Abstract:
BACKGROUND:Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. METHODS:We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants. RESULTS:Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased. CONCLUSIONS:The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute. TRIAL REGISTRATION:NCT00281216 , ClinicalTrials.gov.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Freeman CM,Martinez CH,Todt JC,Martinez FJ,Han MK,Thompson DL,McCloskey L,Curtis JLdoi
10.1186/s12931-015-0251-1subject
Has Abstractpub_date
2015-08-05 00:00:00pages
94eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-015-0251-1journal_volume
16pub_type
临床试验,杂志文章abstract:BACKGROUND:It has been confirmed that NF-κB p65 signaling pathway is involved in the regulation of alveolar hypercoagulation and fibrinolysis inhibition in acute respiratory distress syndrome (ARDS). Whether SN50, a NF-κB cell permeable inhibitor, could attenuate alveolar hypercoagulation and fibrinolysis inhibition in...
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pub_type: 杂志文章
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journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/1465-9921-6-81
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章,随机对照试验
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doi:10.1186/1465-9921-12-100
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2013-12-21 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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