Innate and Adaptive Immunity in COPD Exacerbations: Prospective Cohort Study

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.