Sex Plays a Multifaceted Role in Asthma Pathogenesis

Biomolecules. 2022 Apr 29;12(5):650. doi: 10.3390/biom12050650.

Abstract

Sex is considered an important risk factor for asthma onset and exacerbation. The prevalence of asthma is higher in boys than in girls during childhood, which shows a reverse trend after puberty-it becomes higher in adult females than in adult males. In addition, asthma severity, characterized by the rate of hospitalization and relapse after discharge from the emergency department, is higher in female patients. Basic research indicates that female sex hormones enhance type 2 adaptive immune responses, and male sex hormones negatively regulate type 2 innate immune responses. However, whether hormone replacement therapy in postmenopausal women increases the risk of current asthma and asthma onset remains controversial in clinical settings. Recently, sex has also been shown to influence the pathophysiology of asthma in its relationship with genetic or other environmental factors, which modulate asthmatic immune responses in the airway mucosa. In this narrative review, we highlight the role of sex in the continuity of the asthmatic immune response from sensing allergens to Th2 cell activation based on our own data. In addition, we elucidate the interactive role of sex with genetic or environmental factors in asthma exacerbation in women.

Keywords: airway epithelial cells; bronchial asthma; cluster of differentiation 8+ T cells; dendritic cells; eosinophils; estradiol; psychological stress; respiratory tract infection; sex; single nucleotide polymorphism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma* / drug therapy
  • Female
  • Gonadal Steroid Hormones
  • Humans
  • Male
  • Prevalence
  • Puberty
  • Risk Factors

Substances

  • Gonadal Steroid Hormones

Grants and funding

This work was supported in part by a Grant-in-Aid for Research Activity Start-up (No. 25893222), a Grant-in-Aid for Young Scientists (B) (No. 16K19608), for Young Scientists (No. 19K17913), and for Scientific Research (C) (No. 22K08548) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The funders played no role in the study design, collection, analysis, and interpretation of data, or preparation of the manuscript.