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Chronic obstructive pulmonary disease (COPD) is a common chronic disease of middle-aged and older adults, with an estimated prevalence of diagnosed COPD of almost 14 million individuals in the United States.1 This condition leads to substantial morbidity, disability, impaired quality of life, increased health care costs, and mortality.2 In addition to persons with diagnosed COPD, it has been estimated that 60% of individuals living in the United States with obstructive lung disease have not been diagnosed3; these individuals appear to experience impaired health status,4 activities of daily living,4 and outcomes.3
It is understandable that COPD, which has been defined as “a common preventable and treatable disease… characterized by persistent airflow limitation that is usually progressive,”2 may remain unrecognized. The irreversible airflow obstruction (ie, airflow obstruction that persists after inhalation of an inhaled bronchodilator) develops gradually over many years. A person with only mild airflow obstruction may truly be asymptomatic, especially if a sedentary lifestyle does not include vigorous exertion that might provoke dyspnea. A person with moderately advanced airflow obstruction might attribute gradually reduced exercise tolerance, such as dyspnea climbing stairs, to growing older or being “out of shape” and might not seek medical attention or think to mention reduced exercise tolerance to a physician seen for other reasons.
In this context, the US Preventive Services Task Force (USPSTF) has undertaken a thorough systematic review5 to update its 2008 report, assessing published evidence on the benefits and risks of screening for COPD among asymptomatic adults. This Evidence Report,5 which supports the USPSTF Recommendation Statement,6 both of which are published in this issue of JAMA, considers the accuracy of various screening tools, including screening questionnaires and prebronchodilator spirometry; whether screening for COPD improves the delivery and uptake of targeted preventive services or leads to benefits in terms of morbidity, mortality, or health-related quality of life; and the possible harms of screening for and treatment of mild to moderate COPD. This review and synthesis of the available evidence leads the USPSTF to recommend “against screening for COPD in asymptomatic adults” and to classify this as a D recommendation, indicating that “there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”7 The USPSTF notes that this recommendation applies only to asymptomatic adults who do not recognize or report respiratory symptoms to their clinician. Critical to the assessment is the USPSTF’s reasonable conclusion that current medical treatments for COPD reduce symptoms and exacerbations while not necessarily altering natural history or reducing mortality. In persons with screen-detected rather than clinically diagnosed COPD, symptoms may be absent and exacerbations infrequent, so treatments that reduce symptoms and exacerbation frequency may provide less benefit.
Even though the USPSTF recommends against screening asymptomatic adults, its report points out that this recommendation is not applicable to “at-risk persons who present to clinicians with symptoms.” For patients presenting with dyspnea and other respiratory symptoms, clinically appropriate diagnostic testing, perhaps including pulmonary function testing, is certainly warranted. The USPSTF Recommendation Statement also “encourages clinicians… to pursue active case-finding for COPD in patients with risk factors, such as exposure to cigarette smoke….”6 These recommendations require consideration of the difference between screening, ie, testing large numbers of apparently healthy people to detect unrecognized disease at an earlier stage, and case-finding, ie, evaluating subgroups of people at increased risk of having a disease to make a diagnosis earlier than would occur by waiting for them to present with symptoms or signs. The distinction between persons who are truly asymptomatic and those who have symptoms they have not reported—perhaps because they have not been asked—is a challenging concept in clinical care and research.
A number of the studies reviewed by the USPSTF used questionnaire-based approaches to help clinicians detect relevant symptoms, the clinical importance of which may be unappreciated by the patient.8 Such a questionnaire could be considered a focused and relevant “review of systems.”9 Several of these approaches have enhanced the identification of previously undiagnosed COPD, with the majority of the patients identified having mild to moderate airflow obstruction. As noted in the USPSTF Evidence Report,5 no prospective studies have confirmed improved morbidity, mortality, and health status in patients identified using these case-finding approaches with currently available therapeutic approaches.
The group that conducted the systematic review for USPSTF explicitly excluded analyses of studies that identified previously undiagnosed patients with severe airflow obstruction given their relative rarity in population-based spirometric screening studies (<5%).5 Currently available therapies have been shown to improve multiple measures of disease burden in this group, and accurate diagnosis and the institution of appropriate treatment have been recommended for these patients.2,10 Thus, case-finding approaches that can identify these patients with more severe disease in the primary care setting may be warranted. One investigative group has used a systematic approach to identify the optimal items that can be incorporated in a case-finding questionnaire to identify previously undiagnosed patients who have moderate to severe airflow obstruction or are at risk of COPD exacerbation.9,11 Prospective validation of such a targeted questionnaire-based case-finding approach, possibly combined with simple physiological testing such as peak expiratory flow rate measurement,12,13 is an important area for research.
While the USPSTF recommends against screening asymptomatic adults for COPD, it does recommend that clinicians ask all adult patients about their use of tobacco and offer tobacco cessation interventions to users of tobacco products.14 However, the advice to quit smoking often goes unheeded by patients. It is a logical hypothesis that screening all smokers with spirometry would sometimes reveal evidence of mild airflow obstruction and that awareness of this evidence of developing disease would in turn increase the rate of smoking cessation by affected smokers who want to prevent the progression from early to more advanced COPD. As reviewed in the current USPSTF Evidence Report,5 4 of 5 trials testing this hypothesis found that smoking cessation rates were not improved by screening spirometry. As smoking cessation is an intervention that does appear to alter the natural history of COPD progression,15 it is discouraging that an early COPD detection strategy does not appear to consistently increase cessation rates.
The USPSTF has done an admirable job in reviewing and interpreting available evidence, and the recommendation against screening of truly asymptomatic patients for COPD is well reasoned, as such screening has not been shown to result in a clear net benefit. More research is needed, however, with respect to the “active case-finding for COPD,” among patients with risk factors, that is encouraged by the USPSTF report. The effect of COPD case-finding approaches on health outcomes and health care expenditure has yet to be demonstrated. Additional investigation is required to develop innovative formats to identify persons with undiagnosed yet more severe COPD, or risk of developing severe airflow obstruction, that may be amenable to available treatments. Prospective examination of the benefit of such case-finding approaches on health care delivery and clinical outcomes is vital. Furthermore, if future therapies are developed that alter natural history and long-term health outcomes of “early” or “mild” COPD, the use of case-finding or even screening approaches may need to be reconsidered.
Corresponding Author: Fernando J. Martinez, MD, MS, Department of Medicine, Weill Cornell Medical College, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, 525 East 68th St, Room M-522, Box 130, New York, NY 10065 (firstname.lastname@example.org).
Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Martinez reported having received support from Forest, Janssen, GlaxoSmithKline, Nycomed/Takeda, Amgen, Astra Zeneca, Boehringer Ingelheim, Carden Jennings, CSA Medical, Ikaria/Bellerophon, Genentech, Merck, Novartis, Pearl, Pfizer, Roche, Sunovion, Theravance, Axon, CME Incite, the California Society for Allergy and Immunology, Annenberg, Inova Health System, Integritas, InThought, Miller Medical, the National Association for Continuing Education, Paradigm, Peer Voice, UpToDate, Haymarket Communications, St John’s Hospital, St Mary’s Hospital, the Western Society of Allergy and Immunology, Informa, Bioscale, Unity Biotechnology, Centocor, Gilead, Promedior, Ikaria, Kadmon, Vertex, Veracyte, the American Thoracic Society, Academic CME, Falco, MedScape, the National Association for Continuing Education, Axon Communication, Genzyme, Johnson & Johnson, Spectrum Health System, University of Texas Southwestern, and Biogen and having received grants from the National Institutes of Health and National Heart, Lung, and Blood Institute. Dr O’Connor reported receiving research funding from the National Heart, Lung, and Blood Institute via a subcontract from Dimagi, Inc, in which he has no financial interest.
Funding/Support: Funding for this editorial in part comes from the National Institutes of Health via grant 1R01 HL1144055 (Dr Martinez) and contract HHSN268201200010C (Dr O’Connor).
Role of the Funder/Sponsor: The National Institutes of Health had no role in the preparation, review, or approval of the manuscript.
Martinez FJ, O’Connor GT. Screening, Case-Finding, and Outcomes for Adults With Unrecognized COPD. JAMA. 2016;315(13):1343–1344. doi:10.1001/jama.2016.3274