Bronchitis, Chronic, Immunity, Innate, Inflammation, Pulmonary Disease, Chronic Obstructive, Toll-Like Receptors
Conditions
Brief summary
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.
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.
Interventions
None listed
Sponsors
University of Washington
Novartis Pharmaceuticals
VA Puget Sound Health Care System
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
MALE
Age
50 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine production (TNF-alpha, IL-6, IL-8, IL-10, IL-1RA, G-CSF, IL-1B, MCP-1). | This is a cross-sectional study with no follow-up period. Therefore the study outcomes were measured at the baseline visit (Time = day 0) | 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. |
Countries
United States
Outcome results
None listed