Asthma Phenotypes in Japanese Adults - Their Associations with the CCL5 ADRB2 Genotypes

Kaneko, Yoshiko; Masuko, Hironori; Sakamoto, Tohru; Iijima, Hiroaki; Naito, Takashi; Yatagai, Yohei; Yamada, Hideyasu; Konno, Satoshi; Nishimura, Masaharu; Noguchi, Emiko; Hizawa, Nobuyuki

doi:10.2332/allergolint.12-oa-0467

Cited by 43 publications

(44 citation statements)

References 25 publications

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“…Frequent exacerbators are also a well-defined phenotype because of its major source of disease. Such clusters have been replicated in adult and paediatric cohorts in the Western world [24][25][26][27] as well as in Korean and Japanese cohorts 28,29 , with greater concordance in clusters related to severe asthma. Patients on high-dose inhaled corticosteroid therapy made up of clusters 4 and 5 of the adult SARP cohort, often taken together with oral corticosteroid treatment, are usually associated with severe airflow obstruction (Fig.…”

Section: Phenotyping Based On Clustering Of Clinical-physiological Datamentioning

confidence: 76%

Phenotyping Asthma: Linking Clinical Features to Biomolecular Pathways

Chung¹

2016

BRN

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Asthma presents in various clinical forms and levels of severity and has a complex pathophysiology. Unbiased clustering was initially performed on clinical features, but the addition of biomarkers such as sputum and blood cellular profiles has led to the description of several phenotypes and enabled the prediction of responses to targeted therapies. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, associated with severe airflow obstruction. Concordance between symptoms and sputum eosinophilia is observed in an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum or blood eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper-2 cytokine, interleukin-5. Low T-helper-2 expression predicts poor therapeutic response to inhaled corticosteroid therapy. Much less is known about 'non-eosinophilic' or non-T-helper-2 asthma. Clustering on transcriptomic and/or proteomic data is leading to definition of molecular phenotypes and potential mechanisms. The definition of endotypes and biomarkers of disease and therapeutic responses will pave the way towards personalized medicine and healthcare for asthma. For the clinician, these will translate into useful tools and means for managing patients with asthma, particularly severe asthma. Corresponding author : Kian Fan Chung, f.chung@imperial.ac.uk

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Section: Phenotyping Based On Clustering Of Clinical-physiological Datamentioning

confidence: 76%

Phenotyping Asthma: Linking Clinical Features to Biomolecular Pathways

Chung¹

2016

BRN

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“…IL-4 is particularly important for the development and perpetuation of allergic asthma which is characterized by increased IgE levels (Kaneko et al, 2013). OVAinduced mouse asthma model was generated as previously described .…”

Section: Acetylation Of H3k9 Associated With Asthma In Il-4/stat6 Patmentioning

confidence: 99%

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Wang

Duan

et al. 2015

The Anatomical Record

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IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Ige via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Ige promoter regions. Our results revealed that the Ige gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.

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“…Indeed, Kaneko et al 7 examined phenotypes in Japanese patients with adult asthma. They also used cluster analysis and identified six phenotypes (A: older age at onset, no airflow obstruction; B: childhood onset, normal-to-mild airflow obstruction; C: childhood onset, the longest disease duration, and moderate-to-severe airflow obstruction; D: older age at onset, severe airflow obstruction; E: middle-age at onset, no airflow obstruction; F: older age at onset, mild-to-moderate airflow obstruction).…”

mentioning

confidence: 99%

“…He described the usefulness of identifying phenotypes, which enable physicians to treat the patients appropriately. 8 To date, six articles have been published, [3][4][5][6][7][8] …”

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confidence: 99%

Asthma phenotypes: An important step for tailor‐made therapy

Nakamoto

Saraya

Takizawa

2017

J of Gen and Family Med

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Recently, many bronchial asthma patients have achieved good control with inhaled corticosteroid and long-acting beta2-agonists. However, some patients suffer from persistent asthmatic symptoms and have asthma attacks despite treatment with high doses of inhaled corticosteroid. This condition is called severe asthma, refractory asthma, or difficult-to-treat asthma. Severe asthma is a serious socio-medical problem that affects 5%-10% of patients, and the associated medical costs are high. 1

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Asthma Phenotypes in Japanese Adults - Their Associations with the CCL5 ADRB2 Genotypes

Abstract: The current cluster analysis identified meaningful adult asthma phenotypes linked to the functional CCL5 and ADRB2 genotypes. Genetic and phenotypic data have the potential to elucidate the phenotypic heterogeneity and pathophysiology of asthma.

Cited by 43 publications

References 25 publications

Phenotyping Asthma: Linking Clinical Features to Biomolecular Pathways

Phenotyping Asthma: Linking Clinical Features to Biomolecular Pathways

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Asthma phenotypes: An important step for tailor‐made therapy

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