EDITORIALS Choosing Wisely® in Pulmonary Medicine Several years ago, medical ethicist Howard Brody suggested that professional societies develop lists of diagnostic tests or treatments that are commonly ordered but “have been shown by the currently available evidence not to provide any meaningful benefit to at least some major categories of patients” (1). This suggestion gave rise to the American Board of Internal Medicine (ABIM) Foundation’s Choosing Wisely Campaign, which charged professional societies to develop lists of five common medical services “that patients and physicians should question” (2). The top five list for adult pulmonary medicine was developed by the American Thoracic Society and American College of Chest Physicians. The list was initially published on the ABIM website, and an accompanying policy statement appeared recently in Chest (3, 4). To generate the list, a task force comprised of representatives from each organization reviewed the literature, identified candidate items, and, using a Delphi approach, chose the five they believed to be most appropriate. Criteria used to evaluate items for inclusion in the list included (1) strength of evidence (the task force’s confidence that their suggestion was correct), (2) prevalence (how common is the issue?), (3) aggregate cost (how large are the anticipated cost savings?), (4) relevance (to what extent is it a core issue, rather than an ancillary issue?), and (5) innovation (how much does the suggestion change practice, rather than confirm practice?) (3). The Delphi method is a consensus approach that involves an iterative process of soliciting input from all participants while avoiding undue influence by one or more vocal or opinionated individuals. In this case, the process was informed by an evidence synthesis and prespecified criteria were established to prioritize items for inclusion. Unlike clinical practice guidelines, formal methods were not used to rate the quality of evidence or determine the strength of recommendations. The final list was approved by the leadership of both societies and consists of the following suggestions (4): 1. “Do not perform computed tomography (CT) surveillance for evaluation of indeterminate pulmonary nodules at more frequent intervals or for a longer period of time than recommended by established guidelines.” This suggestion is based on the absence of evidence that more intensive surveillance improves outcomes (3). In fact, the optimal frequency and duration of CT surveillance of small pulmonary nodules is unknown. Current recommendations are based largely on uncontrolled studies of the association between cancer risk and nodule characteristics such as size and attenuation. Imprecise measurement limits the ability to detect growth, presumptive evidence of malignancy, over short intervals of time. Thus, surveillance that is more frequent than recommended provides uncertain benefits, but is likely to result in detection of additional false positive

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“incidentalomas,” and will increase exposure to ionizing radiation. “Do not routinely offer pharmacologic treatment with advanced vasoactive agents approved only for the management of pulmonary arterial hypertension to patients with pulmonary hypertension resulting from left heart disease or hypoxemic lung diseases (groups 2 or 3 pulmonary hypertension).” This suggestion is based on the lack of consistent evidence that advanced vasoactive agents benefit such patients, as well as evidence that these agents can harm such patients (e.g., hypoxemia and, possibly, increased mortality) (3). It is consistent with the Hippocratic principle that caregivers should first do no harm. “For patients recently discharged on supplemental home oxygen following hospitalization for an acute illness, do not renew the prescription without assessing the patient for ongoing hypoxemia.” This suggestion is based on evidence that 30–50% of patients prescribed home oxygen during an acute illness no longer meet criteria for home oxygen therapy 2–3 months later and, therefore, probably derive no benefit from ongoing use, as well as recognition that home oxygen can be harmful and burdensome (3). “Do not perform chest CT angiography to evaluate for possible pulmonary embolism (PE) in patients with a low clinical probability and negative results of a highly sensitive D-dimer assay.” This suggestion is based on evidence that clinically important pulmonary embolism is essentially excluded by a negative D-dimer in the setting of low clinical probability of PE, as well as recognition that such testing exposes patients unnecessarily to radiation, intravenous contrast, and the risks associated with false-positive results (additional diagnostic testing, unnecessary anticoagulant therapy) (3). “Do not perform CT screening for lung cancer among patients at low risk for lung cancer.” This suggestion is based on the absence of evidence that CT screening reduces lung cancer mortality in low-risk patients. Even among the group of high-risk individuals who participated in the National Lung Screening Trial, very few deaths from lung cancer were averted in those at the lower end of the spectrum of risk (5). Harms of screening, including radiation exposure and false positive test results, can be expected to occur independently of lung cancer risk.

It is important to recognize that none of the Choosing Wisely recommendations were designed to serve as fully specified performance measures. Rather, they are suggestions about common practices that provide limited value and should be “questioned by doctors and patients.” That said, there is great interest among health services researchers and health systems to measure adherence with the recommendations from

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EDITORIALS various professional societies. However, many of the lists include recommendations that are difficult to operationalize, because either the numerator (those who receive the low-value intervention) or denominator (those who are eligible to receive it) is not clearly defined. This does not seem to be a limitation for most of the items on the list for pulmonary disease, with the possible exception of the recommendation not to perform CT screening in the somewhat ill-defined population of individuals at low risk for lung cancer. Also worth mentioning is that naive measurement approaches may not account for necessary testing that is prompted by signs or symptoms. For example, it might be difficult using structured data from electronic health records to distinguish between a CT scan that was performed for screening a low-risk patient and one that was performed to evaluate persistent cough or hemoptysis in a similar low-risk patient. Caution should therefore be exercised when interpreting results from studies of adherence with Choosing Wisely recommendations, as not all nonadherence represents low-value care. Change in practice invariably results in both winners and losers. Who stands to gain from implementing the list for pulmonary disease? It is interesting that three of the task force’s recommendations discourage use of low-value imaging and two of them focus on inappropriate medication prescribing, but that none of them targets a procedure performed by pulmonologists. A similar observation has been made about Choosing Wisely lists developed by other professional societies (6). Future lists for pulmonary medicine should look closely at indications for bronchoscopic procedures and pulmonary function tests to identify any that represent low value. Our specialty, our patients, and

society at large will all ultimately benefit from a healthy dose of self-appraisal. n Author disclosures are available with the text of this article at www.atsjournals.org. Kevin C. Wilson, M.D. Boston University School of Medicine Boston, Massachusetts Michael K. Gould, M.D., M.S. Kaiser Permanente Southern California Pasadena, California

References 1. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med 2010;362:283–285. 2. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA 2012;307:1801–1802. 3. Wiener RS, Ouellete DR, Diamond E, Fan VS, Mauer JR, Mularski RA, Peters JI, Halpern SD. An official American Thoracic Society/American College of Chest Physicians policy statement: the Choosing Wisely top 5 list in adult pulmonary medicine. Chest 2014;145:1383–1391. 4. American Board of Internal Medicine (ABIM) Foundation. Choosing Wisely. Philadelphia, PA: ABIM Foundation; 2013. Available from: http://www.choosingwisely.org/ 5. Kovalchik SA, Tammemagi M, Berg CD, Caporaso NE, Riley TL, Korch M, Silvestri GA, Chaturvedi AK, Katki HA. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med 2013;369:245–254. 6. Morden NE, Colla CH, Sequist TD, Rosenthal MB. Choosing Wisely–-the politics and economics of labeling low-value services. N Engl J Med 2014;370:589–592.

Copyright © 2014 by the American Thoracic Society

Endothelial Progenitor Cells for Acute Respiratory Distress Syndrome Treatment: Support Your Local Sheriff! In the 1969 American western film Support Your Local Sheriff, the calm and competent traveler Jason McCullough becomes sheriff of Calendar, Colorado. Supported by a few citizens, he keeps the resident bandits and killers under control and tames the lawless Old West frontier town with a diversity of intelligent and efficient methods. At around the same time, in 1967, the acute respiratory distress syndrome (ARDS) made its debut, and it still remains one of the feared killers on intensive care units today. Pneumonia is the most prevalent cause of ARDS, but it may also be precipitated by sepsis due to nonpulmonary infections, aspiration of gastric contents, major trauma, acute pancreatitis, transfusions, or drug reactions (1). ARDS is defined as respiratory failure with sudden onset (,1 wk), bilateral

Supported by Deutsche Forschungsgemeinschaft (SFB-TR84 “Innate Immunity of the Lung”) and German Ministry of Education and Research (CAPSyS–Systems Medicine of Community Acquired Pneumonia).

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infiltrates, and hypoxemia (PaO2/FIO2 < 300 mm Hg under positive end-expiratory pressure > 5 cm H2O) that cannot be attributed to heart failure or hypervolemia (2). Decades of intense research efforts substantially improved our understanding of ARDS pathophysiology, which comprises hyperinflammation, uncontrolled coagulation, and injury of the pulmonary endo–epithelial barrier, as well as tightly controlled resolution of inflammation and tissue repair (1). Numerous promising therapeutic targets have been identified, and multiple novel approaches attenuated lung injury in preclinical studies. However, only two strategies are clinically proven to reduce ARDS mortality at present: low tidal volume ventilation and prone positioning (3, 4). Mortality rates of ARDS are still ranging between 20 and 25% in clinical trials and are probably even higher under “normal” conditions (1). Thus, intelligent therapies efficient in taming ARDS are highly desirable. Adult tissue–derived stem cells have the potential for self-renewal and differentiation into multiple cell types to promote regeneration of

American Journal of Respiratory and Critical Care Medicine Volume 189 Number 12 | June 15 2014

Choosing Wisely(®) in pulmonary medicine.

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