Booth, S. (2008) · International Journal of COPD · doi:10.2147/copd.s698 · Cited by 78 · see citing works
Dimova, S., Hoet, P., Dinsdale, D. D., & Nemery, B. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.03.005 · Cited by 78 · see citing works
Sauer, U. G., Vogel, S., Hess, A., Kolle, S. N., Ma‐Hock, L., van Ravenzwaay, B., & Landsiedel, R. (2012) · Toxicology in Vitro · doi:10.1016/j.tiv.2012.10.007 · Cited by 77 · see citing works
“Paracetamol is not regarded as a respiratory toxicant, even though it has been observed to cause asthma in human patients upon long-term oral treatment in high dosages (Shaheen et al., 2000).”
The impact of therapeutic doses of paracetamol on serum total antioxidant capacity
Nuttall, S., Khan, J. N., Thorpe, G. H. G., Langford, N. J., & Kendall, M. J. (2003) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.2003.00493.x · Cited by 76 · see citing works
Prenatal determinants of neonatal lung function in high-risk newborns
Bisgaard, H. F., Loland, L., Holst, K. K., & Pipper, C. B. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.11.036 · Cited by 76 · see citing works
The relation between paracetamol use and asthma: a GA2LEN European case–control study
Shaheen, S. O., Potts, J. A., Gnatiuc, L., Makowska, J. S., Kowalski, M. L., Joos, G. F., Zele, T. V., van Durme, Y., Rudder, I. D., Wöhrl, S., et al. (2008) · European Respiratory Journal · doi:10.1183/09031936.00039208 · Cited by 75 · see citing works
Self-citationPrenatal Exposure to Acetaminophen and Asthma in Children
Kang, E. M., Lundsberg, L. S., Illuzzi, J. L., & Bracken, M. B. (2009) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e3181c225c0 · Cited by 72 · see citing works
The role of platelets in the pathophysiology of asthma
Kornerup, K. N., & Page, C. P. (2007) · Platelets · doi:10.1080/09537100701230436 · Cited by 72 · see citing works
“Further evidence to support this hypothesis shows that paracetamol administration increases the clinical severity of asthma, probably due to its depletory effect on glutathione peroxidase in the lung [83].”
BackgroundSimilarities in features of autism and asthma and a possible link to acetaminophen use
Becker, K. G., & Schultz, S. T. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.08.033 · Cited by 69 · see citing works
“Most importantly, acetaminophen use in the first year of life has been strongly associated with a later increased risk of asthma, and related phenotypes of asthma [58].”
BackgroundAcetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases
Wang, J., Liu, L., Chen, C., Huang, Y.-W., Hsiung, C. A., & Tsai, H. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt121 · Cited by 69 · see citing works
Opioid and non-opioid analgesics
Schug, S. A., Garrett, W. R., & Gillespie, G. (2003) · Best practice & research. Clinical anaesthesiology · doi:10.1053/bean.2003.0267 · Cited by 68 · see citing works
Epistemology of causal inference in pharmacology
Landes, J., Osimani, B., & Poellinger, R. (2017) · European Journal for Philosophy of Science · doi:10.1007/s13194-017-0169-1 · Cited by 67 · see citing works
“For instance, going back to our debate about the possible causal association between paracetamol and asthma, a series of reviews (Shaheen et al. 2000, 2008; Katayoun 2005; Henderson and Shaheen 2013; Allmers et al. 2009; McBride 2011; Heintze 2013; Martinez-Gimeno and Garcı́a-Marcos 2013) present…”
BackgroundAmberbir, A., Medhin, G., Alem, A., Britton, J. R., Davey, G., & Venn, A. J. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201006-0989oc · Cited by 66 · see citing works
Paracetamol in early infancy: the risk of childhood allergy and asthma
Bakkeheim, E., Mowinckel, P., Carlsen, K. H., Håland, G., & Carlsen, K. C. L. (2010) · Acta Paediatrica · doi:10.1111/j.1651-2227.2010.01942.x · Cited by 66 · see citing works
“in the multinational cross-sectional ISAAC study (3), whereas frequent paracetamol use, but not the use of aspirin, was associated with asthma morbidity and allergic rhinitis in British adults (4).”
BackgroundDavey, G., Berhane, Y., Duncan, P., Aref-Adib, G., Britton, J. R., & Venn, A. J. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.05.045 · Cited by 66 · see citing works
Alchin, J., Dhar, A., Siddiqui, K., & Christo, P. J. (2022) · Current Medical Research and Opinion · doi:10.1080/03007995.2022.2049551 · Cited by 65 · see citing works
Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?
Ishitsuka, Y., Kondo, Y., & Kadowaki, D. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00722 · Cited by 63 · see citing works
Prevalence and risk factors for allergic rhinitis in primary school children
Tamay, Z., Akcay, A., Ones, U., Guler, N., Kilic, G., & Zencir, M. (2007) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2006.11.013 · Cited by 64 · see citing works
“An explanation for the association between paracetamol use and allergic disease was the ability of paracetamol to deplete antioxidant defences and promote Th2 response [32].”
Extrahepatic toxicity of acetaminophen: critical evaluation of the evidence and proposed mechanisms
Kennon‐McGill, S., & McGill, M. R. (2017) · Journal of Clinical and Translational Research · doi:10.18053/jctres.03.201703.005 · Cited by 64 · see citing works
“It has been suggested that chronic exposure to APAP can deplete GSH in the lungs and that this could explain a connection between APAP and respiratory diseases if it enhances susceptibility to oxidants, such as reactiveoxygen species produced by inflammatory cells or even environmental oxidants [20].”
BackgroundThe effects of early and late paracetamol exposure on asthma and atopy: a birth cohort
Wickens, K. L., Beasley, R. W., Town, I. G., Epton, M., Pattemore, P., Ingham, T. R., Crane, J., & the New Zealand Asthma and Allergy Cohort Study Group (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03610.x · Cited by 62 · see citing works
Symptoms of asthma and atopic disorders in preschool children: prevalence and risk factors
Wong, G., Leung, T. F., Ma, Y., Liu, E. K. H., Yung, E. C.-M., & Lai, C.-Y. (2007) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2007.02649.x · Cited by 59 · see citing works
Key questions concerning paracetamol and NSAIDs for osteoarthritis
Courtney, P., & Doherty, M. (2002) · Annals of the Rheumatic Diseases · doi:10.1136/ard.61.9.767 · Cited by 57 · see citing works
“Firstly, one UK case-control study suggested that frequent (weekly or daily) paracetamol may be associated with asthma and rhinitis 46 (discussed below).”
BackgroundParacetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?
Sestili, P., & Fimognari, C. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.579944 · Cited by 58 · see citing works
Impact of ‘mild’ asthma on health outcomes: findings of a systematic search of the literature
Chapman, K. R. (2005) · Respiratory Medicine · doi:10.1016/j.rmed.2005.03.020 · Cited by 52 · see citing works
TRPA 1 gene polymorphisms and childhood asthma
Gallo, V., Dijk, F. N., Holloway, J. W., Ring, S. M., Koppelman, G. H., Postma, D. S., Strachan, D. P., Granell, R., de Jongste, J. C., Jaddoe, V. W. V., et al. (2016) · Pediatric Allergy and Immunology · doi:10.1111/pai.12673 · Cited by 51 · see citing works
“Following our initial discovery of an association between frequent paracetamol (acetaminophen) use and asthma in adults (8), we and others have reported that maternal use of paracetamol in pregnancy was associated with an increased risk of childhood asthma, wheezing and elevated total IgE concentration (9).”
Self-citationAcetaminophen (paracetamol) for the common cold in adults
Li, S., Yue, J., Dong, B. R., Yang, M. J., Lin, X., & Wu, T. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008800.pub2 · Cited by 50 · see citing works
Acetaminophen use: A risk for asthma?
Allmers, H., Skudlik, C., & John, S. M. (2009) · Current Allergy and Asthma Reports · doi:10.1007/s11882-009-0024-3 · Cited by 49 · see citing works
Dietary patterns and adult asthma: population‐based case–control study
Bakolis, I., Hooper, R., Thompson, R. L., & Shaheen, S. O. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.02215.x · Cited by 48 · see citing works
“After allowing for likely wrong addresses, the overall response rate was 55% (19).”
BackgroundSelf-citationNew Insights Into the Pathogenesis of Cystic Fibrosis
Hudson, V. M. (2004) · Treatments in Respiratory Medicine · doi:10.2165/00151829-200403060-00003 · Cited by 48 · see citing works
Melas, I. N., Sakellaropoulos, T., Iorio, F., Alexopoulos, L. G., Loh, W., Lauffenburger, D. A., Sáez-Rodríguez, J., & Bai, J. P. F. (2015) · Integrative Biology · doi:10.1039/c4ib00294f · Cited by 47 · see citing works
Twycross, R., Pace, V., Mihalyo, M., & Wilcock, A. (2013) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2013.08.001 · Cited by 44 · see citing works
Over-the-counter Analgesics: A Toxicologic Perspective
Jones, A. L. (2002) · American Journal of Therapeutics · doi:10.1097/00045391-200205000-00010 · Cited by 44 · see citing works
Leroy, S., Mosca, A., Landre-Peigne, C., Cosson, M.-A., & Pons, G. (2007) · Archives de Pédiatrie · doi:10.1016/j.arcped.2007.01.012 · Cited by 41 · see citing works
Prevalence and risk factors for allergic rhinitis in primary schoolchildren in Budapest
Sultész, M., Katona, G., Hirschberg, A., & Gálffy, G. (2010) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2010.02.008 · Cited by 41 · see citing works
“The use of paracetamol in adults has been associated with rhinitis in non-asthmatic individuals [19].”
The Use of Analgesics in Patients with Asthma
Levy, S., & Volans, G. N. (2001) · Drug Safety · doi:10.2165/00002018-200124110-00004 · Cited by 41 · see citing works
The Acetaminophen Enigma in Asthma
Holgate, S. T. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201007-1135ed · Cited by 40 · see citing works
Intake of Paracetamol and Risk of Asthma in Adults
Thomsen, S. F., Kyvik, K. O., Skadhauge, L. R., Steffensen, I., & Backer, V. (2008) · Journal of Asthma · doi:10.1080/02770900802165998 · Cited by 37 · see citing works
“Likewise, if we had had an asthma severity score we would have been able to test the robustness of our association as has also been done by others (3).”
BackgroundResultInfluentialDoedée, A., Boland, G. J., Pennings, J. L. A., de Klerk, A., Berbers, G. A. M., van der Klis, F. R. M., de Melker, H. E., Loveren, H. V., & Janssen, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098175 · Cited by 36 · see citing works
Factors Associated with Severe Disease in a Population of Asthmatic Children of Bogota, Colombia
Martínez, C., Sossa, M., & Goss, C. (2008) · Journal of Asthma · doi:10.1080/02770900701840253 · Cited by 20 · see citing works
“It has been speculated that frequent use of acetaminophen might influence asthma and rhinitis by depleting levels of reduced glutathione in the nose and airways, thus shifting the oxidant/antioxidant balance in favor of oxidative stress and increasing inflammation (45).”
BackgroundParacetamol in the Treatment of Osteoarthritis Pain
Brandt, K. D. (2003) · Drugs · doi:10.2165/00003495-200363992-00005 · Cited by 34 · see citing works
Does paracetamol cause asthma?
Nuttall, S. L., Williams, J., & Kendall, M. J. (2003) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.2003.00492.x · Cited by 34 · see citing works
The acetaminophen and asthma hypothesis 10 years on: A case to answer
Farquhar, H., Crane, J., Mitchell, E. A., Eyers, S., & Beasley, R. W. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.07.037 · Cited by 32 · see citing works
“ACETAMINOPHEN USE IN ADULTS The initial evidence of an association between acetaminophen use and asthma in adults came from a United Kingdom–based case-control study.(10) This study reported both a dose-dependent association between acetaminophen use and asthma and a progressively greater risk in those with more sever…”
BackgroundNoble, M., Burden, A., Stirling, S., Clark, A., Musgrave, S. D., Alsallakh, M. A., Price, D. B., Davies, G. A., Pinnock, H., Pond, M., et al. (2021) · British Journal of General Practice · doi:10.3399/bjgp.2020.1042 · Cited by 32 · see citing works
“asthma(20)), lower respiratory tract infection (LRTI) consultations, allergic rhinitis diagnosis), the codes were queried between 01/01/2010 and 31/12/2010.”
Older Adult Pain Communication and the Brief Pain Inventory Short Form
McDonald, D. D., Shea, M., Fedo, J., Rose, L., Bacon, K., Noble, K., & Stewart, J. (2008) · Pain Management Nursing · doi:10.1016/j.pmn.2008.03.001 · Cited by 31 · see citing works
Until RCT proven? On the asymmetry of evidence requirements for risk assessment
Osimani, B. (2013) · Journal of Evaluation in Clinical Practice · doi:10.1111/jep.12039 · Cited by 31 · see citing works
Kuschnir, F. C., & da Cunha, A. J. L. A. (2006) · Pediatric Allergy and Immunology · doi:10.1111/j.1399-3038.2006.00477.x · Cited by 30 · see citing works
“This association has been described as much in adults as in children, whether through ecological studies relating the increase in sales of the medicine to the prevalence of asthma measured by ISAAC in different countries, or by case–control studies (17, 34).”
BackgroundAcetaminophen use and the symptoms of asthma, allergic rhinitis and eczema in children.
Karimi, M., Mirzaei, M., & Ahmadieh, M. H. (2006) · PubMed · Cited by 30 · see citing works
Frequent acetaminophen use and allergic diseases: Is the association clear?
Allmers, H. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.07.019 · Cited by 29 · see citing works
Hunting Side Effects and Explaining Them: Should We Reverse Evidence Hierarchies Upside Down?
Osimani, B. (2013) · Topoi · doi:10.1007/s11245-013-9194-7 · Cited by 28 · see citing works
“However, this hypothesis was soon discounted on grounds that, if this had been the case, then one should have observed a decrease of asthma incidence when aspirin was first introduced (Shaheen et al. 2000).”
BackgroundEarly exposure to acetaminophen and allergic disorders
García‐Marcos, L., Sánchez‐Solís, M., & Pérez‐Fernández, V. (2011) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e3283464c28 · Cited by 26 · see citing works
Association of Acetaminophen and Ibuprofen Use With Wheezing in Children With Acute Febrile Illness
Matok, I., Elizur, A., Perlman, A., Ganor, S., Levine, H., & Kozer, E. (2016) · Annals of Pharmacotherapy · doi:10.1177/1060028016678006 · Cited by 26 · see citing works
Acetaminophen and the Developing Lung: Could There Be Lifelong Consequences?
Wright, C. J. (2021) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2021.02.026 · Cited by 26 · see citing works
Effect of whey protein to modulate immune response in children with atopic asthma
Lothian, J. B., Grey, V., & Lands, L. C. (2006) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637480600738294 · Cited by 26 · see citing works
“Asthma is associated with frequent use of acetominophen (Shaheen et al. 2000), which can lower GSH concentrations even at therapeutic dosages (Dimova et al. 2000).”
BackgroundEnvironmental Factors and Allergic Disorders
Tanaka, K., Miyake, Y., & Kiyohara, C. (2007) · Allergology International · doi:10.2332/allergolint.r-07-143 · Cited by 25 · see citing works
The association between paracetamol and asthma is still under debate
Lourido-Cebreiro, T., Salgado, F. J., Valdés, L., & González‐Barcala, F. J. (2016) · Journal of Asthma · doi:10.1080/02770903.2016.1194431 · Cited by 25 · see citing works
“Furthermore, this association was maintained independently of aspirin use [22].”
BackgroundMedications and laboratory parameters as prognostic factors in amyotrophic lateral sclerosis
Qureshi, M., Shui, A. M., DiBernardo, A., Brown, R. H., Schoenfeld, D., & Cudkowicz, M. (2008) · Amyotrophic Lateral Sclerosis · doi:10.1080/17482960802163614 · Cited by 25 · see citing works
“Regular use of acetaminophen has been alleged to decreased lung function (19).”
BackgroundAmino acids and asthma: a case-control study
Fogarty, A., Broadfield, E., Lewis, S., Lawson, N., & Britton, J. R. (2004) · European Respiratory Journal · doi:10.1183/09031936.04.00090404 · Cited by 25 · see citing works
The association between paracetamol use and asthma: causation or coincidence?
Weatherall, M., Ioannides, S. J., Braithwaite, I. E., & Beasley, R. W. (2014) · Clinical & Experimental Allergy · doi:10.1111/cea.12410 · Cited by 24 · see citing works
Augusto Peñaranda, S., Aristizábal, G., García, E., Vásquez, C., & Rodríguez‐Martínez, C. E. (2012) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2012.01.010 · Cited by 23 · see citing works
“The proposed explanation for the association between acetaminophen use and allergic diseases lies in the ability of acetaminophen to diminish antioxidants and promote the Th2 response [41].”
BackgroundResultThe Effect of a Single Dose of Acetaminophen on Airways Response in Children With Asthma
Soferman, R., Tsivion, A., Farber, M., & Sivan, Y. (2012) · Clinical Pediatrics · doi:10.1177/0009922812462764 · Cited by 23 · see citing works
Del-Rio-Navarro, B. E., Berber, A. C., Vijil, V. B., Ramírez-Aguilar, M., Romieu, I., Chanona, N. R., Heras-Acevedo, S., Serrano-Sierra, A., Barraza‐Villarreal, A., Baeza-Bacab, M. A., et al. (2006) · Allergy and Asthma Proceedings · doi:10.2500/aap.2006.27.2874 · Cited by 23 · see citing works
E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance
Pretis, F. D., Landes, J., & Osimani, B. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01317 · Cited by 23 · see citing works
“…could be explained by the drop of aspirin prescription, was however undermined by simply considering that, if it were true, then one should have observed an equal prevalence of asthma before aspirin was introduced into the market, and a decrease after its introduction (Shaheen et al., 2000).”
BackgroundAllergic rhinitis and associated factors in schoolchildren from Bogota, Colombia
Augusto Peñaranda, S., Aristizábal, G., García, E., Vasquez, C., Rodríguez‐Martínez, C. E., & Satizábal, C. L. (2012) · Rhinology Journal · doi:10.4193/rhino11.175 · Cited by 22 · see citing works
Factors associated with allergic rhinitis in children from northern Mexico City.
Del-Rio-Navarro, B. E., Luna-Pech, J. A., Berber, A. C., Zepeda-Ortega, B., Ávila-Castañón, L., del Río-Chivardí, J. M., Baeza-Bacab, M. A., & Sienra-Monge, J. J. L. (2007) · PubMed · Cited by 22 · see citing works
- Authors
- Shaheen, S. O.
- Affiliations
- King's College London (GB)
- Corresponding author
- Shaheen, S. O
- ORCID
- Shaheen, S. O
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2000-04-01
- Volume
- 55
- Issue
- 4
- Pages
- 266-270
- ISSN
- 0040-6376 (ISSN-L)
- PMC
- PMC1745727
- OpenAlex
- W2025295475
- Cited by
- 226
- References
- 34
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 12 · 2013: 14 · 2012: 9
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- paracetamol, asthma, aspirin, analgesic use, glutathione depletion, airway inflammation, dietary antioxidants, asthma severity, quality of life, adults
- MeSH terms
- Acetaminophen, Adolescent, Adult, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Asthma, Glutathione, United Kingdom, Humans, Male, Middle Aged, Risk Factors, Case-Control Studies, Analgesics, Non-Narcotic
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