Innate and Adaptive Immunity in Individuals Experiencing Chronic Obstructive Pulmonary Disease Exacerbations
Condition: Pulmonary Disease, Chronic Obstructive; Lung Diseases; 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
      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.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Recruited from pulmonary and general medicine clinics
      
Biospecimen description: 
      serum, sputum
    
Keywords: Chronic Obstructive Pulmonary Disease; COPD