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Editorial |

Should We Screen for Pulmonary Embolism in Severe COPD Exacerbations? Not Just Yet, Primum Non Nocere FREE TO VIEW

Seung Won Ra, MD, PhD; Don D. Sin, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

aCentre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada

bDepartment of Medicine (Respiratory Division), University of British Columbia, Vancouver, BC, Canada

cUlsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

CORRESPONDENCE TO: Don D. Sin, MD, FCCP, Room 8446, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(3):523-524. doi:10.1016/j.chest.2016.09.018
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Published online

Acute exacerbations of COPD are responsible for 1.5 million emergency visits and 700,000 hospitalizations per year in the United States. Although most exacerbations are thought to be triggered by microbial agents, approximately 25% to 50% are thought to be noninfectious events, driven by diverse etiologies including air pollution, acute heart failure, ischemic heart disease, and anxiety. Early identification of these noninfectious events is important because standard antiexacerbation therapies including systemic corticosteroids and antibiotics are unlikely to be clinically useful for these etiologies and, of importance, may result in delays in the diagnosis and treatment of noninfectious causes of exacerbation such as acute coronary syndromes or congestive heart failure, leading to poor clinical outcomes.

FOR RELATED ARTICLE SEE PAGE 544

In this issue of CHEST, Aleva et al performed a systematic review of the literature and identified another common noninfectious and noninflammatory cause of acute exacerbations of COPD: pulmonary embolism (PE). Through their search, Aleva et al discovered seven well-conducted studies, which they carefully meta-analyzed. They found that the overall prevalence of PE during acute exacerbations was 16%. Of these events, 32% (39/120) were isolated subsegmental PEs, the clinical significance of which was unknown. Of importance, they also found that the prevalence of PE varied widely depending on the severity of the exacerbation episode and patient symptoms. For instance, in patients who presented to the ED with typical features of a respiratory tract infection including fever, sore throat, or increased sputum volume or purulence, the prevalence of PE was only 3%. However, in hospitalized patients with COPD, the prevalence increased to 30% (50/172). When patients with infectious features were excluded from the analysis, the prevalence of PE in hospitalized patients was reduced to 25%. In 2009, we reported a similar prevalence of PE (20%, n = 550). The current updated systematic review added five studies to our previous meta-analysis, increasing the total number of patients with COPD to 888, which made the results more generalizable and robust. Additionally, the authors carefully evaluated the topology of PE by assessing images from CT pulmonary angiography (CTPA). They found that two-thirds of the emboli were found in sites where anticoagulant treatment may be clinically indicated. However, before accepting this notion, it is important to carefully consider the role of CTPA in detection of PE.

Advances in CTPA technology and the ease of access have made CTPA the modality of choice for the diagnosis of PE. Over time, the increased use of CTPA has also increased the rate of detection and treatment of PE in the community. Of interest, however, the use of this technology has had minimal impact on the overall mortality related to PE, suggesting that many of the extra cases of PE, especially those in the subsegmental arteries, detected by CTPA, may not have been clinically relevant. Thus, it is debatable whether the subsegmental PEs associated with acute COPD exacerbations required treatment with anticoagulation, especially if there was no evidence of an accompanying DVT. In both meta-analyses, the prevalence of DVT was relatively low at 10% and 12%, respectively. Given these relatively low rates of DVT, we cannot discount the possibility that some of the PEs were (in situ) thrombotic rather than embolic events. In trauma patients, 61% of PEs are in situ thrombosis. These events, compared with embolic ones, tend to occur in peripheral sites, are more likely to be unilateral and singular, and be associated with lung inflammation.

Although CTPA provides nice pictures and increases the detection of PEs, there is insufficient evidence at the present time to advocate its widespread use in the evaluation of patients with acute exacerbations. Indeed, there is some theoretical possibility that this may cause harm rather than benefit. For instance, CTPA exposes patients to potentially unnecessary radiation, leading to increased cancer risks and IV contrast agents, which may lead to renal dysfunction or anaphylaxis in some patients. CTPA may also unveil incidental “nodules” that may increase investigative burden, adding costs to the health care system and provoking anxiety for patients. Unnecessary use of anticoagulations may also increase the risk of bleeding, causing harm.

There is a clear and compelling need for more high-quality evidence to determine the value of detecting PEs in patients with acute COPD exacerbations. There is an urgent need to understand the risks as well as the benefits of using CTPA in the evaluation of acute COPD exacerbations. To fill this critical gap in knowledge, a Spanish group is conducting a randomized clinical trial to examine the clinical benefits and safety of “routinely” deploying CTPA in the evaluation of hospitalized COPD patients with acute exacerbations (NCT02238639). The primary outcome is a composite end point of all-cause mortality, symptomatic VTE recurrence, and hospital readmissions during 90 days of follow-up. Major bleeding is included as a secondary outcome.

What should clinicians do until high-quality data from these and other studies are available? We suggest that, in patients with typical infectious symptoms (eg, increased cough, change in sputum volume or color), CTPA is probably not required. CTPA may be considered for those who present with “atypical” exacerbation symptoms (eg, pleuritic chest pain, signs of cardiac failure, no clear identification of infectious origin) and in those with a history of thromboembolic disease. Although we agree with Aleva and colleagues that the prevalence of PE is common (approximately 20% to 25%) in unexplained COPD exacerbations, we remain unconvinced that all of these events require active treatment with anticoagulant therapy. Until compelling data from well-conducted randomized controlled trials are available, we suggest a conservative “primum non nocere” (first, no harm) approach to the management of acute exacerbations of COPD and use CTPA judiciously.

References

Ford E.S. .Croft J.B. .Mannino D.M. .et al COPD surveillance–United States, 1999-2011. Chest. 2013;144:284-305 [PubMed]journal. [CrossRef] [PubMed]
 
MacIntyre N. .Huang Y.C. . Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:530-535 [PubMed]journal. [CrossRef] [PubMed]
 
Aleva F.E. .Voets L.W.L.M. .Simons S.O. .et al Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2017;151:544-554 [PubMed]journal
 
Rutschmann O.T. .Cornuz J. .Poletti P.A. .et al Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease? Thorax. 2007;62:121-125 [PubMed]journal. [CrossRef] [PubMed]
 
Akpinar E.E. .Hosgun D. .Akpinar S. .et al Incidence of pulmonary embolism during COPD exacerbation. J Bras Pneumol. 2014;40:38-45 [PubMed]journal. [CrossRef] [PubMed]
 
Tillie-Leblond I. .Marquette C.H. .Perez T. .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 [PubMed]journal. [CrossRef] [PubMed]
 
Rizkallah J. .Man S.F. .Sin D.D. . Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135:786-793 [PubMed]journal. [CrossRef] [PubMed]
 
Wiener R.S. .Schwartz L.M. .Woloshin S. . Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171:831-837 [PubMed]journal. [PubMed]
 
Ikesaka R. .Carrier M. . Clinical significance and management of subsegmental pulmonary embolism. J Thromb Thrombolysis. 2015;39:311-314 [PubMed]journal. [CrossRef] [PubMed]
 
Van Gent J.M. .Zander A.L. .Olson E.J. .et al Pulmonary embolism without deep venous thrombosis: de novo or missed deep venous thrombosis? J Trauma Acute Care Surg. 2014;76:1270-1274 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Ford E.S. .Croft J.B. .Mannino D.M. .et al COPD surveillance–United States, 1999-2011. Chest. 2013;144:284-305 [PubMed]journal. [CrossRef] [PubMed]
 
MacIntyre N. .Huang Y.C. . Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:530-535 [PubMed]journal. [CrossRef] [PubMed]
 
Aleva F.E. .Voets L.W.L.M. .Simons S.O. .et al Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2017;151:544-554 [PubMed]journal
 
Rutschmann O.T. .Cornuz J. .Poletti P.A. .et al Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease? Thorax. 2007;62:121-125 [PubMed]journal. [CrossRef] [PubMed]
 
Akpinar E.E. .Hosgun D. .Akpinar S. .et al Incidence of pulmonary embolism during COPD exacerbation. J Bras Pneumol. 2014;40:38-45 [PubMed]journal. [CrossRef] [PubMed]
 
Tillie-Leblond I. .Marquette C.H. .Perez T. .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 [PubMed]journal. [CrossRef] [PubMed]
 
Rizkallah J. .Man S.F. .Sin D.D. . Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135:786-793 [PubMed]journal. [CrossRef] [PubMed]
 
Wiener R.S. .Schwartz L.M. .Woloshin S. . Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171:831-837 [PubMed]journal. [PubMed]
 
Ikesaka R. .Carrier M. . Clinical significance and management of subsegmental pulmonary embolism. J Thromb Thrombolysis. 2015;39:311-314 [PubMed]journal. [CrossRef] [PubMed]
 
Van Gent J.M. .Zander A.L. .Olson E.J. .et al Pulmonary embolism without deep venous thrombosis: de novo or missed deep venous thrombosis? J Trauma Acute Care Surg. 2014;76:1270-1274 [PubMed]journal. [CrossRef] [PubMed]
 
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