Moua and Wood The estimated annual incidence of pulmonary embolism is 23–69 cases per 100,000 persons with hospitalizations resulting in 676,700 inpatient days (Kozak et al 2005). Approximately 187,000 new cases occur each year in individuals older than 45, half of which are considered idiopathic (Cushman et al 2004). A compilation of studies examining the incidence of DVT in patients with COPD reported a rate of 10%–12%, with the majority discov- ered by surveillance studies and clinically asymptomatic (Prescott et al 1981; Erelel et al 2002; Ambrosetti et al 2003). Autopsy studies have reported the incidence of PE in patients with COPD to be 28%–51% without deﬁn- ing the percentage of suspected antemortem diagnoses (Prescott et al 1981). Retrospective work by Mispelaere and colleagues (2002) reported a 20% prevalence of PE in 50 patients presenting with COPD exacerbation of nonin- fectious etiology and a prospective study of 31 patients by the same investigators found a prevalence of 29% (9 of 31 patients). Tillie-Leblond and colleagues (2006) similarly reported PE in 25% of patients presenting with noninfec- tious COPD exacerbation. Using the Geneva score, three clinical features were statistically associated with PE; 1) prior history of malignancy, 2) history of DVT or PE, and 3) drop in PaCO2 greater than 5 mmHg. Lower extremity Doppler studies conﬁrmed DVT in 51% of patients (Tillie- Leblond et al 2006). However, Rutschmann and colleagues (2007) found only 4 cases of computed tomography (CT) proven PE out of 123 consecutive patients presenting with COPD exacerbation, representing a prevalence of 3.3%. As further studies are pursued, it is likely the prevalence of COPD-associated PE will become more apparent, making it important to include thromboembolism in the differential for COPD patients presenting with acute dyspnea. The prevalence of PE in patients with COPD is important because of combined morbidity and mortality. In a follow- up of 1487 patients from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, Carson and colleagues (1996) found an adjusted estimated rela- tive risk of death at one year with COPD and PE of 1.94, compared with 1.1 for patients with PE alone. The one year mortality of those with COPD and PE was 53.3%, in contrast to 15% of those with PE alone (Carson et al 1996). The clinical evaluation The clinical difﬁculty of diagnosing PE in the setting of COPD was described by Sharma and Sasahara (1975). Non- speciﬁc ﬁndings such as pleuritic pain, tachypnea, tachycar- dia, and fever were common presentations of the two diseases 278 (Sharma and Sasahara 1975). It is valuable to review the presenting features of each to appreciate their overlap. Physical exam In 1819, Laennec recorded the ﬁrst clinical descriptions of COPD as dyspnea, hyperresonant chest wall, diminished breath sounds, and wheezing. Contemporarily, classic exam ﬁndings of barrel chest with hyperinﬂated lungs, pursed lip breathing and accessory muscle use continue to signify airway obstruction. McGee (2001) reported 3 ﬁndings that strongly support the diagnosis of COPD exacerbation: early inspiratory crackles, absence of cardiac dullness on percus- sion, and decreased breath sounds. Absence of cardiac dull- ness over the left lower sternal border had a sensitivity of 15%, but speciﬁcity of 99%, while unforced wheeze was only 13%–56% sensitive and 86%–99% speciﬁc. Other clinical features of COPD exacerbation include productive cough secondary to an inciting respiratory infection, decreased exercise tolerance, and a breath – sound score of less than 9 (a scoring system of listening to over 6 locations on the chest wall, and then rating and totaling breath sounds at each site from 0 [absent] to 4 [louder than normal]). McGee (2001) suggested clinically combining a historical picture of 70 or more pack-years of smoking, prior diagnosis of COPD, and decreased breath sounds to gain a likelihood ratio of 25.7 for active COPD exacerbation. Stein’s evaluation of patients presenting with acute PE found dyspnea and tachypnea in 73% of patients, tachycardia in 30%, and pleuritic pain in 66% (Stein et al 1991). Rales were heard in approximately half of patients. More speciﬁc ﬁndings in PE include hemoptysis, elevated neck veins, a loud P2 component of S2, and asymmetry in size of the lower extremities or calf tenderness. Of patients diagnosed with PE, only 45% had a presentation of pleuritic chest pain and hemoptysis (Pineda et al 2001). Other investigators noted only a history of cancer, asymmetric lower extremity swelling, or tachycardia as being reliable in arguing for a PE diagnosis, while a heart rate of less than 90 argued against it (McGee 2001). The reliability of lower extremity edema or asymmetry with calf pain (Homan’s sign) concerning for DVT has fallen out of favor in recent years due to nonspeci- ﬁcity of the ﬁnding. A review of the clinical features of each disease suggests appreciable overlap making differentiation difﬁcult. For example, rales were prevalent in 58% of patients with PE while inspiratory crackles were 25%–77% sensitive and 98% speciﬁc in COPD (McGee 2001). Lesser et al found rales in 81% of patients with COPD and PE compared to 53% in International Journal of COPD 2008:3(2)