Changes in Cytokine Levels During an Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): blood draw
Intervention type(s): Other
Intervention description(s): All subjects undergo blood draws at study visits and at the time of COPD exacerbation visits.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Emergency room and clinics
      
Keywords: Chronic Obstructive Pulmonary Disease; COPD