Cluster analysis of obesity and asthma phenotypes.
Cluster analysis of obesity and asthma phenotypes.
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DOI：
10.1371/journal.pone.0036631
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Asthma Clinical Research Network
中科院分区：
文献类型：
--
作者：
Sutherland ER;Goleva E;King TS;Lehman E;Stevens AD;Jackson LP;Stream AR;Fahy JV;Leung DY;Asthma Clinical Research Network
Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC). Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype. In a cohort of clinical trial participants (n = 250), minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα) and induction of MAP kinase phosphatase-1 (MKP-1) expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m2) and severity of asthma symptoms (AEQ score) the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively). Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ) and control (ACQ), exhaled nitric oxide concentration (FENO) and airway hyperresponsiveness (methacholine PC20) but were similar with regard to measures of lung function (FEV1 (%) and FEV1/FVC), airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP). Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasone Obesity is an important determinant of asthma phenotype in adults. There is heterogeneity in expression of clinical and inflammatory biomarkers of asthma across obese individuals. Reduced expression of the dominant functional isoform of the GCR may mediate GC insensitivity in obese asthmatics.
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DOI：
10.1016/j.jaci.2008.07.007
发表时间：
2008-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Goleva E;Hauk PJ;Hall CF;Liu AH;Riches DW;Martin RJ;Leung DY
通讯作者：
Leung DY
DOI：
10.1164/rccm.200507-1046oc
发表时间：
2006-03-15
影响因子：
24.7
作者：
Goleva, E;Li, LB;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
5.8
作者：
Dahlman, I;Kaaman, M;Arner, P
通讯作者：
Arner, P
影响因子：
9.6
作者：
Farah, Claude S.;Kermode, Jessica A.;Salome, Cheryl M.
通讯作者：
Salome, Cheryl M.
影响因子：
1.9
作者：
Dixon, Anne E.;Shade, David M.;Wise, Robert A.
通讯作者：
Wise, Robert A.