Innate Immune Response in COPD

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic; Immunity, Innate; Toll-Like Receptors

Detailed Description

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 (Actual): 30

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with a clinical history of COPD recruited from a pulmonary subspecialty clinic at an academic medical center

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: VA Puget Sound Health Care System
• Collaborators: Novartis Pharmaceuticals; University of Washington
• Investigators: Principal Investigator: Vincent Fan, MD MPH, VA Puget Sound Health Care System

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Estimate): December 22, 2015
• Last Update Submitted That Met QC Criteria: December 18, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Inflammation; Bronchitis; Bronchitis, Chronic
• Other Study ID Numbers: 01439