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Novel Insights on Sex-Related Differences in Asthma

  • Peng Zhang
  • Joe ZeinEmail author
Asthma (V Ortega, Section Editor)
  • 63 Downloads
Part of the following topical collections:
  1. Topical Collection on Asthma

Abstract

Purpose of Review

Asthma, a common respiratory disease that affects about 10% of the US population, represents a significant public health issue. In the last decade, cumulative evidence has demonstrated sex disparities in asthma, including significant differences in epidemiology, clinical presentation, response to therapies, and health outcomes. Understanding sex-related differences in asthma enables clinicians to provide personalized asthma care and improve asthma outcome.

Recent Findings

Recent studies on sex-related differences in asthma inform us on mechanism underlying asthma pathogenesis across all age groups. Sex hormones directly modulate immune pathways crucial in asthma pathogenesis and affect individual’s response to environmental triggers and medications, such as leukokotriene inhibitors. Not surprisingly, the use of external sex hormone supplementations appears to modulate asthma risk. Identification of sex-specific asthma risk loci through genome-wide association studies also provides supporting evidence on sex-related differences in asthma. There is an interaction between sex and obesity, an interaction that could place females at higher risk for systemic inflammation and, consequently, asthma.

Summary

In this article, we review epidemiological and clinical studies on sex-related differences in asthma, with a special focus on the role of sex hormones, including hormonal therapies and the asthma-obesity interaction.

Keywords

Asthma Sex-related difference Menopause Oral contraception pills Menopausal hormone replacement therapy Obesity 

Notes

Acknowledgments

We thank Kimberly Yeager, Ph.D. for her valuable input on the review.

Funding Information

Joe G. Zein: NIH-NHLBI K08HL133381.

Compliance with Ethical Standards

Conflict of Interest

Peng Zhang and Joe Zein declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Abraham B, Antó JM, Barreiro E, Bel EHD, Bonsignore G, Bousquet J, et al. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur Respir J. 2003;22:470–7.  https://doi.org/10.1183/09031936.03.00261903.CrossRefGoogle Scholar
  2. 2.
    Zein JG, Denson JL, Wechsler ME. Asthma over the adult life course. Clin Chest Med. 2019;40:149–61.  https://doi.org/10.1016/j.ccm.2018.10.009.CrossRefPubMedGoogle Scholar
  3. 3.
    Zein JG, Dweik RA, Comhair SA, Bleecker ER, Moore WC, Peters SP, et al. Asthma is more severe in older adults. PLoS One. 2015.  https://doi.org/10.1371/journal.pone.0133490.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    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;152:1183–8.  https://doi.org/10.1164/ajrccm.152.4.7551368.CrossRefPubMedGoogle Scholar
  5. 5.
    Gómez Real F, Svanes C, Björnsson EH, Franklin K, Gislason D, Gislason T, et al. Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey. Thorax. 2006;61:34–40.  https://doi.org/10.1136/thx.2005.040881.CrossRefPubMedGoogle Scholar
  6. 6.
    Real FG, Svanes C, Omenaas ER, Antò JM, Plana E, Jarvis D, et al. Lung function, respiratory symptoms, and the menopausal transition. J Allergy Clin Immunol. 2008;121:72–80.e3.  https://doi.org/10.1016/j.jaci.2007.08.057.CrossRefPubMedGoogle Scholar
  7. 7.
    Matulonga-Diakiese B, Courbon D, Fournier AAAAA, Sanchez M, Bédard A, Mesrine S, et al. Risk of asthma onset after natural and surgical menopause: results from the French E3N cohort. Maturitas. 2018;118:44–50.  https://doi.org/10.1016/j.maturitas.2018.10.006.CrossRefPubMedGoogle Scholar
  8. 8.
    Myers RA, Scott NM, Gauderman WJ, Qiu W, Mathias RA, Romieu I, et al. Genome-wide interaction studies reveal sex-specific asthma risk alleles. Hum Mol Genet. 2014;23:5251–9.  https://doi.org/10.1093/hmg/ddu222.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hunninghake GM, Soto-Quirós ME, Avila L, Kim HP, Lasky-Su J, Rafaels N, et al. TSLP polymorphisms are associated with asthma in a sex-specific fashion. Allergy 2010;65:1566–75.  https://doi.org/10.1111/j.1398-9995.2010.02415.x.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dijkstra A, Howard TD, Vonk JM, Ampleford EJ, Lange LA, Bleecker ER, et al. Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. J Allergy Clin Immunol. 2006;117:604–11.  https://doi.org/10.1016/j.jaci.2005.11.023.CrossRefPubMedGoogle Scholar
  11. 11.
    Bloodworth MH, Rusznak M, Bastarache L, Wang J, Newcomb DC. Association of estrogen receptor α polymorphism rs1999805 with asthma. Ann Allergy Asthma Immunol. 2019;122:208–10.  https://doi.org/10.1016/j.anai.2018.11.005.CrossRefPubMedGoogle Scholar
  12. 12.
    Laffont S, Blanquart E, Savignac M, Cénac C, Laverny G, Metzger D, et al. Androgen signaling negatively controls group 2 innate lymphoid cells. J Exp Med. 2017;214:1581–92.  https://doi.org/10.1084/jem.20161807.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    • Cephus JY, Stier MT, Fuseini H, Yung JA, Toki S, Bloodworth MH, et al. Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation. Cell Rep. 2017.  https://doi.org/10.1016/j.celrep.2017.10.110 Key paper describing the effect of androgens on T2 inflammation.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Takeda M, Tanabe M, Ito W, Ueki S, Konnno Y, Chihara M, et al. Gender difference in allergic airway remodelling and immunoglobulin production in mouse model of asthma. Respirology. 2013;18:797–806.  https://doi.org/10.1111/resp.12078.CrossRefGoogle Scholar
  15. 15.
    Ma J, Xiao L. Association of general and central obesity and atopic and nonatopic asthma in US adults. J Asthma. 2013;50:395–402.  https://doi.org/10.3109/02770903.2013.770014.CrossRefPubMedGoogle Scholar
  16. 16.
    • Dixon AE, Poynter ME. Mechanisms of asthma in obesity pleiotropic aspects of obesity produce distinct asthma phenotypes. Am J Respir Cell Mol Biol. 2016;54:601–8.  https://doi.org/10.1165/rcmb.2016-0017PS This is a comprehensive reivew on relationship between obesity and asthma.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Carey MA, Card JW, Voltz JW, Arbes SJ, Germolec DR, Korach KS, et al. It’s all about sex: gender, lung development and lung disease. Trends Endocrinol Metab. 2007;18:308–13.  https://doi.org/10.1016/j.tem.2007.08.003.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Harms C, Smith J, Kurti S. Gender, sex hormones and respiratory disease. Cham: Springer International Publishing; 2016.  https://doi.org/10.1007/978-3-319-23998-9.CrossRefGoogle Scholar
  19. 19.
    Wijga A, Tabak C, Postma DS, Kerkhof M, Wieringa MH, Hoekstra MO, et al. Sex differences in asthma during the first 8 years of life: the prevention and incidence of asthma and mite allergy (PIAMA) birth cohort study. J Allergy Clin Immunol. 2011;127:275–7.  https://doi.org/10.1016/j.jaci.2010.09.022.CrossRefPubMedGoogle Scholar
  20. 20.
    Nicolai T, Pereszlenyiova-Bliznakova L, Illi S, Reinhardt D, Von Mutius E. Longitudinal follow-up of the changing gender ratio in asthma from childhood to adulthood: role of delayed manifestation in girls. Pediatr Allergy Immunol. 2003;14:280–3.  https://doi.org/10.1034/j.1399-3038.2003.00047.x.CrossRefPubMedGoogle Scholar
  21. 21.
    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.  https://doi.org/10.1016/S1081-1206(10)61533-5.CrossRefGoogle Scholar
  22. 22.
    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;56:180–7.  https://doi.org/10.1016/S0895-4356(02)00593-0.CrossRefPubMedGoogle Scholar
  23. 23.
    Salam MT, Wenten M, Gilliland FD. Endogenous and exogenous sex steroid hormones and asthma and wheeze in young women. J Allergy Clin Immunol. 2006;117:1001–7.  https://doi.org/10.1016/j.jaci.2006.02.004.CrossRefPubMedGoogle Scholar
  24. 24.
    • 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;141:1510–1513.e8.  https://doi.org/10.1016/j.jaci.2017.11.034 This is a meta-analysis on effect of internal and external sex hormone on asthma risk.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    • DeBoer MD, Phillips BR, Mauger DT, Zein J, Erzurum SC, Fitzpatrick AM, et al. Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma. BMC Pulm med. 2018;18:1–10.  https://doi.org/10.1186/s12890-018-0612-x Key paper that correlate sex hormones with lung function and symptoms among adolescents with asthma.CrossRefGoogle Scholar
  26. 26.
    Minelli C, van der Plaat DA, Leynaert B, Granell R, Amaral AFS, Pereira M, et al. Age at puberty and risk of asthma: a Mendelian randomisation study. PLoS Med. 2018;15:e1002634.  https://doi.org/10.1371/journal.pmed.1002634.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gupta R, Margevicius S, DeBoer M, Myers R, Bacharier LB, Li N, et al. Children with severe asthma are LIkely to become less severe during adolescence: preliminary results of the SARP III pediatric longitudinal study. Am Thorac Soc Int Meet. 2018;44:A7806.Google Scholar
  28. 28.
    Farha S, Asosingh K, Laskowski D, Hammel J, Dweik RA, Wiedemann HP, et al. Effects of the menstrual cycle on lung function variables in women with asthma. Am J Respir Crit Care Med. 2009;180:304–10.  https://doi.org/10.1164/rccm.200904-0497OC.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Tan KS, McFarlane LC, Lipworth BJ. Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual responsiveness to adenosine monophosphate in stable female asthmatic patients. Thorax. 1997;52:608–11.  https://doi.org/10.1136/thx.52.7.608.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Agarwal AK, Shah A. Menstrual-linked asthma. J Asthma. 1997;34:539–45.  https://doi.org/10.3109/02770909709055398.CrossRefPubMedGoogle Scholar
  31. 31.
    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.  https://doi.org/10.1016/S1081-1206(10)63111-0.CrossRefGoogle Scholar
  32. 32.
    Sánchez-Ramos JL, Pereira-Vega AR, Alvarado-Gómez F, Maldonado-Pérez JA, Svanes C, Gómez-Real F. Risk factors for premenstrual asthma: a systematic review and meta-analysis. Expert Rev Respir Med. 2017;11:57–72.  https://doi.org/10.1080/17476348.2017.1270762.CrossRefPubMedGoogle Scholar
  33. 33.
    Rao CK, Moore CG, Bleecker E, Busse WW, Calhoun W, Castro M, et al. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the severe asthma research program. Chest. 2013;143:984–92.  https://doi.org/10.1378/chest.12-0973.CrossRefGoogle Scholar
  34. 34.
    Schatz M. Interrelationships between asthma and pregnancy: a literature review. J Allergy Clin Immunol. 1999;103:S330–6.  https://doi.org/10.1016/S0091-6749(99)70258-7.CrossRefPubMedGoogle Scholar
  35. 35.
    Mendola P, Männistö TI, Leishear K, Reddy UM, Chen Z, Laughon SK. Neonatal health of infants born to mothers with asthma. J Allergy Clin Immunol. 2014;133:85–90.e4.  https://doi.org/10.1016/j.jaci.2013.06.012.CrossRefPubMedGoogle Scholar
  36. 36.
    Bonham CA, Patterson KC, Strek ME. Asthma outcomes and management during pregnancy. Chest. 2018;153:515–27.  https://doi.org/10.1016/j.chest.2017.08.029.CrossRefPubMedGoogle Scholar
  37. 37.
    Gade EJ, Thomsen SF, Lindenberg S, Backer V. Fertility outcomes in asthma: a clinical study of 245 women with unexplained infertility. Eur Respir J. 2016;47:1144–51.  https://doi.org/10.1183/13993003.01389-2015.CrossRefPubMedGoogle Scholar
  38. 38.
    Kwon HL, Belanger K, Holford TR, Bracken MB. Effect of fetal sex on airway lability in pregnant women with asthma. Am J Epidemiol. 2006;163:217–21.  https://doi.org/10.1093/aje/kwj032.CrossRefPubMedGoogle Scholar
  39. 39.
    Murphy VE, Gibson PG, Giles WB, Zakar T, Smith R, Bisits AM, et al. Maternal asthma is associated with reduced female fetal growth. Am J Respir Crit Care Med. 2003;168:1317–23.  https://doi.org/10.1164/rccm.200303-374OC.CrossRefPubMedGoogle Scholar
  40. 40.
    Osei-Kumah A, Smith R, Jurisica I, Caniggia I, Clifton VL. Sex-specific differences in placental global gene expression in pregnancies complicated by asthma. Placenta. 2011;32:570–8.  https://doi.org/10.1016/j.placenta.2011.05.005.CrossRefPubMedGoogle Scholar
  41. 41.
    Saif Z, Hodyl NA, Hobbs E, Tuck AR, Butler MS, Osei-Kumah A, et al. The human placenta expresses multiple glucocorticoid receptor isoforms that are altered by fetal sex, growth restriction and maternal asthma. Placenta. 2014;35:260–8.  https://doi.org/10.1016/j.placenta.2014.01.012.CrossRefPubMedGoogle Scholar
  42. 42.
    Balzano G, Fuschillo S, De Angelis E, Gaudiosi C, Mancini A, Caputi M. Persistent airway inflammation and high exacerbation rate in asthma that starts at menopause. Monaldi Arch Chest Dis 2016;67.  https://doi.org/10.4081/monaldi.2007.484.
  43. 43.
    Triebner K, Johannessen A, Puggini L, Benediktsdottir B, Bertelsen RJ, Bifulco E, et al. Menopause as a predictor of new-onset asthma: A longitudinal Northern European population study. J Allergy Clin Immunol. 2016;137:50–57.e6.  https://doi.org/10.1016/j.jaci.2015.08.019.CrossRefGoogle Scholar
  44. 44.
    Zemp E, Schikowski T, Dratva J, Schindler C, Probst-Hensch N. Asthma and the menopause: a systematic review and meta-analysis. Maturitas. 2012;73:212–7.  https://doi.org/10.1016/j.maturitas.2012.08.010.CrossRefPubMedGoogle Scholar
  45. 45.
    Banerji A, Clark S, Afilalo M, Blanda MP, Cydulka RK, Camargo CA. Prospective multicenter study of acute asthma in younger versus older adults presenting to the emergency department. J Am Geriatr Soc. 2006;54:48–55.  https://doi.org/10.1111/j.1532-5415.2005.00563.x.CrossRefPubMedGoogle Scholar
  46. 46.
    Zein JG, Udeh BL, Teague WG, Koroukian SM, Schlitz NK, Bleecker ER, et al. Impact of age and sex on outcomes and hospital cost of acute asthma in the United States, 2011-2012. PLoS One. 2016;11:e0157301.  https://doi.org/10.1371/journal.pone.0157301.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hsu J, Chen J, Mirabelli MC. Asthma Morbidity, Comorbidities, and Modifiable Factors Among Older Adults. J Allergy Clin Immunol Pract. 2018;6:236–243.e7.  https://doi.org/10.1016/j.jaip.2017.06.007.CrossRefPubMedGoogle Scholar
  48. 48.
    Keselman A, Fang X, White PB, Heller NM. Estrogen signaling contributes to sex differences in macrophage polarization during asthma. J Immunol. 2017;199:1573–83.  https://doi.org/10.4049/jimmunol.1601975.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    • Yung JA, Fuseini H, Newcomb DC. Hormones, sex, and asthma. Ann Allergy Asthma Immunol. 2018;120:488–94.  https://doi.org/10.1016/j.anai.2018.01.016 This is a comprehensive review on interation between sex hormones and various immune pathways.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Smith LC, Moreno S, Robertson L, Robinson S, Gant K, Bryant AJ, et al. Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells. Respir Res. 2018.  https://doi.org/10.1186/s12931-018-0861-5.
  51. 51.
    Kovats S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol. 2015;294:63–9.  https://doi.org/10.1016/j.cellimm.2015.01.018.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    de Oliveira APL, Peron JPS, Damazo AS, dos Santos Franco AL, Domingos HV, Oliani SM, et al. Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. Respir Res. 2010.  https://doi.org/10.1186/1465-9921-11-115.
  53. 53.
    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;33:1457–63.  https://doi.org/10.1046/j.1365-2222.2003.01743.x.CrossRefPubMedGoogle Scholar
  54. 54.
    Kunzmann S, Ottensmeier B, Speer CP, Fehrholz M. Effect of progesterone on Smad signaling and TGF-β/Smad-regulated genes in lung epithelial cells. PLoS One. 2018;13:e0200661.  https://doi.org/10.1371/journal.pone.0200661.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Fuseini H, Yung JA, Cephus JY, Zhang J, Goleniewska K, Polosukhin VV, et al. Testosterone decreases house dust mite–induced type 2 and IL-17A–mediated airway inflammation. J Immunol. 2018;201:1843–54.  https://doi.org/10.4049/jimmunol.1800293.CrossRefPubMedGoogle Scholar
  56. 56.
    Espinoza J, Montaño LM, Perusquía M. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a Guinea pig asthma model. J Steroid Biochem Mol Biol. 2013;138:174–82.  https://doi.org/10.1016/j.jsbmb.2013.05.009.CrossRefPubMedGoogle Scholar
  57. 57.
    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;31:461–71.  https://doi.org/10.2500/aap.2010.31.3384.CrossRefPubMedGoogle Scholar
  58. 58.
    Dong G-H, Chen T, Liu M-M, Wang D, Ma Y-N, Ren W-H, et al. Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study. PLoS One. 2011;6:e22470.  https://doi.org/10.1371/journal.pone.0022470.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Syamlal G, Mazurek JM, Dube SR. Gender differences in smoking among U.S. working adults. Am J Prev Med. 2014.  https://doi.org/10.1016/j.amepre.2014.06.013.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Bjerg A, Ekerljung L, Eriksson J, Ólafsdóttir IS, Middelveld R, Franklin KA, et al. Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA2LEN Study. PLoS One. 2013.  https://doi.org/10.1371/journal.pone.0054137.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Fuentes N, Cabello N, Nicoleau M, Chroneos ZC, Silveyra P. Modulation of the lung inflammatory response to ozone by the estrous cycle. Physiol Rep. 2019;7:e14026.  https://doi.org/10.14814/phy2.14026.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    • Pace S, Pergola C, Dehm F, Rossi A, Gerstmeier J, Troisi F, et al. Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males. J Clin Invest. 2017:127, 3167–3176.  https://doi.org/10.1172/JCI92885 Key finding of sex-specific pharmacologic response.CrossRefPubMedGoogle Scholar
  63. 63.
    Sessa M, Mascolo A, D’Agostino B, Casciotta A, D’Agostino V, De Michele F, et al. Relationship between gender and the effectiveness of montelukast: an Italian/Danish register-based retrospective cohort study. Front Pharmacol. 2018;9:1–12.  https://doi.org/10.3389/fphar.2018.00844.CrossRefGoogle Scholar
  64. 64.
    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;155:1273–7.  https://doi.org/10.1164/ajrccm.155.4.9105066.CrossRefPubMedGoogle Scholar
  65. 65.
    Macsali F, Real FG, Omenaas ER, Bjorge L, Janson C, Franklin K, et al. Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey. J Allergy Clin Immunol. 2009;123:391–7.  https://doi.org/10.1016/j.jaci.2008.10.041.CrossRefPubMedGoogle Scholar
  66. 66.
    Nwaru BI, Sheikh A. Hormonal contraceptives and asthma in women of reproductive age: analysis of data from serial national Scottish health surveys. J R Soc Med. 2015;108:358–71.  https://doi.org/10.1177/0141076815588320.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Liao PV, Dollin J. Half a century of the oral contraceptive pill: historical review and view to the future. Can Fam Physician 2012.Google Scholar
  68. 68.
    Zhang P, Zein JG. Menopausal hormone replacement therapy and risk of asthma. Am J Respir Crit Care Med 2019;199:A7089Google Scholar
  69. 69.
    Taylor B, Mannino D, Brown C, Crocker D, Twum-Baah N, Holguin F. Body mass index and asthma severity in the National Asthma Survey. Thorax. 2008;63:14–20.  https://doi.org/10.1136/thx.2007.082784.CrossRefPubMedGoogle Scholar
  70. 70.
    Bibi H, Shoseyov D, Feigenbaum D, Genis M, Friger M, Peled R, et al. The relationship between asthma and obesity in children: is it real or a case of over diagnosis? J Asthma. 2004;41:403–10.  https://doi.org/10.1081/JAS-120026097.CrossRefPubMedGoogle Scholar
  71. 71.
    Castro-Rodríguez JA, Holberg CJ, Morgan WJ, Wright AL, Martinez FD. Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years. Am J Respir Crit Care Med. 2001;163:1344–9.  https://doi.org/10.1164/ajrccm.163.6.2006140.CrossRefPubMedGoogle Scholar
  72. 72.
    Murray CS, Canoy D, Buchan I, Woodcock A, Simpson A, Custovic A. Body mass index in young children and allergic disease: gender differences in a longitudinal study. Clin Exp Allergy. 2011;41:78–85.  https://doi.org/10.1111/j.1365-2222.2010.03598.x.CrossRefPubMedGoogle Scholar
  73. 73.
    Ho WC, Lin YS, Caffrey JL, Lin MH, Hsu HT, Myers L, et al. Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study. BMC Public Health. 2011;11.  https://doi.org/10.1186/1471-2458-11-542.
  74. 74.
    Wang D, Qian Z, Wang J, Yang M, Lee YL, Liu F, et al. Gender-specific differences in associations of overweight and obesity with asthma and asthma-related symptoms in 30056 children: result from 25 districts of northeastern China. J Asthma. 2014;51:508–14.  https://doi.org/10.3109/02770903.2014.892963.CrossRefPubMedGoogle Scholar
  75. 75.
    Willeboordse M, van den Bersselaar DLCM, van de Kant KDG, Muris JWM, van Schayck OCP, Dompeling E. Sex differences in the relationship between asthma and overweight in Dutch children: a survey study. PLoS One. 2013.  https://doi.org/10.1371/journal.pone.0077574.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Ekström S, Magnusson J, Kull I, Andersson N, Bottai M, Pour MB, et al. Body mass index development and asthma throughout childhood. Am J Epidemiol. 2017;186:255–63.  https://doi.org/10.1093/aje/kwx081.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Wadden D, Allwood Newhook L-A, Twells L, Farrell J, Gao Z. Sex-specific association between childhood BMI trajectories and asthma phenotypes. Int J Pediatr. 2018;2018:1–9.  https://doi.org/10.1155/2018/9057435.CrossRefGoogle Scholar
  78. 78.
    Choi H, Dostal M, Pastorkova A, Rossner P, Sram RJ, Ho SM. Greater susceptibility of girls to airborne benzo[a]pyrene for obesity-associated childhood asthma. Environ Int. 2018;121:308–16.  https://doi.org/10.1016/j.envint.2018.08.061.CrossRefPubMedGoogle Scholar
  79. 79.
    Chen Y, Dales R, Tang M, Krewski D. Obesity may increase the incidence of asthma in women but not in men: longitudinal observations from the Canadian National Population Health Surveys. Am J Epidemiol. 2002;155:191–7.  https://doi.org/10.1093/aje/155.3.191.CrossRefPubMedGoogle Scholar
  80. 80.
    Loerbroks A, Apfelbacher CJ, Amelang M, Stürmer T. Obesity and adult asthma: potential effect modification by gender, but not by Hay fever. Ann Epidemiol. 2008;18:283–9.  https://doi.org/10.1016/j.annepidem.2007.11.001.CrossRefPubMedGoogle Scholar
  81. 81.
    Jarjour NN, Erzurum SC, Bleecker ER, Calhoun WJ, Castro M, Comhair SAA, et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute severe asthma research program. Am J Respir Crit Care Med. 2012;185:356–62.  https://doi.org/10.1164/rccm.201107-1317PP.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    To M, Hitani A, Kono Y, Honda N, Kano I, Haruki K, et al. Obesity-associated severe asthma in an adult Japanese population. Respir Investig. 2018;56:440–7.  https://doi.org/10.1016/j.resinv.2018.07.003.CrossRefPubMedGoogle Scholar
  83. 83.
    Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, et al. Impact of abdominal visceral adiposity on adult asthma symptoms. J Allergy Clin Immunol Pract. 2018;7:1–13.  https://doi.org/10.1016/j.jaip.2018.11.014.CrossRefGoogle Scholar
  84. 84.
    Orfanos S, Jude J, Deeney BT, Cao G, Rastogi D, van Zee M, et al. Obesity increases airway smooth muscle responses to contractile agonists. Am J Physiol Cell Mol Physiol. 2018;315:L673–81.  https://doi.org/10.1152/ajplung.00459.2017.CrossRefGoogle Scholar
  85. 85.
    Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001;4:499–502.  https://doi.org/10.1097/00075197-200111000-00006.CrossRefPubMedGoogle Scholar
  86. 86.
    Pan J, Xu L, Lam TH, Jiang CQ, Zhang WS, Jin YL, et al. Association of adiposity with pulmonary function in older Chinese: Guangzhou biobank cohort study. Respir Med. 2017;132:102–8.  https://doi.org/10.1016/j.rmed.2017.10.003.CrossRefPubMedGoogle Scholar
  87. 87.
    Rowe A, Hernandez P, Kuhle S, Kirkland S. The association between anthropometric measures and lung function in a population-based study of Canadian adults. Respir Med. 2017;131:199–204.  https://doi.org/10.1016/j.rmed.2017.08.030.CrossRefPubMedGoogle Scholar
  88. 88.
    Frühbeck G, Catalán V, Rodríguez A, Ramírez B, Becerril S, Salvador J, et al. Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome. Sci Rep. 2017;7:6619.  https://doi.org/10.1038/s41598-017-06997-0.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Roemmich JN, Clark PA, Berr SS, Mai V, Mantzoros CS, Flier JS, et al. Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Phys. 1998;4:261–3.  https://doi.org/10.1080/08858198909528020.CrossRefGoogle Scholar
  90. 90.
    Quek Y-W, Sun H-L, Ng Y-Y, Lee H-S, Yang S-F, Ku M-S, et al. Associations of serum leptin with atopic asthma and allergic rhinitis in children. Am J Rhinol Allergy. 2010;24:354–8.  https://doi.org/10.2500/ajra.2010.24.3483.CrossRefPubMedGoogle Scholar
  91. 91.
    Böttner A, Kratzsch J, Müller G, Kapellen TM, Blüher S, Keller E, et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab. 2004;89:4053–61.  https://doi.org/10.1210/jc.2004-0303.CrossRefPubMedGoogle Scholar
  92. 92.
    Sood A, Shore SA. Adiponectin, leptin, and Resistin in asthma: Basic Mechanisms through Population Studies. J Allergy 2013.  https://doi.org/10.1155/2013/785835.CrossRefGoogle Scholar
  93. 93.
    Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol. 2005;115:103–9.  https://doi.org/10.1016/j.jaci.2004.10.007.CrossRefPubMedGoogle Scholar
  94. 94.
    Ballantyne D, Scott H, MacDonald-Wicks L, Gibson PG, Wood LG. Resistin is a predictor of asthma risk and resistin:adiponectin ratio is a negative predictor of lung function in asthma. Clin Exp Allergy. 2016;46:1056–65.  https://doi.org/10.1111/cea.12742.CrossRefPubMedGoogle Scholar
  95. 95.
    Han B, Wu WH, Bae JM, Son S-J, Lee JH, Han TY. Serum leptin and adiponectin levels in atopic dermatitis (AD) and their relation to disease severity. J Am Acad Dermatol. 2016;75:629–31.  https://doi.org/10.1016/j.jaad.2016.04.036.CrossRefPubMedGoogle Scholar
  96. 96.
    Di Filippo P, Scaparrotta A, Rapino D, De Giorgis T, Petrosino MI, Attanasi M, et al. Insulin resistance and lung function in obese asthmatic pre-pubertal children. J Pediatr Endocrinol Metab. 2018;31:45–51.  https://doi.org/10.1515/jpem-2017-0182.CrossRefPubMedGoogle Scholar
  97. 97.
    Zein JG, Yaqoob Z, Deboer M, Teague WG, Gaston BM, Erzurum SC, et al. Polycystic ovary syndrome is associated with a higher risk for asthma. Am J Respir Crit Care Med. 2017;195:A1307.Google Scholar
  98. 98.
    Zierau L, Cortes R, Thomsen SF, Jimenez-Solem E, Lindenberg S, Backer V. Asthma severity and fertility outcome in women with polycystic ovary syndrome: a registry-based study. ERJ Open Res. 2018;4:00138–2017.  https://doi.org/10.1183/23120541.00138-2017.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Telenga ED, Tideman SW, Kerstjens HAM, ten Hacken NHT, Timens W, Postma DS, et al. Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Allergy. 2012;67:1060–8.  https://doi.org/10.1111/j.1398-9995.2012.02855.x.CrossRefPubMedGoogle Scholar
  100. 100.
    Scott HA, Gibson PG, Garg ML, Upham JW, Wood LG. Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype. Allergy Eur J Allergy Clin Immunol. 2016;71:1037–47.  https://doi.org/10.1111/all.12891.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.From the Respiratory InstituteCleveland ClinicClevelandUSA

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