China has a tiered hospital system nationwide. Teaching hospitals are usually medical centers that are mainly responsible for treating critically ill patients and patients with difficult diseases, teaching medical students and leading the development of new drugs and new treatment. Second-tier hospitals, which are in the middle of the three tiers, are often responsible for local medical services and provide treatment for patients with common and chronic diseases. Community hospitals have insufficient medical resources and focus on health consultation, chronic disease maintenance and prevention. Data reveal that there were approximately 2749 teaching hospitals, 9687 second-tier hospitals and 11264 community hospitals in 2019 in China3. Ideally, COPD should be first diagnosed and critical, difficult disease should be treated in teaching hospitals. Common and standardized treatments are performed in second-tier hospitals, and disease maintenance, prevention and education are provided in community hospitals. However, the structure of the disease population exhibits a pattern opposite of this pyramid pattern.
Spirometry is a core part of COPD diagnosis and assessment. Our study showed that the use of PFT is insufficient, especially in second-tier hospitals and community hospitals. The rates of PFT at first diagnosis were 69.4% and 29.9%, and PFT follow-up in the previous year was 24.9% and 28.9% in these two tiers of hospitals, respectively, which are far lower than those in teaching hospitals. Inadequate spirometer availability and people’s awareness contribute to the difference between teaching hospitals and the other two tiers of hospitals. PFT in China began in the 1930s, increased in the late 1970s and began to develop rapidly in the late 1990s; the duration of the whole process is still less than 100 years4. Unsurprisingly, spirometers are far less popular than blood pressure meters and blood glucose meters at present in China. The PFT rate among residents aged 40 years or older in China is very low5, and only 12.0% of people with COPD reported a previous PFT1. All of the surveyed doctors in the teaching group recommended PFT to symptomatic patients, and the proportion was relatively lower in the other two groups (100% vs. 94% vs. 90.7%, P = 0.051). It was not until 2015 that China started standardized training and assessment of the clinical application and quality control of PFT nationally6. To date, not only is there a shortage of professional technicians nationwide, but measurement standardization is also not guaranteed. Patients’ awareness was also different among the three groups of hospitals. There were more urban residents and patients with higher education in the teaching group, whereas in the other two tiers of hospitals, more patients were from rural areas and had lower education.
Therefore, to better manage COPD, it is necessary to promote and widely install spirometers to make PFT as convenient as blood pressure/glucose measurement. In view of the relatively high difficulty in interpreting and measuring associated with PFT, training for doctors and technicians should be improved. Emphasis should also be placed on popularizing PFT and educating patients on the importance of PFT.
In recent years, portable spirometers have been popularized worldwide7,8, and a clinical study in China involving 980 healthy subjects with COPD showed that one kind of portable spirometer was as accurate as 95.3%9. Compared with traditional spirometers, portable spirometers are cheaper and more convenient. Therefore, portable spirometers are suitable for the routine physical examination and screening of healthy people. Moreover, relying on Internet of Things technology10, some portable spirometers can upload, store and view measurement data in the cloud, which is convenient for doctors to compare and evaluate patient data and adjust treatment plans, which helps narrow the medical gap between different tiers of hospitals.
HNPPV can improve pulmonary function, relax respiratory muscles11, reset the sensitivity of the respiratory center to CO212, and improve sleep quality in severe COPD patients with stable disease13, which are important components of pulmonary rehabilitation therapy14. In our study, only a small proportion of patients received HNPPV (3% vs. 10.5% vs. 1.0% in teaching hospital vs. second-tier hospital vs. community hospital group), whereas the proportions of patients with very severe airflow limitation (GOLD 4) were 8.9%, 6.9% and 2.0% in the 3 tiers of hospitals, respectively. A meta-analysis including 21 RCTs and 12 observational studies evaluating 51 085 patients showed that home bilevel positive airway pressure and noninvasive home mechanical ventilators were all significantly beneficial to COPD patients with hypercapnia15,16. Murphy’s study17 showed that among patients with persistent hypercapnia following an AE of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. A meta-analysis involving 767 Chinese patients from 14 studies also showed that HNPPV could reduce the mortality of patients with stable and severe COPD (P = 0.002) and improve gas exchange, lung function, and quality of life18.
The reasons for the low acceptance and popularity of HNPPV are as follows. First, HNPPV requires specialized equipment and is more expensive. HNPPV equipment is not yet covered by health insurance in China. Second, some patients complained about the uncomfortable feeling of wearing a ventilator and were unable to obtain assistance in time. Therefore, doctors should not only attach importance to drug therapy but also strengthen education and guidance on pulmonary rehabilitation therapy, including HNPPV. Internet of Things technology can also be used in parameter monitoring, technical guidance, data feedback and other aspects in the long-term HNPPV process. In this way, HNPPV can be more beneficial to COPD patients.
Pneumococcal and influenza vaccination could decrease lower respiratory tract infections, which is the most common cause of COPD AE19. In 2016–2017, the median influenza vaccine coverage for individuals with chronic medical conditions in Europe was 44.9%, ranging from 15.7–57.1% across the 7 reporting member states20. In 2019–2020, coverage of high-risk adults between 18 and 64 years with influenza vaccine was 51.4% in the US21. Pneumococcal vaccination coverage among adults between 19 and 64 years at increased risk for pneumococcal disease was 24.5% in 2017 in the US22.
Our multivariate regression analysis revealed that both vaccines were beneficial in preventing AE and improving symptoms. However, the vaccination rates remain low; approximately 10.9%, 1.7% and 9.6% of COPD patients in the three tiers of hospitals received an influenza vaccine, and 21.8%, 6.9% and. 32% of COPD patients received a pneumococcal vaccine. According to data from Shanghai, China, in the sample of 2,531,227 individuals aged 15 years or older with hypertension, diabetes and COPD, 22.8% were vaccinated for pneumonia and 0.4% for influenza in 201723. In 2014–2015, the pneumococcal vaccination rate was only 0.8% in COPD patients aged 40 years or older in China24.
In China, vaccination is performed only in community hospitals, and doctors have more time to educate patients about the importance and benefits of pneumococcal and influenza vaccination, which partially explains why the vaccination rate in community hospitals is relatively higher than that in teaching and second-tier hospitals. It is believed that in the post-COVID-19 period, people will pay more attention to vaccines, and the increase in government fiscal investment in vaccine development, delivery and publicity will also allow vaccines to protect more people.
Bronchodilator medication is the cornerstone of stable COPD management based on the drug’s pharmacological role of widening the airway and reducing dynamic hyperinflation at rest and during exercise. Our survey showed a large difference in inhaled medication use among the 3 tiers of hospitals. The proportion of patients without or irregular inhaled drug use was 2% vs. 24.6% vs. 78.8%, respectively. Medication unavailability and doctors’ lack of awareness of the importance in community hospitals might contribute to the lower coverage of inhaled therapy in COPD patients. Since 2014, GOLD has recommended regular long-acting LABA + LAMA for selective group B, group C and group D COPD patients. Experiments confirmed that compared with patients treated with ICS + LABA, patients treated with LAMA + LABA have fewer exacerbations, a larger improvement in FEV, a lower risk of pneumonia, and more frequent improvement in quality of life25,26. Our study investigated the Chinese population at the end of 2018 and found gaps between the situation in China and the international guidelines. Only 10.4%, 1.1% and 0.5% of COPD patients received double long-acting bronchodilators in the 3 tiers of hospitals, which is even lower than the rates for single long-acting bronchodilators and double or triple therapies with ICS.
Considering the differences in the pathogenesis of COPD and asthma and steroid-related side effects, GOLD recommends prescribing ICS (including ICS double/triple therapy) only for selected COPD patients, for example, more severe, prone to exacerbation and more symptomatic patients. In recent years, blood eosinophils have been adopted as a biomarker to predict the ICS response in COPD patients27. The IMPACT trial showed that in patients with COPD and a history of exacerbations, triple LAMA + LABA + ICS therapy is more effective than LABA + LAMA in individuals with blood eosinophil counts of 310 cells/µL or more than in individuals with counts less than 90 cells/µL28. Without considering eosinophil counts, the triple combination of LAMA + LABA + ICS is as effective as LABA + LAMA in preventing AE in real-world clinical practice29 and is associated with an increased cardiovascular risk in patients with COPD30. In our study, the proportions of patients receiving ICS + LABA or ICS + LABA + LAMA therapy were 53.5%, 56.0% and 14.7% in teaching, second-tier and community hospitals, respectively. Most stable COPD patients do not undergo blood eosinophil tests during the initial evaluation and follow-up period, except for those suffering an exacerbation. There are still some deficiencies in keeping up with international treatment guidelines in China, and eosinophils should be given much attention.
Theophylline and expectorants are two major alternative medications for Chinese COPD patients, especially in community hospitals. Inhaled drug unavailability and doctors’ knowledge might be partially responsible for this finding. The proportion of patients prescribed theophylline was 4.0%, 28.0% and 34% in three tiers of hospitals, respectively. Theophylline has uncertain efficacy for symptoms of COPD. Some clinical trial results show that theophylline combined with LABA produces a greater improvement in lung function and symptoms than LABA alone31, and low-dose theophylline increases the efficacy of ICS in COPD patients by reducing the incidence of exacerbations32. However, other data suggest that for people with COPD at high risk of exacerbation, low-dose oral theophylline plus ICS confers no overall clinical, health or economic benefit33. However, GOLD still recommends theophylline or theophylline plus bronchodilators as alternative therapies for some COPD patients. The application of expectorants for COPD is currently recommended by clinical practice and guidelines. In our study, approximately 31.7–46.0% of Chinese COPD patients were treated with mucoactive agents.
Airflow limitation, symptoms and AE are the foundation of stable COPD management (Fig. 4). Our multivariable regression analysis revealed that a reduction in AE frequency helped maintain lung function and improve symptoms. Patients with higher pulmonary function have a lower risk of future exacerbation. Regular follow-up PFT and inhaled medication are two major interventions to improve symptoms and quality of life, which eventually delay lung function decline. Influenza and pneumococcal vaccination are worth popularizing in patients with COPD, and the advantages of these vaccines are clearly shown in COPD management. HNPPV and home oxygen therapy should be recommended to select patients with more serious disease.