Natural history of COPD: gaps and opportunities

Abstract

Understanding the natural history of a disease is as important as knowing its cause(s) for effective disease prevention and treatment. Yet, our current understanding of the natural history of chronic obstructive pulmonary disease (COPD) is incomplete and often controversial. This article discusses the current gaps, and hence opportunities for research, in this field. In particular, it discusses the following six specific questions. 1) Is COPD a "single" disease? 2) Is COPD "only" a lung disease? 3) When does COPD begin or what is "early" COPD? 4) How does COPD "progress"? 5) How do we assess disease "severity"? 6) Can COPD be prevented (beyond smoking cessation) or its course be modified once detected?

FIGURE 1

a) Biological onset (inception), pre-clinical and clinical phases of the natural history of a disease. Four different preventive strategies are also illustrated. Tx: treatment. b) Target population and goals of these four preventive strategies. Reproduced from https://www.med.uottawa.ca/sim/data/Prevention_e.htm

FIGURE 2

Different lung function trajectories potentially relevant for the understanding of the natural history of chronic obstructive pulmonary disease. a) Lung function growth and development through the lifespan of a normal subject. b) Reduced maximally attained lung function. c) Reduced duration of the plateau phase of maximal lung function. Accelerated lung function could begin in early adulthood and be d) gradual, e) episodic (e.g. exacerbations) or f) could begin in late life. None of these trajectories are exclusive. Reproduced from [16] with permission from the publisher.

FIGURE 3

The EASI model structured around four modules (exposure (top left), activity (bottom left), severity (top right) and impact (bottom right)), each of which presents the parameter values used to calculate it and the relevant steady-state activation functions linking inputs from previous module (x-axis) to module outputs (y-axis). In the exposure module, the solid line indicates daily smoking exposure (packs per day; left y-axis) as a function of age (x-axis), whereas the dashed line corresponds to the cumulative smoking exposure (pack-years, right y-axis) of that theoretical individual. The EASI model also includes two central panels. The top one presents a longitudinal summary of the age-related trajectories of exposure, activity, forced expiratory volume in 1s (FEV1) (right y-axis) and symptoms. The bottom centre panel presents a heat map of these same four variables by decade of age. This particular example illustrates the EASI relationships for a susceptible continuous smoker. Reproduced with from [69] with permission from the publisher.