Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent airflow limitation that is usually progressive and not completely reversible (1). The late stage of the disease is often accompanied by systemic multi-system chronic diseases, including cardiovascular diseases, metabolic syndrome, osteoporosis, depression, anxiety, and lung cancer, which contribute to the overall severity in patients (2, 3).

The clinical diagnosis of COPD is primarily based on pulmonary function tests (PFTs) (4), but some constraints remain in detecting early changes in lung structure or function. As a general function test, the accurate assessment of local pulmonary function damage is difficult. Also, it has been reported in the literature that clinical symptoms will be present or changes in PFTs will appear when more than 30% of the total lung parenchyma has been destroyed (5). Although the forced expiratory volume in one second percentage (FEV₁%) may be unchanged, there can be significant changes in imaging findings (6). The Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease 2020 report suggests that further in-depth research is needed to study those patients without evidence of airflow limitation but who have evidence of structural lung disease upon chest imaging, such as emphysema, that is consistent with what is found in patients with COPD (7).

Computed tomography (CT) is the modality of choice for the imaging characterization of COPD patients, and it can be used to describe the changes in lung parenchyma in patients with COPD (8). In the past years, with the rapid development of high-resolution computed tomography (HRCT) technology and continuous development of image post-processing and reconstruction techniques, CT imaging has been recognized as an important method for the assessment of COPD (9). The emphysema index (EI) (10, 11), air trapping index (ATI) (12–14), and mean lung density (MLD) (15, 16) are the most common functional imaging parameters. However, these have rarely been evaluated in a population of patients at risk for developing COPD.

The primary aim of our research was therefore to evaluate the differences in HRCT emphysema parameters, air trapping parameters, and lung density parameters between patients with high and low risk of developing COPD, and to investigate the relationships between CT metrics and pulmonary function parameters.

This retrospective and single-center cohort study was carried out at The First Affiliated Hospital of Wenzhou Medical University in China. Ethical approval was obtained, and all participants consented to be included in the trial.

Our observational study on 158 patients who were at risk of developing COPD demonstrates that HRCT measurements of emphysema index and air trapping index were negatively correlated with FEV₁/FVC from PFT, whereas the mean expiratory lung density showed a positive correlation. Patients in the high-risk group exhibited a significantly higher air trapping index but lower mean expiratory lung density than those in the low-risk group.

COPD is a chronic inflammatory airway disease that is characterized by airflow limitations that are not fully reversible (20). At the early stage of the disease, patients are often asymptomatic or exhibit only mild chronic cough or dyspnea (21, 22). However, as the disease progresses, patients may experience chest pain, expectoration, fatigue, weight loss, and can also develop acute lower respiratory infections, cardiovascular disease, or lung cancer that continue to place an enormous burden on society (23, 24). According to the latest research, the prevalence of COPD in China is continually increasing, and the subgroup of patients over 40 years of age has nearly 99 million people, accounting for 13.7% (25). Therefore, early detection and timely management are imperative.

There has been interest in the diagnostic value of HRCT for COPD, and its combined use with advanced postprocessing software will provide important clinical applications for COPD. Several studies (25–27) have established the relationship between pulmonary function parameters such as FEV₁/FVC, RV/TLC, and CT findings. Some CT scans have been previously used to classify the severity in COPD patients. However, articles discussing CT findings in patients at risk of developing COPD are scarce. The present study shows that the HRCT EI, ATI, and the mean expiratory lung density are all independent diagnostic factors for patients at risk of developing COPD, and represent independent imaging biomarkers (28, 29).

We find from Table 1 that compared with the low-risk group, there was no statistically significant difference in the clinical features (age, sex, BMI categories, dust exposure, and smoking index) and the clinical symptom scores (mMRC, CAT, and CCQ) for the high-risk group. However, the differences in the forced expiratory volume in the first second/forced vital capacity and forced expiratory volume in the first second as a percentage of the expected value showed significant difference (p < 0.01) between the two groups. This suggests that based on behavioral observation and recordings, the severity of COPD in the different states was indistinguishable. These results were in agreement with the findings of Sunmin Kim et al. (30). Their conclusion shows that the choice of symptom scale can alter the group assignment of COPD. The clinical features and the clinical symptom scores can be used to assist in gauging the condition, but there were limitations to the evaluation at the individual level. It is clear that additional indicators need to be comprehensively assessed in combination.

Comparing the CT parameters of the low-risk and high-risk COPD groups, the CT images of patients from the high-risk group exhibit certain clinical characteristics and typical imaging features. Higher lung volume and emphysema index, and lower mean lung density in the inspiratory phase and expiratory phase were present. This result demonstrates that in COPD high-risk patients, pulmonary hyperinflation and lung volume increased. Patients in the high-risk group have a significantly higher air trapping index but lower mean expiratory lung density as compared to the low-risk group. As for the emphysema index and the mean inspiratory lung density, this trend in the high and low-risk group was not statistically significant. Therefore, it is suggested that the air trapping index was more accurate at predicting the risk state of COPD and pulmonary function decline than the emphysema index. In other words, using HRCT imaging for the study of lung pathologies in the early stage of the disease, the CT scans obtained at expiration were more informative than those at inspiration. In previous studies, the choice of an end inspiration or end expiration image remained controversial (31). Some demonstrated the greater diagnostic sensitivity of inspiratory lung volumes for COPD (32). CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung with COPD.

Our study on the correlation between CT parameters and pulmonary function shows that the left, right, and bilateral lung emphysema index and air trapping index were significantly inversely correlated with FEV₁/FVC. This indicates that the emphysema index theoretically has the potential to use HRCT to assess evidence of emphysema and small airway disease. Our results indicate that the presence of increasing lung volume, persistent airflow limitation, and air trapping can also be present in those with undiagnosed COPD, which can in turn lead to pulmonary function changes. In our study, we also found that the left, right, and bilateral lung mean expiratory lung density showed significantly positive correlation with FEV₁/FVC. This is in accordance with the conclusion arrived at by previously published studies (33–35). There was high predictive value of CT density parameters for detecting pulmonary ventilation.

The aim of our study was to assess the HRCT and pulmonary function status of people at risk of COPD and provide a useful supplement for the early and comprehensive assessment of the disease. Therefore, the key population we focus on in this study was low-risk and high-risk patients of undiagnosed COPD. Since many studies have proved that HRCT and pulmonary function test can be used to evaluate the severity of COPD patients (36–38), we consider that these two indicators have certain significance as an assessment of the risk of COPD.

Our study has several limitations. First, the study was conducted in a single center in China and was carried out at an outpatient clinic where patients had morbid conditions, and thus, inpatients were not included in the study. Second, the study population was relatively small and predominantly male. The results might be different in a larger population. Third, we did not enroll patients with confirmed COPD as controls, and therefore, the extrapolation of these findings to COPD cohorts must be performed with care. Last, no follow-up of the patients was performed.

In summary, our original study demonstrates that the emphysema index, air trapping index and the mean expiratory lung density obtained by HRCT show significant correlation with FEV₁/FVC, which can be used to assess the pulmonary function status of people at risk of COPD, and as an indicator for distinguishing between high and low-risk for patients of COPD and provide a useful supplement for the early and comprehensive assessment of the disease.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics committee of The First Affiliated Hospital of Wenzhou Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

LY, XH, and YiW conceived and designed the study, responsible for the integrity and accuracy of the data, and had full access to the study. RL and HJ contributed to drafting and writing this manuscript. MX took responsibility for obtaining written consent from patients, obtaining ethical approval, collecting samples, and confirming data accuracy. PS, YaW, and DY made substantial contributions to data acquisition, analysis, and interpretation. All authors had strictly revised the manuscript, agreed to be responsible for all aspects of the work, and finally approved the version to be published.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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