Autor: Sandstrom, Thomas - Prolib Integro

Skocz do pozycji: 1.

Tytuł:: The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts
Autorzy:: Fan Chung, Kian
Sanak, Marek
Caruso, Massimo
Cheng, Xiaojing
Dahlen, Sven-Erik
Adcock, Ian M.
Sterk, Peter J.
Sousa, Ana R.
De Meulder, Bertrand
Krug, Norbert
Montuschi, Paolo
Dahlen, Barbro
Hou, Ruihua
Fowler, Stephen J.
Skipp, Paul J.
Bakke, Per S.
Sandström, Thomas
Horváth, Ildikó
Djukanovic, Ratko
Ye, Gang
Howarth, Peter H.
Schofield, James P.R.
Auffray, Charles
Shaw, Dominic E.
Opis:: Background: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. Methods: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. Results: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). Conclusions: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Tytuł:: U-BIOPRED clinical adult asthma clusters linked to a subset of sputum -omics
Autorzy:: Shaw, Dominic E.
Fleming, Louise J.
Lefaudeux, Diane
Horvath, Ildiko
Chung, Kian. F.
Dahlen, Sven-Erik
Sandstrom, Thomas
Bakke, Per S.
Bansal, Aruna T.
Djukanovic, Ratko
Sousa, Ana R.
Montuschi, Paolo
Loza, Matthew J.
Chanez, Pascal
Sanak, Marek
Baribaud, Frédéric
Lutter, Rene
Krug, Norbert
Auffray, Charles
Caruso, Massimo
Pandis, Ioannis
De Meulder, Bertrand
Corfield, Julie
Adcock, Ian M.
Rowe, Anthony
Sterk, Peter J.
Roberts, Graham
Peffer, Nancy
Singer, Florian
Fowler, Stephen J.
Opis:: Background: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided. Objectives: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Methods: Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinicphysiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Results: Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Conclusion: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Tytuł:: IL-17high asthma with features of a psoriasis immunophenotype
Autorzy:: Pandis, Ioannis
Sousa, Ana R.
Sanak, Marek
Howarth, Peter
Horvath, Ildiko
Krug, Norbert
Montuschi, Paolo
Sandstrom, Thomas
Bakke, Per S.
Djukanovic, Ratko
Bigler, Jeanette
Auffray, Charles
Östling, Jörgen
Sterk, Peter J.
Guo, Yike
Schofield, James P. R.
Fowler, Stephen J.
Shaw, Dominick E.
Jevnikar, Zala
Sun, Kai
Dahlen, Sven-Erik
Caruso, Massimo
Vaarala, Outi
Lutter, Rene
Ward, Jonathan
van Geest, Marleen
Wilson, Susan
Skipp, Paul J.
Chung, Kian Fan
Adcock, Ian M.
Opis:: Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n 5 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and b-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Tytuł:: Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort
Autorzy:: Shaw, Dominic E.
Rossios, Christos
Fleming, Louise J.
Loza, Matthew
Lefaudeux, Diane
Horvath, Ildiko
Dahlen, Sven-Erik
Sun, Kai
Musiał, Jacek
Pavlidis, Stelios
Sandstrom, Thomas
Bansal, Aruna T.
Djukanovic, Ratko
Dahlen, Barbro
Sousa, Ana R.
Montuschi, Paolo
Chanez, Pascal
Chung, Kian Fan
Lutter, Rene
Krug, Norbert
Hoda, Uruj
Caruso, Massimo
Auffray, Charles
Hu, Sile
Corfield, Julie
de Meulder, Bertrand
Baribaud, Frederic
Bhavsar, Pankaj
Adcock, Ian M.
Takahashi, Kentaro
Sterk, Peter J.
Guo, Yike
Singer, Florian
Ng Kee Kwong, Francois
Howarth, Peter H.
Fowler, Stephen J.
Opis:: Background: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short-acting beta-agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T-helper type-17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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