Natural Progression of Childhood Asthma Symptoms and Strong Influence of Sex and Puberty

Fu, Liang; Freishtat, Robert J.; Gordish‐Dressman, Heather; Teach, Stephen J.; Resca, Lorenzo; Hoffman, Eric P.; Wang, Zuyi

doi:10.1513/annalsats.201402-084oc

Cited by 81 publications

(69 citation statements)

References 47 publications

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“…Asthma prevalence increases in females at the time of puberty, and epidemiological studies have associated puberty, measured by increasing Tanner stages, with decreased asthma symptoms in boys and increased asthma symptoms in girls (Fu et al, 2014). Several studies in women showed changes in hormone levels, either during the menstrual cycle or in taking oral contraceptives, modulated asthma symptoms (Fuseini and Newcomb, 2017).…”

Section: Discussionmentioning

confidence: 99%

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

et al. 2017

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Summary Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. Group 2 innate lymphoid cells (ILC2) are increased in asthma, and we investigated how testosterone attenuated ILC2 function. In patients with moderate to severe asthma, we determined that women had increased circulating ILC2 numbers compared to men. In mice, ILC2 from adult females had increased IL-2-mediated ILC2 proliferation versus ILC2 from adult males and pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreased lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers and cytokine expression as well as decreasing expression of IL-33 and TSLP, ILC2 stimulating cytokines. Collectively, these findings provide a foundational understanding in the sexual dimorphism in ILC2 function.

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Section: Discussionmentioning

confidence: 99%

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

et al. 2017

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“…As children age, the switch in asthma prevalence from highest in males to highest in females coincided with the age of puberty onset (5, 14). The Childhood Asthma Management Program (CAMP) study longitudinally tracked the average asthma symptom score as well as progression through puberty, using the Tanner stage metric, in boys and girls ages 4–17 (15•). At approximately age 10, when the Tanner scores start increasing in girls, the average asthma symptom score also increased in girls and declined in boys (15•).…”

Section: Asthma Prevalence Changes During Pubertymentioning

confidence: 99%

“…The Childhood Asthma Management Program (CAMP) study longitudinally tracked the average asthma symptom score as well as progression through puberty, using the Tanner stage metric, in boys and girls ages 4–17 (15•). At approximately age 10, when the Tanner scores start increasing in girls, the average asthma symptom score also increased in girls and declined in boys (15•). Further, asthma symptoms continued to increase in girls as Tanner stages increased (15•).…”

Section: Asthma Prevalence Changes During Pubertymentioning

confidence: 99%

Mechanisms Driving Gender Differences in Asthma

Fuseini

Newcomb

2017

Curr Allergy Asthma Rep

349

226

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Purpose of Review Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis. Recent Findings Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mφ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated. Summary Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.

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“…The age of this gender switch has not been precisely determined, with conflicting research on whether pubertal stages or puberty are associated with the switch in prevalence [1, 4, 5]. These differences appear to stem from biological differences between sexes as well as sociocultural and environmental differences.…”

Section: Introductionmentioning

confidence: 99%

Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts

et al. 2017

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Sex discordance in asthma prevalence has been previously reported, with higher prevalence in males before puberty, and in females after puberty; the adolescent “switch”. However, cross-sectional studies have suggested a narrowing of this discordance in recent decades. We used a combination of cross-sectional and longitudinal modelling to examine sex differences in asthma, wheeze and longitudinal wheezing phenotypes in two UK birth cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC; born 1991–92 with data from age 0–18 years) and the Millennium Cohort Study (MCS; born 2000–02 with data from age 3–10 years). We derived measures of asthma and wheeze from questionnaires completed by mothers and cohort children. Previously-derived ALSPAC wheezing phenotype models were applied to MCS. Males had a higher prevalence of asthma at 10.7 years in ALSPAC (OR 1.45 95%CI: 1.26, 1.66 n = 7778 for current asthma) and MCS (OR 1.42 95%CI: 1.29, 1.56 n = 6726 for asthma ever) compared to females, decreasing in ALSPAC after puberty (OR 0.94 95%CI: 0.79, 1.11 n = 5023 for current asthma at 16.5 years). In longitudinal models using restricted cubic splines, males had a clear excess for asthma in the last 12 months and wheeze in the last 12 months up until 16.5 years of age in ALSPAC. Males had an increased risk of all derived longitudinal wheezing phenotypes in MCS when compared to never wheeze and no evidence of being at lower risk of late wheeze when compared to early wheeze. By comparing data in two large, contemporary cohorts we have shown the persistence of sex discordance in childhood asthma, with no evidence that the sex discordance is narrowing in recent cohorts.

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Natural Progression of Childhood Asthma Symptoms and Strong Influence of Sex and Puberty

Cited by 81 publications

References 47 publications

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Mechanisms Driving Gender Differences in Asthma

Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts

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