Pulmonary Embolism in Patients with Unexplained Exacerbation of COPD: Prevalence and Risk Factors Isabelle Tillie-Leblond, MD, PhD; Charles-Hugo Marquette, MD, PhD; Thierry Perez, MD Ann Intern Med. 2006;144:

Background Diagnosis of pulmonary embolism (PE) is difficult in patients with COPD and exacerbation. Incidence of PE in studies done postmortem of patients with COPD ranges from 28% to 51% In the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study 108 patients with COPD and suspected PE; 21 (19%) received diagnoses of PE by pulmonary angiography.

Objective To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. Design Prospective cohort study. Setting University-affiliated hospital in France.

Methods 211 consecutive patients All patients smoked or former smokers. Asthma, invasive mechanical ventilation were not included. Unknown origin Severe exacerbation acute deterioration from a stable condition that Required hospitalization. April 1999 and December 2002 within 48 hours spiral CTA and color Doppler venous lower-limb ultrasonography. D-dimer determination ventilation–perfusion scanning

Spiral CTA In 1999 (37, singleslice CT scan) 3 mm X 3 mm, and a scanning time of 0.75 second per revolution January 2000 and December 2002 (160, multislice CT scan) 4 mm X 1 mm, and a rotation time of 0.5 second. Ultrasonography common femoral vein and including the calf vein

Definition PE positive (positive results on spiral CTA or negative results on spiral CTA and positive results on US) PE negative (negative results on spiral CTA and negative results on US or negative results on spiral CTA and no recurrence of PE at follow-up 3 months later).

Results 14 (inconclusive or iodine intolerance) exclusion 197 patients with COPD and severe exacerbation of unknown origin. 165 men 32 women 211 consecutive patients 136 patients (69%) ED, 61 (31%) inpatients American Thoracic Society: grade I, FEV1 >50% (66 [41%]) grade II, FEV1 35%~50% (67 [42%]); grade III, FEV1 <35% (27 patients [17%])

Table 1. The Geneva Score and the Modified Geneva Score low (< 4) intermediate (5-8) high (> 9)

Results CTA 49 of 197 patients (25%) DVT

Table 2. Results of Spiral Computed Tomography Angiography in Patients Initially Referred for Suspected Acute Pulmonary Embolism

Table 3. Bivariate Analysis of Baseline Characteristics of the 197 Patients with Chronic Obstructive Pulmonary Disease according to the Presence or Absence of Pulmonary Embolism

Table 4. Bivariate Analysis of Clinical Characteristics at Admission of the 197 Patients with Chronic Obstructive Pulmonary Disease according to the Presence or Absence of Pulmonary Embolism

Table 5. Probabilities of Pulmonary Embolism for the 197 Patients with Chronic Obstructive Pulmonary Disease Computed from the Geneva Score and from the Modified Geneva Score Underlying malignant disease (29%) (57/197) 20 lung cancer, 7 breast cancer, 5 bowel cancer, 2 gastric cancer, 11 prostate cancer, 8 head and neck cancer, and 4 other types. We recalculated the Geneva score by replacing “surgery” with “associated underlying malignant disease”.

Discussion Only 1 study (23 of 26) with emphysema and PE had autopsy data. [did not include, who required invasive mechanical ventilation] In our study, color Doppler and venous ultrasonography identified deep venous thrombosis in 51% of patients with PE. Color Doppler and venous ultrasonography as first-line tests in patients with COPD and suspected PE.

Discussion Spiral CT technology has gradually replaced pulmonary angiography in many institutions. ( as small as 2 to 3 mm in diameter ) The negative predictive value of multislice spiral CTA should be higher than that of single-slice CT. Perrier and colleagues lower-limb ultrasonography is not needed to rule out PE when multidetector-row CT is used. 3 months to exclude the possibility of false-negative CT results.

Discussion The Geneva score upper bound of the CI for probability of PE is 15.9%. the use of the modified Geneva score. - 7% in the Geneva study vs 3%, recent surgery. - 13% in the Geneva study vs 29%, malignant disease. For low-risk patients, the modified Geneva score yielded a probability of PE of 3.2% (CI, 0% to 9.1%). The possibility that the actual false-negative rate has an upper CI as high as 9.1% limits the clinical utility of the modified score.

Limitations This study was done in only single center. Patients with COPD requiring invasive mechanical ventilation in the ICU were not included. The classification of COPD exacerbation of unknown origin was based on the clinician’s assessment, not on a standard evaluation for all patients.

Limitations The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. Although the modified score had a lower false-negative rate than the Geneva score, this analysis is exploratory and requires additional study.

Conclusion This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. (previous thromboembolic disease, malignant disease, and decrease in PaCO2 from baseline.)

Conclusion Color Doppler and venous lower-limb US should be done as a first-line evaluation because DVT was identified in 51% of patients receiving PE diagnoses. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.