COPD, PE, or Both?
Abstract & Commentary
By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of Medicine—Huntsville Regional Medical Campus. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Pulmonary embolism occurs commonly in patients with unexplained exacerbations of chronic obstructive pulmonary disease.
Source: Tillie-Leblond I, et al. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. Ann Intern Med. 2006;144:390-396.
The symptoms of pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) overlap one another at the intersection of worsening dyspnea and hemoptysis. Tillie-Leblond and colleagues from the Lille University Hospital set out to determine the presence of PE in patients with acute exacerbation of COPD of unknown origin. In addition, they looked for factors that are associated with PE in COPD.
Two hundred eleven (211) consecutive patients with COPD as defined by the American Thoracic Society (ATS), who were referred to the Lung Department with severe exacerbation of undetermined origin, were eligible for inclusion in the study. Exclusion criteria included patients with asthma, lower respiratory tract infection, pneumothorax, or lung consolidation, and those needing intubation and ventilation. All patients underwent spiral computerized tomographic angiography (CTA) of the lungs and color Doppler and venous ultrasonography (US) of the legs. D-dimer and ventilation-perfusion scans were performed at the attending physician's discretion. Each patient's symptoms were quantified by the Geneva score.1 The Geneva score takes into account 8 variables (recent surgery, previous thromboembolic event, older age, hypocapnia, hypoxemia, tachycardia, band atelectasis, and elevation of a hemidiaphragm on chest x-ray film) and assigns a score. The score then stratifies patients into low (≤ 4), intermediate (5-8), and high risk for PE (≥ 9). PE was diagnosed if either the CTA or US were positive. It was ruled out if both were negative and there was no clinical recurrence during 3 months of follow up.
Fourteen patients were excluded from the study, leaving 197 for analysis. They were predominantly male (84%) and middle-aged (average, 60.5 years). Most (69%) were referred from the emergency department; the rest were inpatients who had an acute COPD exacerbation during hospitalization. Based on the ATS severity criteria, 41% were grade I, 42% grade II, and 17% grade III. One-quarter were on long-term oxygen. Fifty-seven patients (29%) had a cancer diagnosis (lung, breast, colon, head and neck, gastric, and prostate accounted for 93%). Forty-nine patients (25%) had PE.
On bivariate analysis, only a decrease in PaCO2 of at least 5 mm Hg from baseline, history of thromboembolic disease, and a cancer diagnosis were associated with PE. Dyspnea, pleuritic pain, hemoptysis, tachycardia, lower extremity edema, the need for long-term oxygen therapy, the level of hypoxemia on admission, the level of hypocapnia on admission, and recent trauma or surgery were not associated with PE.
When the patients were stratified by Geneva score, 119 (60%) were low-risk, 75 (38%) were intermediate risk, and 3 (1.5%) were high risk. PE was confirmed in 11 (9%), 35 (47%), and 3 (100%), respectively. The authors modified the Geneva score by substituting "associated underlying malignant disease" for "recent surgery" and recalculated the scores. Under the modified score, 93 patients (47%) were low risk, 88 (45%) intermediate risk, and 16 (8%) high risk. PE was confirmed in 3 (3%), 34 (39%), and 12 (75%), respectively.
Commentary
The raison d'etre of clinical decision tools, such as the Geneva score, is to identify patients at low risk for a particular condition and who do not need any further diagnostic testing ("sensitivity") from those who are at high risk and do ("specificity"). A good rule of thumb is a highly specific test (> 95%) when positive rules in disease, and a highly sensitive test (> 95%) when negative rules out disease. In this study the original Geneva score identified 119 low-risk patients, 11 who had PE, and 108 who didn't. If we combine the intermediate- and high-risk groups, 38 patients out of 78 had PE, and 40 didn't. This yields a sensitivity of 78% (38/38 + 11), a specificity of 73% (108/108 + 40), a positive predictive value (PPV) of 49% (38/38 + 40), and a negative predictive value (NPV) of 9% (11/11 + 108). Not good enough to rule in or rule out PE. Applying the same analysis to the modified Geneva score, the sensitivity is 94% (46/46 + 3), the specificity is 87% (90/90 + 58), the PPV is 44% (46/46 + 58), and the NPV is 3% (3/3 + 90). Better, especially the sensitivity, but still not ready for prime time. Now remember that this study was performed on a highly select population. It's reasonable to infer that patients coming to a Lung Department might not have garden-variety COPD, and the large percentage of patients with a coexisting malignancy signals that this population is not one seen in primary care offices. The prevalence of PE (25%) was high. PPV and NPV are sensitive to the prevalence of the disease in the population. In a population with a lower prevalence (our folks) the PPV will fall and the NPV will rise. (If your eyes are glazing over with this inundation of statistics, I suggest you read Loong's terrific article in BMJ.2) The take-away message here is that you might consider PE in your COPD patients with unexplained exacerbations and proceed with additional testing. This study did not use D-dimer to diagnose PE. You might want to include it in your evaluation. A recent randomized trial3 concluded that PE occurs very infrequently (< 1%) in low-risk patients with negative D-dimer results and that additional diagnostic testing can be withheld.
References
1. Wicki J, et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med. 2001;161:92-97.
2. Loong TW. Understanding sensitivity and specificity with the right side of the brain. BMJ. 2003;327:716-719.
3. Kearon C, et al. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial. Ann Intern Med. 2006;144:812-821.
Pulmonary embolism occurs commonly in patients with unexplained exacerbations of chronic obstructive pulmonary disease.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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