The pathology and impact of
chronic obstructive pulmonary disease (
COPD) results from an abnormal inflammatory process resulting in tissue damage with ineffective repair in response to toxic inhalants (especially cigarette
smoke). Identification of mechanisms provides the opportunity to develop new
therapies and a personalized approach to management. The collection of multiple genetic and detailed biochemical data from small and large patient cohorts has led to an explosion of studies investigating
biomarkers to achieve these aims. Despite widespread enthusiasm and many statistically significant associations, the interpretation of
COPD biomarker results requires thought and leaves many questions unanswered. The present review assesses the importance of these associations, whether they represent cause or effect, reflect disease severity or activity, the complexity of the pathway to the final pathogenic and hence interventional step, and problems with interpreting cross-sectional studies without knowing individual disease trajectories. The complexity of
biomarker specificity without sufficient clinical phenotype and endotype information contributes to problems of interpretation. A strategic change is needed to develop useful
COPD biomarkers; this includes focusing on endotype
biomarkers within specific clinical phenotypes,
biomarkers in early
COPD, exacerbation subtype
biomarkers, and
biomarkers to predict or measure drug effects.