Lung function changes over 8 years and testosterone markers in both sexes: UK Biobank

Lenoir, Alexandra; Fuertes, Elaine; Gómez-Real, Francisco; Leynaert, Bénédicte; Plaat, Diana A van der; Jarvis, Déborah

doi:10.1183/23120541.00070-2020

Cited by 15 publications

(11 citation statements)

References 44 publications

(52 reference statements)

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“…26 In addition, a recent large study using UK biobank data showed that the effects of testosterone markers on FEV1 decline over the 8 year follow-up were small in both women (mean age; 53.5) and men (mean age; 55.3). 27 The differential effects of sex hormone on lung function decline need to be further evaluated. Taken together, these findings and our observations suggest that the associations between body composition changes and FEV1 decline are more prominent in men than in women, particularly in middle-aged healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals

Park

Lee

et al. 2021

J cachexia sarcopenia muscle

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BackgroundThe associations between long-term changes in body mass composition and decline in lung function in healthy adults are unknown. Methods Using a well-defined health check-up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m) 2 ] or FM index (FMI) [FM (kg)/height (m) 2 ] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups. Results A total of 15 476 middle-aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5-9) over an average follow-up period of 8.95 years (IQR: 6.73-11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10 À9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10 À10 and P < 2.0 × 10 À16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m 2 in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m 2 in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10 À9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10 À10 and P < 2.0 × 10 À16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss). Conclusions Change in body composition over time can be used to identify healthy middle-aged individuals at high risk for rapid FEV1 decline.

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Section: Discussionmentioning

confidence: 99%

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals

Park

Lee

et al. 2021

J cachexia sarcopenia muscle

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“…[53] found that early menopause was associated with a significantly lower risk of airflow obstruction. Meanwhile, an analysis of the role of testosterone levels and lung function also utilising UK biobank found higher FEV 1 levels among individuals with higher testosterone after adjustment for multiple confounders including age, height, body mass index (BMI), smoking and multiple lifestyle factors [54]. A contribution of the X chromosome to COPD susceptibility is suggested by an increased risk of early onset COPD in females who smoke and also have a mother with COPD.…”

Section: Copdmentioning

confidence: 99%

Just breathe: a review of sex and gender in chronic lung disease

Somayaji

Chalmers

2022

Eur Respir Rev

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Chronic lung diseases are the third leading cause of death worldwide and are increasing in prevalence over time. Although much of our traditional understanding of health and disease is derived from study of the male of the species – be it animal or human – there is increasing evidence that sex and gender contribute to differences in disease risk, prevalence, presentation, severity, treatment approach, response and outcomes. Chronic obstructive pulmonary disease, asthma and bronchiectasis represent the most prevalent and studied chronic lung diseases and have key sex- and gender-based differences which are critical to consider and incorporate into clinical and research approaches. Mechanistic differences present opportunities for therapeutic development whereas behavioural and clinical differences on the part of patients and providers present opportunities for greater education and understanding at multiple levels. In this review, we seek to summarise the sex- and gender-based differences in key chronic lung diseases and outline the clinical and research implications for stakeholders.

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“…In mice, testosterone treatment restored asthmatic lung exacerbation by attenuating airway inflammation 45 . Population-based studies further supported this concept by showing strong associations between testosterone levels and lung function in men 46 . Although future studies are required to understand these androgen and/or estrogen controlled transcription pathways in improved long-term lung health, these data further support the concept that balanced sex hormone levels are critical for lung health.…”

Section: Discussionmentioning

confidence: 77%

“…Testosterone is produced in the gonads of boys at the age of 10-12 years, peaking in adulthood and declining slowly with increasing age. Agedependent testosterone deficiency may pose another risk factor for reduced lung health 46 .…”

Section: Discussionmentioning

confidence: 99%

CYP19A1 mediated sex hormone metabolism promotes severe SARS-CoV-2 disease outcome in males.

Stanelle-Bertram

Beck

Kouassi

et al. 2021

Preprint

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Male sex belongs to one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a male abundant host factor that contributes to worsened disease outcome in SARS-CoV-2 infected male hamsters. Pulmonary CYP19A1 transcription is further elevated upon viral infection in males correlating with reduced testosterone and increased estradiol levels. Dysregulated circulating sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated plasma sex hormone levels and was associated with improved lung function and health in male but not female animals compared to placebo controls. Whole human exome sequencing data analysis using a Machine Learning approach revealed a CYP19A1 activity increasing mutation being associated with the development of severe COVID-19 for men. In human autopsy-derived lungs CYP19A1 was expressed to higher levels in men who died of COVID-19, at a time point when most viral RNA was cleared. Our findings highlight the role of the lung as a yet unrecognized but critical organ regulating metabolic responses upon respiratory virus infection. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.

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Lung function changes over 8 years and testosterone markers in both sexes: UK Biobank

Cited by 15 publications

References 44 publications

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals

Just breathe: a review of sex and gender in chronic lung disease

CYP19A1 mediated sex hormone metabolism promotes severe SARS-CoV-2 disease outcome in males.

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