The clinical problem: Chronic obstructive pulmonary disease (COPD) affects an estimated 16 million people in the USA, and it is projected to increase from the sixth to the third most common cause of death worldwide by 2020. COPD imposes a burden on patients by restricting their everyday activities (e.g. walking up stairs), as well as a financial burden on society because hospitalizations for treatment of exacerbations are increasing. However, COPD is frequently underdiagnosed and more sensitive and specific biomarkers of the disease could potentially reduce its burden on patients and society, facilitate earlier diagnosis, monitor response to treatment, and identify subtypes of patients who will benefit from tailored treatments. A new solution the problem: Recent studies have shown that human breath contains many volatile organic compounds in low concentrations, and some of them are biomarkers of diseases including COPD. More than 70 studies of breath VOC biomarkers of pulmonary diseases have been reported, and biomarkers of COPD have been tentatively identified with mass spectrometry (MS) and electronic noses. A rapid new point-of-care breath test for volatile biomarkers, the BreathLink system, may offer an accurate, painless, and completely safe test for COPD. The goal of the research is to develop and validate a rapid and accurate onsite breath test for COPD. Phase 1 research: In months 1-12 (biomarker discovery phase) we will analyze breath VOCs with GCxGC TOF MS in three groups of human subjects (n=50 in each group): a. COPD; b. controls with no pulmonary disease (as shown by a negative chest CT), and c. controls with another pulmonary disease (biopsy-proven lung cancer). We will identify statistically significant breath VOC biomarkers of COPD, develop multivariate predictive algorithms for the disease, and determine their sensitivity and specificity. Phase 2 researches: In months 12-24 (onsite system optimization) we will: 1. Obtain pure biomarker VOCs identified in Phase 1 either from commercial vendors or from a consultant chemist who will synthesize those employing known synthetic routes. 2. Evaluate and optimize candidate onsite platforms (including GC SAW) to identify the instrument with optimal sensitivity and selectivity for the pure VOC biomarkers of COPD. In months 25-36 (clinical study of POC breath test) we will evaluate the selected POC platform in a clinical study of a new set of human subjects employing the same study design as the Phase 1 research. Expected impact of the research: A rapid, accurate, and cost-effective onsite breath test could potentially facilitate earlier diagnosis of COPD, monitor response to treatment, and identify subtypes of patients who will benefit from tailored treatments. Potential for commercial application: In order to market the onsite breath test for COPD in the USA we will apply to the Food & Drug Administration (FDA) for pre-marketing approval, and a CE Mark in the EU.