Reliability of Pulmonary Function Tests in Patients with Chronic Obstructive Pulmonary Disease

Background

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung disease characterized by persistent respiratory symptoms such as dyspnea, coughing, sputum production, and/or exacerbations. It results from structural changes in the airways and alveoli that lead to persistent, often progressive airflow limitation.¹ In the appropriate clinical context, airflow obstruction that is not fully reversible, demonstrated by spirometry, is the most important diagnostic finding. Although COPD is a well-established lung disease, most of the subjects remain underdiagnosed in population based studies.² The most significant reason of underdiagnosis is the low rate of pulmonary function tests (PFT), especially spirometry utilization. Additionally, technical errors related to the quality of spirometric tests frequently result in incorrect diagnoses.³

Previous research has identified that the proportion of high-quality spirometry in COPD cases was only 22.6% of the study group.⁴ These findings highlight significant challenges in access to spirometry and the proper execution of spirometry tests on a national scale.

Recent reports have emphasized that the reliability of spirometry largely depends on strict adherence to international standards for performance, calibration, and quality control.^5–7 Studies from different countries have shown that suboptimal test quality, inadequate technician training, and inconsistent use of reference equations significantly affect diagnostic accuracy and the estimation of COPD prevalence.^8,9

Therefore, evaluating the technical quality and reporting standards of pulmonary function tests in routine clinical practice remains crucial for ensuring diagnostic validity and improving patient outcomes.

This study aims to assess the quality of spirometric testing in patients diagnosed with COPD. Understanding the errors in PFT reporting and interpretation could be valuable in developing and targeting interventions to improve COPD diagnosis.

Methods

This multicenter, prospective, and observational study was conducted by collecting spirometry test reports from six tertiary healthcare centers across three different cities in Turkey that agreed to participate between May and July 2020. The PFT laboratories of the participating centers met the standards, were qualified, and staffed with experienced PFT technicians who were well-trained and skilled. The study included post-bronchodilator spirometry reports of patients over 40 years of age, with a history of smoking >10 pack-years, and who were previously followed with a confirmed diagnosis of COPD based on clinical and pulmonary function tests (Table 1). These test reports were evaluated by two independent pulmonary specialists with expertise in the field.

Table 1 Distribution of Pulmonary Function Tests Evaluated from the Participating Centers

The reports were reviewed by the interpreters to collect information on patient demographics, body composition, technician details, device specifications, flow rates, reference values, graphs, test noncompliance, and errors. These details were then recorded in patient follow-up forms.

Statistical analyses were performed using SPSS version 22.0, with a significance level set at p<0.05. Descriptive statistics were employed to present data with a normal distribution, expressed as numbers (percentage) and mean ± standard deviation or median (min-max). The statistical reliability between the two interpreters was measured using Cohen’s Kappa Test (K). A Kappa coefficient 0.21–0.40 fair agreement, 0.41–0.60 moderate agreement, 0.61–0.80 substantial agreement, 0.81–1.00 almost perfect agreement was interpreted as indicating agreement between the two interpreters.¹⁰

In cases with very low event frequency or high agreement by chance, prevalence-adjusted bias-adjusted kappa (PABAK) values were also computed to account for the potential influence of prevalence and bias on K estimates. These adjusted values were used only for error categories with limited occurrences, such as mouth leak and mouthpiece obstruction.

Ethics Committee approval was granted by the Gazi University (Assessment and Evaluation Ethics Sub-Working Group) Human Research Ethics Committee with no 2019–106.

Results

A total of 560 spirometry tests reports of distinct patients were included in the study were reviewed by two independent interpreters. The mean age of the patients was found to be 65.92 ± 10.25 years. The study population consisted of 124 (22.14%) female and 436 (77.85%) male cases, with a mean body mass index (BMI) of 27.81 ± 6.14 kg/m².

The interpreters classified 443 (79.1%) tests as showing obstruction, 32 (5.7%) as suggestive of restriction, 15 (2.68%) as a mixed pattern, 38 (6.7%) as normal, 31 (5.53%) as non-compliant, and 1 (0.18%) as upper airway obstruction (Table 2).

Table 2 Pulmonary Function Tests Interpretation Results

When the spirometry test reports were reviewed, no written diagnosis was found in 289 (51.6%) tests. Obstruction was reported in 5 (1.84%) cases, and 4 (1.47%) cases were documented as erroneous tests. For 15 (2.68%) cases, it was indicated that the test was the first one, 291 (51.96%) cases were identified as follow-up tests, and no information regarding test sequence was provided for 254 (45.35%) cases.

Of all the spirometry tests, 488 (87.14%) were routine post-bronchodilator tests, while 72 (12.85%) were post-reversibility tests. Among the post-reversibility test group (n=72), the mean increase in FEV1 (% predicted) was 7 ± 1.2.

As for the reference values, 343 (86.4%) tests used ECSC, 36 (8.93%) tests used GLI, and 1 (0.25%) test used NHANES. In 180 (32.14%) reports, there was no information provided regarding which reference values were used. Some tests included both ECSC and GLI reference values.

The volume-time graph was present in 495 (88.5%) tests, while the flow-volume graph was available in 556 (99.64%) tests. The inspiratory limb was demonstrated in 550 (98.74%) tests. Increased concavity was reported in 83.2% of the tests (K=0.683), and small airway obstruction was noted in 87.1% of the tests (K=0.709) by the interpreters.

The mean FEV₁ and FVC values of the study group were 1.49 ± 0.7 L (57.17 ± 23.09, % predicted) and 2.41 ± 0.95 L (72.7 ± 24.96, % predicted), respectively, with a mean FEV₁/FVC ratio of 61.91 ± 14.31. The mean forced expiratory time (FET) was calculated as 5.61 ± 1.88 seconds (Table 3).

Table 3 Maximal Expiratory Flow Rates and FET

Participants were stratified according to WHO BMI categories as underweight (n = 33, <18.5 kg/m²), normal weight (n = 290, 18.5–24.9 kg/m²), overweight (n = 148, 25.0–29.9 kg/m²), and obese (n = 89, ≥30 kg/m²). When all cases were categorized according to standard BMI classifications, no significant differences were observed in the overall spirometry values across these categories. The obese group had significantly lower mean FVC, L and FVC % predicted values compared with the non-obese participants (2.07 ± 0.34 vs 2.63 ± 0.85 L, p = 0.04; 70.1 ± 27.34 vs 73.5 ± 14.62, p=0.03). Although the mean FEV₁/FVC ratio was higher in the obese group (63.91 ± 11.44 vs 60.23 ± 15.32), the difference was not statistically significant.

Regarding the inconclusive and erroneous test results identified by the two interpreters, variable and insufficient effort was the most frequently reported cause, noted in 67 (12%) tests (K=0.563). This was followed by early termination in 43 (7.7%) tests (K=0.852), rapid expiration in 19 (3.4%) tests (K=0.354), mouth leak in 17 (3%) tests (K=0.305), cough in the first second of respiration in 17 (3%) tests (K=0.677), and mouthpiece obstruction in 5 (0.9%) tests (K=0.332) (Table 4). Since the frequencies of some test errors were low, prevalence-adjusted bias-adjusted kappa (PABAK) analysis was performed as a more appropriate measure of inter-rater reliability. The PABAK values for mouth leak, mouthpiece obstruction, and rapid expiration were 0.94, 0.96, and 0.93, respectively (Table 4).

Table 4 The Rates of Inconclusive and Erroneous Tests in Pulmonary Function Tests Evaluation

Discussion

In this study, spirometry reports of patients diagnosed with COPD from various centers were evaluated to assess the quality of spirometry tests across the country. COPD is defined as a chronic lung disease characterized by persistent, and often progressive, airflow obstruction resulting from abnormalities in the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema), which lead to chronic respiratory symptoms such as dyspnea, cough, sputum production, and/or exacerbations.¹

The post-bronchodilator FEV₁/FVC ratio of less than 70% in spirometry testing, which measures forced expiratory flow rates, is a mandatory criterion for the diagnosis of COPD. In this study, the evaluation of spirometry reports for the diagnosis of COPD was based on a FEV₁/FVC ratio of less than 70%. The 2022 ATS/ERS guideline emphasizes the importance of PFTs for classifying physiological impairments rather than solely for establishing clinical diagnoses.⁵ Spirometry is the most reproducible and objective test for confirming airway obstruction and diagnosing COPD. It is non-invasive, inexpensive, relatively simple to perform, and widely accessible.

However, the number of patients diagnosed with COPD is significantly lower than the estimated prevalence. One of the main reasons for this discrepancy is the inadequate performance of spirometry tests, including the use of improper techniques and poor test quality.

The rationale for selecting tertiary care centers, emphasizing that these PFT labs meet international standards and have experienced technicians, thus highlighting the significance of finding quality issues even in these high-standard settings.

During patient follow-ups, it is crucial to distinguish whether a change in lung function over time reflects a true respiratory variation or merely test variability. Therefore, the reproducibility of parameters monitored during follow-up should be periodically verified using biological controls to exclude laboratory-induced variability. Variations originating from laboratory conditions can largely be eliminated by adhering to national and international consensus guidelines regarding equipment, personnel, and laboratory standards.⁹

In this study, spirometry tests performed in tertiary healthcare facilities across different cities were analyzed. The advanced mean age and higher proportion of males among the cases align with COPD’s typical demographic characteristics. The slightly lower smoking rate among women might explain this male predominance. However, it is essential to note that women often have higher rates of biomass exposure and increased susceptibility to smoking and air pollutants. Nevertheless, significant barriers to the effective treatment of women with COPD include a higher rate of underdiagnosis compared to men, fewer spirometry tests performed, and less frequent medical consultations.^11,12

The presence of airflow obstruction in spirometry is essential for the diagnosis of COPD. In this study, the interpretation of some spirometry results as restrictive or mixed ventilatory impairment emerged as a point of debate. In such cases, factors such as inadequate effort, obesity, cardiovascular system diseases, newly developed pleural effusion, neuromuscular defects or other comorbidities may contribute to the restrictive pattern. Additionally, COPD patients with a prior history of obstructive spirometry who later demonstrate normal spirometric findings may exhibit reversible airflow limitation. In cases where there is a significant improvement in symptoms and airflow limitation at postbronchodilator spirometry, the COPD diagnosis should be reconsidered. It should be noted that different spirometry reference norms can yield varying obstruction rates within the same population, and evaluations based on the fixed ratio criterion in the GOLD guidelines may lead to misdiagnosis in more than 20% of cases.¹³

A similar finding was reported in the Sator L. et al study, where a substantial proportion of individuals with a prior COPD diagnosis did not exhibit obstructive spirometry. Among 16,177 participants, 919 (5.7%) had a self-reported COPD diagnosis; however, post-bronchodilator spirometry was unobstructed in 569 (61.9%), indicating a high rate of false-positive diagnoses. Similarly, when using the fixed FEV₁/FVC ratio criterion, overdiagnosis was observed in 55.3% of cases. These findings align with our study, suggesting that a considerable number of patients diagnosed with COPD may not have persistent airflow obstruction upon objective testing.¹⁴

Pulmonary function test reports are required to clearly indicate the reference equations utilized for each parameter.¹⁵ When interpreting results, it is important to exercise caution if different reference equations or a combination of reference equations are applied, as discrepancies can occur due to variations in the populations from which these equations were derived. Expiratory airflow is typically evaluated using spirometry, with key indices including FEV₁, FVC, and the FEV₁/FVC ratio. In healthy lungs, airflow is influenced by the strength of expiratory driving pressure (generated by expiratory muscles and elastic recoil) as well as the size and viscoelastic properties of the lungs and airways.

The criterion proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD)¹ and the ATS/ERS⁵ COPD guidelines, which defines obstructive ventilatory defects based on a fixed FEV₁/FVC ratio of 70%, was adopted in this study. Alternatively, an obstructive ventilatory defect may also be diagnosed when the FEV₁/FVC ratio falls below the lower limit of normal (LLN), corresponding to the 5th percentile of a healthy population as recommended by the 1991 ATS⁶ and 2005 ATS/ERS¹⁶ guidelines.

In this study, it was determined that spirometry reports predominantly used ECSC as the reference value, while a portion utilized GLI in combination. Although the 2005 ATS/ERS interpretation document does not provide specific recommendations,¹⁶ the European Community for Steel and Coal (ECSC) equations have been predominantly used as reference values. Differences exist between the predicted values of ECSC and GLI, with GLI consistently providing higher predicted values compared to ECSC.^14–17

The 2005 ATS/ERS interpretation strategy¹⁶ recommends the use of National Health and Nutrition Examination Survey (NHANES) III spirometry reference equations for individuals in North America. While NHANES III spirometry data are included within the GLI equations, there are some notable distinctions between the two. NHANES III derived separate equations for Mexican Americans and Caucasians, whereas the GLI equations do not make this distinction. Furthermore, GLI equations cover a broader age range (3–95 years) compared to NHANES III (8–80 years). Significant differences in predicted values have been observed between the two equations, particularly for adults over 65 years of age.^18,19

GLI reference ranges for the FEV₁/FVC ratio appear largely unaffected by population differences, enabling more consistent interpretations across various groups.

Z-scores quantify how far a measured lung function value deviates from the predicted value, taking into account factors such as sex, age, height, and ancestry, and are expressed in standard deviation units. This approach is recommended for defining the lower limit of normal and assessing the degree of lung function impairment. Percentile values, derived from z-scores, indicate the probability that a healthy individual would have a result below a given level and show where the individual’s result falls within the healthy population. While percentile values are particularly useful for interpreting results near the normal range, they are less effective for evaluating extreme values.²⁰

The high prevalence of technical errors found in our study, particularly variable or insufficient effort and early termination, necessitates a stronger discussion on their clinical consequences. According to recent literature, substandard spirometry performance is not merely a technical failing; it directly compromises diagnostic accuracy. Studies have shown that poor effort or premature cessation often leads to an underestimation of FEV1 and overestimation of the FEV1/FVC ratio, potentially causing both false-positive diagnoses of obstruction (when effort is variable) and, more critically, false-negative results in patients with mild COPD (when the maneuver is too short).²¹ This confirms the urgency of our finding regarding the need for standardized reporting and enhanced technical training.Furthermore, our finding that the ECSC reference equation is overwhelmingly the most used highlights a significant methodological issue. The 2012 GLI equations are now widely endorsed by the ATS/ERS as the gold standard, overcoming the age, ethnic, and height limitations of the older ECSC and NHANES III sets. Multiple comparative analyses have demonstrated that switching from ECSC to GLI often leads to a reclassification of patients, typically resulting in a higher prevalence of both obstructive and restrictive patterns, particularly in older adults.^22,23 Since the ECSC equation may overestimate predicted values in certain demographics, its continued widespread use, as observed in our cohort, increases the risk of under-diagnosing airflow obstruction (COPD), thereby delaying crucial treatment. This emphasizes that standardizing the reference equations used in PFT labs is as critical for diagnostic accuracy as improving the quality of patient maneuver performance.

The volume-time graph and flow-volume graph are essential components of a spirometry report, and in our study, they were present in the majority of the reports. Forced vital capacity is measured following a deep inhalation to total lung capacity (TLC) and is performed through a rapid and forceful maximal exhalation, with the results displayed graphically as volume-time or flow-volume curves.

During spirometric measurement, the volume-time graph for each maneuver should be carefully examined. This graphical analysis helps determine whether the patient’s effort was sufficient at the start of the test. A rapid and forceful initiation of exhalation is crucial for the accuracy of FEV₁ and other parameters derived from the expiratory curve.

The shape of the flow-volume loop provides detailed insights into the underlying pathology.²⁴ In patients with intrathoracic airway obstruction, the expiratory curve initially loses its linearity and adopts a curvilinear appearance. As the severity of obstruction increases, the peak expiratory flow (PEF) decreases, and the terminal portion of the curve becomes progressively prolonged.²⁵

Increased concavity and small airway obstruction are critical spirometric findings in COPD cases. In COPD, airflow obstruction results from a combination of small airway disease, which raises airway resistance, and parenchymal destruction (emphysema), which diminishes the lung’s normal elastic recoil. The extent to which each factor contributes varies among individuals.

Inconclusive and erroneous spirometry tests are a significant challenge in pulmonary function testing, as they can impact the reliability of results and the accuracy of clinical interpretations.²⁶ These issues can arise due to various factors related to patient effort, testing technique, and equipment functionality. Regarding the inconclusive and erroneous test, variable and insufficient effort was the most frequently reported, This was followed by early termination, rapid expiration, mouth leak, cough in the first second of respiration, and mouthpiece obstruction. The presence of volume-time and flow-volume graphs in the test report is important for identifying erroneous and inappropriate tests. Analyzing the expiratory flow-volume loop can be particularly valuable for detecting upper airway obstructions. Although some error types such as mouth leak and mouthpiece obstruction showed relatively lower kappa values, this is likely due to the small number of these events. Therefore, these findings should be interpreted as limited by event frequency rather than reflecting true disagreement between raters.

Technical and procedural errors during spirometry can have important clinical implications. Insufficient expiratory effort may lead to an underestimation of FVC and FEV₁, resulting in a false-positive diagnosis of airway obstruction. Conversely, premature termination of exhalation can underestimate disease severity in patients with true obstruction. Inaccurate results may therefore lead to inappropriate treatment decisions and misclassification of disease. Ensuring optimal patient cooperation and technician training is crucial for improving test reliability and clinical interpretation.^5,27

Volume-time graph helps determine whether the patient completed the maneuver correctly and sustained effort throughout the expiration. Flow-volume graph provides insights into specific patterns of airway obstruction or restriction and highlights errors such as abrupt terminations or irregular flow patterns.³

The limitations of this study include a few factors that could influence the interpretation of the findings. One limitation is the use of different spirometry devices across various PFT units, which may result in variability in test results due to differences in calibration, sensitivity, or performance of the equipment.

Another limitation is the lack of detailed information about how the diagnosis of COPD was established in the study population. Without standardized criteria for diagnosis, there is a possibility of variability in the inclusion of patients.

Additionally, data on patients’ comorbidities were not available, which could have provided valuable context for interpreting spirometry results and their clinical implications.

Obesity is a common factor that can influence pulmonary function results. Increased body mass index (BMI) may lead to a restrictive spirometric pattern due to mechanical limitations of the chest wall and diaphragm rather than true parenchymal restriction. Excess adipose tissue around the thoracic and abdominal regions reduces chest wall compliance and functional residual capacity, leading to proportionally decreased FEV₁ and FVC values while the FEV₁/FVC ratio remains normal or mildly increased. Several clinical and physiological studies have demonstrated this relationship, and therefore reductions in lung volumes associated with obesity should be interpreted with caution, as they do not necessarily indicate intrinsic restrictive lung disease.²⁸

Despite these limitations, the primary focus of this study was to assess and reveal the quality and state of spirometry testing, rather than to investigate clinical outcomes or diagnostic methods in detail. This objective aligns with the study’s scope and highlights the importance of spirometry as a critical tool in pulmonary function assessment.

Conclusions

The reports frequently lack adequate information on preliminary diagnoses, whether the test was the first one, as well as details about the technician and the equipment. Reference values are predominantly based on ECSC values. The rates of non-compliant and erroneous tests are low due to variable effort, insufficient effort, leaks from the mouthpiece, mouthpiece closure, and rapid expiratory flow. There is a high level of agreement between interpreters in identifying erroneous tests. Obstructive tests are predominant, and in tests with obstruction, increased concavity and small airway obstruction are the most commonly observed findings. To enhance the diagnostic validity of spirometry for COPD, mandatory reporting standards must be implemented, explicitly requiring the inclusion of technician and device details, systematic flagging of technical errors, and physician awareness of clinically significant graphical patterns like increased concavity.