Physiological Measures and Novel Sputum Biomarkers to Distinguish Subjects with Mild to Moderate COPD from Asymptomatic Current Smokers, Former Smokers and Never-Smokers

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by progressive airflow limitation, with globally increasing prevalence. Although efforts to simplify COPD diagnosis to a single repeatable test using spirometry has proved critical in the day-to-day diagnosis and management of the disease, it is clear that COPD is a complex disease whose phenotypes may not be adequately captured by spirometry alone. Moreover, suitable biomarkers for the diagnosis, treatment and prognosis are still lacking. Therefore, we conducted a case-control study designed to identify a biomarker (panel) for the differentiation of subjects with mild and moderate COPD, asymptomatic current, former and never-smokers and to compare physiological measurements and quality of life (QoL) across the study groups (NCT01780298). Our data shows that there are a number of subjects that would be diagnosed as healthy using spirometry alone. However, these data also suggest that complementary tests such as CT chest imaging or lung sound analysis may prove helpful in identifying asymptomatic smokers at risk or with subclinical disease. Potential biomarkers identified by ‘omics’ analyses may support this stratification further. For example, sputum analysis detected cigarette smoking-related alterations in the transcriptome and proteome, which were further augmented in COPD smokers. Strikingly, proteomics data could distinguish COPD from asymptomatic smokers with a similar accuracy as the combination of three commonly used physiological parameters, FEV1, TLCO % and total COPD score.