Age-Related Clinical Characteristics, Inflammatory Features, Phenotypes, and Treatment Response in Asthma

Wang, Ji; Zhang, Xin; Zhang, Li; Liu, Ying; Zhang, Hong Ping; Wang, Lei; Kang, De Ying; Oliver, Brian G.; Wan, Hua Jing; McDonald, Vanessa M.; Hsu, Alan; Liú, Dan; Li, Wei Min; Birring, Surinder S.; Wang, Gang

doi:10.1016/j.jaip.2022.09.029

Cited by 20 publications

(28 citation statements)

References 55 publications

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“…57 However, our results confirmed earlier studies that aging was associated with FAO and lower FeNO concentrations as demonstrated by the evidence that asthmatics with FAO were significantly older and tended to have lower FeNO levels, albeit statistically insignificant, than asthmatics with nFAO. 58 Previous studies reported that non atopy, asthma duration, and BMI before antiasthma treatment are important factors related to airway remodeling in patients with asthma, 59 which was consistent with the present data showing that there was no significant difference in atopic status and serum total IgE levels between groups and FAO individuals had significantly longer disease duration than nFAO counterpart despite no BMI association. Our study also confirmed prior studies that there was no association between asthmatics with concurrent allergic rhinitis and FAO.…”

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confidence: 92%

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Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Maneechotesuwan¹,

Wongsurakiat²,

Assawabhumi³

et al. 2023

JAA

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Transforming growth factor-β-associated kinase 1 (TAK1) mediates non-canonical TGF-β signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-β 1 . However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. Patients and Methods: A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-β 1 concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Results: Asthmatic patients with FAO had much greater sputum TGF-β 1 concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-β 1 levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre-and postbronchodilator FEV 1 /FVC ratio. Conclusion: TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact.

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supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Maneechotesuwan¹,

Wongsurakiat²,

Assawabhumi³

et al. 2023

JAA

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“…Elderly people with asthma also exhibit greater sputum cytokines levels, including IL-6 and IL-1β, which were both associated with increased likelihood of hospitalization due to asthma [ 37 ]. In a similar study, sputum neutrophils were greater than eosinophils in total cell number and percentage in elderly asthmatics [ 9 ]. This elderly asthma cohort also had increased IFNγ and IL-17 levels in sputum, while levels of type 2 markers, IgE and FeNO, were lower than those in younger asthma patients.…”

Section: Asthma In the Elderly Pathogenesismentioning

confidence: 95%

“…As a leading risk factor for COPD, cigarette smoke induces oxidative stress and lung inflammation that includes Th17 inflammation and senescence [ 96 , 97 ]. Smoking history is common in elderly individuals with asthma, making it an important influencing factor in asthma pathogenesis [ 9 ]. Asthma–COPD overlap (ACO), a syndrome with persistent airflow obstruction and distinct clinical presentation, is an additional consideration that may be important to understanding asthma in aging populations [ 98 , 99 ].…”

Section: Factors and Comorbidities That May Influence Asthma In The E...mentioning

confidence: 99%

“…Asthma endotypes with increased type 1 or 17 inflammation have increased neutrophil infiltration and are mediated by effector cytokines, namely IFNγ and IL-17A, respectively. Recent studies show the presence of type 1 and 17 inflammation, characterized by increased neutrophils and IL-17A and IFNγ levels, are more common in older individuals with asthma [ 9 ]. These inflammatory endotypes in asthma are associated with corticosteroid insensitivity, poor symptom control, and greater asthma severity [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma

Ford

Ruwanpathirana

Lewis

et al. 2023

IJMS

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Asthma in elderly populations is an increasing health problem that is accompanied by diminished lung function and frequent exacerbations. As potent anti-inflammatory drugs, corticosteroids are commonly used to reduce lung inflammation, improve lung function, and manage disease symptoms in asthma. Although effective for most individuals, older patients are more insensitive to corticosteroids, making it difficult to manage asthma in this population. With the number of individuals older than 65 continuing to increase, it is important to understand the distinct mechanisms that promote corticosteroid insensitivity in the aging lung. In this review, we discuss corticosteroid insensitivity in asthma with an emphasis on mechanisms that contribute to persistent inflammation and diminished lung function in older individuals.

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Cellular senescence in asthma: from pathogenesis to therapeutic challenges

Wan,

Srikaram,

Guntupalli

et al. 2023

eBioMedicine

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Age-Related Clinical Characteristics, Inflammatory Features, Phenotypes, and Treatment Response in Asthma

Cited by 20 publications

References 55 publications

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma

Cellular senescence in asthma: from pathogenesis to therapeutic challenges

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