REAL is the first nationwide study designed to collect prospective longitudinal data on the management and clinical outcomes of Chinese outpatients with COPD managed at secondary and tertiary hospitals. Overall, findings from the study revealed a high burden of severe exacerbations, airflow limitation, and symptoms in this population. This high disease burden may be explained by the lack of adherence to guideline-recommended treatment among healthcare providers, as well as poor medication adherence and disease awareness among patients, highlighting the need for more effective management.
Our study enrolled a nationally representative population of adults aged ≥ 40 years with COPD. The majority of patients in our study were male, which is consistent with previous studies. Nationwide cross-sectional studies in China have demonstrated a higher prevalence of COPD among males [21, 27], while the prevalence is more similar between the sexes in Europe and the US . These data further demonstrate that the population in the REAL study is nationally representative. Compared with previous studies [16, 29], our study also comprised a larger patient population and included patients from a broader range of geographic regions.
Most COPD outpatients had moderate-to-very-severe airflow limitation, with GOLD stages II–IV accounting for 90% of the study population. More than one-third of patients were classified as GOLD Group D, with persistent symptoms and a high risk of exacerbations. This could be explained by the enrolment of patients from secondary and tertiary hospitals, where patients with mild disease are not routinely managed. This could also be due to patients at early stages of the disease with mild symptoms not seeking medical attention for COPD symptoms or not being diagnosed by physicians .
One of the key goals of the study was to collect data on the annual exacerbation rate. Overall, about 30% of patients experienced at least one exacerbation during the 1-year follow-up, which was lower than that reported in the year prior to study enrolment (49.4%). The annual exacerbation rates in our study are lower than those reported previously (37–71%) [31–33], which may be explained by underreporting of exacerbations, particularly those of moderate severity. Previous studies have shown that a large number (50–68%) of COPD exacerbations are not reported and are, therefore, left untreated, which increases the risk of disease progression [19, 20]. In our study, a high proportion of patients experienced severe exacerbations regardless of COPD severity. Our findings highlight the need to optimize the management of patients with COPD, and indicate there may be a need to increase understanding of risk factors for exacerbation to facilitate earlier detection and reduce treatment delays. This in turn may prevent exacerbations from becoming severe. The ECLIPSE study has shown that patients with severe COPD have a history of frequent exacerbations, and that past exacerbation may predict the occurrence of future exacerbations . To facilitate increased knowledge of exacerbations among physicians, further analysis of risk factors for COPD exacerbation in the REAL study is underway and will subsequently published.
Underreporting of COPD exacerbations may have been more marked during the COVID-19 pandemic, which led to fewer hospital visits. Conversely, COVID-19 control measures, such as use of masks and implementation of lockdowns, may have had a positive effect on COPD outcomes due to reduced upper respiratory tract infections. Accordingly, a national level analysis from the UK showed a 48% reduction in emergency admissions for COPD exacerbations during the UK-wide COVID-19 lockdown . Moreover, reporting of moderate exacerbations in this study could have been influenced by variations in the standard indications for COPD hospitalisation across China, with less strict administration and control.
A large proportion of patients had persistent COPD symptoms, including dyspnoea, wheezing, chest tightness, and cough, throughout the study follow-up. Presence of shortness of breath, wheezing, or chest tightness may indicate disease progression, as these symptoms were more common in severe/very severe cases than in mild/moderate cases. Understanding the symptoms associated with COPD may help improve physician’s disease awareness and facilitate early intervention before substantial disease progression. Symptoms including dyspnoea, wheezing, and chronic cough were previously shown to be associated with exacerbation occurrence in the ECLIPSE study . Further analysis of symptoms associated with exacerbation severity in the REAL study will subsequently published.
The substantial burden of severe exacerbations, airflow limitation, and persistent symptoms in this study suggest suboptimal management of COPD in China. Accordingly, we found substantial discrepancies between the real-world treatment patterns and the treatment guidelines for clinical practice , supporting previous findings [16, 29] but providing evidence that these discrepancies are likely nationwide. The most prescribed maintenance therapies in the REAL study were ICS/LABA, ICS/LABA + LAMA, and LAMA; however, their prescription rates varied (range: 15.3–36.0%). In addition, 11.6% of patients were not prescribed ICS or long-acting bronchodilators, the mainstay long-term inhaled medications for symptom alleviation and exacerbation risk reduction. Compared with baseline, there was an improvement in the prescription rate of ICS/LABA at 1 year (26.4% vs 36.0%); however, prescription rates of ICS/LABA + LAMA (17.5% vs 17.7%) and LAMA (15.1% vs 15.3%) were comparable between baseline and follow-up, respectively . Notably, prescription rates for ICS-containing therapies were similar across GOLD groups, indicating that they were not prescribed based on exacerbations risk. Conversely, prescription rates for ICS-containing therapies differed based on airflow limitation (ICS/LABA therapy prescribed more frequently in patients with mild disease and ICS/LABA + LAMA in patients with stage III or IV disease). These data may explain the improved FEV1 in patients with GOLD stages III and IV disease but not those with GOLD stages I and II disease. These findings suggest that the main goal of COPD maintenance therapy in China is to relieve symptoms, and that attention to history of acute exacerbation is lacking. Indeed, COPD maintenance therapy is mostly prescribed based on pulmonary function rather than exacerbation risk in China, given that exacerbation risk evaluation is more complex . These data, however, highlight the need for physicians to prescribe treatment based on exacerbation risk to prevent disease progression and improve patient outcomes.
Our findings reinforce those in previous studies and further emphasize the need for COPD management and treatment standardization nationwide in accordance with existing guidelines. In addition, our findings support the importance of increasing physicians’ disease and symptom awareness to enable early intervention and improve treatment based on exacerbation risk. Among patients, treatment adherence is key, and this has been shown to be influenced by patients’ understanding of their disease . We and others have demonstrated that patients with COPD are poorly informed about their disease and its treatment . It is thus critical to also put in place strategies to improve patients’ awareness and knowledge of COPD. To fully address the challenges of COPD management in China, substantial attention should be on improving both physicians’ and patients’ disease knowledge.
The study results should be viewed in the context of the following limitations. Firstly, patients with early-stage COPD and those with mild symptoms were underrepresented as the study only included patients who were diagnosed with COPD and visited the outpatient respiratory department of secondary and tertiary hospitals. This suggests that the symptoms, exacerbation rates, and treatment patterns reported in this study did not reflect that of patients with mild COPD. It is important for these patients to be characterised to help improve early detection and intervention of the disease. Secondly, the COVID-19 pandemic may have discouraged patients with COPD from visiting the hospitals, which may have resulted in underreporting of outcomes. Thirdly, the fixed-dose combinations of LABA/LAMA dual therapy and ICS/LABA/LAMA triple therapy were not available in China during the study period. In addition, the implementation of the national hierarchical medical system allowed some patients to obtain their prescription medications from a community hospital, and the prescription rates in the community hospitals were not captured in the reporting of treatment patterns in this study. These factors may impact the extent to which our findings represent current treatment patterns among COPD patients in China. Nonetheless, our findings reinforce the discrepancies identified in previous studies between real-world clinical practice and current treatment guidelines, and further demonstrate that standardisation efforts should be rolled out nationwide. Finally, data were confined to examinations and tests performed in routine clinical practice; thus, not all assessment data were available.