A sum greater than its parts.

The pursuit of the perfect biomarker in chronic obstructive pulmonary disease (COPD) has been fraught with peril. The dream, of course, is of a single, accessible and inexpensive laboratory test that can more accurately diagnose COPD, define its severity, or fluctuate in accordance with disease progression and remission. In its ideal form, it would allow for earlier diagnosis of disease or earlier identification of the most severely affected patients, all with high sensitivity and specificity. Or it would properly indicate to a physician whether a particular COPD treatment has worked or failed. One only has to look to cardiology and its use of the troponin assay for the diagnosis of a myocardial infarction or to nephrology and its reliance on creatinine as a measure of renal function for such examples. If a similar biomarker is realised in COPD, it would significantly bolster what we can now predict through spirometry alone [1]. However, 20 years of painstaking research has led us no closer to this Holy Grail of biomarkers. To date, not one blood-based biomarker has reached meaningful clinical significance in COPD. Even the most promising candidates like C-reactive protein and fibrinogen, both of which have been shown to at least predict mortality in COPD, are nonspecific and lack the ability to distinguish manifestations of COPD from other inflammatory disorders [2, 3]. Pneumoproteins like surfactant protein D and club cell secretory protein, which are primarily produced in the lung, could theoretically circumvent these limitations. However, only weak associations have been found between these biomarkers and important clinical benchmarks like exacerbation risk and lung function decline [4, 5]. As a result, these tests remain the domain of research laboratories, intellectually interesting to ponder but largely irrelevant when considered within the context of actual patient management.