Introduction
Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory disease characterized by persistent airflow limitation [1]. Despite ongoing efforts to optimize treatment, COPD is the third leading cause of death globally, with underdiagnosis still common [2,3]. In 2022, the Lancet Commission published a position paper outlining strategies for the elimination of COPD [4]. In line with this, novel concepts such as pre-COPD and early COPD have emerged to facilitate early detection and intervention [5]. In addition, technological advances, such as advanced chest computed tomography (CT) techniques and forced oscillometry, may enhance early diagnosis beyond traditional pulmonary function tests (PFTs) [6,7]. For example, CT can detect dysanapsis, a mismatch between airway tree dimensions and lung size, which could influence lung function trajectories and may be risk factor of COPD development [8]. Additionally, respiratory oscillometry can assess increased airway resistance, a key pathological feature in COPD progression [9]. Nevertheless, PFTs remain central to the diagnosis and management of COPD [10]. This review will discuss the current challenges of performing spirometry in clinical practice and share potential solutions for the future.
The Challenges of Obtaining and Interpreting Spirometry in Clinical Practice
Spirometry plays an important role in the diagnosis and management of multiple respiratory diseases, including COPD. The usual indications of PFTs are as follows [11]: (1) diagnosing respiratory diseases, such as COPD, asthma, and interstitial lung diseases; (2) assessing the severity and progression of known respiratory diseases, enabling clinicians to monitor how the disease evolves and how effective current treatments are; (3) preoperative evaluations, particularly before surgeries that may impact respiratory function, which is especially relevant for patients with existing lung conditions; and (4) conducting epidemiological survey to enhance public health. However, the role of PFTs in screening high-risk populations, such as smokers or individuals with significant occupational exposures, remains uncertain. It has not been definitively proven that screening asymptomatic individuals for COPD provides significant benefits in terms of improving quality of life, reducing morbidity, or mortality [12]. However, there is evidence that screening symptomatic individuals, also called case finding, can reduce healthcare utilization [13].
The primary issue with spirometry as a method of diagnosis for COPD in primary care is its limited availability compared to other testing methods for common chronic conditions [14,15]. In particular, spirometry is often underused in primary care compared to sphygmomanometers, which are routinely used for hypertension diagnosis. Most primary care clinics have multiple devices to measure blood pressure that medical assistants are proficient in using. Home use of automated sphygmomanometers is also widely available and inexpensive. Many patients own their own devices and can provide multiple blood pressure readings to their physicians [16].
In contrast, PFTs usually require a well-trained technician to perform the test, and the procedure itself is more intricate [17]. Data suggest that spirometry can be performed within primary care, with reliability comparable to that seen in pulmonary function laboratories [18-20]. Nevertheless, if testing is performed infrequently, then test quality and the ability to interpret results can wane. Ongoing support is a key factor in improving the use and quality of spirometry in primary care [21,22]. Moreover, interpreting PFT results is challenging, as multiple parameters should be adjusted for factors such as age, sex, and height [23,24]. This complexity contributes to the perception—particularly in Korea—that PFTs should be conducted exclusively by respiratory specialists or in general hospitals [25].
Further adding to the confusion, multiple interpretation guidelines have been published. Global Initiative for Chronic Obstructive Lung Disease (GOLD) continues to advocate for diagnostic criteria based on a post-bronchodilator fixed ratio (forced expiratory volume in 1 second [FEV1]/forced vital capacity <0.7) which is easy to remember and interpret [5]. A criticism has been raised that this criterion may be insensitive to early COPD. While the lower limit of normal (LLN) has been proposed as an alternative diagnostic criterion, it may be harder to implement in primary care settings and could also contribute to overdiagnosis in the elderly population. LLN values are based on the normal distribution and classify the bottom 5% of the healthy population as abnormal. An equivalent approach is to use z-scores (equivalent to the number of standard deviations the observed value is above or below the mean value). A z-score of -1.645 is equivalent to the 5th percentile. This approach for COPD diagnosis is highly dependent upon the reference population equations which is another reason GOLD advocates for the use of the fixed ratio.
In terms of disease severity, percent predicted values referenced against normal values have historically provided a standardized method to establish stage severity [11,26]. These values have traditionally been calculated based on demographic factors such as age, sex, height, and race [27]. However, in recent years, American Thoracic Society (ATS) and European Respiratory Society (ERS) have recommended using z-scores as opposed to percent predicted values to stage COPD. This approach proposes a tiered severity system: z-scores >-1.65 are normal; -1.65 to -2.5 are mild disease; -2.51 to -4 are moderate disease, and <-4.1 are severe disease [28]. Some patients will be classified differently depending on severity as determined by z-scores. However, most clinical trial data supporting disease management have been based on the GOLD percent predicted staging criteria. In addition, currently GOLD recommends using the recently published, race-neutral Global Lung function Initiative (GLI)-Global equations for reference values, which are also recommended by ATS and ERS [29]. In Korea, Choi’s formula was the first to be introduced, and another updated formula, along with the GLI formula, is also used to calculate predicted values [29-31].
Potential Solutions
Unfortunately, from a primary care perspective, the debate over reference equations and staging severity systems is likely to have only introduced further confusion in an area where primary care clinicians were already uncomfortable. To encourage the widespread use of spirometry, it may be necessary to expand indications and simplify procedures in certain circumstances. Other methods for identifying patients with COPD may also need to be considered.
1. Use of prebronchodilator values
While GOLD defines the presence of COPD based on post-bronchodilator spirometry, administration of a bronchodilator is time-consuming and adds another hurdle to the more widespread use of spirometry. A concern raised regarding the use of pre-bronchodilator values for the diagnosis of COPD has been the potential for overdiagnosis, as some individuals may not satisfy COPD diagnosis criteria based on post-bronchodilator values. Interestingly, a study using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort has shown that when airflow limitation is observed in pre-bronchodilator values, the risk of developing COPD increases, even if no airflow limitation is observed on the post-bronchodilator test [32]. In addition, pre-bronchodilator lung function predicted mortality similarly to post-bronchodilator lung function [33]. To address this, GOLD now suggests that pre-bronchodilator spirometry should be used as an initial test to screen for COPD, and if abnormal, post-bronchodilator spirometry should then be performed. This allows for a simpler test to be performed in primary care with post-bronchodilator spirometry being performed in a more formal pulmonary function laboratory.
2. Use of raw values without predicted values
The multiple pulmonary function reference equations now available as well as the multiple methods that have been proposed for how they should be applied have caused confusion even among pulmonologists and represent another potential barrier to the widespread use of spirometry in primary care settings [34,35]. In this context, the use of raw spirometry values in the management of COPD could enhance the accessibility and comprehension of PFT results for the public and non-specialists.
Further to this point, there has been renewed attention on the utility of the FEV1 quotient (FEV1Q), a value derived by dividing the raw FEV1 by a constant [36]. FEV1Q is calculated by dividing FEV1 by 0.5 L for men and 0.4 L for women, with values closer to 1 indicating worse lung function [37]. If FEV1Q could represent COPD severity and predict outcomes as effectively as FEV1 percent predicted, it could allow for a more straightforward interpretation of PFTs. However, the optimal cut-off value for FEV1Q in defining abnormality remains unclear at the current moment. Additionally, further validation is required across various subgroups, including race, age, COPD etiotypes, and comorbidities [38]. More extensive research will be needed to explore the generalizability and clinical utility of FEV1Q.
3. Impulse oscillometry
Impulse oscillation system (IOS) is a technique used to measure airway resistance and reactance [39]. The technique employs rapid pressure pulses to measure the resistance of small airways and detect small airway dysfunction. Forced oscillation technique (FOT) is similar to IOS, but uses continuous sinusoidal pressure waves to assess small airway function. More specifically, classical FOT transmits sound waves of different frequencies sequentially as a mixture of sinusoidal waveforms, whereas IOS delivers an impulse in the form of a rectangular waveform, which can be mathematically decomposed into multiple frequencies [40]. IOS is considered more user-friendly and may be more practical in primary care settings as it only requires normal breathing as opposed to the forced breathing maneuvers used in spirometry. Several studies suggest that IOS may be useful in the diagnosis of COPD or, at a minimum, identifying patients who should proceed to spirometric testing [41,42].
Discussion
The current challenges and potential solutions were summarized in Figure 1.
Kim: Just as blood pressure and blood glucose can provide a preventive strategy for future disease development, parameters from PFTs may play a role in the early detection and intervention of lung diseases. However, PFTs have not yet been widely recognized as a standard tool for routine screening. What could be the solution to this issue?
Han: I fully agree with you that the lack of widespread use of spirometry has significantly contributed to the underdiagnosis of COPD. While we discuss several potential solutions here, I think that if we could impress upon both the public and primary care providers the importance of spirometry as well as make spirometers with automatic interpretation more widely available similar to automated blood pressure cuffs, this would be a huge improvement. We don’t need spirometry done in the home or primary care office to be perfect. We just need to identify people who should go on for confirmatory testing in a pulmonary function lab.
Kim: Although the current GOLD document suggests that a pre-bronchodilator test can be used to screen for the presence of airflow limitation, the diagnosis of COPD still mandates performing a bronchodilator test. Could the widespread utilization of PFTs become more feasible if COPD could be diagnosed without a bronchodilator test? While there is a risk of overdiagnosis and misdiagnosis when relying on pre-bronchodilator values, is it possible, at least in primary clinics for specific populations, such as those at risk of underdiagnosed airflow limitation?
Han: This is a good question. What I can say is that this is a different patient population from those studied in clinical trials, so we don’t know for sure what their benefits to current therapies are. We do know that patients who do not have obstruction based on post-bronchodilator values but do have obstruction based on pre-bronchodilator values are at high risk and need to be monitored closely. For now, I continue to stand by the GOLD recommendation that pre-bronchodilator values be used for screening.
Kim: What do you think about using raw PFT values in the management of COPD, such as FEV1Q? For more precise information, adjustments should be used, however, it is undeniable that body weight is more intuitive than body mass index to the public. Public interest in lung function assessment may increase as acceptable lung function values from direct measurements become more widely understood.
Han: Again, we don’t know much about a patient population diagnosed with this method versus fixed ratio post-bronchodilator spirometry. We would need more information before widespread dissemination.
Conclusion
PFTs are central to diagnosing and managing chronic respiratory diseases, yet they are not as widely utilized as they should be. To facilitate the utilization of PFTs, efforts should focus on expanding their indications, simplifying testing procedures, and making interpretation more accessible. Ultimately, these steps could lead to the increased use of PFTs in health screenings and clinical practice.
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