Changes in Cytokine Levels During an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

January 28, 2016 updated by: Jeffrey L. Curtis, University of Michigan

Innate and Adaptive Immunity in COPD Exacerbations: Severe AE-COPD Clinical Course Study

The purpose of this study is to determine whether there is a statistical association between changes in sputum serial levels of two cytokines, interleukin (IL)-17 and IL-6, during the treatment course of a severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and during the clinical course itself (i.e., rate of recovery or potential complicated course). AE-COPD is defined as an episode requiring emergency room (ER) evaluation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

COPD is one of the most pressing healthcare problems facing our nation. AE-COPD is responsible for the bulk of healthcare costs, and much of the morbidity and decline in health status among individuals with this common disease. The lack of accepted animal models of AE-COPD necessitates novel approaches using human samples. Advances in the understanding of the pathogenesis have been slowed, in part, due to controversy as to how exacerbations should be defined. The prevailing paradigm has defined AE-COPD as event-based. Such definitions clearly identify groups of patients with accelerated loss of pulmonary function and increased mortality. However, limited data show that symptom-based definitions of AE-COPD also capture episodes inducing significant morbidity and functional decline, and hence of concern to patients. Fundamental mechanisms are lacking to explain AE-COPD defined by either means.

Controversy also surrounds triggers of AE-COPD. Bacteria and viruses are involved in some episodes, but the relative importance of each is intertwined with disputes over the definition of AE-COPD. Progress at linking specific pathogens to molecular pathogenesis has been slow, both due to their diversity, and to the high rates of bacterial colonization of patients with COPD, even in the stable state. Moreover, in many AE-COPD cases, no pathogen can be identified. Without negating the value of analyzing infections with specific species of pathogens, it appears that progress in molecular pathogenesis could be accelerated by focusing on unifying features of the pulmonary immune response during AE-COPD.

DESIGN NARRATIVE:

The research protocol will involve a prospective, observational analysis. Participants will include acutely ill COPD patients having an AE-COPD who are enrolled during an ER evaluation or hospitalization at Ann Arbor VA Hospital or the University of Michigan Health Systems ER, clinic, or wards. All non-study diagnostic testing, decisions to discharge from the ER or admit to hospital, prescription of medications, and non-study follow-up will be left to the discretion of the primary caregivers.

Participants who are either being or anticipate being discharged to their usual residence from the ER will be enrolled while still in the ER. Participants who were discharged to their usual residence may be contacted by telephone and enrolled up to 24 hours later, if willing to return to the Medical Center for study initiation. Hospitalized patients will be enrolled within the first 48 hours. Study physicians and coordinators will be on call to capture people at presentation, prior to steroids and antibiotics, if possible. However, clinically indicated treatment will not be delayed to permit enrollment or collection of research samples. Participants will be questioned about the status of five respiratory symptoms (dyspnea, cough, sputum production, sputum viscosity, sputum purulence) using a published Respiratory Symptom score instrument. Each symptom will be scored for severity using the following three-point scale: 1) Usual level; 2) Somewhat worse than usual; 3) Much worse than usual. An acute exacerbation of chronic bronchitis (AECB) will be defined symptomatically as a minor worsening (score of 2) for two or more symptoms, or a major worsening (score of 3) for one or more symptoms.

A clinical score will be generated using a previously used system (Chest 2000; 118:1557-1565) in which 10 clinical parameters will be assessed (overall feeling of well-being, dyspnea, cough, sputum production, sputum viscosity, sputum purulence, overall appearance, respiratory rate, wheezing, and rales); severity of each parameter will be scored using the same three-point scale. Thus the scores will range from 10 to 30.

The following additional data will be obtained: vital signs (blood pressure, pulse, temperature, respiratory rate, oxygen saturation level); dyspnea assessment (MMRC & University of California San Diego SOBQ); estimate of daily sputum production over last 72 hours; sputum color (using a standardized color "paint-chip" scale); changes in medication usage, with special attention to elicit any history of increased use of potent inhaled steroids, or patient-initiated use of oral steroids or antibiotics. If there is fever or focal findings on chest examination, a chest X-ray will be obtained as part of usual clinical care.

Sputum and blood samples will be collected for measurement of IL-6 and IL-17 levels at time 0 in the ER or hospital, and then 5-7 days, 10-12 days, 33-35 days, and 56-58 days later. Specimens may be obtained from participants requiring mechanical ventilation during the first 24 hours of intubation only, and only if they are not suspected to have pneumonia.

Subjects are reimbursed $25 per scheduled return visit following hospital discharge to help defray travel expenses.

Study Type

Observational

Enrollment (Actual)

37

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan at Ann Arbor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Emergency room and clinics

Description

Inclusion criteria:

  • Diagnosis of COPD (following American Thoracic Society guidelines) and/or chronic bronchitis
  • ER visit and/or hospitalization with AE-COPD
  • Current or former smokers with more than 20 pack-years
  • Willingness to participate in follow-up studies defined in the protocol
  • Ability to give informed consent

Exclusion criteria:

  • Unstable cardiovascular disease
  • Other systemic disease in which survival of more than 2 years is unlikely
  • Mental incompetence or active psychiatric illness
  • Currently taking more than 20 mg/day of Prednisone
  • Participation in another experimental protocol within 6 weeks of study entry
  • Asthma
  • Cystic fibrosis
  • Clinically significant bronchiectasis
  • Lung cancer
  • Other inflammatory or fibrotic lung disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Research subjects
All participants undergo the same testing in this observational trial. There is no randomization, and no interventions other than blood drawing.
Other: blood draw
All subjects undergo blood draws at study visits and at the time of COPD exacerbation visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
biomarker analysis at the time of exacerbation, no clinical outcome
Time Frame: at each exacerbation
at each exacerbation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (ACTUAL)

June 1, 2010

Study Completion (ACTUAL)

July 1, 2010

Study Registration Dates

First Submitted

January 20, 2006

First Submitted That Met QC Criteria

January 20, 2006

First Posted (ESTIMATE)

January 24, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

January 29, 2016

Last Update Submitted That Met QC Criteria

January 28, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1325
  • R01HL082480 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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