Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease
<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis fac...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-02-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://respiratory-research.com/content/13/1/12 |
| _version_ | 1818528858257752064 |
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| author | Loza Matthew J Watt Rosemary Baribaud Frédéric Barnathan Elliot S Rennard Stephen I |
| author_facet | Loza Matthew J Watt Rosemary Baribaud Frédéric Barnathan Elliot S Rennard Stephen I |
| author_sort | Loza Matthew J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.</p> <p>Methods</p> <p>Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab. Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109). Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.</p> <p>Results</p> <p>Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins. This profile was largely independent of smoking status, age, and clinical phenotype. The majority of these associations of serum analytes with COPD are novel findings. Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement. Infliximab did not affect this systemic inflammatory profile.</p> <p>Conclusions</p> <p>A robust systemic inflammatory profile was associated with COPD. This profile was generally independent of disease severity. Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov, <it>No</it>.: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00056264">NCT00056264</a>.</p> |
| first_indexed | 2024-12-11T06:55:29Z |
| format | Article |
| id | doaj.art-bacbb4086453463f872b195550ec08c3 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-11T06:55:29Z |
| publishDate | 2012-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-bacbb4086453463f872b195550ec08c32022-12-22T01:16:46ZengBMCRespiratory Research1465-99212012-02-011311210.1186/1465-9921-13-12Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary diseaseLoza Matthew JWatt RosemaryBaribaud FrédéricBarnathan Elliot SRennard Stephen I<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.</p> <p>Methods</p> <p>Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab. Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109). Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.</p> <p>Results</p> <p>Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins. This profile was largely independent of smoking status, age, and clinical phenotype. The majority of these associations of serum analytes with COPD are novel findings. Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement. Infliximab did not affect this systemic inflammatory profile.</p> <p>Conclusions</p> <p>A robust systemic inflammatory profile was associated with COPD. This profile was generally independent of disease severity. Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov, <it>No</it>.: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00056264">NCT00056264</a>.</p>http://respiratory-research.com/content/13/1/12chronic obstructive pulmonary diseaseinflammationbiological biomarkerstumor necrosis factor-alphainfliximab |
| spellingShingle | Loza Matthew J Watt Rosemary Baribaud Frédéric Barnathan Elliot S Rennard Stephen I Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease Respiratory Research chronic obstructive pulmonary disease inflammation biological biomarkers tumor necrosis factor-alpha infliximab |
| title | Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| title_full | Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| title_fullStr | Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| title_full_unstemmed | Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| title_short | Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| title_sort | systemic inflammatory profile and response to anti tumor necrosis factor therapy in chronic obstructive pulmonary disease |
| topic | chronic obstructive pulmonary disease inflammation biological biomarkers tumor necrosis factor-alpha infliximab |
| url | http://respiratory-research.com/content/13/1/12 |
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