Current Allergy and Asthma Reports

, Volume 7, Issue 2, pp 143–150 | Cite as

Are there reasons why adult asthma is more common in females?

  • Barbro N. Melgert
  • Anuradha Ray
  • Machteld N. Hylkema
  • Wim Timens
  • Dirkje S. Postma
Article

Abstract

Many epidemiological studies suggest that women are at increased risk of developing adult-onset asthma and also suffer from more severe disease than men. These gender differences appear to be the product of biological sex differences as well as sociocultural and environmental differences. The biological sex differences include genetic, pulmonary, and immunological factors. There is compelling evidence that sex hormones are major determinants of at least these biological sex differences. This paper explores the current literature regarding effects of sex hormones on immune function, resident lung cells, and regulation of local processes in the lung to shed light on underlying mechanisms of gender differences in asthma. More research is needed to understand these mechanisms in order to improve treatment of women with asthma.

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References and Recommended Reading

  1. 1.
    Myers TR: Pediatric asthma epidemiology: incidence, morbidity, and mortality. Respir Care Clin N Am 2000, 6:1–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Schatz M, Camargo CA Jr: The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organization. Ann Allergy Asthma Immunol 2003, 91:553–558.PubMedGoogle Scholar
  3. 3.
    Becklake MR, Kauffmann F: Gender differences in airway behaviour over the human life span. Thorax 1999, 54:1119–1138.PubMedGoogle Scholar
  4. 4.
    ENFUMOSA: The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003, 22:470–477.CrossRefGoogle Scholar
  5. 5.
    Lee JH, Haselkorn T, Chipps BE, et al.: Gender differences in IgE-mediated allergic asthma in the epidemiology and natural history of asthma: Outcomes and Treatment Regimens (TENOR) study. J Asthma 2006, 43:179–184.PubMedCrossRefGoogle Scholar
  6. 6.
    Baibergenova A, Thabane L, Akhtar-Danesh N, et al.: Sex differences in hospital admissions from emergency departments in asthmatic adults: a population-based study. Ann Allergy Asthma Immunol 2006, 96:666–672.PubMedGoogle Scholar
  7. 7.
    Ostrom NK: Women with asthma: a review of potential variables and preferred medical management. Ann Allergy Asthma Immunol 2006, 96:655–665.PubMedCrossRefGoogle Scholar
  8. 8.
    Watson L, Boezen HM, Postma DS: Differences between males and females in the natural history of asthma and COPD. In European Respiratory Monograph. Edited by Wouters EFM. Sheffield, UK: European Respiratory Society; 2003:50–73.Google Scholar
  9. 9.
    Salam MT, Wenten M, Gilliland FD: Endogenous and exogenous sex steroid hormones and asthma and wheeze in young women. J Allergy Clin Immunol 2006, 117:1001–1007.PubMedCrossRefGoogle Scholar
  10. 10.
    Apter D, Reinila M, Vihko R: Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood. Int J Cancer 1989, 44:783–787.PubMedCrossRefGoogle Scholar
  11. 11.
    Vrieze A, Postma DS, Kerstjens HA: Perimenstrual asthma: a syndrome without known cause or cure. J Allergy Clin Immunol 2003, 112:271–282.PubMedCrossRefGoogle Scholar
  12. 12.
    Forbes L: Do exogenous oestrogens and progesterone influence asthma? Thorax 1999, 54:265–267.PubMedGoogle Scholar
  13. 13.
    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, 36:609–613.PubMedCrossRefGoogle Scholar
  14. 14.
    Lange P, Parner J, Prescott E, et al.: Exogenous female sex steroid hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population. Thorax 2001, 56:613–616.PubMedCrossRefGoogle Scholar
  15. 15.
    Forastiere F, Sunyer J, Farchi S, et al.: Number of offspring and maternal allergy. Allergy 2005, 60:510–514.PubMedCrossRefGoogle Scholar
  16. 16.
    Gluck JC: The change of asthma course during pregnancy. Clin Rev Allergy Immunol 2004, 26:171–180.PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt M, Naumann H, Weidler C, et al.: Inflammation and sex hormone metabolism. Ann N Y Acad Sci 2006, 1069:236–246.PubMedCrossRefGoogle Scholar
  18. 18.
    Kwon HL, Belanger K, Holford TR, Bracken MB: Effect of fetal sex on airway lability in pregnant women with asthma. Am J Epidemiol 2006, 163:217–221.PubMedCrossRefGoogle Scholar
  19. 19.
    Baibergenova A, Thabane L, Akhtar-Danesh N, et al.: Is fetal gender associated with emergency department visits for asthma during pregnancy? J Asthma 2006, 43:293–299.PubMedCrossRefGoogle Scholar
  20. 20.
    Troisi RJ, Speizer FE, Willett WC, et al.: Menopause, postmenopausal estrogen preparations, and the risk of adultonset asthma. A prospective cohort study. Am J Respir Crit Care Med 1995, 152:1183–1188.PubMedGoogle Scholar
  21. 21.
    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, 35:1496–1503.PubMedCrossRefGoogle Scholar
  22. 22.
    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, 57:562–567.PubMedCrossRefGoogle Scholar
  23. 23.
    Hellings PW, Vandekerckhove P, Claeys R, et al.: Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma. Clin Exp Allergy 2003, 33:1457–1463.PubMedCrossRefGoogle Scholar
  24. 24.
    Ligeiro de Oliveira AP, Oliveira-Filho RM, Lucia da Silva Z, et al.: Regulation of allergic lung inflammation in rats: interaction between estradiol and corticosterone. Neuroimmunomodulation 2004, 11:20–27.PubMedCrossRefGoogle Scholar
  25. 25.
    Yang KD, Liu CA, Chang JC, et al.: Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases. Clin Exp Allergy 2004, 34:32–37.PubMedCrossRefGoogle Scholar
  26. 26.
    Szczeklik W, Sanak M, Szczeklik A: Functional effects and gender association of COX-2 gene polymorphism G-765C in bronchial asthma. J Allergy Clin Immunol 2004, 114:248–253.PubMedCrossRefGoogle Scholar
  27. 27.
    Levy H, Raby BA, Lake S, et al.: Association of defensin beta-1 gene polymorphisms with asthma. J Allergy Clin Immunol 2005, 115:252–258.PubMedCrossRefGoogle Scholar
  28. 28.
    Adjers K, Karjalainen J, Pessi T, et al.: Epistatic effect of TLR4 and IL4 genes on the risk of asthma in females. Int Arch Allergy Immunol 2005, 138:251–256.PubMedCrossRefGoogle Scholar
  29. 29.
    Dijkstra A, Howard TD, Vonk JM, et al.: Estrogen receptor 1 polymorphisms are associated with airway hyper-responsiveness and lung function decline, particularly in female subjects with asthma. J Allergy Clin Immunol 2006, 117:604.PubMedCrossRefGoogle Scholar
  30. 30.
    Hepper PG, Shannon EA, Dornan JC: Sex differences in fetal mouth movements. Lancet 1997, 350:1820.PubMedCrossRefGoogle Scholar
  31. 31.
    McMillan EM, King GM, Adamson IY: Sex hormones influence growth and surfactant production in fetal lung explants. Exp Lung Res 1989, 15:167.PubMedGoogle Scholar
  32. 32.
    Patrone C, Cassel TN, Pettersson K, et al.: Regulation of postnatal lung development and homeostasis by estrogen receptor beta. Mol Cell Biol 2003, 23:8542–8552.PubMedCrossRefGoogle Scholar
  33. 33.
    Madan T, Kishore U, Singh M, et al.: Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest 2001, 107:467–475.PubMedGoogle Scholar
  34. 34.
    Dammann CE, Ramadurai SM, McCants DD, et al.: Androgen regulation of signaling pathways in late fetal mouse lung development. Endocrinology 2000, 141:2923.PubMedCrossRefGoogle Scholar
  35. 35.
    Hamilton LM, Torres-Lozano C, Puddicombe SM, et al.: The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma. Clin Exp Allergy 2003, 33:233–240.PubMedCrossRefGoogle Scholar
  36. 36.
    Merkus PJ, Borsboom GJ, Van Pelt W, et al.: Growth of airways and air spaces in teenagers is related to sex but not to symptoms. J Appl Physiol 1993, 75:2045.PubMedGoogle Scholar
  37. 37.
    Irvin CG: Interaction between the growing lung and asthma: role of early intervention. J Allergy Clin Immunol 2000, 105:S540–546.PubMedCrossRefGoogle Scholar
  38. 38.
    Manfreda J, Sears MR, Becklake MR, et al.: Geographic and gender variability in the prevalence of bronchial responsiveness in Canada. Chest 2004, 125:1657–1664.PubMedCrossRefGoogle Scholar
  39. 39.
    Dimitropoulou C, White RE, Ownby DR, Catravas JD: Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels. Am J Respir Cell Mol Biol 2005, 32:239–247.PubMedCrossRefGoogle Scholar
  40. 40.
    Foster PS, Goldie RG, Paterson JW: Effect of steroids on beta-adrenoceptor-mediated relaxation of pig bronchus. Br J Pharmacol 1983, 78:441–445.PubMedGoogle Scholar
  41. 41.
    Tan KS, McFarlane LC, Lipworth BJ: Paradoxical down-regulation and desensitization of beta2-adrenoceptors by exogenous progesterone in female asthmatics. Chest 1997, 111:847–851.PubMedGoogle Scholar
  42. 42.
    Ray A, Cohn L: Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest 1999, 104:985–993.PubMedCrossRefGoogle Scholar
  43. 43.
    Lambert KC, Curran EM, Judy BM, et al.: Estrogen receptor alpha (ERalpha) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17beta-estradiol acts through ERalpha to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation. J Immunol 2005, 175:5716–5723.PubMedGoogle Scholar
  44. 44.
    Delpy L, Douin-Echinard V, Garidou L, et al.: Estrogen enhances susceptibility to experimental autoimmune myasthenia gravis by promoting type 1-polarized immune responses. J Immunol 2005, 175:5050–5057.PubMedGoogle Scholar
  45. 45.
    Koch M, Witzenrath M, Reuter C, et al.: Role of local pulmonary IFN-gamma expression in murine allergic airway inflammation. Am J Respir Cell Mol Biol 2006, 35:211–219.PubMedCrossRefGoogle Scholar
  46. 46.
    Karpuzoglu E, Ahmed SA: Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, and apoptosis. Nitric Oxide 2006, 15:177–186.PubMedCrossRefGoogle Scholar
  47. 47.
    Sandberg JK, Ljunggren HG: Development and function of CD1d-restricted NKT cells: influence of sphingolipids, SAP and sex. Trends Immunol 2005, 26:347–349.PubMedCrossRefGoogle Scholar
  48. 48.
    Akbari O, Faul JL, Hoyte EG, et al.: CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med 2006, 354:1117–1129.PubMedCrossRefGoogle Scholar
  49. 49.
    Akbari O, Stock P, Meyer E, et al.: Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med 2003, 9:582–588.PubMedCrossRefGoogle Scholar
  50. 50.
    Bebo BF Jr, Schuster JC, Vandenbark AA, Offner H: Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells. J Immunol 1999, 162:35–40.PubMedGoogle Scholar
  51. 51.
    Verthelyi D, Klinman DM: Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo. Immunology 2000, 100:384–390.PubMedCrossRefGoogle Scholar
  52. 52.
    Piccinni MP, Beloni L, Livi C, et al.: Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med 1998, 4:1020–1024.PubMedCrossRefGoogle Scholar
  53. 53.
    Moro MH, Bjornsson J, Marietta EV, et al.: Gestational attenuation of Lyme arthritis is mediated by progesterone and IL-4. J Immunol 2001, 166:7404–7409.PubMedGoogle Scholar
  54. 54.
    Ostroukhova M, Ray A: CD25+ T cells and regulation of allergen-induced responses. Curr Allergy Asthma Rep 2005, 5:35–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Polanczyk MJ, Carson BD, Subramanian S, et al.: Estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment. J Immunol 2004, 173:2227–2230.PubMedGoogle Scholar
  56. 56.
    Prieto GA, Rosenstein Y: Oestradiol potentiates the suppressive function of human CD4 CD25 regulatory T cells by promoting their proliferation. Immunology 2006, 118:58–65.PubMedCrossRefGoogle Scholar
  57. 57.
    Vellutini M, Viegi G, Parrini D, et al.: Serum immunoglobulins E are related to menstrual cycle. Eur J Epidemiol 1997, 13:931–935.PubMedCrossRefGoogle Scholar
  58. 58.
    Kanda N, Tamaki K: Estrogen enhances immunoglobulin production by human PBMCs. J Allergy Clin Immunol 1999, 103:282–288.PubMedCrossRefGoogle Scholar
  59. 59.
    Grimaldi CM, Cleary J, Dagtas AS, et al.: Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest 2002, 109:1625–1633.PubMedCrossRefGoogle Scholar
  60. 60.
    Paharkova-Vatchkova V, Maldonado R, Kovats S: Estrogen preferentially promotes the differentiation of CD11c+CD11b (intermediate) dendritic cells from bone marrow precursors. J Immunol 2004, 172:1426–1436.PubMedGoogle Scholar
  61. 61.
    Nalbandian G, Paharkova-Vatchkova V, Mao A, et al.: The selective estrogen receptor modulators, tamoxifen and raloxifene, impair dendritic cell differentiation and activation. J Immunol 2005, 175:2666–2675.PubMedGoogle Scholar
  62. 62.
    Bengtsson AK, Ryan EJ, Giordano D, et al.: 17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells. Blood 2004, 104:1404–1410.PubMedCrossRefGoogle Scholar
  63. 63.
    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, 155:191–197.PubMedCrossRefGoogle Scholar
  64. 64.
    Saad MF, Damani S, Gingerich RL, et al.: Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997, 82:579–584.PubMedCrossRefGoogle Scholar
  65. 65.
    Sood A, Ford ES, Camargo CA Jr: Association between leptin and asthma in adults. Thorax 2006, 61:300–305.PubMedCrossRefGoogle Scholar
  66. 66.
    Shore SA, Schwartzman IN, Mellema MS, et al.: Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol 2005, 115:103–109.PubMedCrossRefGoogle Scholar
  67. 67.
    Bulow B, Ahren B, Fisker S, et al.: The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones. Clin Endocrinol (Oxf) 2003, 59:482–486.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Barbro N. Melgert
    • 1
  • Anuradha Ray
  • Machteld N. Hylkema
  • Wim Timens
  • Dirkje S. Postma
  1. 1.Division of PulmonaryUniversity of Pittsburgh Medical CenterPittsburghUSA

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