Expired CO2/O2 Analysis to Diagnose Pulmonary Embolism

DESCRIPTION (provided by applicant): A rapid, noninvasive, and accurate, point-of-care device to diagnose and exclude pulmonary embolism (PE) remains an unmet need, especially for patients with conditions that activate inflammatory and coagulation pathways and therefore predispose to PE. These conditions include surgery, cancer, age >70 years, prolonged hospitalization, hemodialysis, connective tissue and infectious diseases. In patients with these conditions, the quantitative blood D-dimer assay consistently shows a diagnostic specificity below 25% for PE, thus limiting its usefulness as a rule-out test in the patients who engender the most worry for PE. Although many diseases elevate the D-dimer, few diseases besides PE obstruct blood flow to large volumes of alveoli. The novel diagnostic device, the Carboximeter(r), measures the effect of high-ventilation, low-perfusion mismatch from PE on the composition of exhaled breaths. The central hypothesis states that the instantaneous ratio of the expired partial pressure of CO2/O2 at the end of the alveolar phase of steady- state tidal breathing (Carboximetry(r)) will accurately discriminate patients with PE from patients who have other conditions that mimic PE. Three prior clinical trials of 370 patients (n=77 PE+) have demonstrated that the CO2/O2 ratio >0.45 has diagnostic sensitivity and specificity at least equivalent to the quantitative D-dimer 0.45 or a D-dimer 98% and specificity >50%. These highly feasibly specific aims will provide background data needed to establish Carboximetry as a viable alternative or adjunct to the D-dimer to screen for PE in high-risk patients. The condition of clots in the lung, termed pulmonary embolism (PE), is the second leading cause of sudden, unexpected death in the U.S. Physicians lack a quick, accurate method to diagnose and exclude PE at the bedside, especially in patients at risk for PE. This project will fund a clinical study designed to test the diagnostic accuracy of a hand- held breath device that detects the altered gas exchange physiology caused by PE in post-surgical and other patients at high risk for PE.