Innate and Adaptive Immunity in Individuals Experiencing Chronic Obstructive Pulmonary Disease Exacerbations

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

Innate and Adaptive Immunity in COPD Exacerbations: Prospective Cohort Study

The purpose of this study is to determine whether there is a statistical association between the changes from baseline in the levels of two cytokines interleukin (IL)-17A and IL-6 in the sputum of patients with chronic obstructive pulmonary disease (COPD) and the severity of acute exacerbations of COPD (AE-COPD). These sputum cytokine levels are taken as measures of the adaptive immune response (IL-17A) and the innate immune response (IL-6), respectively. Sputum will be collected either spontaneously or will be obtained by induction; cytokine levels will be measured by ELISA. The primary analysis, comparisons of sputum cytokine levels between clinical states, will be done using random effects modeling.

Study Overview

Status

Completed

Conditions

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:

A prospective patient cohort will be studied extensively physiologically, functionally, and immunologically upon enrollment while in the stable state. As part of the study, participants will be trained in the use of peak flow meters, so that they can record daily first morning peak expiratory flow rates (PEFR). To confirm the range of fluctuations in their basal state, participants will be then be followed at three-month intervals for face-to-face interviews and more limited physiological and functional testing described below. Participants will also be reminded at each scheduled visit to contact the study coordinator when they feel that an AE-COPD may be present. If they do contact the study coordinator, they will be evaluated at one of the study sites within 48 hours.

A diagnosis of AE-COPD will incorporate a modification of the definition used by the COPD Clinical Research Network (CCRN). The diagnosis will be made in one of two ways: severe AE-COPD will be defined as a change in respiratory symptoms above the participant's baseline measurements plus evaluation in the emergency room (ER) or requiring hospitalization; or mild-to-moderate AE-COPD will be defined as a change in respiratory symptoms above the participant's baseline measurements and requiring a change in therapy (addition of either antibiotics, oral steroids, or both), but without evaluation in the ER or hospitalization. In the latter case, therapy could be changed either at the advice of the patient's own caregivers or a study physician based on clinical judgment, or could be self-initiated in the case of participants authorized to do so by their caregiver. A concerted effort will be made to capture these milder AE-COPD during both winter and non-winter seasons.

Upon enrolling participants, the following will be performed: review of medical history; review of demographic and smoking history; physical examination, blood and sputum collection; six-minute walk test; and questionnaires to assess shortness of breath (MMRC and University of California San Diego SOBQ), sputum production (modified Chronic Bronchitis Symptom Questionnaire), health status (SF-36 and St. George's Respiratory Questionnaire), and psychological traits (Hospital Anxiety/Depression Score, Illness Perception Questionnaire, Coping Index, and an individualized 30-minute clinical interview via telephone).

Participants will attend study visits every 3 months to review symptoms. During an AE-COPD (episode of acute bronchitis), sputum and blood will be collected, and a five-symptom questionnaire will be filled out.

Subjects are reimbursed $25 per scheduled visit and $50 per unscheduled visit (at the time of perceived exacerbation) to help defray travel expenses.

Study Type

Observational

Enrollment (Actual)

10

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

Recruited from pulmonary and general medicine clinics

Description

Inclusion criteria:

  • Diagnosis of COPD (following American Thoracic Society guidelines) and/or chronic bronchitis
  • Forced Expiratory Volume in 1 second of less than 70% predicted value after bronchodilator
  • Current or former smokers with more than 20 pack-years
  • Daily productive cough for 3 months of the year for 2 consecutive years
  • At least one AE-COPD requiring medical attention in each year for the previous 3 years
  • Willingness to participate in follow-up studies defined in the protocol

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
length of hospital stay
Time Frame: hospital discharge
hospital discharge

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)

September 1, 2010

Study Completion (Actual)

September 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

  • 1324
  • 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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