[The most important methodological problems in studies of mortality and disease progression in patients with chronic...

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incompletely reversible airflow obstruction associated with an anomalous inflammatory response of the lungs, mainly to tobacco smoke. The best indicator of disease progression and severity is measurement of airflow obstruction (forced expiratory volume in 1 second), expressed as a percentage of the predicted value derived from a healthy reference population. Most of the treatments available for COPD have not been shown to clearly affect disease progression or mortality, probably because COPD is a heterogeneous, longstanding process and because there is wide variety in patients' phenotypes, clinical situations, and clinical course. In the last few years, the number of studies on disease progression and mortality in COPD has markedly increased, making survival analysis one of the most important tools for exploiting the resulting data. However, certain methodological factors associated with this type of research, such as the study design, the variables used to measure effect, and determination of the sample, have influenced the conclusions of these studies. Moreover, analysis of disease progression and mortality rates usually entails prolonged follow-up periods and a large number of participants, limiting the funding and continuity of this type of study. In the case of studies of mortality associated with COPD, there are the additional difficulties of identifying the specific cause of death and of identifying the prognostic factors of mortality from the disease, which are the main methodological factors that hamper the possibility of obtaining conclusive data.