A threshold regression model for recurrent exacerbations in chronic obstructive pulmonary disease

Objective: Respiratory exacerbations are a major source of morbidity in patients with chronic obstructive pulmonary disease (COPD). In this article, we model COPD health status as a formal stochastic process. A successful model will provide a suitable statistical structure for analysis of the effects of medical interventions on a patient's health status, and, possibly, offer new insights into the underlying disease process. Study Design and Setting: Our approach uses a regression methodology for time-to-event data called threshold regression (TR). We test the methodology on COPD data from a randomized clinical trial. Two TR models are studied: one based on a Poisson process and the other, a Wiener diffusion process. Results: Both models provide reasonably accurate fits to the clinical trial data. The insights offered by the fitted models are interpreted. Analysis of the clinical trial data set using these TR models revealed that patients who experienced multiple exacerbations showed a progressive acceleration in rate of exacerbations, and successive shortening of stable intervals between exacerbations. Conclusion: TR techniques allow for realistic modeling of the COPD health state. A hybrid Poisson/Wiener diffusion TR model that incorporates the causal determinants of disease operating in each patient may be preferable. (C) 2010 Elsevier Inc. All rights reserved.