Characteristics of Subjects With Undiagnosed COPD Based on Post-Bronchodilator Spirometry Data

Discussion

This study aimed to explore the characteristics of subjects with undiagnosed COPD from the NHANES dataset (2007–2012). The statistical analysis showed a multitude of factors that characterize the subjects. Overall, their health status was superior to that of diagnosed subjects given that they had fewer symptoms and were less limited in their daily lives. The undiagnosed subjects also had better lung function as exhibited by higher FEV₁ and FVC.

A study by Martinez et al⁸ explored the characteristics of undiagnosed COPD based on the NHANES dataset. However, their analysis was based on pre-bronchodilator spirometry, and COPD should be confirmed based only on post-bronchodilator spirometry.² In our study, we therefore focused on subjects in whom post-bronchodilator spirometry had been performed and who had a post-bronchodilator FEV₁/FVC < 0.7. The study by Martinez et al⁸ identified the following characteristics of subjects with undiagnosed COPD from the NHANES dataset 2007–2012: female sex, higher age, lower body mass index (BMI), fewer respiratory symptoms, and higher FEV₁. These results partly mirror our findings where fewer respiratory symptoms, and a higher FEV₁ characterized subjects with undiagnosed COPD. However, in our study neither higher age, female sex, nor lower BMI was statistically significantly associated with undiagnosed COPD.

The results of our study are comparable to those of a Norwegian study, which also found that undiagnosed subjects with COPD were characterized by better lung function and fewer respiratory symptoms than diagnosed subjects. Similar results were also found in an international study by Lamprecht et al¹² in which undiagnosed COPD was related to less severe air-flow limitation. However, the results from Lamprecht et al differs from our findings because they found, among other things, that undiagnosed subjects were more likely to be male, younger, and have lower education.¹² The findings of our study also mirror those of a Brazilian study, which found an association between undiagnosed COPD and less wheezing and less severe disease.⁹ Thus there seems to be general agreement between these studies and ours, subjects with undiagnosed COPD have better lung function and fewer symptoms than those diagnosed with the disease. However, the significance of other characteristics such as age, income, and educational level still needs to be determined.

Based on the results of this study, we are unable to explain why the subjects remained undiagnosed even though they had a post-bronchodilator FEV₁/FVC < 0.7. Our data does not reveal whether the undiagnosed subjects failed to see a doctor or if the doctor failed to diagnose the subjects. Fromer et al¹⁹ found that lack of knowledge and awareness of COPD may cause health care professionals to delay COPD diagnosis until the severity of the disease has progressed. COPD may be challenging to diagnose at an early stage due to milder symptoms. This mirrors the findings of Akamatsu et al,²⁰ who found that approximately half of their subjects with COPD never had any respiratory symptoms. Thus, patients with mild symptoms may be less inclined to see a doctor. In addition, one may assume that it is difficult for the doctor to determine a COPD diagnosis if the patient does not complain about respiratory symptoms. The rate of undiagnosed subjects in our study is very high: of 1,098 subjects with a post-bronchodilator FEV₁/FVC < 0.7, 1,005 subjects (91.53%) reported no previous diagnosis. This may be explained by the study definition of undiagnosed COPD. The subjects were asked if their doctor had ever told them that they had chronic bronchitis or emphysema. There is a risk that some subjects may not have understood the question and consequently responded negatively to the question despite a previous diagnosis. However, the fact that the undiagnosed subjects had fewer respiratory symptoms may also explain the high rate of undiagnosed subjects.

Spirometry criteria are also an important factor in COPD diagnosis.²¹ GOLD argues that the threshold of post-bronchodilator FEV₁/FVC < 0.7 should remain,²² whereas multiple studies argue that LLN should be used as an alternative threshold for defining COPD.^23–27 Woodruff et al²⁸ found that current or former smokers who did not meet the existing criteria for COPD had evidence of airway disease. Current or former smokers in their study had exacerbations, were limited in their activities, and were commonly treated with respiratory medication. These findings suggest that spirometry alone may not be sufficient to diagnose COPD correctly.²⁸ Similarly, Brusasco et al²⁹ concluded that spirometry should not be the only pulmonary function test in COPD. Further investigation of alternative pulmonary function tests is recommended to avoid misclassification of COPD.

Overdiagnosis also represents a challenge in COPD. A recent study by Spero et al³⁰ found that approximately one third of hospitalized subjects with a COPD diagnosis might not have COPD. Several factors were associated with overdiagnosis, including various comorbidities, high BMI, and less smoking.³⁰ These findings are in line with other studies that have explored the rate of COPD overdiagnosis, with a rate ranging from 27.2–51.6%.³¹ Future research may explore the characteristics of overdiagnosed patients to optimize COPD diagnosis.

A report by the U.S. Preventive Services Task Force concluded that no direct evidence supports that screening patients for COPD using spirometry will improve their health outcomes in the long term.³² This conclusion echoes the most recent recommendations by GOLD, which state that no evidence supports the introduction of screening spirometry to inform management decisions or improve outcomes in subjects without significant symptoms. However, GOLD does recommend active COPD case finding.³ A study based on data from the Burden of Obstructive Lung Disease Study (BOLD) suggests that focused case findings based on a simple peak-flow assessment will improve COPD case finding as opposed to using a screening questionnaire.³³ Another study by Jordan et al³⁴ found that a case finding approach including questionnaires would identify significantly more new cases of COPD.³⁴ We may safely assume that strategies for COPD case finding still require further development and testing. Our study adds input to that development, and we assume that a focused algorithm based on known characteristics of undiagnosed patients with COPD may improve COPD case finding.

This study has some limitations. One is the fact that the included subjects were not asked directly if they had a COPD diagnosis. Instead, we presumed the presence of a diagnosis if the subjects responded affirmatively when asked if they had been told that they had chronic bronchitis or emphysema. Some subjects with a COPD diagnosis may therefore have been wrongfully defined as undiagnosed, and vice versa. However, the procedure of defining diagnosed COPD as a positive response to having chronic bronchitis/emphysema was used in similar studies,^8,35 and it is considered the best available solution when using the NHANES dataset. Another limitation is that the presumed COPD diagnosis is based solely on spirometry, as a COPD diagnosis should ideally rest on a more holistic assessment.² However, spirometry is the key to COPD diagnosis,² which justifies the use of a spirometry-based definition of COPD. This study was limited by the fact that not all potential characteristics of subjects with undiagnosed COPD were available in the NHANES data set, so history of lower respiratory tract infection, peripheral artery disease, peptic ulcer, and edema were not considered. Future studies may find it relevant to look into these characteristics as well. Finally, our sample may not be representative across all COPD severity grades as one may assume that the more severe cases are less likely to participate in a survey such as the NHANES. Thus, precaution is required when applying the present results to all COPD severity grades.