Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

References

• Global Initiative for Asthma. Global strategy for asthma management and prevention; 2021. Available from: www.ginasthma.org. Accessed September 27, 2021.
   Google Scholar
• Murray CJ, Aravkin AY, Zheng P, et al.Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222. doi:10.1016/S0140-6736(20)30925-9
   PubMed Web of Science ®Google Scholar
• Dodge RR, Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am Rev Respir Dis. 1980;122(4):567–575. doi:10.1164/arrd.1980.122.4.567
   PubMedGoogle Scholar
• Anderson HR, Pottier AC, Strachan DP. Asthma from birth to age 23: incidence and relation to prior and concurrent atopic disease. Thorax. 1992;47(7):537–542. doi:10.1136/thx.47.7.537
   PubMed Web of Science ®Google Scholar
• Yunginger JW, Reed CE, O’Connell EJ, Melton LJ, O’Fallon WM, Silverstein MD. A community-based study of the epidemiology of asthma. Incidence rates, 1964–1983. Am Rev Respir Dis. 1992;146(4):888–894. doi:10.1164/ajrccm/146.4.888
   PubMed Web of Science ®Google Scholar
• Sears MR, Burrows B, Flannery EM, Herbison GP, Holdaway MD. Atopy in childhood. I. Gender and allergen related risks for development of hay fever and asthma. Clin Exp Allergy. 1993;23(11):941–948. doi:10.1111/j.1365-2222.1993.tb00279.x
   PubMed Web of Science ®Google Scholar
• Harju T, Keistinen T, Tuuponen T, Kivelä SL. Hospital admissions of asthmatics by age and sex. Allergy. 1996;51(10):693–696.
   PubMed Web of Science ®Google Scholar
• Ciccone G, Camarlengo A, Bugiani M, et al.Asthma and respiratory symptoms in 6–7 yr old Italian children: gender, latitude, urbanization and socioeconomic factors. SIDRIA (Italian Studies on Respiratory Disorders in Childhood and the Environment). Eur Respir J. 1997;10(8):1780–1786. doi:10.1183/09031936.97.10081780
   PubMed Web of Science ®Google Scholar
• de Marco R, Locatelli F, Sunyer J, Burney P. Differences in incidence of reported asthma related to age in men and women. A retrospective analysis of the data of the European Respiratory Health Survey. Am J Respir Crit Care Med. 2000;162(1):68–74. doi:10.1164/ajrccm.162.1.9907008
   PubMed Web of Science ®Google Scholar
• de Marco R, Locatelli F, Cerveri I, Bugiani M, Marinoni A, Giammanco G. Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J Allergy Clin Immunol. 2002;110(2):228–235. doi:10.1067/mai.2002.125600
   PubMed Web of Science ®Google Scholar
• Chen Y, Stewart P, Johansen H, McRae L, Taylor G. Sex difference in hospitalization due to asthma in relation to age. J Clin Epidemiol. 2003;56(2):180–187. doi:10.1016/S0895-4356(02)00593-0
   PubMed Web of Science ®Google Scholar
• Schatz M, Camargo CA. The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organization. Ann Allergy Asthma Immunol. 2003;91(6):553–558. doi:10.1016/S1081-1206(10)61533-5
   PubMed Web of Science ®Google Scholar
• Debley JS, Redding GJ, Critchlow CW. Impact of adolescence and gender on asthma hospitalization: a population-based birth cohort study. Pediatr Pulmonol. 2004;38(6):443–450. doi:10.1002/ppul.20108
   PubMed Web of Science ®Google Scholar
• Almqvist C, Worm M, Leynaert B. Impact of gender on asthma in childhood and adolescence: a GA2LEN review. Allergy. 2008;63(1):47–57. doi:10.1111/j.1398-9995.2007.01524.x
   PubMed Web of Science ®Google Scholar
• Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents’ Individual Lives Survey (TRAILS) study. J Allergy Clin Immunol. 2010;126(3):498–504. doi:10.1016/j.jaci.2010.06.018
   PubMed Web of Science ®Google Scholar
• Gershon AS, Guan J, Wang C, To T. Trends in asthma prevalence and incidence in Ontario, Canada, 1996–2005: a population study. Am J Epidemiol. 2010;172(6):728–736. doi:10.1093/aje/kwq189
   PubMed Web of Science ®Google Scholar
• Kankaanranta H, Tuomisto LE, Ilmarinen P. Age-specific incidence of new asthma diagnoses in Finland. J Allergy Clin Immunol Pract. 2017;5(1):189–191. doi:10.1016/j.jaip.2016.08.015
   PubMed Web of Science ®Google Scholar
• Honkamäki J, Hisinger-Mölkänen H, Ilmarinen P, et al. Age- and gender-specific incidence of new asthma diagnosis from childhood to late adulthood. Respir Med. 2019;154:56–62. doi:10.1016/j.rmed.2019.06.003
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. Asthma: data, statistics, and surveillance; 2019. Available from: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. Accessed September 27, 2021.
   Google Scholar
• Larsson L. Incidence of asthma in Swedish teenagers: relation to sex and smoking habits. Thorax. 1995;50(3):260–264. doi:10.1136/thx.50.3.260
   PubMed Web of Science ®Google Scholar
• Torén K, Hermansson BA. Incidence rate of adult-onset asthma in relation to age, sex, atopy and smoking: a Swedish population-based study of 15813 adults. Int J Tuberc Lung Dis. 1999;3(3):192–197.
   PubMed Web of Science ®Google Scholar
• Lundbäck B, Rönmark E, Jönsson E, Larsson K, Sandström T. Incidence of physician-diagnosed asthma in adults–a real incidence or a result of increased awareness? Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med. 2001;95(8):685–692. doi:10.1053/rmed.2001.1126
   PubMed Web of Science ®Google Scholar
• Thomsen SF, Ulrik CS, Kyvik KO, et al. The incidence of asthma in young adults. Chest. 2005;127(6):1928–1934. doi:10.1378/chest.127.6.1928
   PubMed Web of Science ®Google Scholar
• Eagan TM, Brøgger JC, Eide GE, Bakke PS. The incidence of adult asthma: a review. Int J Tuberc Lung Dis. 2005;9(6):603–612.
   PubMed Web of Science ®Google Scholar
• Torén K, Ekerljung L, Kim JL, et al. Adult-onset asthma in west Sweden–incidence, sex differences and impact of occupational exposures. Respir Med. 2011;105(11):1622–1628. doi:10.1016/j.rmed.2011.06.003
   PubMed Web of Science ®Google Scholar
• Leynaert B, Sunyer J, Garcia-Esteban R, et al. Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort. Thorax. 2012;67(7):625–631. doi:10.1136/thoraxjnl-2011-201249
   PubMed Web of Science ®Google Scholar
• Hansen S, Probst-Hensch N, Keidel D, et al. Gender differences in adult-onset asthma: results from the Swiss SAPALDIA cohort study. Eur Respir J. 2015;46(4):1011–1020. doi:10.1183/13993003.02278-2014
   PubMed Web of Science ®Google Scholar
• de Marco R, Locatelli F, Cazzoletti L, Bugianio M, Carosso A, Marinoni A. Incidence of asthma and mortality in a cohort of young adults: a 7-year prospective study. Respir Res. 2005;6(1):95. doi:10.1186/1465-9921-6-95
   PubMed Web of Science ®Google Scholar
• Borna E, Nwaru BI, Bjerg A, et al. Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016. Allergy. 2019;74(9):1703–1715. doi:10.1111/all.13840
   PubMed Web of Science ®Google Scholar
• Pallasaho P, Juusela M, Lindqvist A, Sovijärvi A, Lundbäck B, Rönmark E. Allergic rhinoconjunctivitis doubles the risk for incident asthma–results from a population study in Helsinki, Finland. Respir Med. 2011;105(10):1449–1456. doi:10.1016/j.rmed.2011.04.013
   PubMed Web of Science ®Google Scholar
• Basagaña X, Sunyer J, Zock JP, et al. Incidence of asthma and its determinants among adults in Spain. Am J Respir Crit Care Med. 2001;164(7):1133–1137. doi:10.1164/ajrccm.164.7.2012143
   PubMed Web of Science ®Google Scholar
• Prescott E, Lange P, Vestbo J. Effect of gender on hospital admissions for asthma and prevalence of self-reported asthma: a prospective study based on a sample of the general population. Copenhagen City Heart Study Group. Thorax. 1997;52(3):287–289. doi:10.1136/thx.52.3.287
   PubMed Web of Science ®Google Scholar
• Australian Institute of Health and Welfare. Asthma: impact; 2020. Available from: https://www.aihw.gov.au/reports/chronic-respiratory-conditions/asthma/contents/deaths. Accessed September 27, 2021.
   Google Scholar
• Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol. 2004;113(1):101–108. doi:10.1016/j.jaci.2003.10.041
   PubMed Web of Science ®Google Scholar
• de Nijs SB, Venekamp LN, Bel EH. Adult-onset asthma: is it really different? Eur Respir Rev. 2013;22(127):44–52. doi:10.1183/09059180.00007112
   PubMedGoogle Scholar
• Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–725. doi:10.1038/nm.2678
   PubMed Web of Science ®Google Scholar
• Pakkasela J, Ilmarinen P, Honkamäki J, et al. Age-specific incidence of allergic and non-allergic asthma. BMC Pulm Med. 2020;20(1):9. doi:10.1186/s12890-019-1040-2
   PubMed Web of Science ®Google Scholar
• Ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH. Factors associated with persistent airflow limitation in severe asthma. Am J Respir Crit Care Med. 2001;164(5):744–748. doi:10.1164/ajrccm.164.5.2011026
   PubMed Web of Science ®Google Scholar
• Tan DJ, Walters EH, Perret JL, et al. Clinical and functional differences between early-onset and late-onset adult asthma: a population-based Tasmanian Longitudinal Health Study. Thorax. 2016;71(11):981–987. doi:10.1136/thoraxjnl-2015-208183
   PubMed Web of Science ®Google Scholar
• Honkamäki J, Piirilä P, Hisinger-Mölkänen H, et al. Asthma remission by age at diagnosis and gender in a population-based study. J Allergy Clin Immunol Pract. 2021;9(5):1950–1959. doi:10.1016/j.jaip.2020.12.015
   PubMed Web of Science ®Google Scholar
• Rönmark E, Lindberg A, Watson L, Lundbäck B. Outcome and severity of adult onset asthma–report from the obstructive lung disease in northern Sweden studies (OLIN). Respir Med. 2007;101(11):2370–2377. doi:10.1016/j.rmed.2007.06.011
   PubMed Web of Science ®Google Scholar
• Tuomisto LE, Ilmarinen P, Niemelä O, Haanpää J, Kankaanranta T, Kankaanranta H. A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study. Respir Med. 2016;117:223–229. doi:10.1016/j.rmed.2016.06.017
   PubMed Web of Science ®Google Scholar
• Westerhof GA, Coumou H, de Nijs SB, Weersink EJ, Bel EH. Clinical predictors of remission and persistence of adult-onset asthma. J Allergy Clin Immunol. 2018;141(1):104–109. doi:10.1016/j.jaci.2017.03.034
   PubMed Web of Science ®Google Scholar
• Almqvist L, Rönmark E, Stridsman C, et al. Remission of adult-onset asthma is rare: a 15-year follow-up study. ERJ Open Res. 2020;6(4):00620–2020. doi:10.1183/23120541.00620-2020
   PubMedGoogle Scholar
• Sözener Z, Aydın Ö, Mungan D, Mısırlıgil Z. Prognosis of adult asthma: a 7-year follow-up study. Ann Allergy Asthma Immunol. 2015;114(5):370–373. doi:10.1016/j.anai.2015.02.010
   PubMed Web of Science ®Google Scholar
• Sood A, Qualls C, Schuyler M, et al. Adult-onset asthma becomes the dominant phenotype among women by age 40 years. the longitudinal CARDIA study. Ann Am Thorac Soc. 2013;10(3):188–197. doi:10.1513/AnnalsATS.201212-115OC
   PubMedGoogle Scholar
• Melgert BN, Ray A, Hylkema MN, Timens W, Postma DS. Are there reasons why adult asthma is more common in females? Curr Allergy Asthma Rep. 2007;7(2):143–150. doi:10.1007/s11882-007-0012-4
   PubMed Web of Science ®Google Scholar
• Zhang GQ, Bossios A, Rådinger M, Nwaru BI. Sex steroid hormones and asthma in women: state-of-the-art and future research perspectives. Expert Rev Respir Med. 2020;14(6):543–545. doi:10.1080/17476348.2020.1741351
   PubMed Web of Science ®Google Scholar
• Laffont S, Blanquart E, Guéry JC. Sex differences in asthma: a key role of androgen-signaling in group 2 innate lymphoid cells. Front Immunol. 2017;8:1069. doi:10.3389/fimmu.2017.01069
   PubMed Web of Science ®Google Scholar
• Sheikh A, Mukherjee M. We need a robust evidence base to unravel the relationship between sex hormones and asthma. Thorax. 2020;75(10):826–827. doi:10.1136/thoraxjnl-2020-215566
   PubMed Web of Science ®Google Scholar
• McCleary N, Nwaru BI, Nurmatov UB, Critchley H, Sheikh A. Endogenous and exogenous sex steroid hormones in asthma and allergy in females: a systematic review and meta-analysis. J Allergy Clin Immunol. 2018;141(4):1510–1513. doi:10.1016/j.jaci.2017.11.034
   PubMed Web of Science ®Google Scholar
• Minelli C, van der Plaat DA, Leynaert B, et al. Age at puberty and risk of asthma: a Mendelian randomisation study. PLoS Med. 2018;15(8):e1002634. doi:10.1371/journal.pmed.1002634
   PubMed Web of Science ®Google Scholar
• Chen YC, Fan HY, Yang C, Lee YL. Early pubertal maturation and risk of childhood asthma: a Mendelian randomization and longitudinal study. Allergy. 2020;75(4):892–900. doi:10.1111/all.14009
   PubMed Web of Science ®Google Scholar
• Sheehan NA, Didelez V, Burton PR, Tobin MD. Mendelian randomisation and causal inference in observational epidemiology. PLoS Med. 2008;5(8):e177. doi:10.1371/journal.pmed.0050177
   PubMed Web of Science ®Google Scholar
• Mendle J, Turkheimer E, Emery RE. Detrimental psychological outcomes associated with early pubertal timing in adolescent girls. Dev Rev. 2007;27(2):151–171. doi:10.1016/j.dr.2006.11.001
   PubMed Web of Science ®Google Scholar
• Jenkins MA, Dharmage SC, Flander LB, et al. Parity and decreased use of oral contraceptives as predictors of asthma in young women. Clin Exp Allergy. 2006;36(5):609–613. doi:10.1111/j.1365-2222.2006.02475.x
   PubMed Web of Science ®Google Scholar
• Matheson MC, Burgess JA, Lau MY, et al. Hormonal contraception increases risk of asthma among obese but decreases it among nonobese subjects: a prospective, population-based cohort study. ERJ Open Res. 2015;1(2):00026–2015. doi:10.1183/23120541.00026-2015
   PubMedGoogle Scholar
• Forastiere F, Sunyer J, Farchi S, et al. Number of offspring and maternal allergy. Allergy. 2005;60(4):510–514. doi:10.1111/j.1398-9995.2005.00736.x
   PubMed Web of Science ®Google Scholar
• Troisi RJ, Speizer FE, Willett WC, Trichopoulos D, Rosner B. Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma. A prospective cohort study. Am J Respir Crit Care Med. 1995;152(4 Pt 1):1183–1188. doi:10.1164/ajrccm.152.4.7551368
   PubMed Web of Science ®Google Scholar
• Triebner K, Johannessen A, Puggini L, et al. Menopause as a predictor of new-onset asthma: a longitudinal Northern European population study. J Allergy Clin Immunol. 2016;137(1):50–57. doi:10.1016/j.jaci.2015.08.019
   PubMed Web of Science ®Google Scholar
• Matulonga-Diakiese B, Courbon D, Fournier A, et al. Risk of asthma onset after natural and surgical menopause: results from the French E3N cohort. Maturitas. 2018;118:44–50. doi:10.1016/j.maturitas.2018.10.006
   PubMed Web of Science ®Google Scholar
• Shah SA, Tibble H, Pillinger R, et al. Hormone replacement therapy and asthma onset in menopausal women: national cohort study. J Allergy Clin Immunol. 2021;147(5):1662–1670. doi:10.1016/j.jaci.2020.11.024
   PubMed Web of Science ®Google Scholar
• Wei J, Gerlich J, Genuneit J, et al. Hormonal factors and incident asthma and allergic rhinitis during puberty in girls. Ann Allergy Asthma Immunol. 2015;115(1):21–27. doi:10.1016/j.anai.2015.04.019
   PubMed Web of Science ®Google Scholar
• Nwaru BI, Pillinger R, Tibble H, et al. Hormonal contraceptives and onset of asthma in reproductive-age women: population-based cohort study. J Allergy Clin Immunol. 2020;146(2):438–446. doi:10.1016/j.jaci.2020.02.027
   PubMed Web of Science ®Google Scholar
• Zhang GQ, Chen JL, Luo Y, et al. Menopausal hormone therapy and women’s health: an umbrella review. PLoS Med. 2021;18(8):e1003731. doi:10.1371/journal.pmed.1003731
   PubMed Web of Science ®Google Scholar
• Hansen ESH, Aasbjerg K, Moeller AL, Gade EJ, Torp-Pedersen C, Backer V. Hormone replacement therapy and development of new asthma. Chest. 2021;160(1):45–52. doi:10.1016/j.chest.2021.01.054
   PubMed Web of Science ®Google Scholar
• Han YY, Forno E, Celedón JC. Sex steroid hormones and asthma in a nationwide study of U.S. adults. Am J Respir Crit Care Med. 2020;201(2):158–166. doi:10.1164/rccm.201905-0996OC
   PubMed Web of Science ®Google Scholar
• Han YY, Yan Q, Yang G, Chen W, Forno E, Celedon JC. Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults. Thorax. 2020;75(10):849–854. doi:10.1136/thoraxjnl-2020-214875
   PubMed Web of Science ®Google Scholar
• Bulkhi AA, Shepard KV, Casale TB, Cardet JC. Elevated testosterone is associated with decreased likelihood of current asthma regardless of sex. J Allergy Clin Immunol Pract. 2020;8(9):3029–3035. doi:10.1016/j.jaip.2020.05.022
   PubMed Web of Science ®Google Scholar
• Arathimos R, Granell R, Haycock P, et al. Genetic and observational evidence supports a causal role of sex hormones on the development of asthma. Thorax. 2019;74(7):633–642. doi:10.1136/thoraxjnl-2018-212207
   PubMed Web of Science ®Google Scholar
• Fu L, Freishtat RJ, Gordish-Dressman H, et al. Natural progression of childhood asthma symptoms and strong influence of sex and puberty. Ann Am Thorac Soc. 2014;11(6):939–944. doi:10.1513/AnnalsATS.201402-084OC
   PubMedGoogle Scholar
• Vrieze A, Postma DS, Kerstjens HA. Perimenstrual asthma: a syndrome without known cause or cure. J Allergy Clin Immunol. 2003;112(2):271–282. doi:10.1067/mai.2003.1676
   PubMed Web of Science ®Google Scholar
• Suzuki K, Hasegawa T, Sakagami T, et al. Analysis of perimenstrual asthma based on questionnaire surveys in Japan. Allergol Int. 2007;56(3):249–255. doi:10.2332/allergolint.O-06-475
   PubMedGoogle Scholar
• Rao CK, Moore CG, Bleecker E, et al. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program. Chest. 2013;143(4):984–992. doi:10.1378/chest.12-0973
   PubMed Web of Science ®Google Scholar
• Eid RC, Palumbo ML, Cahill KN. Perimenstrual asthma in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2020;8(2):573–578. doi:10.1016/j.jaip.2019.08.054
   PubMed Web of Science ®Google Scholar
• Eliasson O, Scherzer HH, DeGraff AC. Morbidity in asthma in relation to the menstrual cycle. J Allergy Clin Immunol. 1986;77(1 Pt 1):87–94. doi:10.1016/0091-6749(86)90328-3
   PubMed Web of Science ®Google Scholar
• Agarwal AK, Shah A. Menstrual-linked asthma. J Asthma. 1997;34(6):539–545. doi:10.3109/02770909709055398
   PubMed Web of Science ®Google Scholar
• Shames RS, Heilbron DC, Janson SL, Kishiyama JL, Au DS, Adelman DC. Clinical differences among women with and without self-reported perimenstrual asthma. Ann Allergy Asthma Immunol. 1998;81(1):65–72. doi:10.1016/S1081-1206(10)63111-0
   PubMed Web of Science ®Google Scholar
• Thornton J, Lewis J, Lebrun CM, Licskai CJ. Clinical characteristics of women with menstrual-linked asthma. Respir Med. 2012;106(9):1236–1243. doi:10.1016/j.rmed.2012.05.003
   PubMed Web of Science ®Google Scholar
• Lenoir RJ. Severe acute asthma and the menstrual cycle. Anaesthesia. 1987;42(12):1287–1290. doi:10.1111/j.1365-2044.1987.tb05275.x
   PubMed Web of Science ®Google Scholar
• Beynon HL, Garbett ND, Barnes PJ. Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone. Lancet. 1988;332(8607):370–372. doi:10.1016/S0140-6736(88)92837-1
   Google Scholar
• Kisiel M, Berglund C, Janson C, et al. Quality of life and asthma control related to hormonal transitions in women’s lives. J Asthma. 2021;1–9. doi:10.1080/02770903.2021.1963768
   PubMed Web of Science ®Google Scholar
• Gluck JC, Gluck P. The effects of pregnancy on asthma: a prospective study. Ann Allergy. 1976;37(3):164–168.
   PubMedGoogle Scholar
• Schatz M, Harden K, Forsythe A, et al. The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis. J Allergy Clin Immunol. 1988;81(3):509–517. doi:10.1016/0091-6749(88)90187-X
   PubMed Web of Science ®Google Scholar
• Schatz M. Interrelationships between asthma and pregnancy: a literature review. J Allergy Clin Immunol. 1999;103(2 Pt 2):S330–S336. doi:10.1016/S0091-6749(99)70258-7
   PubMed Web of Science ®Google Scholar
• Schatz M, Dombrowski MP, Wise R, et al. Asthma morbidity during pregnancy can be predicted by severity classification. J Allergy Clin Immunol. 2003;112(2):283–288. doi:10.1067/mai.2003.1516
   PubMed Web of Science ®Google Scholar
• Murphy VE, Gibson P, Talbot PI, Clifton VL. Severe asthma exacerbations during pregnancy. Obstet Gynecol. 2005;106(5 Pt 1):1046–1054. doi:10.1097/01.AOG.0000185281.21716.02
   PubMed Web of Science ®Google Scholar
• Belanger K, Hellenbrand ME, Holford TR, Bracken M. Effect of pregnancy on maternal asthma symptoms and medication use. Obstet Gynecol. 2010;115(3):559–567. doi:10.1097/AOG.0b013e3181d06945
   PubMed Web of Science ®Google Scholar
• Ali Z, Nilas L, Ulrik CS. Determinants of low risk of asthma exacerbation during pregnancy. Clin Exp Allergy. 2018;48(1):23–28. doi:10.1111/cea.13033
   PubMed Web of Science ®Google Scholar
• Bokern M, Robijn A, Jensen ME, et al. Factors associated with asthma exacerbations during pregnancy. J Allergy Clin Immunol Pract. 2021;9:4343–4352.e4. doi:10.1016/j.jaip.2021.07.055
   PubMed Web of Science ®Google Scholar
• Gluck JC, Gluck PA. The effect of pregnancy on the course of asthma. Immunol Allergy Clin North Am. 2006;26(1):63–80. doi:10.1016/j.iac.2005.10.008
   PubMed Web of Science ®Google Scholar
• Gelber M, Sidi Y, Gassner S, et al. Uncontrollable life-threatening status asthmaticus–an indicator for termination of pregnancy by cesarean section. Respiration. 1984;46(3):320–322. doi:10.1159/000194705
   PubMed Web of Science ®Google Scholar
• Shanies HM, Venkataraman MT, Peter T. Reversal of intractable acute severe asthma by first-trimester termination of pregnancy. J Asthma. 1997;34(2):169–172. doi:10.3109/02770909709075662
   PubMed Web of Science ®Google Scholar
• Murphy VE, Gibson PG, Smith R, Clifton VL. Asthma during pregnancy: mechanisms and treatment implications. Eur Respir J. 2005;25(4):731–750. doi:10.1183/09031936.05.00085704
   PubMed Web of Science ®Google Scholar
• Meulenberg PM, Hofman JA. Maternal testosterone and fetal sex. J Steroid Biochem Mol Biol. 1991;39(1):51–54. doi:10.1016/0960-0760(91)90012-T
   PubMed Web of Science ®Google Scholar
• Clifton VL, Murphy VE. Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta. 2004;25(Suppl A):S45–S52. doi:10.1016/j.placenta.2004.01.004
   PubMed Web of Science ®Google Scholar
• Murphy VE, Gibson PG, Giles WB, et al. Maternal asthma is associated with reduced female fetal growth. Am J Respir Crit Care Med. 2003;168(11):1317–1323. doi:10.1164/rccm.200303-374OC
   PubMed Web of Science ®Google Scholar
• Mitchell AM, Palettas M, Christian LM. Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy. Brain Behav Immun. 2017;60:32–37. doi:10.1016/j.bbi.2016.06.015
   PubMed Web of Science ®Google Scholar
• Scott NM, Hodyl NA, Murphy VE, et al. Placental cytokine expression covaries with maternal asthma severity and fetal sex. J Immunol. 2009;182(3):1411–1420. doi:10.4049/jimmunol.182.3.1411
   PubMed Web of Science ®Google Scholar
• Kwon HL, Belanger K, Holford TR, Bracken MB. Effect of fetal sex on airway lability in pregnant women with asthma. Am J Epidemiol. 2006;163(3):217–221. doi:10.1093/aje/kwj032
   PubMed Web of Science ®Google Scholar
• Dodds L, Armson BA, Alexander S. Use of asthma drugs is less among women pregnant with boys rather than girls. BMJ. 1999;318(7189):1011. doi:10.1136/bmj.318.7189.1011
   PubMed Web of Science ®Google Scholar
• Beecroft N, Cochrane GM, Milburn HJ. Effect of sex of fetus on asthma during pregnancy: blind prospective study. BMJ. 1998;317(7162):856–857. doi:10.1136/bmj.317.7162.856
   PubMed Web of Science ®Google Scholar
• Bakhireva LN, Schatz M, Jones KL, et al. Fetal sex and maternal asthma control in pregnancy. J Asthma. 2008;45(5):403–407. doi:10.1080/02770900801971826
   PubMed Web of Science ®Google Scholar
• Kircher S, Schatz M, Long L. Variables affecting asthma course during pregnancy. Ann Allergy Asthma Immunol. 2002;89(5):463–466. doi:10.1016/S1081-1206(10)62082-0
   PubMed Web of Science ®Google Scholar
• Baibergenova A, Thabane L, Akhtar-Danesh N, Levine M, Gafni A. Is fetal gender associated with emergency department visits for asthma during pregnancy? J Asthma. 2006;43(4):293–299. doi:10.1080/02770900600622984
   PubMed Web of Science ®Google Scholar
• Firoozi F, Ducharme FM, Lemière C, et al. Effect of fetal gender on maternal asthma exacerbations in pregnant asthmatic women. Respir Med. 2009;103(1):144–151. doi:10.1016/j.rmed.2008.07.013
   PubMed Web of Science ®Google Scholar
• Campbell B, Davis SR, Abramson MJ, et al. Menopause, lung function and obstructive lung disease outcomes: a systematic review. Climacteric. 2018;21(1):3–12. doi:10.1080/13697137.2017.1392504
   PubMed Web of Science ®Google Scholar
• Tang R, Fraser A, Magnus MC. Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study. BMJ Open. 2019;9(10):e030318. doi:10.1136/bmjopen-2019-030318
   PubMed Web of Science ®Google Scholar
• Triebner K, Matulonga B, Johannessen A, et al. Menopause is associated with accelerated lung function decline. Am J Respir Crit Care Med. 2017;195(8):1058–1065. doi:10.1164/rccm.201605-0968OC
   PubMed Web of Science ®Google Scholar
• Campbell B, Bui DS, Simpson JA, et al. Early age at natural menopause is related to lower post-bronchodilator lung function. A longitudinal population-based study. Ann Am Thorac Soc. 2020;17(4):429–437. doi:10.1513/AnnalsATS.201902-180OC
   PubMed Web of Science ®Google Scholar
• van der Plaat DA, Pereira M, Pesce G, et al. Age at menopause and lung function: a Mendelian randomisation study. Eur Respir J. 2019;54(4):1802421. doi:10.1183/13993003.02421-2018
   PubMed Web of Science ®Google Scholar
• Lam SM, Huang SC. Premenstrual asthma: report of a case with hormonal studies. J Microbiol Immunol Infect. 1998;31(3):197–199.
   PubMedGoogle Scholar
• Matsuo N, Shimoda T, Matsuse H, Kohno S. A case of menstruation-associated asthma: treatment with oral contraceptives. Chest. 1999;116(1):252–253. doi:10.1378/chest.116.1.252
   PubMed Web of Science ®Google Scholar
• Derimanov GS, Oppenheimer J. Exacerbation of premenstrual asthma caused by an oral contraceptive. Ann Allergy Asthma Immunol. 1998;81(3):243–246. doi:10.1016/S1081-1206(10)62820-7
   PubMed Web of Science ®Google Scholar
• Tan KS, McFarlane LC, Lipworth BJ. Modulation of airway reactivity and peak flow variability in asthmatics receiving the oral contraceptive pill. Am J Respir Crit Care Med. 1997;155(4):1273–1277. doi:10.1164/ajrccm.155.4.9105066
   PubMed Web of Science ®Google Scholar
• Mandhane PJ, Hanna SE, Inman MD, et al. Changes in exhaled nitric oxide related to estrogen and progesterone during the menstrual cycle. Chest. 2009;136(5):1301–1307. doi:10.1378/chest.09-0604
   PubMed Web of Science ®Google Scholar
• Salam MT, Wenten M, Gilliland FD. Endogenous and exogenous sex steroid hormones and asthma and wheeze in young women. J Allergy Clin Immunol. 2006;117(5):1001–1007. doi:10.1016/j.jaci.2006.02.004
   PubMed Web of Science ®Google Scholar
• Nwaru BI, Tibble H, Shah SA, et al. Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study. Thorax. 2021;76(2):109–115. doi:10.1136/thoraxjnl-2020-215540
   PubMed Web of Science ®Google Scholar
• Kos-Kudła B, Ostrowska Z, Marek B, Ciesielska-Kopacz N, Kajdaniuk D, Kudła M. Effects of hormone replacement therapy on endocrine and spirometric parameters in asthmatic postmenopausal women. Gynecol Endocrinol. 2001;15(4):304–311. doi:10.1080/gye.15.4.304.311
   PubMed Web of Science ®Google Scholar
• Lieberman D, Kopernik G, Porath A, Lazer S, Heimer D. Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women. Maturitas. 1995;21(2):153–157. doi:10.1016/0378-5122(94)00890-J
   PubMed Web of Science ®Google Scholar
• Hepburn MJ, Dooley DP, Morris MJ. The effects of estrogen replacement therapy on airway function in postmenopausal, asthmatic women. Arch Intern Med. 2001;161(22):2717–2720. doi:10.1001/archinte.161.22.2717
   PubMedGoogle Scholar
• Sedgwick P. Before and after study designs. BMJ. 2014;349:g5074. doi:10.1136/bmj.g5074
   PubMed Web of Science ®Google Scholar
• Sterne JAC, Hernán MA, McAleenan A, Reeves BC, Higgins JPT. Chapter 25: assessing risk of bias in a non-randomized study. In: Higgins JPT, Thomas J, Chandler J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Chichester (UK): John Wiley & Sons; 2019:621–642.
   Google Scholar
• Nwaru BI, Shah SA, Tibble H, et al. Hormone replacement therapy and risk of severe asthma exacerbation in perimenopausal and postmenopausal women: 17-year national cohort study. J Allergy Clin Immunol Pract. 2021;9(7):2751–2760. doi:10.1016/j.jaip.2021.02.052
   PubMed Web of Science ®Google Scholar
• DeBoer MD, Phillips BR, Mauger DT, et al. Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma. BMC Pulm Med. 2018;18(1):58. doi:10.1186/s12890-018-0612-x
   PubMed Web of Science ®Google Scholar
• Russell RJ, Brightling C. Pathogenesis of asthma: implications for precision medicine. Clin Sci. 2017;131(14):1723–1735. doi:10.1042/CS20160253
   PubMed Web of Science ®Google Scholar
• Fahy JV. Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol. 2015;15(1):57–65. doi:10.1038/nri3786
   PubMed Web of Science ®Google Scholar
• Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391(10122):783–800. doi:10.1016/S0140-6736(17)33311-1
   PubMed Web of Science ®Google Scholar
• Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45–56. doi:10.1038/ni.3049
   PubMed Web of Science ®Google Scholar
• Yung JA, Fuseini H, Newcomb DC. Hormones, sex, and asthma. Ann Allergy Asthma Immunol. 2018;120(5):488–494. doi:10.1016/j.anai.2018.01.016
   PubMed Web of Science ®Google Scholar
• Fuseini H, Newcomb DC. Mechanisms driving gender differences in asthma. Curr Allergy Asthma Rep. 2017;17(3):19. doi:10.1007/s11882-017-0686-1
   PubMed Web of Science ®Google Scholar
• Keselman A, Heller N. Estrogen signaling modulates allergic inflammation and contributes to sex differences in asthma. Front Immunol. 2015;6:568. doi:10.3389/fimmu.2015.00568
   PubMed Web of Science ®Google Scholar
• Cephus JY, Stier MT, Fuseini H, et al. Testosterone attenuates group 2 innate lymphoid cell-mediated airway inflammation. Cell Rep. 2017;21(9):2487–2499. doi:10.1016/j.celrep.2017.10.110
   PubMed Web of Science ®Google Scholar
• Malmhäll C, Weidner J, Rådinger M. MicroRNA-155 expression suggests a sex disparity in innate lymphoid cells at the single-cell level. Cell Mol Immunol. 2020;17(5):544–546. doi:10.1038/s41423-019-0303-4
   PubMed Web of Science ®Google Scholar
• Newcomb DC, Cephus JY, Boswell MG, et al. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma. J Allergy Clin Immunol. 2015;136(4):1025–1034. doi:10.1016/j.jaci.2015.05.046
   PubMed Web of Science ®Google Scholar
• Warren KJ, Sweeter JM, Pavlik JA, et al. Sex differences in activation of lung-related type 2 innate lymphoid cells in experimental asthma. Ann Allergy Asthma Immunol. 2017;118(2):233–234. doi:10.1016/j.anai.2016.11.011
   PubMed Web of Science ®Google Scholar
• Takeda M, Tanabe M, Ito W, et al. Gender difference in allergic airway remodelling and immunoglobulin production in mouse model of asthma. Respirology. 2013;18(5):797–806. doi:10.1111/resp.12078
   PubMed Web of Science ®Google Scholar
• Blacquière MJ, Hylkema MN, Postma DS, Geerlings M, Timens W, Melgert BN. Airway inflammation and remodeling in two mouse models of asthma: comparison of males and females. Int Arch Allergy Immunol. 2010;153(2):173–181. doi:10.1159/000312635
   PubMed Web of Science ®Google Scholar
• Melgert BN, Postma DS, Kuipers I, et al. Female mice are more susceptible to the development of allergic airway inflammation than male mice. Clin Exp Allergy. 2005;35(11):1496–1503. doi:10.1111/j.1365-2222.2005.02362.x
   PubMed Web of Science ®Google Scholar
• Antunes MA, Abreu SC, Silva AL, et al. Sex-specific lung remodeling and inflammation changes in experimental allergic asthma. J Appl Physiol. 2010;109(3):855–863. doi:10.1152/japplphysiol.00333.2010
   PubMed Web of Science ®Google Scholar
• Hayashi T, Adachi Y, Hasegawa K, Morimoto M. Less sensitivity for late airway inflammation in males than females in BALB/c mice. Scand J Immunol. 2003;57(6):562–567. doi:10.1046/j.1365-3083.2003.01269.x
   PubMed Web of Science ®Google Scholar
• Fuseini H, Yung JA, Cephus JY, et al. Testosterone decreases house dust mite-induced type 2 and IL-17A-mediated airway inflammation. J Immunol. 2018;201(7):1843–1854. doi:10.4049/jimmunol.1800293
   PubMed Web of Science ®Google Scholar
• Laffont S, Blanquart E, Savignac M, et al. Androgen signaling negatively controls group 2 innate lymphoid cells. J Exp Med. 2017;214(6):1581–1592. doi:10.1084/jem.20161807
   PubMed Web of Science ®Google Scholar
• Corteling R, Trifilieff A. Gender comparison in a murine model of allergen-driven airway inflammation and the response to budesonide treatment. BMC Pharmacol. 2004;4:4. doi:10.1186/1471-2210-4-4
   PubMedGoogle Scholar
• Riffo-Vasquez Y, Ligeiro de Oliveira AP, Page CP, Spina D, Tavares-de-lima W. Role of sex hormones in allergic inflammation in mice. Clin Exp Allergy. 2007;37(3):459–470. doi:10.1111/j.1365-2222.2007.02670.x
   PubMed Web of Science ®Google Scholar
• Ligeiro de Oliveira AP, Peron JP, Santos Franco AL, et al. Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery. PLoS One. 2013;8(6):e65674. doi:10.1371/journal.pone.0065674
   PubMed Web of Science ®Google Scholar
• Fuentes N, Nicoleau M, Cabello N, et al. 17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner. Am J Physiol Lung Cell Mol Physiol. 2019;317(5):L702–l716. doi:10.1152/ajplung.00176.2019
   PubMed Web of Science ®Google Scholar
• Matsubara S, Swasey CH, Loader JE, et al. Estrogen determines sex differences in airway responsiveness after allergen exposure. Am J Respir Cell Mol Biol. 2008;38(5):501–508. doi:10.1165/rcmb.2007-0298OC
   PubMed Web of Science ®Google Scholar
• Degano B, Prévost MC, Berger P, et al. Estradiol decreases the acetylcholine-elicited airway reactivity in ovariectomized rats through an increase in epithelial acetylcholinesterase activity. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1849–1854. doi:10.1164/ajrccm.164.10.2102009
   PubMed Web of Science ®Google Scholar
• Kalidhindi RSR, Ambhore NS, Bhallamudi S, Loganathan J, Sathish V. Role of estrogen receptors α and β in a murine model of asthma: exacerbated airway hyperresponsiveness and remodeling in ERβ knockout mice. Front Pharmacol. 2019;10:1499. doi:10.3389/fphar.2019.01499
   PubMed Web of Science ®Google Scholar
• Cephus JY, Gandhi VD, Shah R, et al. Estrogen receptor-α signaling increases allergen-induced IL-33 release and airway inflammation. Allergy. 2021;76(1):255–268. doi:10.1111/all.14491
   PubMed Web of Science ®Google Scholar
• Carey MA, Card JW, Bradbury JA, et al. Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice. Am J Respir Crit Care Med. 2007;175(2):126–135. doi:10.1164/rccm.200509-1493OC
   PubMed Web of Science ®Google Scholar
• Ambhore NS, Kalidhindi RSR, Loganathan J, Sathish V. Role of differential estrogen receptor activation in airway hyperreactivity and remodeling in a murine model of asthma. Am J Respir Cell Mol Biol. 2019;61(4):469–480. doi:10.1165/rcmb.2018-0321OC
   PubMed Web of Science ®Google Scholar
• Hellings PW, Vandekerckhove P, Claeys R, Billen J, Kasran A, Ceuppens JL. Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma. Clin Exp Allergy. 2003;33(10):1457–1463. doi:10.1046/j.1365-2222.2003.01743.x
   PubMed Web of Science ®Google Scholar
• Mitchell VL, Gershwin LJ. Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model. Clin Exp Allergy. 2007;37(2):276–286. doi:10.1111/j.1365-2222.2007.02658.x
   PubMed Web of Science ®Google Scholar
• Fuseini H, Cephus JY, Wu P, et al. ERα signaling increased IL-17A production in Th17 cells by upregulating IL-23R expression, mitochondrial respiration, and proliferation. Front Immunol. 2019;10:2740. doi:10.3389/fimmu.2019.02740
   PubMed Web of Science ®Google Scholar
• Tam A, Wadsworth S, Dorscheid D, Man SF, Sin DD. Estradiol increases mucus synthesis in bronchial epithelial cells. PLoS One. 2014;9(6):e100633. doi:10.1371/journal.pone.0100633
   PubMed Web of Science ®Google Scholar
• Choi HJ, Chung YS, Kim HJ, et al. Signal pathway of 17beta-estradiol-induced MUC5B expression in human airway epithelial cells. Am J Respir Cell Mol Biol. 2009;40(2):168–178. doi:10.1165/rcmb.2007-0377OC
   PubMed Web of Science ®Google Scholar
• Bhallamudi S, Connell J, Pabelick CM, Prakash YS, Sathish V. Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2020;318(1):L112–l124. doi:10.1152/ajplung.00206.2019
   PubMed Web of Science ®Google Scholar
• Yu CK, Liu YH, Chen CL. Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice. J Microbiol Immunol Infect. 2002;35(3):199–202.
   PubMedGoogle Scholar
• Liou CJ, Huang WC. Dehydroepiandrosterone suppresses eosinophil infiltration and airway hyperresponsiveness via modulation of chemokines and Th2 cytokines in ovalbumin-sensitized mice. J Clin Immunol. 2011;31(4):656–665. doi:10.1007/s10875-011-9529-3
   PubMed Web of Science ®Google Scholar
• Wenzel SE, Robinson CB, Leonard JM, Panettieri RA. Nebulized dehydroepiandrosterone-3-sulfate improves asthma control in the moderate-to-severe asthma results of a 6-week, randomized, double-blind, placebo-controlled study. Allergy Asthma Proc. 2010;31(6):461–471. doi:10.2500/aap.2010.31.3384
   PubMed Web of Science ®Google Scholar
• Chowdhury NU, Guntur VP, Newcomb DC, Wechsler ME. Sex and gender in asthma. Eur Respir Rev. 2021;30(162):210067. doi:10.1183/16000617.0067-2021
   PubMed Web of Science ®Google Scholar
• Ciudad-Gutiérrez P, Fernández-Rubio B, Guisado-Gil AB. Gender bias in clinical trials of biological agents for severe asthma: a systematic review. PLoS One. 2021;16(9):e0257765. doi:10.1371/journal.pone.0257765
   PubMed Web of Science ®Google Scholar
• Bousquet J, Cabrera P, Berkman N, et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy. 2005;60(3):302–308. doi:10.1111/j.1398-9995.2004.00770.x
   PubMed Web of Science ®Google Scholar
• Busse WW, Paggiaro P, Muñoz X, et al. Impact of baseline patient characteristics on dupilumab efficacy in type 2 asthma. Eur Respir J. 2021;58(4):2004605. doi:10.1183/13993003.04605-2020
   PubMed Web of Science ®Google Scholar
• Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–659. doi:10.1016/S0140-6736(12)60988-X
   PubMed Web of Science ®Google Scholar
• Ferguson GT, FitzGerald JM, Bleecker ER, et al. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2017;5(7):568–576. doi:10.1016/S2213-2600(17)30190-X
   PubMed Web of Science ®Google Scholar
• Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–2127. doi:10.1016/S0140-6736(16)31324-1
   PubMed Web of Science ®Google Scholar
• FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–2141. doi:10.1016/S0140-6736(16)31322-8
   PubMed Web of Science ®Google Scholar
• Panettieri RA, Welte T, Shenoy KV, et al. Onset of effect, changes in airflow obstruction and lung volume, and health-related quality of life improvements with benralizumab for patients with severe eosinophilic asthma: phase IIIb randomized, controlled trial (SOLANA). J Asthma Allergy. 2020;13:115–126. doi:10.2147/JAA.S240044
   PubMed Web of Science ®Google Scholar