Systemic inflammatory profile and response to anti-tumor necrosis factor therapy
in chronic obstructive pulmonary disease.
Author(s): Loza MJ, Watt R, Baribaud F, Barnathan ES, Rennard SI.
Affiliation(s): Immunology Biomarkers, Janssen Research & Development, LLC, Malvern, PA, USA.
Mloza@its.jnj.com
Publication date & source: 2012, Respir Res. , 13:12
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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