Innate Immune Response in COPD

VA Puget Sound Health Care System30 enrolled

Overview

The purpose of this study is to determine whether the response of the immune system to bacterial components differs between patients with severe COPD compared to those with less severe COPD.

The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by TLR 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Pulmonary Disease, Chronic Obstructive Immunity, Innate Inflammation Bronchitis, Chronic Toll-Like Receptors

Eligibility

Sex: MALEMin age: 50 YearsMax age: 89 Years

Medical Language ↔ Plain English

Inclusion Criteria: * post-bronchodilator FEV1/FVC \<0.7 * FEV1 \< 80% * \> 10 pack-years tobacco smoking * no respiratory illnesses or prednisone or antibiotics in the last 4 weeks Exclusion Criteria: * Primary diagnosis of asthma * \> 15% change in FEV1 * Chronic inflammatory or infectious disease * Cancer * Autoimmune disease * Chronic renal failure with a creatinine \> 1.5 * Chronic liver disease * Chronic antibiotic use Note: Due to difficulty recruiting patients after 6 participants were enrolled, the exclusion criteria were modified to allow patients with \> 15% change in FEV1. The exclusion criteria were also changed to allow chronic renal failure not requiring dialysis, and non-metastatic cancer provided there was no diagnosis of lung cancer.

Locations (1)

VA Puget Sound Health Care System

Seattle, Washington, United States

Outcomes

Primary Outcomes

Cytokine production (TNF-alpha, IL-6, IL-8, IL-10, IL-1RA, G-CSF, IL-1B, MCP-1).

A whole blood stimulation assay was performed on blood samples from study participants. The whole blood was stimulated using several pathogen-associated molecular patterns that were agonists to seven different TLR receptors: 1) Pam3SCK4, 2) Zymosan, 3) FSL-1, 4) LPS, 5) flagellin, 6) R848. After stimulation with the PAMP, the cytokine levels (TNF-alpha, IL-6, IL-8, IL-10, IL-1RA, G-CSF, IL-1B, and MCP-1) were measured and the cytokine level results are in picograms per liter. Note, there is no treatment in this observational non-interventional trial. Therefore the multiple cytokine levels for each patient will not be aggregated or summarized into one measure. This study was a small pilot study and the results are exploratory.

Time frame: This is a cross-sectional study with no follow-up period. Therefore the study outcomes were measured at the baseline visit (Time = day 0)

Data from ClinicalTrials.gov

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