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Abstract
Chronic obstructive pulmonary disease (COPD) is regarded as one of the leading causes of morbidity and mortality across the world, yet its proper diagnosis remains a challenge. Community-based population studies conducted in North and South America, Europe, Australia, and Asia have revealed that 10% to 12% of adults aged 40 years or older have evidence of persistent airflow limitation on spirometry, but only 20% to 30% of these subjects have been diagnosed with COPD. These studies collectively suggest that approximately 70% of COPD worldwide may be underdiagnosed. Conversely, other studies have shown that between 30% and 60% of patients with a previous physician diagnosis of COPD do not actually have the disease, and hence they have been overdiagnosed. In this review, we define under- and overdiagnosis and explore the prevalence and the burden of under- and overdiagnosis of COPD on both patients and healthcare systems. We further describe potential solutions to reduce the incidence of under- and overdiagnosis of COPD.
The 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) document defines chronic obstructive pulmonary disease (COPD) as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases” (1, 2). Symptoms of COPD are characterized by dyspnea, cough, and/or sputum production. Spirometry is required to establish a diagnosis of COPD in a patient with respiratory symptoms; the presence of a post-bronchodilator FEV1/FVC of less than 0.70 or a post-bronchodilator FEV1/FVC less than the fifth percentile of the lower limit of normal (LLN) confirms the presence of persistent airflow limitation and thus of COPD in patients with appropriate symptoms and a significant history of exposure to noxious stimuli.
Like other chronic diseases, the population prevalence of COPD is commonly measured either from health administrative data to determine the prevalence of diagnosed COPD in the population or via population surveys that determine the proportion of individual subjects within the community who report a previous physician diagnosis of COPD. The major limitation of these methodologies is that confirmatory spirometry demonstrating persistent airflow obstruction is rarely available to validate the diagnosis. Alternatively, the prevalence of disease can be estimated based on recruitment of randomly chosen adult volunteers from the population who receive spirometry to test for persistent airflow limitation. This methodology also has its limitations, because some subjects with persistent airflow limitation may be asymptomatic and therefore do not meet the diagnostic criteria for COPD, and others may have other causes of airflow limitation, such as asthma or bronchiectasis.
Heterogeneity in study methodology has resulted in significant variation in reported prevalence estimates (3). In the United States, 6.5% of adults self-reported having received a diagnosis of COPD in 2011 (4). A meta-analysis by Halbert and colleagues of 62 studies that included prevalence estimates of COPD from 28 different countries between 1990 and 2004 reported a pooled prevalence of COPD of 9.8% (when COPD was defined as post- bronchodilator FEV1/FVC < 0.70) (5). Estimates from 12 sites from the BOLD (Burden of Obstructive Lung Disease) study reported a prevalence of COPD of 10.1% when using the GOLD II–IV definition of COPD (post-bronchodilator FEV1/FVC < 0.70 and post-bronchodilator FEV1 < 80% predicted) (5). With the aforementioned data in mind, it is important to note that diagnosis of COPD is complex and is dependent on multiple factors, including a history of chronic exposure to inhaled substances, the presence of persistent airflow obstruction on spirometry, and the presence of symptoms suggestive of COPD (6).
Underdiagnosis occurs when a patient living with COPD has not been identified as having the condition. Underdiagnosis can occur either because the patient has not communicated his/her symptoms to a physician, because the physician has chosen not to assign a disease diagnosis to explain the patient’s symptoms, or because the physician has attributed the patient’s respiratory symptoms to a disease other than COPD. Conversely, overdiagnosis occurs when a patient is identified as having COPD when in fact the patient’s respiratory symptoms are not caused by COPD.
Both under- and overdiagnosis are associated with inappropriate treatment; underdiagnosis leads to failure to prescribe appropriate pharmaceutical and nonpharmaceutical therapies for COPD, and overdiagnosis leads to prescription of nonindicated therapies, which may expose the patient to adverse effects of medications without the potential for benefit.
The objective of this narrative review is to describe the prevalence of underdiagnosis and overdiagnosis of COPD globally and its burden on patients and healthcare systems. The causes of under- and overdiagnosis of COPD are explored, along with potential strategies to reduce the incidence of under- and overdiagnosis. Relevant articles pertaining to this topic were retrieved from the Medline and PubMed databases using the following search terms: COPD overdiagnosis, COPD underdiagnosis, COPD misdiagnosis, undiagnosed COPD, and COPD case finding. The search for articles was limited to the period between 2008 to 2018. Abstracts were assessed for potential relevance to the topic, and applicable articles were included in the review.
Lamprecht and colleagues investigated the prevalence of undiagnosed persistent airflow limitation and its determinants using data from four epidemiologic surveys in 27 countries (7). COPD was spirometrically defined in this study as post-bronchodilator FEV1/FVC less than the fifth percentile of the LLN for a healthy, nonsmoking population. Among the 30,874 participants, the prevalence of undiagnosed persistent airflow obstruction showed considerable variation across sites. Overall, 9.7% of adults had physiologic evidence of persistent airflow obstruction, defined as a post-bronchodilator FEV1/FVC less than LLN, and, in 81.4% of these subjects, chronic airflow obstruction had not been previously diagnosed (7).
Miravitlles and colleagues looked at the prevalence of persistent airflow limitation in Spain using a definition of post-bronchodilator FEV1/FVC less than 0.70. Among 4,274 adults aged 40 to 80 years, the prevalence of persistent airflow obstruction was 10.2%, with only 27% of those subjects identified having previously received a diagnosis of COPD (8). Similarly, the NHANES (National Health and Nutrition Examination Survey) study found obstructive lung disease (based on prebronchodilator spirometry) in 11.8% of randomly selected U.S. adults aged 20 to 79 years, and 72% reported having no previous physician diagnosis of obstructive lung disease (9). Analysis of the COLD (Canadian Obstructive Lung Disease) study, a population-based cohort, demonstrated that in 1,403 randomly selected participants, 244 (17.4%) had persistent airflow obstruction, and 192 of these 244 (79%) were undiagnosed (10).
The problem of underdiagnosis of persistent airflow obstruction is global and ubiquitous and extends beyond Western Europe and North America. For example, the prevalence of underdiagnosis in China is very similar to that for western countries. A population-based study in China sampled 20,245 adults and found an overall prevalence of persistent airflow obstruction of 8.2%. Of those subjects who had post-bronchodilator airflow obstruction (FEV1/FVC < 0.70), only 35% had a previous physician diagnosis of COPD, suggesting that 65% of subjects with chronic airflow obstruction in China remain undiagnosed (11).
Taken together, these studies suggest that approximately 10% of adults aged 40 years or older in the developed world have evidence of persistent airflow obstruction on spirometry but that only 20% to 35% of these subjects have been previously diagnosed with COPD. The data consistently point to the fact that 65% to 80% of subjects living with chronic airflow limitation in the community remain undiagnosed.
A recent study by Çolak and colleagues sought to investigate the prevalence of symptomatic, undiagnosed COPD in the population using a cohort of 95,288 individuals aged 20 to 100 years from the Copenhagen General Population Study. From the assembled cohort, 32,518 individuals (34%) were deemed to be at high risk for COPD on the basis of an age 40 years or older, a cumulative tobacco consumption of 10 pack-years or more, and without a previous diagnosis of asthma. These subjects underwent prebronchodilator spirometry. COPD was defined as FEV1/FVC of less than 70% and less than the LLN and FEV1 of less than 80% of the predicted normal value. Of 32,518 screened subjects, 3,699 (11% of high-risk adults, 4% of all adults in the cohort) met physiologic criteria for COPD and 2,903 (78%) were undiagnosed, of whom 2,052 (71%) were symptomatic and hence met all diagnostic criteria for COPD (12).
Most individuals with early or undiagnosed COPD are likely to be first encountered in the primary care setting. Studies have shown that underdiagnosis of COPD in primary care is substantial. A study by Hill and colleagues of 1,459 patients from three primary care sites who were 40 years and older and had a smoking history of at least 20 pack-years found that one in every five individuals who visited a primary care practitioner for any given reason had symptomatic COPD (defined as FEV1/FVC < 0.70 and an FEV1 < 80% predicted), and up to two-thirds of these patients were unaware of their diagnosis (13).
Spyratos and colleagues assessed 3,200 Greek subjects attending general practitioner offices to estimate the frequency of COPD underdiagnosis in the primary care setting. The study found that 342 symptomatic subjects (10.7%) had spirometry-defined COPD, of whom 180 (52.6%) had no prior diagnosis (14). Similarly, the PUMA (Prevalence Study and Regular Practice, Diagnosis and Treatment, among General Practitioners in Populations at Risk of COPD in Latin America) study demonstrated the large magnitude of COPD underdiagnosis in primary care. In this study of 1,743 patients, COPD was diagnosed in 309 using diagnostic criteria of a post-bronchodilator FEV1/FVC less than 0.70 and in 226 using LLN criteria. Underdiagnosis of COPD was as high as 77%, and individuals who had never been referred to a specialist were at greater risk of underdiagnosis (15). Table 1 summarizes recent studies investigating the prevalence of undiagnosed persistent airflow obstruction and underdiagnosed COPD within populations and within primary care practices.
| Study | Location and Cohort | Spirometric Definition of COPD | No. of Participants | Age (yr) | Prevalence of Underdiagnosed COPD in Subjects Identified with COPD Based on Definition (%) | Notes |
|---|---|---|---|---|---|---|
| Bednarek et al. (2008) (47) | Poland, Sierpc | Post-bronchodilator FEV1/FVC < 0.7 predicted value | 1,960 | ≥40 | 81.4 | Study limited to primary care practice |
| Miravitlles et al. (2009) (8) | Spain, the EPI-SCAN study | Post-bronchodilator FEV1/FVC < 0.7 | 4,274 | 40–80 | 73.0 | National Spanish epidemiologic cohort covering most of Spain |
| Hill et al. (2010) (13) | Canada, Ontario | FEV1/FVC < 0.7 and FEV1 < 80% predicted | 1,459 | ≥40 | 67.3 | Study limited to primary care practice |
| Queiroz et al. (2012) (48) | Brazil, Aparecida de Goiania | Post-bronchodilator FEV1/FVC < 0.7 | 200 | ≥40 | 71.4 | Study limited to primary care practice |
| Participants included have a >20 pack-year history of smoking or a >80 hour-year history of exposure to biomass smoke and have sought medical attention at one of the selected primary healthcare clinics included in the study | ||||||
| Bárbara et al. (2013) (49) | Portugal, Lisbon | Post-bronchodilator FEV1/FVC < 0.7 | 710 | ≥40 | 86.8 | Study limited to primary care practice |
| Ancochea et al. (2013) (50) | Spain, the EPI-SCAN study | Post-bronchodilator FEV1/FVC < 0.7 | 3,802 | 40–80 | Women: 86.0 | National Spanish epidemiologic cohort covering most of Spain |
| Men: 67.6 | ||||||
| Weiss et al. (2014) (51) | Austria, Salzburg | Post-bronchodilator FEV1/FVC < 0.7 | 1,230 | ≥40 | 77.6 | Study limited to primary care practice |
| Cabrera et al. (2014) (52) | Spain, the Canary Islands | Post-bronchodilator FEV1/FVC < 0.7 | 1,353 | 40–70 | 71.6 | Subjects were randomly selected from a population of 596,478 individuals |
| Martinez et al. (2015) (9) | United States, the NHANES participants | Prebronchodilator FEV1/FVC < 0.7 | 1,636 | 20–79 | 72.0 | No post-bronchodilator spirometry to identify airflow obstruction performed |
| Quach et al. (2015) (53) | Northern France, Lille and Dunkirk, the ELISABET study 2011–2013 | Prebronchodilator FEV1/FVC < 0.7 | 3,276 | 40–64 | 70.0 | Study only limited to middle-aged individuals |
| No post-bronchodilator spirometry to identify airflow obstruction performed | ||||||
| Llordés et al. (2015) (54) | Spain, Catalonia | Post-bronchodilator FEV1/FVC < 0.7 | 1,738 | ≥45 | 56.7 | Study only included smokers in the primary care setting; 84% of study participants are men |
| Lamprecht et al. (2015) (7) | International study, (44 sites, 27 countries) using 4 epidemiologic surveys: BOLD, PLATINO, EPI-SCAN, and PREPOCOL | Post-bronchodilator FEV1/FVC < LLN | 30,874 | Mean, 56 | 81.4 | Heterogeneity of underdiagnosed COPD based on site. Different tools and brands of spirometers with different protocols and maneuvers used in centers |
| Spyratos et al. (2016) (14) | Greece, Thessaloniki | Post-bronchodilator FEV1/FVC < 0.7 | 3,200 | ≥40 | 52.6 | Study limited to primary care practice and to patients who were current or former smokers with at least 10 pack-year smoking history |
| Casas et al. (2016) (15) | Latin America, 4 Latin American countries for the PUMA Study: Argentina, Colombia, Venezuela and Uruguay | Post-bronchodilator FEV1/FVC < 0.7 and the LLN | 1,743 | ≥40 | 77.0 | Study limited to primary care practice |
| Echazarreta et al. (2018) (55) | Argentina, six urban locations, the EPOC.AR study | Post-bronchodilator FEV1/FVC < 0.7 | 3,469 | ≥40 | 77.4 | Study limited to urban settings in Argentina |
| Çolak et al. (2017) (12) | Denmark, Copenhagen General Population Study | Pre-bronchodilator FEV1/FVC < 0.7 and <LLN, and FEV1 < 80% of the predicted normal value | 95,288 | 20–100 | 78.0 | No post-bronchodilator spirometry to identify airflow obstruction performed |
| Gershon et al. (2018) (10) | Canada, CanCOLD Study | Post-bronchodilator FEV1/FVC < 0.7 | 1,403 | ≥40 | 79.0 | Subjects were randomly selected from the population |
Using data from multiple surveys, Lamprecht and colleagues demonstrated that the probability of COPD underdiagnosis increased with male sex, younger age, lower education, a never or current smoking status, lack of previous spirometry, and milder severity of airflow limitation (7). Similar results were demonstrated by Gershon and colleagues using the Canadian COLD cohort (16). In multivariable analysis, older age, male sex, a smoking history of more than 20 pack-years, respiratory symptoms, a codiagnosis of asthma, and low overall comorbidity were more likely in people with undiagnosed COPD than in the general population (16). Using the NHANES cohort, Martinez and colleagues further demonstrated that patients with undiagnosed obstructive diseases (both COPD and asthma) were those who frequently reported better health status on health surveys, had overall low comorbidity burden, and were of an ethnic minority (9).
Studies have shown that an important factor contributing to COPD underdiagnosis is the underuse of spirometry, particularly in the primary care setting (7, 17). Although spirometry is considered an essential test for making a diagnosis of COPD, poor access to spirometers and lack of expertise in performing and interpreting spirometry limit its use in primary care (17).
A U.K. study demonstrated that women had more missed opportunities in primary care for COPD diagnosis than men. A proposed explanation was that general practitioners are less likely to suspect COPD in women than in men (18). Underdiagnosis of COPD in the community can also occur because patients minimize and adapt to their chronic COPD symptoms, resulting in underreporting of respiratory symptoms to their doctors (19).
Very few data exist documenting the burden of underdiagnosed disease in the population. A recent study by Labonté and colleagues examined 505 subjects selected from a random sample of the Canadian population, all of whom had spirometry-defined COPD (20). Of these subjects, 150 had physician-diagnosed COPD and 355 (70%) were undiagnosed. Although subjects with undiagnosed COPD experienced fewer exacerbations than those with diagnosed COPD in 1 year (0.30 vs. 0.63 exacerbations per patient-year), they used health services to treat exacerbation-like events, including hospitalizations, emergency department visits, and unscheduled doctor visits, in an equivalent manner to that of diagnosed subjects (20). In this study, where more than two-thirds of the cohort had undiagnosed COPD, one would appreciate the cost inflicted by COPD exacerbation management in undiagnosed subjects and the possible underestimation of COPD management costs on healthcare systems. Furthermore, the Labonté study demonstrated that even subjects with milder COPD severity contributed significantly to the burden of COPD exacerbations, highlighting that burden on healthcare systems is experienced across all COPD severity groups.
A recent study by Gershon and colleagues sought to investigate the healthcare services burden of underdiagnosed COPD using data from 1,403 Canadian subjects. The study demonstrated that undiagnosed participants attended ambulatory care visits significantly more often than those without COPD (10). Patients with mild undiagnosed disease (GOLD I) had similar rates of hospitalizations and emergency department visits compared with subjects with normal spirometry but had slightly higher rates of ambulatory care visits than people without COPD. Patients with moderate to severe undiagnosed COPD (GOLD II–IV) visited hospital 60% more frequently than people without COPD (10). A retrospective study in the United Kingdom demonstrated that individuals with undiagnosed COPD used considerable health services in the period before they were diagnosed but did not compare their use with that of the general population (18).
Using the NHANES cohort, Martinez and colleagues demonstrated that patients with undiagnosed COPD had better lung function than those with physician-diagnosed COPD; however, their mortality risk remained up to 23% greater than subjects without airflow limitation (9).
As with COPD underdiagnosis, COPD overdiagnosis is a potentially important public health problem, although fewer data are available on the extent of its prevalence. Current figures suggest that approximately one-third to one-half of patients labeled with COPD in the primary care setting have been overdiagnosed (21–23).
Collins and colleagues analyzed 5,493 U.S. veterans with a previous physician diagnosis of COPD (24). Of these subjects, 48% did not have evidence of airflow obstruction on post-bronchodilator spirometry and thus did not meet diagnostic criteria for COPD (24). A population-based cohort study demonstrated that in 1,403 randomly selected Canadian participants 72 (5.1%) were overdiagnosed and 52 (3.7%) had correctly diagnosed COPD, suggesting that up to 58% of Canadians labeled with COPD have been overdiagnosed (10). Patients from this study were from Ontario, Canada, where only about one-third of individuals with physician-diagnosed COPD have been found to receive spirometry to confirm their diagnosis (25).
Spyratos and colleagues conducted a cross-sectional study of 3,200 adults aged 40 years or older in Greek primary care (14). In their assembled cohort, 468 subjects had a prior physician diagnosis of COPD and had been prescribed inhaled drugs for at least 12 consecutive months during the last 5 years. Of these subjects, 306 (65%) had no evidence of post-bronchodilator airflow obstruction, suggesting that in these subjects COPD was overdiagnosed (14).
A study of an underserved, mostly uninsured cohort in the United States found that only 14 out of 80 subjects (18%) treated for a previous diagnosis of COPD or on an anticholinergic inhaler had undergone previous spirometry testing. Spirometry testing of these subjects revealed that 42% had no airflow obstruction (26). Data extrapolated from London general practices identified 3,537 of 310,775 patients with a physician diagnosis of COPD. Spirometry was recorded for only 2,458 (69%) of these patients, of whom 709 (29%) did not meet GOLD criteria for COPD (27). These results collectively indicate that the prevalence of COPD overdiagnosis is dependent on the clinical setting and type of population in which it is being estimated, with a recurrent theme of spirometry underuse in making the diagnosis. Table 2 summarizes recent studies investigating the prevalence of overdiagnosed COPD.
| Study | Location and Cohort | Definition of COPD | No. of Participants | Age (yr) | Prevalence of Overdiagnosed COPD in Subjects Previously Diagnosed or Treated for COPD but Not Meeting COPD Criteria (%) | Notes |
|---|---|---|---|---|---|---|
| White et al. (2013) (27) | United Kindom, London | Prebronchodilator FEV1/FVC < 0.7 | 3,537 | Mean, 70 | 29 | Study limited to primary care practice |
| Ghattas et al. (2013) (26) | United States | Post-bronchodilator FEV1/FVC < 0.7 | 80 | Mean, 53 | 42.5 | Study limited to an uninsured and underserved population in the United States |
| Collins et al. (2014) (24) | United States | Post-bronchodilator FEV1/FVC < LLN | 5,493 | Mean, 64 | 48 | Participants were limited to veterans with previous COPD diagnosis from three Pacific Northwest veterans’ hospitals |
| Spyratos et al. (2016) (14) | Greece, Thessaloniki | Post-bronchodilator FEV1/FVC < 0.7 | 3,200 | ≥40 | 65 | Study limited to primary care practice and to patients who were current or former smokers with at least 10 pack-year smoking history |
| Gershon et al. (2018) (10) | Canada, CanCOLD Study | Post-bronchodilator FEV1/FVC < 0.7 | 1,403 | ≥40 | 58 | Subjects were randomly selected from the population |
Table 3 summarizes known risk factors associated with overdiagnosis of COPD. Gershon and colleagues demonstrated that, compared with people with true COPD, people with overdiagnosed COPD were more likely to be younger, nonsmokers, and have older physicians (16). The Gershon study also demonstrated that COPD overdiagnosis was associated with underuse of spirometry (16). Presumably underuse of spirometry can lead to nonspecific symptoms, such as dyspnea and productive cough, being labeled as COPD without use of formal post-bronchodilator spirometry to confirm the diagnosis.
| Overdiagnosis | Underdiagnosis |
|---|---|
| Underuse of spirometry in making diagnosis (17) | Underuse of spirometry in making diagnosis (17) |
| Technical errors in performing and interpreting spirometry (31–35) | Codiagnosis of asthma (16) |
| Younger age (16) | Male sex (7) |
| Diagnosis by an older physician (16) | Lower education levels (7) |
| Nonsmoking history (16) | Ethnic minority background (9) |
| Other comorbidities affecting spirometry interpretation or comorbidities that present with clinical symptoms that overlap with symptoms of COPD: | Minimization of symptoms and underreporting of symptoms to physicians (9, 16) |
| Obesity | |
| Congestive heart failure | |
| Asthma |
Unfortunately, even when spirometry is performed, it may not meet the quality standards for proper identification of COPD. A recent systematic scoping review found that overdiagnosis of COPD most commonly occurred because of an incorrect threshold used for defining COPD, errors linked to the spirometry test itself, errors in differentiating COPD from other diseases, and, finally, patient-related factors affecting spirometry interpretation (e.g., obesity). Most of these errors were noted to take place predominantly in the primary care setting (17). Clinical audits looking at medical care delivered to patients with COPD in the outpatient and inpatient settings have demonstrated potential variability in the assessment, clinical interventions, and adherence to current COPD practice guidelines among different healthcare settings. This variability could potentially also introduce a source for COPD misdiagnosis (28–30).
Improvements in COPD diagnosis in primary care may require more than the simple provision of spirometry equipment to these practices. Many other barriers have been reported, such as lack of time, shortage of trained medical assistants to perform testing, lack of training in interpreting the spirometry, and the perception that having spirometry results will not add benefit. Ongoing support is a key factor in improving use and quality of spirometry in primary care (31–35).
An additional potential cause of overdiagnosis of COPD can involve the problem of diagnostic instability in spirometry testing. Diagnostic instability is defined as the transient crossing of the COPD diagnostic threshold (defined as FEV1/FVC < 0.70, or an FEV1/FVC ratio below the 5% percentile of LLN) that occurs and then reverses on subsequent testing. Fluctuation in spirometric measures below the FEV1/FVC threshold for defining airflow limitation can lead to a shift in which a patient being labeled as having COPD on one visit would be labeled as normal on subsequent visits.
Using data from the LHS (Lung Health Study) and the CanCOLD (Canadian Cohort of Obstructive Lung Disease) study cohorts, Aaron and colleagues demonstrated that in subjects with mild to moderate airflow obstruction, diagnostic instability occurred commonly (36). Over the 5-year duration of the LHS, diagnostic instability occurred in 19.5% when using the 5% LLN threshold. Investigators from the PLATINO (Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar) group have also described diagnostic instability in two population-based surveys of subjects repeatedly tested with spirometry (37). Inconsistent diagnosis of mild COPD was observed in 11.7% when using FEV1/FVC less than 0.70 and 4.1% when using the GOLD II–IV criteria. These findings suggest that subjects with mild or moderate airflow obstruction and those whose post-bronchodilator spirometry results fall close to the diagnostic threshold for COPD might be at higher risk of a false-positive COPD diagnosis on the basis of a single post-bronchodilator spirometric measurement. For this reason, the GOLD 2018 document currently recommends that for post-bronchodilator FEV1/FVC ratios between 0.6 and 0.8 on a single measurement, a repeat spirometry on a separate occasion should be performed, as the ratio may change secondary to biological variation. This recommendation is also important because individuals who exhibit significant variability from one visit to the next in their FEV1 and FEV1/FVC ratio, in the absence of exacerbations or changes in treatment, should also be tested for the possible diagnosis of asthma (1, 38).
Emerging studies regarding smokers who exhibit COPD symptoms, such as coughing, increased sputum production, and missed work days, but do not meet the standard spirometric criteria of airflow obstruction defined as FEV1/FVC less than 70% raise the question as to whether a new entity for the clinical definition of COPD should be considered in smokers. On the basis of our aforementioned discussion, these subjects could potentially be labeled as “overdiagnosed” COPD because of lack of evidence of airflow obstruction on spirometry despite their symptoms and similar use of medications and health services compared with individuals with confirmed COPD. These observations point to the possibility that the strict spirometric definition of COPD might result in considerable underestimation of disease burden in certain groups of individuals (39, 40).
Studies have investigated the burden of COPD overdiagnosis, particularly with respect to medication costs and hospitalizations that are otherwise not indicated. The cohort study by Spyratos and colleagues found that 65% of subjects with a diagnosis of COPD had been overdiagnosed, and 35% of these subjects were being treated with inhaled drugs that were potentially not indicated. The authors calculated that more than 55% of the costs of inhaled drugs in their cohort were wasted because of overtreatment and overdiagnosis (14).
Gershon and colleagues studied the healthcare burden of COPD overdiagnosis and demonstrated that individuals with overdiagnosed COPD had 89% higher rates of hospitalizations, 42% higher rates of emergency department visits, and 52% higher rates of ambulatory care visits compared with people without COPD after adjustment for age and sex (10). The authors concluded that people with overdiagnosed COPD use more health services, because their true condition causing their respiratory symptoms remains untreated or undertreated and therefore symptomatic.
As of yet, no studies have been done to determine if correction of overdiagnosis of COPD, with treatment of the correct disease or condition that causes respiratory symptoms, would result in improved healthcare outcomes for patients and a reduced burden on healthcare systems. However, a population observational study of patients with physician-diagnosed COPD demonstrated that those who received spirometry to confirm their diagnosis were less likely to die or be admitted to the hospital than those who did not (41).
A recent systemic review published by the U.S. Preventative Task Force aimed at assessing the evidence available on the risks and benefits of screening for COPD among asymptomatic adults found no evidence to support using questionnaires or office-based screening pulmonary function testing or benefits of treatment in screen-detected populations (42). In light of these findings, the U.S. Preventative Task Force’s current recommendation is against screening for COPD in asymptomatic adults, as there are insufficient data available to support improvement of health-related quality of life, morbidity, or mortality (43).
It is important to distinguish the difference between screening, which involves the testing of a large number of individuals who are asymptomatic and otherwise healthy to detect a disease at an earlier stage, and case finding, which involves evaluating subgroups of individuals at a higher risk of having a disease, or subgroups with respiratory symptoms that remain unexplained, to make a diagnosis earlier than would otherwise be made.
A case-finding approach has been proposed as a potential means of identifying individuals at high risk of COPD and/or those with symptoms of COPD who remain undiagnosed. Although no one strategy has proved to be superior to another, individual studies have used different methods of targeting at-risk populations. A study by Jordan and colleagues using the Health Survey of England cohort demonstrated that an active case-finding strategy targeting ever-smokers aged 40 to 79 years, which involved mailing a symptoms questionnaire in addition to opportunistic identification by general or nurse practitioners, could potentially identify 70% more new cases of clinically significant COPD compared with opportunistic identification alone (36).
Nelson and colleagues proposed a staged approach to COPD case finding in adults for detecting clinically significant airflow obstruction while avoiding the need to conduct diagnostic spirometry on all individuals at risk (44). The three-stage approach consisted of a questionnaire-based screening test to detect COPD risk factors, followed by pocket spirometry to detect a peak expiratory flow (PEF) less than 70%, followed by diagnostic spirometry if PEF was less than 70% of predicted. This diagnostic approach demonstrated sensitivity and specificity of 40.7% and 97.7%, respectively, at detecting individuals with significant COPD, suggesting the strategy is feasible for detecting airflow obstruction in the general population. However, the low sensitivity means that many subjects with undiagnosed COPD were missed (44).
A cross-sectional, case-control study by Martinez and colleagues proposed a novel case-finding approach for screening and identifying individuals with COPD in the primary care setting who would benefit from treatment (45). The study included 186 case subjects with COPD and at least one exacerbation in the past year or with an FEV1 less than 60% predicted without exacerbations in the past year, and 160 control subjects with no COPD or mild COPD defined as FEV1 greater than 60% predicted and no exacerbations in the past year. The CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk) instrument, composed of a simple patient-completed five-item questionnaire, followed by PEF measurements demonstrated a sensitivity of 90% and a specificity of 78% at differentiating cases from all control subjects and a sensitivity of 90% and a specificity of 93% at differentiating cases from control subjects without COPD (45).
Better education of clinicians on how to diagnose COPD and ensuring accessible spirometry are probably the most important steps to prevent the problem of COPD overdiagnosis. Avoiding COPD overdiagnosis starts by obtaining a proper history, including an environmental and occupational exposure history, and a physical examination. In all cases, the workup should include spirometry to determine whether the patient meets or does not meet diagnostic criteria for COPD. In Figure 1 we propose a potential algorithm for COPD diagnosis that can be used in both a primary care or specialized clinical setting.
Figure 1. Clinical approach to the diagnosis of COPD. CBC = complete blood count; COPD = chronic obstructive pulmonary disease; CT = computed tomography; ILD = interstitial lung disease; LLN = lower limit of normal.
[More] [Minimize]Studies that have assessed diagnostic instability suggest that subjects whose spirometry results fall close to the diagnostic threshold for COPD might be at higher risk of a false-positive COPD diagnosis on the basis of a single spirometry measurement (36, 37). Repeating spirometry at a second visit in subjects with readings close to the diagnostic threshold is a potential strategy to avoid overdiagnosis of COPD.
Although not currently recommended, there is new emerging evidence suggesting that spirometry performed before hospital discharge could have a potential role in improving the diagnosis of COPD. In a study of 179 patients admitted with COPD exacerbations, post-bronchodilator spirometry was performed before discharge and 8 weeks after discharge in 100 subjects. The results demonstrated that predischarge spirometry can be performed with acceptability and reproducibility criteria and has acceptable reliability when compared with spirometry performed at baseline, despite some variation in the classification of spirometric severity. These results demonstrated the potential role of spirometry performed during hospital admission for correct diagnosis and characterization of patients with COPD (46).
Under- and overdiagnosis of COPD remains a prevalent challenge and results in a significant burden on healthcare systems and patients. Many barriers continue to delay the recognition and diagnosis of COPD in primary care, including potential underreporting of respiratory symptoms and activity limitation by patients, limited access to spirometry, lack of expertise in spirometry interpretation, and lack of recognized and effective case-finding methods.
There are consequences to the underdiagnosis and overdiagnosis of COPD. Underdiagnosis leads to failure to prescribe appropriate pharmaceutical and nonpharmaceutical therapies for COPD. Overdiagnosis leads to a missed opportunity to diagnose the true cause of a patient’s symptoms and results in prescription of nonindicated therapies, which may expose the patient to adverse effects of medications and costs that could be avoided.
Case-finding strategies to identify subjects with unreported respiratory symptoms and those with higher risk of COPD could prove useful to help reduce the prevalence of undiagnosed COPD in communities. Better education of clinicians on how to diagnose COPD and ensuring accessible spirometry are important first steps to prevent the problem of COPD overdiagnosis. Ongoing support for primary care practitioners may be necessary to improve use and quality of spirometry in primary care. Translating quality care initiatives for COPD diagnosis into community practice would best be done in the context of research studies that could assess process changes and their effects on individuals’ health outcomes.
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Author Contributions: Conception and design: S.D.A. Data collection and synthesis: N.D., A.S.G., D.D.S., W.C.T., J.B., L.-P.B., and S.D.A. Drafting the manuscript for important intellectual content: N.D., A.S.G., D.D.S., W.C.T., J.B., L.-P.B., and S.D.A.
CME will be available for this article at www.atsjournals.org.
Originally Published in Press as DOI: 10.1164/rccm.201804-0621CI on July 6, 2018
Author disclosures are available with the text of this article at www.atsjournals.org.
