Differences in airway remodeling and airway inflammation among moderate-severe asthma clinical phenotypes

Ye, Wenjing; Xu, Weiguo; Guo, Xuejun; Han, Fengfeng; Peng, Juan; Li, Xiaoming; Guan, Wei; Yu, Liwei; Sun, Jinyuan; Cui, Zhi; Lin, Shiu‐Ru; Zhang, Yue; Wang, Yanmin; Yang, Tianyun; Ge, Xiahui; Di, Yao; Liu, Song

doi:10.21037/jtd.2017.08.01

Cited by 16 publications

(16 citation statements)

References 29 publications

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“…The imbalance of Th17 and Treg is implicated in many allergic diseases in respiratory system [52,53]. Especially, Th17 mediated inflammatory responses are crucial for the onset, exacerbation and control of Asthma and Chronic Obstructive Pulmonary Disease [54][55][56][57][58][59]. The role of STAT3 in Treg/Th17 imbalance in widely reported for allergic diseases.…”

Section: Discussionmentioning

confidence: 99%

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters

Zhong

et al. 2020

Respir Res

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Background: Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. Methods: To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to Tcell differentiation in both primary T-cells and mice treated with PM. Results: We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. Conclusions: Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

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Section: Discussionmentioning

confidence: 99%

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters

Zhong

et al. 2020

Respir Res

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“…Several features of the existing studies on asthma phenotypes are notable. First, and most importantly, nearly all of these studies have been conducted in HICs, with the exception of a small study in Brazil [ 22 ] which did not directly address the issue of phenotypes and a recent study from China [ 23 ]. The key strength of the study protocol presented here is that it is the first to undertake complex phenotype analyses in LMICs and to compare the results with those in HICs using the same methodology.…”

Section: Introductionmentioning

confidence: 99%

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration

et al. 2018

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The World Asthma Phenotypes (WASP) study started in 2016 and has been conducted in five centres, in the UK, New Zealand, Brazil, Ecuador and Uganda.The objectives of this study are to combine detailed biomarker and clinical information in order to 1) better understand and characterise asthma phenotypes in high-income countries (HICs) and low and middle-income countries (LMICs), and in high and low prevalence centres; 2) compare phenotype characteristics, including clinical severity; 3) assess the risk factors for each phenotype; and 4) assess how the distribution of phenotypes differs between high prevalence and low prevalence centres.Here we present the rationale and protocol for the WASP study to enable other centres around the world to carry out similar analyses using a standardised protocol. Large collaborative and integrative studies like this are essential to further our understanding of asthma phenotypes. The findings of this study will help elucidate the aetiological mechanisms of asthma and might potentially identify new causes and guide the development of new treatments, thereby enabling better management and prevention of asthma in both HICs and LMICs.

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“…Asthma is one of the most common chronic respiratory diseases affecting 1%–18% of the population in different countries, which is characterized by chronic airway inflammation with underlying heterogeneous inflammatory mechanisms that result in multiple clinical phenotype. 1 2 3 4 Although there is a positive declining trend for asthma mortality, 5 asthma plus allergic rhinitis is the most frequently diagnosed multiple respiratory disorders, which has a significant impact on disease burden across the Asia-Pacific region. 6 Obesity is also a major public health concern, whose prevalence has dramatically and concurrently increased with asthma over the last decades.…”

Section: Introductionmentioning

confidence: 99%

Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study

Liu

Zheng

Zhang

et al. 2018

Allergy Asthma Immunol Res

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PurposeObesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma.MethodsEligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles.ResultsBody composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma.ConclusionsGC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

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Differences in airway remodeling and airway inflammation among moderate-severe asthma clinical phenotypes

Abstract: Four distinct clinical phenotypes of asthma were identified by cluster analysis. The results of the MSCT and pathological examinations may suggest specific pathogeneses among the phenotypes.

Cited by 16 publications

References 29 publications

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration

Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study

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