From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma‐Obesity

Wang, Carolyn J.; Noble, Peter B.; Elliot, John; Wang, Kimberley C. W.

doi:10.1002/cphy.c220011

Cited by 4 publications

(1 citation statement)

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“…To conclude, we have demonstrated that airway-associated adipose tissue can accumulate in the absence of body adiposity and identified Kiss1 / Kiss1r signalling as a genetic origin. We previously hypothesized that airway-associated adipose tissue may impact airway structure–function in comorbid asthma-obesity [ 37 ]; the present study re-emphasizes airway-associated adipose tissue as another feature of airway remodelling that may become important in later life with inevitable exposure to environmental triggers. The full life impact of airway-associated adipose tissue should continue to be examined as well as potential therapies beyond weight loss that may optimize respiratory health.…”

Section: Discussionmentioning

confidence: 53%

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model

Wang,

Smith,

et al. 2023

Clinical Science

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Airway-associated adipose tissue increases with body mass index and is a local source of pro-inflammatory adipokines that may contribute to airway pathology in asthma co-existing with obesity. Genetic susceptibility to airway adiposity was considered in the present study through kisspeptin/kisspeptin receptor signalling, known to modulate systemic adiposity and potentially drive airway remodelling. Therefore, the aim of the study was to determine the effects of kisspeptin/kisspeptin receptor signalling in the lung, focusing on airway-associated adipose tissue deposition and impact on airway structure-function. Wildtype, heterozygous and kisspeptin receptor knockout mice were studied at 6- or 8-weeks of age. Lung mechanics were assessed before and after methacholine challenge and were subsequently fixed for airway morphometry. A separate group of mice underwent glucose tolerance testing and bronchoalveolar lavage. At 6-weeks of age, kisspeptin/kisspeptin receptor signalling did not affect body adiposity, airway inflammation, wall structure or function. Despite no differences in body adiposity, there was a greater accumulation of airway-associated adipose tissue in knockout mice. By 8-weeks of age, female knockout mice displayed a non-diabetic phenotype with increased body adiposity, but not males. Airway-associated adipose tissue area was also increased in both knockout females and males at 8-weeks of age, but again no other respiratory abnormality was apparent. In summary, airway-associated adipose tissue is decoupled from body adiposity in prepubescent mice which supports a genetic susceptibility to fatty deposits localised to the airway wall. There was no evidence that airway-associated adipose tissue drives pathology or respiratory impairment in the absence of other environmental exposures.

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Section: Discussionmentioning

confidence: 53%

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model

Wang,

Smith,

et al. 2023

Clinical Science

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Association between asthma and visceral adipose tissue in adults, a cross-sectional study from NHANES 2011–2018

Lin,

Mao,

Huang

et al. 2024

Sci Rep

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Asthma is a chronic inflammatory disease that affects millions of people worldwide. Obesity, particularly visceral adipose tissue (VAT), is known to secrete adipokines and pro-inflammatory factors, which are closely associated with various metabolic and cardiovascular diseases. Research indicates that these metabolic disturbances can exacerbate inflammatory conditions, contributing to both cardiovascular and respiratory diseases, including asthma. Despite these associations, studies on the specific relationship between VAT and asthma remain limited and warrant further investigation. Utilizing the NHANES database from 2011 to 2018, we included a total of 11,137 participants. Multivariable regression analysis was performed, stratifying subjects based on VAT levels and adjusting for various confounders. Subgroup interaction analysis and nonlinear analysis were conducted to explore potential effect modifiers and nonlinear associations. In this study, 11,137 participants were included, with 49.74% being female. Among the 509 asthma patients, 69.35% were female. The number of asthma patients among Non-Hispanic Whites was 212, representing 41.65% of the total, the highest proportion among the studied groups. The VAT for asthma patients was 529 g, significantly higher than the 455 g in the non-asthma group ( P < 0.001). Multivariable regression analysis showed that for every 200 g increase in VAT, the risk of asthma increased by 10.4% ( P = 0.032), 20.8% ( P < 0.001), and 20.3% ( P = 0.004) across three models (unadjusted, adjusted for demographic factors, and fully adjusted). Subgroup analysis indicated a stronger association between VAT and asthma risk in females and individuals over 40 years old. Nonlinear analysis uncovers a J-shaped relationship between VAT and asthma, with the lowest risk observed at 464.57 g ( P < 0.001). The study findings suggest that increased VAT is associated with elevated asthma risk, particularly among females and older individuals. These results underscore the importance of considering VAT in asthma risk assessment and highlight potential targeted interventions to reduce asthma risk associated with excess visceral adiposity. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-74297-5.

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Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care

Loewenthal,

Busby,

McDowell

et al. 2023

Thorax

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IntroductionAfter puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors.AimTo evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting.MethodsDemographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice.Results3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58).ConclusionsFemales had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.

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From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma‐Obesity

Cited by 4 publications

References 355 publications

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model

Association between asthma and visceral adipose tissue in adults, a cross-sectional study from NHANES 2011–2018

Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care

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