Guidelines for the Diagnosis and Treatment of Common Primary Diseases: Guidelines for the Primary Diagnosis and Treatment and Management of Chronic Obstructive Pulmonary Disease in China (2024)

Authors: Chinese Medical Association, Journal of Chinese Medical Association, General Practice Branch of Chinese Medical Association, Chronic Obstructive Pulmonary Disease Group, Chinese Society of Respiratory Diseases, Editorial Board of Chinese Journal of General Practitioners, Chinese Medical Association, Expert Group for the Development of Guidelines for Primary Diagnosis and Treatment and Management of Respiratory Diseases in ChinaCorresponding Author: Yang Ting, Department of Respiratory and Critical Care Medicine, Respiratory Center, China-Japan Friendship Hospital Chi Chunhua, Department of General Medicine, Peking University First Hospital, Health Management Center, Peking University First HospitalThis article was published in the Chinese Journal of General Practice, 2024. DOI: 10.3760/cma.j.cn114798-20240326-00174 Editor: Bai Xuejia Liu Lan Chronic obstructive pulmonary disease (COPD) (COPD) is the most common chronic respiratory disease, showing the epidemiological characteristics of high prevalence, high mortality and high disease burden in mainland China. With the persistence of a large number of people exposed to smoking and secondhand smoke, indoor and outdoor air pollution, and tuberculosis infection, the prevention and control situation of COPD will be very severe. In recent years, the prevention and control of chronic respiratory diseases represented by COPD has received more and more attention from the state, and a series of support measures have been introduced, including the installation of portable pulmonary function instruments in more than 50% of the country's primary medical and health institutions, laying a solid foundation for early screening and early diagnosis of COPD. With the advancement of the hierarchical diagnosis and treatment policy, the ability of grassroots medical staff to diagnose and treat COPD has also been greatly improved. In order to improve the diagnosis and treatment of COPD by primary medical staff, in 2018, the Chinese Medical Association was entrusted by the Department of Primary Health of the National Health Commission to formulate the Guidelines for the Primary Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2018), which was published in the Chinese Journal of General Practitioners [1⁃2], which is the first guideline for the diagnosis and treatment of COPD at the grassroots level formulated by general practice experts. In the past six years, there has been further evidence-based medical evidence on many aspects of the diagnosis and treatment of COPD, and some new concepts have also been added. To this end, under the leadership of the Chinese Medical Association and the Journal of the Chinese Medical Association, experts from the General Practice Branch of the Chinese Medical Association, the Chronic Obstructive Pulmonary Disease Group of the Chinese Society of Respiratory Diseases, and the Editorial Committee of the Chinese Journal of General Practitioners of the Chinese Medical Association have carried out the update and revision of the guidelines, forming the Guidelines for the Primary Diagnosis and Treatment and Management of Chronic Obstructive Pulmonary Disease in China (2024). This revision still adheres to the previous principles, is jointly formulated by experts in respiratory medicine, general medicine and methodology, and is aimed at the majority of grassroots medical staff, embodying the six-in-one care concept of "promotion, prevention, diagnosis, control, treatment and rehabilitation", highlighting the management characteristics and practicability of the grassroots level, and hoping that the new guidelines will become the guidelines for the standardized management of COPD at the grassroots level and benefit more high-risk groups and patients with COPD. The evidence of the recommendations is mainly based on the Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition) [3] and the Global Strategy for the Diagnosis, Treatment and Prevention of Chronic Obstructive Pulmonary Disease (GOLD 2024) [4], as well as some newly published high-quality literature evidence. The quality of the evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method (Table 1), and the quality of the evidence was divided into four levels: "high, moderate, low, and very low", which were represented by A, B, C, and D, respectively, and the recommendations were divided into two levels: "strong recommendation and weak recommendation".

Part I. Overview

Key takeaways:

●Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with high morbidity, mortality, and disease burden, and is a major chronic disease.

●Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic respiratory symptoms and persistent, progressively worsening airflow limitation.

●COPD is divided into stable and acute exacerbations.

1. Definitions

COPD is a common, preventable and treatable chronic airway disease characterized by persistent airflow limitation and corresponding respiratory symptoms (dyspnea, cough, sputum production); There is significant heterogeneity in COPD due to numerous host factors, such as abnormal inflammatory responses and abnormal lung development, as well as severe comorbidities that may affect disease presentation and mortality [3].

The clinical manifestations of COPD and chronic bronchitis, emphysema, and bronchial asthma (asthma) can be similar, and the diagnostic criteria overlap, but the treatment strategies are different, as shown in Figure 1 [5].

Chronic bronchitis is a chronic non-specific inflammation of the trachea, bronchial mucosa and its surrounding tissues, with cough and sputum production as the main clinical symptoms, or wheezing, and the onset of the disease lasts for 3 months or more every year for 2 years or more. Emphysema is an abnormal, persistent dilation of the air space distal to the terminal bronchioles of the lungs with destruction of the alveoli and bronchioles without significant pulmonary fibrosis and is a common diagnosis on chest CT. When the patient presents with chronic bronchitis and emphysema, further pulmonary function tests must be performed to determine whether the patient meets the diagnostic criteria for COPD, and if the lung function is not airflow-limited, the diagnosis is still based on chronic bronchitis and emphysema, but follow-up pulmonary function is required. Asthma is a chronic airway inflammatory disease involving a variety of cells and cellular components, which is clinically manifested by recurrent episodes of wheezing, shortness of breath, with or without symptoms such as chest tightness or cough, accompanied by airway hyperresponsiveness and variable airflow limitation, which can lead to changes in airway structure with the prolongation of the disease, that is, airway remodeling. The airflow limitation characteristics of asthma are variable and can be restored to normal levels after treatment, and some asthma patients have not been regularly treated for a long time, and the disease is prolonged, resulting in airway remodeling and small airway narrowing, which may lead to irreversible airflow limitation, which is difficult to distinguish from COPD from the perspective of lung function alone. COPD is the end result of gene⁃environmental interactions and accumulation. Regardless of whether it is the "biologically early" or "clinical" stage of COPD, patients have developed symptoms and/or functional and/or structural abnormalities, and based on this, many new terms have been proposed internationally (see Table 2) [4], aiming to combine primary and secondary prevention measures, pay attention to such high-risk groups and patients of COPD, carry out early intervention, long-term follow-up and individualized care, and promote the prevention and control of COPD. At the same time, by clarifying the classification terms of these COPD-related diseases, we can avoid confusion and promote the unification of follow-up research standards.

2. Epidemiology

COPD is a common and frequent disease that seriously endangers human health, seriously affects the quality of life of patients, has a high mortality rate, and brings a heavy economic burden to patients, their families and society. In a 2007 survey of 20,245 adults in seven regions of the mainland, the prevalence of COPD was as high as 8.2% in people aged 40 years and older [6]. According to the results of a 2018 survey of 50,991 adults in 10 provinces and cities in the China Adult Lung Health Study, the prevalence of COPD in adults aged 20 years and older in mainland China was 8.6%, and as high as 13.7% in adults aged 40 years and older, and the number of COPD patients in mainland China was estimated to be nearly 100 million [7]. According to statistics, COPD was the third leading cause of death in mainland China in 2017 [8] and the third leading cause of disability adjusted life years (DALY) in 2017 [9].

With the implementation of standardized diagnosis and treatment and whole-course management of COPD, the mortality rate of COPD in mainland China decreased significantly in 2019, and the age-standardized mortality rate and DALY rate decreased by 70.1% and 69.5%, respectively, compared with 1990, but the incidence and prevalence increased by 61.2% and 67.8%, respectively [10], indicating that early prevention, early diagnosis and standardized treatment of COPD are still a major and arduous task.

3. Staging

(1) Stability period

Symptoms such as cough, sputum production, and shortness of breath are stable or mild, and the condition has largely returned to the state before the acute exacerbation.

(2) Acute weighting phase

Events characterized by dyspnea and/or worsening cough and sputum production for < 14 days, may be accompanied by tachypnea and/or tachycardia, usually associated with increased local and systemic inflammation due to respiratory infection, air pollution, or other lung injury.

Part II: Etiology, risk factors and pathogenesis of COPD

Key takeaways:

●The occurrence and development of COPD depends on the interaction between individual susceptibility factors and environmental factors in the course of life, and is the result of the combined action of multiple factors.

●Smoking is the most important risk factor for COPD, as are indoor and outdoor air pollution, occupational exposures, and early life events (eg, low birth weight, childhood infections).

●Abnormal injury repair processes result in structural remodeling of the airway wall and destruction of the lung parenchyma, which together form the pathological basis of fixed airflow limitation.

1. Etiology and risk factors The occurrence and development of COPD depends on the interaction between individual susceptibility factors and environmental factors in the course of life, and most of them are the result of the joint action of multiple factors, and only a few conditions such as emphysema caused by α1⁃ antitrypsin deficiency have a definite cause [3⁃4], see Table 3.

In clinical practice, it is necessary to ask patients about their risk factors thoroughly, and in addition to exposure to environmental factors such as smoking in adulthood, it is necessary to trace events back to childhood or even earlier in life. Early life factors such as preterm birth, maternal exposure to toxic gases or substances during pregnancy, adolescent smoking, bronchopulmonary dysplasia, severe pneumonia in childhood, and malnutrition can affect the normal development of lung function, thereby increasing the risk of COPD in adulthood.

2. PathogenesisThe pathogenesis of COPD has not been fully understood, and various factors such as oxidative stress, inflammatory response, and protease/antiprotease imbalance lead to tissue remodeling, resulting in chronic respiratory symptoms and airflow limitation. Recent studies have shown that autoimmune regulatory mechanisms, genetic risk factors, and lung development-related factors may also play an important role in the occurrence and development of COPD. 3. Pathological manifestations of COPD: Chronic inflammation of the airway, lung parenchyma and pulmonary blood vessels, airway wall remodeling, and lung parenchymal destruction are the pathological basis of fixed airflow limitation. 4. The main pathophysiological changes of pathophysiological COPD include airflow limitation, gas trapping, dynamic hyperinflation and abnormal gas exchange, which may be accompanied by mucus hypersecretion. As the disease progresses, hypoxemia and/or hypercapnia may develop. Pulmonary hypertension is often present in advanced stages of the disease, leading to chronic cor pulmonale and right heart failure, indicating a poor prognosis. The inflammatory response of COPD is not only limited to the lungs, but can also lead to systemic adverse effects, including increased systemic oxidative load, increased levels of pro-inflammatory cytokines in the circulating blood, and abnormal activation of inflammatory cells, which in turn leads to an increased risk of osteoporosis and cardiovascular disease.

Part III: Screening, diagnosis and comprehensive evaluation of COPD

Key takeaways:

●Patients with suspected COPD can be detected early by screening questionnaires and CT examinations to detect lung structural abnormalities.

●The main symptoms of COPD are dyspnea, chronic cough, and sputum production, and in the early stages, there may be no obvious symptoms.

●The "gold standard" for the diagnosis of COPD is pulmonary function tests, with FEV1/FVC < 0.7 after inhaled bronchodilators being the criterion for persistent airflow limitation.

●Patients with COPD should undergo a comprehensive assessment of symptoms, severity of impaired lung function, risk of exacerbations, and comorbidities.

I. Screening and Case Finding

Screening is done in the general population and asymptomatic individuals are examined based on demographic information (e.g., age, smoking history, etc.), and case finding assesses an individual's exposure to respiratory symptoms and COPD-related risk factors to determine whether pulmonary function tests are needed. At present, there are many scales and tools at home and abroad that are convenient for medical staff to use in primary medical institutions. Patients with previously undiagnosed COPD can be identified by various scales and/or simple physiological measures (e.g., peak expiratory flow rate), and these tools can identify the majority of patients with mild or very mild disease.

The identification of high-risk groups for COPD needs to be combined with various factors such as age, symptoms, risk factors and family history, and the groups that meet at least one risk factor in Table 3 are called high-risk groups for COPD. Pulmonary function tests in high-risk groups can help improve screening efficiency and early detection of COPD patients. The chronic obstructive pulmonary disease screening questionnaire (COPD⁃SQ) [22] (table 4), developed based on the characteristics of Chinese people, is an integrated scale of multiple risk factors for COPD, which is more suitable for high-risk groups of COPD in mainland China. The COPD⁃SQ total score ≥16 is a positive screening questionnaire, COPD is suspected, and further pulmonary function tests are required to confirm COPD (B, strongly recommended). For patients with lung cancer screening by low-dose CT or COPD-related lung abnormalities (emphysema, gas trapping, airway wall thickening, and mucus blockage, etc.) detected by low-dose CT or incidental imaging studies, a detailed assessment of risk factor exposure, symptoms, etc., and pulmonary function tests should be performed (D, strongly recommended).

2. Clinical manifestations and auxiliary examinations (1) Clinical manifestations 1. Symptoms: COPD is more common in middle age, and it is more common in the cold season of autumn and winter, and the common symptoms are dyspnea, chronic cough, sputum production, wheezing, chest pain and fatigue. Dyspnea is a typical symptom that occurs initially only during strenuous activity and gradually worsens, even during daily activities and at rest. It should be noted that some patients do not directly complain of dyspnea, but will express shortness of breath, insufficient breath, wheezing, chest tightness, etc., which need to be carefully questioned and identified by the doctor. Chronic cough is often the first symptom of COPD, with obvious cough in the morning, cough at night, and a few coughs alone without sputum production, or even significant airflow restriction without cough symptoms. The sputum is white foamy or mucous, and the amount of sputum increases when it is infected, turning into purulent sputum. Some patients with mild impairment of lung function may have no obvious respiratory symptoms, or the symptoms may be mild and are thought to be related to increasing age and are not taken seriously. Weight loss, loss of appetite, depression, and/or anxiety are common in the later stages. Hypoxemia and/or hypercapnia develops later, and chronic cor pulmonale and right heart failure may occur.

2 Signs: early signs of COPD may be subtle, but as the disease progresses, the following signs are common:

On inspection: increased anteroposterior diameter of the thoracic cage, widening of the intercostal space, and widening of the substernal angle under the xiphoid process, called barrel chest. Some patients have shallow breathing, increased frequency, and prolonged expiratory phase, and in severe cases, they may have pursed lip breathing and forward leaning position, and in severe cases, contradictory breathing in the chest and abdomen.

Palpation: decreased bilateral fibrillation, sensation of cardiac lift under the xiphoid process.

Percussion: the lungs are too clear, the cardiac dullness is reduced, and the lower and hepatic dullness are reduced.

Auscultation: decreased breath sounds in both lungs, prolonged expiratory phase, wet rales and/or dry rales can be heard in some patients, heart sounds are distant, heart sounds under the xiphoid process are clearer and louder, and the second heart sound in the pulmonary valve area (P2) is stronger than the second heart sound in the aortic valve area (A2) in pulmonary hypertension (P2>A2).

Extrapulmonary signs: mucosal and cutaneous cyanosis may be present in patients with hypoxemia, and bulbar conjunctival edema may be seen in patients with carbon dioxide retention. Patients with right-sided heart failure may have lower extremity edema, ascites, liver enlargement and tenderness, and neuropathological signs in pulmonary encephalopathy. (2) Auxiliary examination1. Pulmonary function test: Pulmonary ventilation function test is an objective indicator for judging airflow limitation, the "gold standard" for the diagnosis of COPD, and the most commonly used index for the evaluation of COPD severity, disease progression monitoring, prognosis and treatment response evaluation. After inhalation of bronchodilators, forced expiratory volume in one second (FEV1) percentage of forced vital capacity (FVC) (FEV1/FVC) <0.7 is the criterion for the presence of persistent airflow limitation, and FEV1 as a percentage of predicted value is an indicator of the severity of airflow limitation. When the FEV1/FVC is 0.6~0.8 for a single measurement, pulmonary function tests should be repeated after 3 months to confirm the diagnosis[4]. In addition to the conventional pulmonary ventilation function test indicators such as FEV1 and FEV1/FVC, it also includes lung volume, diffusion function, small airway function measurement, etc., which is helpful for disease evaluation and differential diagnosis. For people at high risk of COPD, it is recommended to have a pulmonary ventilation function test once a year. Portable pulmonary function instrument can detect routine ventilation function, perform diastolic test, and can be used for early screening, diagnosis and long-term management of grassroots COPD. Impulse oscillometry (IOS) is a non-invasive, non-force-dependent measure of airway resistance, which requires only natural breathing to complete the test, and can be used as an auxiliary diagnostic tool when patients are unable to cooperate with pulmonary ventilation testing. The application of portable IOS in the screening and auxiliary diagnosis of chronic respiratory diseases at the grassroots level is being studied. The degree of reversibility of airflow limitation is not the sole indicator of COPD from asthma, nor does it predict response to long-term treatment with bronchodilators or glucocorticoids. It is not necessary to discontinue inhaled drug therapy until new pulmonary function measurements are obtained during patient follow-up. 2. Chest X-ray: X-ray can help to determine whether there are lung complications and other diseases. The main signs of X-ray in patients with COPD are: hyperinflation of the lungs, increase in lung volume, increase in anterior and posterior diameter of the chest, flattening of the ribs, increased transparency of the lung field, low and flat diaphragm position, long and narrow heart overhang, hilar vascular texture is stump-like, peripheral vascular texture of the lung field is slender and scarce, and sometimes pulmonary bullae can be formed. 3. Chest CT examination: Chest high-resolution CT can distinguish between lobular center and panlobular emphysema, and can also be used for differential diagnosis to help rule out other lung diseases, such as lung cancer, bronchiectasis, pulmonary fibrosis, etc. 4. Pulse oximetry monitoring and blood gas analysis: pulse oximetry can be used to assess the need for oxygen therapy in patients, and pulse oximetry monitoring should be performed in patients with clinical signs of dyspnea, respiratory failure, or heart failure. Blood gas analysis can be used to assess whether a patient has respiratory failure and the type of respiratory failure. 5. Electrocardiogram: It can indicate whether COPD is complicated with cor pulmonale and other cardiovascular diseases (arrhythmia, coronary heart disease, etc.). Chronic obstructive pulmonary pulmonary pulmonary disease (COPD) with chronic pulmonary hypertension or chronic cor pulmonale ECG can be as follows: frontal mean axial ≥+90°; R/S ≥1 in V1, severe clockwise indexing (R/S≤1 in V5), 1.05 mV ≥ RV1+SV5, R/S or R/Q≥1 in aVR, QS, Qr, or qr in V1~V3 (myocardial infarction should be differentiated), pulmonary P wave. 6. Routine blood examination: the peripheral blood eosinophils (EOS) count in the stable phase has a certain reference significance for whether the combination of inhaled corticosteroid (ICS) is required for COPD drug therapy; <55 mmHg (1 mmHg = 0.133 kPa)], peripheral hemoglobin, erythrocytes, and hematocrit (>0.55) may be markedly increased, suggesting the need for long-term home oxygen therapy; some patients may present with anemia. 3. Diagnostic criteria and diagnostic process (1) Diagnostic criteria

The diagnosis of COPD is based on clinical data such as risk factor exposure, symptoms, signs, and pulmonary function tests, and the exclusion of other conditions that can cause similar symptoms and persistent airflow limitation. Persistent airflow limitation on pulmonary function tests is essential for the diagnosis of COPD, and an FEV1/FVC < 0.7 after inhaled bronchodilator confirms the presence of persistent airflow limitation.

(2) Diagnostic process1. Primary care physicians should carefully take a patient history, and in patients with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and/or a history of exposure to COPD risk factors, the possibility of a COPD diagnosis should be considered, and further investigations should be confirmed. 2. Physical examination includes the presence of cyanosis of the lips and nail bed, jugular venous distention, barrel chest, number of breaths, breath sounds, rales, heart rate, heart rhythm, edema of both lower limbs, clubbing of fingers (toes), etc. 3. According to the needs of the patient's condition and the actual situation of the medical institution, the corresponding examination items should be appropriately selected, which are divided into the items that should be done and the recommended items.

(1) The items to be done include: blood routine, pulmonary ventilation function test (including bronchodilator test), chest X-ray, electrocardiogram, pulse oximetry test.

（2）推荐项目包括：动脉血气分析、痰培养、胸部CT检查、诱导痰细胞学分类、呼出气一氧化氮（fractional exhaled nitric oxide，FeNO）检测、超声心动图、24 h动态心电图（Holter）、肺容量和弥散功能检查、6 min步行试验（6-minute walk test，6MWT）、B型利钠肽（B-type natriuretic peptide，BNP）或 N-末端B型利钠肽前体（N-terminal pro-B-type natriuretic peptide，NT-proBNP）、D-二聚体（D-dimer）、C反应蛋白（C reactive protein，CRP）等。 进行推荐项目检查的目的是为了进一步评估慢阻肺病情严重程度、是否有合并症以及鉴别诊断，可根据当地医院条件和患者病情恰当选择或转诊到上级医院完成。

The process of primary screening and diagnosis of COPD is shown in Figure 2.

4. Once COPD is confirmed by pulmonary function tests, in order to guide treatment, the following four basic aspects must be focused on the following four basic aspects of the assessment: the degree of airflow limitation, the nature and severity of current symptoms, the risk assessment of acute exacerbation (history of previous acute exacerbations), and other comorbidities. (1) Assessment of the degree of airflow limitation

Airflow limitation is assessed by lung function, i.e., FEV1 as a percentage of predicted value. The severity of airflow limitation in patients with COPD is classified into four grades according to the GOLD scale [4], as shown in Table 5.

(2) Symptom assessment

可采用改良版英国医学研究委员会（modified Medical Research Council，mMRC）呼吸困难问卷（表6）和慢阻肺患者自我评估测试（chronic obstructive pulmonary disease assessment test，CAT）问卷（表7）进行症状评估。 mMRC仅反映呼吸困难程度， 2级及以上为症状多。 CAT评分为综合症状评分，包括症状、活动耐力和自我评估3方面8个问题，分值0~40分，10分以上为症状多。

(3) Risk assessment of acute exacerbations

慢阻肺急性加重（acute exacerbation of chronic obstructive pulmonary disease, AECOPD）是急性呼吸系统症状的发作，对患者的健康状况影响显著。 急性加重的最佳预测指标是既往有急性加重史，若上一年发生2次及以上中度急性加重，或者1次及以上因急性加重住院，则为急性加重高风险。

(4) Assessment of comorbidities

Patients with COPD often have other chronic diseases, and common comorbidities include cardiovascular disease, metabolic syndrome, osteoporosis, depression and anxiety, lung cancer, malnutrition, and skeletal muscle dysfunction. These comorbidities can increase the poor prognosis of hospitalization and death, and should be identified early, evaluated regularly, and treated accordingly.

(5) Comprehensive assessment and grouping

Based on the above pulmonary function classification and the assessment of symptoms and the risk of acute exacerbation, a comprehensive assessment of the severity of the disease in patients with stable COPD (Fig. 3) is possible, with group A for patients with few symptoms and low risk of exacerbation, group B for patients with many symptoms and low risk of exacerbation, and group E for patients at high risk of exacerbation. Inhaled therapy is selected based on the results of the comprehensive assessment group at the time of initial treatment.

5. Differential diagnosis

COPD should be distinguished from asthma, bronchiectasis, congestive heart failure, tuberculosis, and diffuse panbronchiolitis, especially from asthma, as shown in Table 8.

6. Comorbidities

COPD often coexists with other diseases (comorbidities), which have a significant impact on the course of COPD, hospitalization and mortality rates, and the management of COPD patients should include the identification and treatment of their comorbidities.

(1) Cardiovascular disease

Cardiovascular disease is the most common and important comorbidity of COPD, mainly including heart failure, ischemic heart disease, arrhythmias, peripheral vascular disease, and hypertension.

(2) Lung cancer

Patients with COPD are at increased risk of developing lung cancer, and low-dose chest CT can detect early-stage lung cancer in a timely manner.

(3) Bronchiectasis

The prevalence of bronchiectasis in patients with COPD has been reported to be mixed, ranging from 20%~69%, which needs to be confirmed by chest CT examination. Patients tend to have a longer smoking history, a larger daily sputum volume, more frequent exacerbations, poorer lung function, higher levels of inflammatory biomarkers, and a worse long-term prognosis.

(4) Metabolic syndrome and diabetes

Metabolic syndrome and type 2 diabetes are more common in patients with COPD, and diabetes may affect the prognosis of COPD.

(5) Gastroesophageal reflux disease

Gastroesophageal reflux disease is an independent risk factor for acute exacerbations of COPD.

(6) Osteoporosis

Osteoporosis is often associated with emphysema, weight loss, and low fat. Systemic hormone therapy significantly increases the risk of osteoporosis, and repeated systemic hormone therapy should be avoided as much as possible.

(7) Anemia

Anemia of chronic disease is the most common type of anemia in COPD, followed by iron deficiency anemia, which is mainly associated with chronic systemic inflammation and impaired iron utilization. Patients with comorbid anemia should be treated appropriately.

(8) Anxiety and depression

Anxiety and depression are common comorbidities of COPD, affecting the quality of life of patients, and patients with COPD should be evaluated for anxiety and depression symptoms, and severe cases need to be referred to a psychiatric specialist for diagnosis and treatment.

（九）阻塞性睡眠呼吸暂停（obstructive sleep apnea, OSA）和失眠

The proportion of patients with COPD combined with OSA is higher (20%~55%), and when the two coexist, the blood oxygen drop during sleep is more frequent, and primary doctors can screen for OSA through the sleep screening questionnaire (STOP-bang). Insomnia in patients with COPD is associated with higher rates of outpatient visits and hospitalizations.

Patients with COPD often have one or more comorbidities, and patients with comorbidities should be evaluated regularly and comprehensively intervened, while the treatment plan for patients should be simplified as much as possible.

Part 4 Management of COPD in the stable phase

Key takeaways:

●Stable COPD therapy is aimed at reducing current symptoms and reducing the risk of future exacerbations, including pharmacological and nonpharmacologic therapies.

●Stable drug therapy is the cornerstone of long-term management of patients with COPD, of which inhalation therapy is the preferred treatment modality, and the initial treatment regimen should be selected according to the comprehensive evaluation group of patients, and long-term follow-up, dynamic assessment, and timely adjustment of treatment strategies should be carried out.

●Nonpharmacologic interventions, including smoking cessation, vaccination, and pulmonary rehabilitation, are also important components of COPD therapy.

1. Treatment goals

The goal of stable COPD treatment is to reduce current symptoms and reduce the risk of future exacerbations.

(1) Reducing current symptoms includes relieving symptoms, improving exercise tolerance, and improving health status.

(ii) Reducing the risk of future exacerbations includes preventing disease progression, preventing and treating exacerbations, and reducing case fatality rates.

2. Medication

Drug therapy can relieve symptoms of COPD, reduce the frequency and severity of exacerbations, improve exercise tolerance, and improve health. Stable drug therapy is the core of long-term management, and if there are no obvious adverse drug reactions or exacerbations, long-term regular drug therapy should be maintained at the same level. At present, most of the stable treatment regimens for COPD are inhaled drugs, and the correct grasp of inhalation methods and good compliance are the guarantees of efficacy, and appropriate inhalation drugs and inhalation devices should be selected according to the patient's condition and inspiratory function status.

Commonly used drugs for COPD include bronchodilators, ICS and other drugs, and the commonly used inhaled therapeutic drugs for COPD in stable stage in China are shown in Table 9.

(1) Bronchodilators

Bronchodilators are the cornerstone of COPD treatment by relaxing bronchial smooth muscle, dilating the bronchi, and relieving airflow limitation, thereby reducing the symptoms of COPD (A, strongly recommended). Inhaled formulations are more effective and safer than oral medications, so inhaled therapy is often preferred. The main bronchodilators are beta-2 agonists, anticholinergics, and theophylline, which can be selected according to the effect of the drug and the patient's response to treatment.

1. β2受体激动剂：分为短效β2受体激动剂（short-acting β2 agonist，SABA）和长效β2受体激动剂（long-acting β2agonist，LABA）两种类型。

SABA is mainly used for symptomatic relief and is used as needed. Albuterol and terbutaline are short-acting quantitative nebulized inhalers, which take effect within a few minutes, reach a peak in 15~30 min, and the efficacy lasts for 4~6 h, with a dose of 100~200 mg (100 mg/spray) each time.

Compared with SABA, LABA can dilate the airways more durably, improve lung function and dyspnea symptoms, and can be used as a long-term maintenance therapy for patients with significant airflow limitation (A, strongly recommended). Formoterol is a long-acting fast-acting β2 receptor agonist, which takes effect in 1~3 min and lasts for more than 12 h, and the usual dose is 4.5~9.0mg, twice a day. In recent years, new LABA effects have lasted longer, including indacaterol and vilanterol, which are inhaled once a day.

Adverse effects: Overall, inhaled beta-2 agonists are associated with much lower adverse effects than oral formulations, with relatively common adverse reactions being sinus tachycardia, muscle tremor (usually hand tremor), and less commonly, oropharyngeal irritation.

2. 抗胆碱能药物：通过阻断M1和M3胆碱受体，扩张气道平滑肌，改善气流受限和慢阻肺症状，可分为短效抗胆碱能药物（short-acting muscarinic antagonists，SAMA）和长效抗胆碱能药物（long-acting muscarinic antagonists，LAMA）两种类型。

The main varieties of SAMA are ipratropium bromide aerosol, which can achieve the maximum effect for 30~90 min, can be maintained for 6~8 h, and the dosage is 20~40 mg (20 mg/spray), 3~4 times/d.

LAMA, such as tiotropium, has an effect of more than 24 h, 18 mg (18 mg/inhalation) for dry powder once a day, and 5 mg (2.5 mg/spray) for soft aerosol once a day. LAMA is better than LABA in reducing acute exacerbations of COPD (A, strongly recommended) and frequency of hospitalizations (B, strongly recommended), and long-term use can improve patients' symptoms and health status, as well as reduce the frequency of exacerbations and hospitalizations.

Adverse reactions: Adverse reactions of inhaled anticholinergic drugs are relatively rare, the main adverse reactions are dry mouth, cough, local irritation, etc., and the rare ones are urticaria, aggravated angle-closure glaucoma, urinary retention, and increased heart rate.

3. Theophylline: It can relieve airway smooth muscle spasm and is widely used in the treatment of COPD in mainland China. Extended-release or controlled-release theophylline can be taken orally for 1~2 times/d to achieve stable plasma concentration, which has a certain effect on the treatment of stable COPD (B, weak recommendation). Low-dose theophylline is controversial in reducing exacerbations.

Theophylline is easily available in primary medical institutions, but it should be noted that theophylline preparations may cause arrhythmia or worsen the original arrhythmia, and patients should go to medical institutions to test their heart rhythm when they have symptoms such as palpitations;

4. Combined bronchodilators: The combined application of drugs with different mechanisms of action and duration of action can enhance bronchodilator effect, better improve the patient's lung function and health status, and usually do not increase adverse reactions. SABA plus SAMA (e.g., combined ipratropium bromide aerosol) is better than monotherapy for improving lung function and symptoms (A, strongly recommended). The combination of LABA and LAMA also improves lung function and symptoms and reduces the risk of disease progression (A, strongly recommended). At present, there are a variety of LABA and LAMA combined inhalation preparations, such as formoterol + glycopyrrolate, indacaterol + glycopyrrolate, vilanterol + magnesium bromide, etc.

(2) ICS and combined inhaled drugs

Regular use of ICS alone has been found to prevent the decline of FEV1 and does not alter the mortality rate of patients with COPD, so ICS alone is not recommended for patients with stable COPD, nor is long-term oral corticosteroids recommended.

Recent clinical studies have shown that the ICS+LABA+LAMA triple regimen has advantages over ICS+LABA in reducing exacerbations, improving lung function, and reducing all-cause mortality (A, strongly recommended) [23-24]. At present, there are budesonide + formoterol fumarate + glycopyrrolate, fluticasone furoate + vilanterol + magnesium bromide and beclomethasone propionate + formoterol fumarate + glycopyrrolate and other combination preparations in China.

Adverse reactions: ICS has the risk of increasing the incidence of pneumonia, and other common adverse reactions include oral candida infection, laryngeal irritation, cough, hoarseness, etc. Therefore, it is important to rinse the mouth promptly after using inhalers containing glucocorticoids to avoid local adverse reactions caused by hormone residues. ICS is not recommended in patients with recurrent pneumonia or pulmonary mycobacterial infections.

(3) Other drugs

1. Expectorants and antioxidants: can promote mucus dissolution, facilitate airway drainage, and improve ventilation function. There are many types of mucus-active drugs, but not all of them have both expectorant and antioxidant properties. Commonly used expectorant antioxidant drugs in clinical practice include N-acetyl cysteine (NAC), carbocisteine, fodosteine and ambroxol. Long-term use of NAC (1 200 mg/day) has been shown to reduce the risk of acute exacerbations of COPD [25]. For COPD patients with airway mucus hypersecretion, expectorants can be added to initial therapy, regardless of the stable assessment group (B, weak recommendation).

2. Phosphodiesterase (PDE) inhibitors: To reduce inflammation by inhibiting intracellular cyclic AMP degradation, the currently clinically available PDE-4 inhibitors include roflumilast, which can reduce the risk of moderate to severe exacerbation in patients with chronic bronchitis, severe to very severe, and a history of acute exacerbation [26]. At present, PDE-4 or dual-target PDE-3+4 inhibitors are in clinical studies, and their nebulized dosage forms may reduce adverse reactions.

3. Immunomodulators: Immunomodulatory drugs produced from lysed components of common respiratory tract infection pathogens that reduce the severity and frequency of COPD exacerbations [27-28].

(4) Types and selection of inhalation devices

Inhalation devices are divided into three categories, pressurised metered-dose inhaler (pMDI), dry powder inhaler (DPI), and soft mist inhaler (SMI). The correct inhalation device is selected depending on whether the patient is able to inhale spontaneously, whether there is sufficient inspiratory flow rate, and whether the mouth and hand are coordinated. Nebulized inhalation may be a better option for older and frail patients, with low inspiratory flow rates, severe disease severity, and difficulty using inhalation devices. The path of selection for the inhalation device is shown in Figure 4 [3].

(5) Initial treatment

The initial regimen is intended for patients with newly diagnosed COPD or those who have been previously diagnosed but have never been regularly treated with inhaled drugs. The initial treatment regimen is shown in Figure 5.

1. Group A patients (less symptomatic and less exacerbated) are recommended to be treated with 1 bronchodilator (short-acting or long-acting).

2. Combination therapy with dual long-acting bronchodilators (LABA+LAMA) is recommended for patients in group B (more symptoms and fewer acute exacerbations) because dual long-acting bronchodilators are more effective than single long-acting bronchodilator therapy and do not significantly increase adverse reactions (A, strongly recommended).

3. Combination therapy with LABA+LAMA is recommended for patients in group E (frequent acute exacerbations), but for patients with 300 blood EOS≥/μl or patients with asthma, triple therapy (ICS+LABA+LAMA) is considered for initial treatment (A, strongly recommended).

Repeat lung function is recommended after 3 months of initial treatment to see how lung function responds to drug therapy.

(6) Follow-up treatment

After initial treatment, the patient's return visit is called a follow-up visit. Follow-up visits should follow the principle of "review⁃assessment⁃adjustment" for long-term follow-up and management.

1. First, review the patient's response to treatment, focusing on whether dyspnea and exacerbations have improved.

2. Second, assess the patient's mastery of inhalation techniques, medication adherence, presence of associated symptoms due to comorbidities, and implementation of other non-pharmacological treatments (including pulmonary rehabilitation and self-management education).

3. Finally, identify and adjust any factors that may affect treatment efficacy, consider escalating or downgrading the treatment or changing the inhalation device, and then repeat the follow-up management process of "review⁃assessment⁃adjustment" [4] (Figure 6).

When the initial response to initial therapy is satisfactory after evaluation, the original regimen is maintained, and if dyspnea persists or worsens, or if a new exacerbation occurs, the drug should be adjusted (figure 7) [3]. The management process of "review⁃assessment⁃adjustment" is repeated at the follow-up visit to enable patients to receive individualized treatment and improve prognosis. It is recommended to recheck the lung function again 3 months after each medication adjustment, and if the patient's condition is stable, it is recommended to recheck the lung function every 6~12 months.

(7) Early treatment

Although all COPD patients should be treated according to the comprehensive assessment group, some patients in group A or those with mild to moderate lung function (FEV1≥50% predicted) are often reluctant to receive medication because of mild or no symptoms, and these patients are in the relative "early stages" of the disease However, the rate of decline in lung function is rapid in these patients, and regular use of long-acting bronchodilators can improve lung function and slow the rate of decline in lung function, suggesting that regular drug therapy can delay the progression of slow obstructive pulmonary disease (B, strongly recommended).

(8) Traditional Chinese medicine treatment

TCM treatment for COPD patients should be based on the principle of dialectical treatment, and some TCM has expectorant, bronchial and immunomodulatory effects, which can alleviate clinical symptoms, improve lung function and immune function, and improve quality of life. For details, please refer to the guidelines for the diagnosis and treatment of COPD in mainland China [29-30].

3. Non-drug treatment (1) Health education

Through health education, patients can improve their awareness and ability to deal with the disease, better cooperate with management, strengthen the prevention and treatment of COPD, reduce the risk of future exacerbations, improve symptoms and improve quality of life (see Part 6 of this guideline for details).

(2) Reduce exposure to risk factors

Smoking cessation is the most powerful intervention affecting the natural history of COPD, and smoking cessation counseling should be provided to patients with COPD, and a five-step smoking cessation approach and pharmacological smoking cessation can help patients with COPD [31]. Patients are advised to reduce exposure to outdoor air pollution, reduce exposure to biofuels, use cleaner fuels, improve kitchen ventilation [32], and reduce occupational dust exposure and chemical exposure.

(3) Vaccination

Influenza vaccination reduces severe illness and death in patients with COPD (A, strongly recommended), and Streptococcus pneumoniae vaccine is recommended for all patients aged ≥ 65 years (A, strongly recommended), and in recent years, foreign guidelines or disease control agencies have recommended new respiratory syncytial virus vaccine (A, strong recommendation) and herpes zoster vaccine (B, weak recommendation) for patients with chronic obstructive pulmonary disease, and catch-up vaccination is recommended for patients with chronic obstructive pulmonary disease who have never received diphtheria-pertussis vaccine [33-35]. The novel coronavirus vaccine is effective in preventing hospitalization, intensive care unit (ICU) or emergency department visits in patients with chronic respiratory diseases, and it is recommended to be vaccinated according to the national unified plan.

(4) Physical activity and pulmonary rehabilitation

All COPD patients are encouraged to be active and adopt a healthy lifestyle. Pulmonary rehabilitation is an individualized, comprehensive intervention tailored to the patient after a comprehensive assessment of the patient, and is the most effective non-pharmacological treatment strategy for improving dyspnea, health status, and exercise tolerance (A, strongly recommended), including but not limited to exercise training, education, and self-management (see section VI of this guideline for details).

(5) Oxygen therapy

Specific indications for long-term home oxygen therapy in patients with stable COPD are PaO2≤55 mmHg or oxygen saturation in arterial blood (SaO2) ≤88%, with or without hypercapnia, PaO2 55~60 mmHg or SaO2<89%, pulmonary hypertension, right heart failure, or polycythemia (hematocrit >0.55) (A, strongly recommended). Long-term oxygen therapy is generally inhaled oxygen through nasal cannula, with a flow rate of 1.0~2.0 L/min, and the daily oxygen inhalation duration is > 15 h. The goal of long-term oxygen therapy is to achieve PaO2≥60 mmHg and/or SaO2 rise to 90% at sea level at rest. Long-term oxygen therapy in patients with chronic respiratory failure can improve survival with severe hypoxemia at rest.

(6) Non-invasive ventilation

It has been widely used in patients with very severe COPD stabilization. Non-invasive ventilation combined with long-term oxygen therapy has some benefit in some patients, particularly those with significant daytime hypercapnia (B, strongly recommended). Non-invasive ventilation improves survival but not quality of life. In patients with COPD and OSA, continuous positive pressure ventilation has a clear benefit in improving survival and reducing hospitalization.

(7) Others

Surgical treatment (lung volume reduction, bullectomy, lung transplantation) and bronchoscopic interventions require a detailed specialist evaluation.

Part V: Management of acute exacerbations of COPD

Key takeaways:

●An acute exacerbation of COPD is defined as an event characterized by dyspnea and/or increased cough and sputum production within 14 days, with respiratory tract infection being the most common cause and differentiating it from pneumonia, pulmonary embolism, and heart failure.

●People at high risk of COPD exacerbations should be identified and actively prevented through vaccination, standardized inhaled drug therapy, and pulmonary rehabilitation.

●Treatment of acute COPD exacerbations includes inhalation or nebulization of short-acting bronchodilators, nebulization or systemic use of glucocorticoids, antimicrobial therapy, and respiratory support.

1. Etiology and prevention of acute exacerbation of COPD

The most common cause of COPD exacerbations is respiratory infections. Seventy-eight percent of patients with acute exacerbations have clear evidence of viral or bacterial infection, and other precipitating factors include smoking, air pollution, inhalation of allergens, surgery, and use of sedative drugs [4, 36], while complications or comorbidities such as pneumothorax, pleural effusion, congestive heart failure, arrhythmias, and pulmonary embolism are also common causes of exacerbated respiratory symptoms and need to be differentiated. At present, studies have found that viral infection, air pollution and other factors aggravate airway inflammation, and then induce bacterial infection, which is the main pathogenesis of acute exacerbations.

Acute exacerbation of COPD is an important event in the course of COPD disease, which can reduce the quality of life of patients, accelerate the exacerbation of symptoms, accelerate the deterioration and decline of lung function, increase the risk of cardiovascular events and mortality [37], increase the mortality rate of hospitalized patients, and increase the socioeconomic burden. It is necessary to actively prevent the occurrence of acute exacerbation of COPD, including improving the self-management efficiency of patients, long-term standardized use of inhaled drugs, pulmonary rehabilitation, etc., and the specific preventive measures for the cause of acute exacerbation are shown in Table 10.

2. Characteristics and identification of patients at high risk of acute exacerbation of COPD

(1) Patients at high risk of acute exacerbation of COPD usually have the following characteristics:

1. Have a history of acute exacerbation in the past, and have had 1 or more hospitalizations for acute exacerbation or 2 or more moderate to severe exacerbations in the previous year.

2. Symptoms and poor activity tolerance.

3. Abnormal lung function. FEV1 as a percentage of predicted value <50% or FEV1 decline rate ≥ 40 ml per year.

4. Combined with other chronic diseases, such as cardiovascular disease, asthma, lung cancer, etc.

5. Abnormal biomarker levels. Serum EOS ≥ 300 cells/microliter (the patient must be confirmed to be free of systemic hormone therapy before testing for blood EOS) or plasma fibrinogen ≥3.5 g/L [38].

(2) General identification process for acute exacerbation of COPD

It is necessary to make a clear diagnosis first, some patients are diagnosed with an acute exacerbation of COPD, if the patient has not been diagnosed before, it is necessary to confirm the diagnosis by pulmonary function tests, and then identify whether it is an acute exacerbation of COPD according to the aggravation of symptoms and signs that appear within 14 days, and it is also necessary to identify other diseases that can cause similar symptoms, such as pneumonia, pulmonary embolism, heart failure, etc. The specific identification process is shown in Figure 8.

3. Diagnosis and differential diagnosis of acute exacerbation of COPD

(1) Diagnosis of acute exacerbation of COPD

1. Clinical manifestations: The main symptoms of acute exacerbation of COPD are worsening shortness of breath, often accompanied by wheezing, chest tightness, increased cough, increased sputum volume, changes in sputum color and/or viscosity, and fever, in addition to tachycardia, general malaise, insomnia, drowsiness, fatigue, depression, and mental disorders [39].

2. INVESTIGATIONS:

(1) Routine blood count: the number of EOS, neutrophils and other inflammatory cells in some patients with acute exacerbation of COPD increases at the same time, and the absolute value of lymphocytes decreases indicates impaired immune function or new infection of some viruses.

(2) Procalcitonin (PCT) :P CT is secreted in large quantities in bacterial infection, but is not significantly elevated in viral infection and nonspecific inflammation [40]. It is necessary to combine clinical, imaging findings, and procalcitonin to determine the bacterial infection of patients with acute exacerbation of COPD.

（3）C反应蛋白（C reactive protein，CRP）：CRP是一种常用炎症标志物，可与脓性痰共同用于评估慢阻肺急性加重患者细菌感染与预后[41]。

(4) Arterial blood gas analysis: It provides important tests about arterial blood oxygenation, alveolar ventilation, pulmonary gas exchange and acid-base balance, which is helpful for the diagnosis of respiratory failure in patients with acute exacerbation of COPD.

(5) Chest X-ray: Patients with acute exacerbation of COPD should be routinely underwent chest X-ray examination to preliminarily identify the pulmonary cause of acute exacerbation of dyspnea.

(6) Other examinations: NT-proBNP, troponin, D-dimer, etc., can help evaluate cardiac function and identify the cause of dyspnea. Units with the capacity should carry out sputum smear, sputum culture, throat swab antigen and other pathogenic examinations to guide anti-infection treatment.

(7) Pulmonary function test: It is not recommended for patients with COPD to perform routine pulmonary function tests in the acute exacerbation period, and pulmonary function tests should be performed for patients who have not been diagnosed in the past to confirm the diagnosis.

(2) Differential diagnosis of acute exacerbation of COPD

An acute exacerbation of COPD is an acute process that distinct from the progression of COPD disease that worsens slowly. In diagnosing COPD exacerbations, it is necessary to identify other causes with similar clinical manifestations and classify them as "most common" (pneumonia, pulmonary embolism, heart failure) and "less common" (pneumothorax, pleural effusion, acute coronary syndrome, and arrhythmias) according to their commonness, as shown in Table 11.

(3) Classification of the severity of acute exacerbation of COPD and recommendations for referral and indications for hospitalization

There is currently no clinically useful grading criteria for the severity of acute exacerbations of COPD, and according to the mainland and GOLD guidelines, it is usually graded as:

1. Mild: SABA treatment alone.

2. Moderate: can be treated on an outpatient basis, requiring the use of SABA and antimicrobial drugs, with or without the addition of oral glucocorticoids.

3. Severe: The patient needs to be hospitalized or treated in the emergency department or ICU, and severe acute exacerbation may be complicated by acute respiratory failure.

Acute exacerbations can be life-threatening and require adequate evaluation. First, assess which patients require urgent referral to a higher-level hospital, and second, assess which patients require hospitalization. See Table 12.

4. Treatment of acute exacerbation of COPD

(1) Treatment goals

For patients with acute exacerbation of COPD, appropriate treatment and rehabilitation programs should be selected to help them return to their pre-exacerbation state as much as possible, assist them in self-monitoring and management, and identify and reduce the risk of recurrence of exacerbations in the future.

(2) Treatment plan

1. Bronchodilators: Inhaled long-acting bronchodilators are generally not recommended during acute exacerbations, and the dose and/or frequency of short-acting bronchodilators can be increased, or a combination of SABA and/or SAMA can be used [39]. For those who do not improve by increasing the dose or frequency, nebulized inhalation of SABA, or a combination of SABA + SAMA is recommended.

2. Glucocorticoids: Systemic application of glucocorticoids during acute exacerbation of COPD can shorten recovery time, improve lung function and oxygenation, reduce the risk of early repeated hospitalization and treatment failure, and shorten the length of hospital stay (A, strongly recommended). Oral corticosteroids are as effective as intravenous corticosteroids and should be treated with bronchodilators in addition to bronchocorticoids. Guidelines and expert consensus on the diagnosis and treatment of COPD in China recommend prednisone 30~40 mg/day for 5~7 days [3, 39]. Domestic studies have shown that nebulized ICS has fewer adverse effects than systemic glucocorticoids and can replace or partially replace systemic glucocorticoids [36,42-43]. Among them, nebulized budesonide (4~8 mg/d) is equivalent to intravenous methylprednisolone (40 mg/d) in the treatment of acute exacerbation of COPD, and can be used as the initial treatment regimen for hospitalized patients with acute exacerbation of COPD.

3. Antimicrobials:

(1) Indications for the use of antimicrobial drugs:

(1) The following three symptoms appear at the same time: aggravation of dyspnea, increase in sputum volume and purulent sputum;

(2) only 2 of the above 3 symptoms appeared, but including the symptom of sputum pus;

(3) Severe acute exacerbations requiring invasive or non-invasive mechanical ventilation.

Antimicrobials are generally not recommended for acute exacerbations of COPD with 2 exacerbations of 3 clinical manifestations but no sputum purulence, or for acute exacerbations of COPD with only 1 exacerbation (B, weak recommendation).

(2) Route of administration and duration of treatment: The route of drug therapy (oral or intravenous) depends on the patient's ability to eat and the pharmacokinetics of antimicrobial drugs, and oral therapy is preferred. Improvement in dyspnea and reduction in purulent sputum suggest response to treatment. The recommended course of antimicrobial treatment is 5~7 days, and the course of antimicrobial drugs should be extended to 10~14 days for severe infection, pneumonia, bronchiectasis, etc. [3] (B, strongly recommended).

(3) Recommendations for initial antimicrobial therapy: When choosing antimicrobial drugs, firstly, consider whether the patient has risk factors for poor prognosis: age > 65 years, comorbidities (especially cardiovascular diseases), severe chronic obstructive pulmonary disease, acute exacerbation ≥ 2 times/year, and antimicrobial therapy within 3 months. Second, consider whether the patient has risk factors for pseudomonas aeruginosa (PA) infection: recent hospitalization, history of frequent (>4 times/year) or recent (within the last 3 months) use of antimicrobials, severe impairment of lung function (FEV1 percentage <30%), and oral corticosteroids (prednisone > 10 mg/day for the last 2 weeks). The choice of antimicrobial agent is based on the assessment of these two risk factors (table 13) [44].

4. Other Therapeutic Drugs:

(1) Antiviral drugs: empiric anti-influenza virus therapy (including rhinovirus) is not recommended for patients with acute exacerbation of COPD. It should only be used if symptoms of infection (fever, muscle aches, malaise, and respiratory tract infection) are present at an early stage and are in the midst of an epidemiological outbreak and/or if there is a clear aetiological basis.

(2) Expectorants: including ambroxol hydrochloride, bromhexine hydrochloride, NAC, standard myrtle oil, etc., should be used symptomatically.

5. Respiratory support:

(1) Controlled oxygen therapy: Oxygen therapy is the basic treatment for acute exacerbations of COPD. Patients without serious complications tend to achieve satisfactory oxygenation levels (PaO2>60 mmHg or SpO2>90%) after oxygen therapy. However, the fraction of inhaled oxygen (FiO2) should not be too high to prevent carbon dioxide retention and respiratory acidosis. Routes of oxygen delivery include nasal cannulas or Venturi masks, which are more precise at regulating FiO2. Arterial blood gases should be rechecked 30 minutes after oxygen therapy to meet basic oxygenation without causing carbon dioxide retention.

(2) High-flow nasal cannula oxygen therapy (HFNC): It is a treatment method that continuously provides a relatively constant FiO2 (21%~100%), temperature (31~37 °C) and humidity (8~80 L/min) inhaled gas through high-flow nasal prongs. During this time, patients are able to speak, eat, feel more comfortable, and have better compliance. Indications include mild to moderate respiratory failure (100 mmHg≤ PaO2/FiO2< 300 mmHg, pH ≥ 7.30), mild respiratory distress (respiratory rate >24 breaths/minute), and intolerance or contraindication to conventional oxygen therapy or noninvasive mechanical ventilation (NIV).

Part VI: Primary management of COPD patients

Key takeaways:

●Primary care facilities should play a role in COPD screening, follow-up, comprehensive management, and referral.

●Health education, smoking cessation guidance, pulmonary rehabilitation assessment and treatment, nutrition and psychological status assessment and intervention are the key contents of primary management of COPD stabilization.

●Patients should be encouraged to develop an action plan to develop self-management and improve self-management effectiveness.

1. Management of COPD patients in primary medical institutions

The role of primary medical institutions in the management of COPD: screening and early diagnosis of high-risk groups of COPD, documentation, comprehensive assessment, drug and non-drug treatment and intervention, long-term follow-up management, monitoring of comorbidities and complications for confirmed COPD patients, timely assessment and initiation of two-way referral for cases that need to be referred to higher-level hospitals.

The hierarchical management process of COPD is shown in Figure 9.

(1) Screening and case detection of COPD

Primary care facilities that are able to do so can directly use pulmonary function testing equipment to conduct screening and case detection [45].

基层医疗机构如没有肺功能检测设备，可使用微型肺量计、呼气峰流速仪、问卷调查等方式进行慢阻肺筛查。 目前国外常用问卷有国际初级气道保健组织问卷（international primary airway group questionnaire，IPAG-Q）慢阻肺人群筛查问卷（chronic obstructive pulmonary disease population screener questionnaire，COPD-PS）、CAPTURE（chronic obstructive pulmonary disease assessment in primary care to identify undiagnosed respiratory disease and exacerbation risk）问卷和肺功能问卷（lung function questionnaire，LFQ）等，大陆自行开发的COPD-SQ问卷被认为更适用于国人慢阻肺的筛查[22]，对COPD-SQ问卷总分≥16分的患者，应进行肺功能检查，以明确诊断及严重程度。

(2) Follow-up of COPD

For patients with COPD who have been included in the comprehensive management of chronic diseases, regular follow-up and evaluation should be carried out, and the examination should be done once every 3~6 months, and the contents of the examination should be shown in Table 14.

(3) Referral of COPD patients

According to the severity of the patient's condition, it is divided into general referral and emergency referral.

1. General referral: Patients are advised to be referred to a respiratory specialist in a higher-level hospital in the following situations:

(1) The patient has the need for diagnosis or follow-up, or needs to do pulmonary function tests.

(2) After standardized treatment, the symptoms of dyspnea are not well controlled, and there are still frequent acute exacerbations, and the adverse drug reactions are large.

(3) Further testing or treatment is required to evaluate COPD comorbidities or complications.

(4) Failure of initial drug therapy.

(5) The diagnosis is unclear.

(6) Out-of-hospital treatment is ineffective or local medical conditions cannot meet the needs of diagnosis and treatment.

2. Emergency referral: When patients with COPD have moderate to severe acute exacerbations, and the symptoms are not significantly relieved after emergency treatment, and they need to be hospitalized or treated with mechanical ventilation, emergency referral should be considered. Referral requires oxygen inhalation, open venous access, continuous ECG monitoring, bronchodilators, and prior contact with the referring provider to communicate the patient's condition [46]. Urgent referral to a higher level hospital is required when a patient has the following clinical conditions:

(1) Aggravation of dyspnea, wheezing, chest tightness, aggravation of cough, increase in sputum volume, change in sputum color and/or viscosity, fever, etc.

(2) General malaise, irritability, drowsiness and other mental changes.

(3) Signs of cyanosis of the lips and peripheral edema.

(4) Serious comorbidities such as arrhythmia, heart failure, respiratory failure, etc.

(4) Comprehensive management of COPD

For patients who have been diagnosed, establish personal and family health records, and include them in the comprehensive management of chronic diseases, including health education, smoking cessation intervention, nutritional status assessment and intervention, rehabilitation assessment and intervention, psychological status assessment and intervention, etc.

1. Health education: Systematic and professional health education can not only enable patients to better understand COPD, but also enable patients to master healthy behaviors and lifestyles that are beneficial to COPD prevention and control, eliminate or alleviate risk factors, prevent and delay the occurrence and development of COPD, further control their symptoms, and improve the quality of life of patients. Health education mainly includes COPD-related knowledge, regular medication, smoking cessation, vaccination, pulmonary rehabilitation training, regular follow-up, identification and treatment of acute attacks, etc., which can be carried out in various forms such as face-to-face, health topics, WeChat or video lectures.

2. Smoking cessation intervention: Smoking is the main cause of COPD and the main risk factor for COPD progression and exacerbation. Smoking cessation can improve the progression of COPD, slow the rate of decline in lung function, alleviate clinical symptoms and reduce the risk of acute exacerbations of COPD. Grassroots doctors should establish a smoking history system for high-risk personnel, ask about the smoking history of each outpatient patient, and simply evaluate the degree of nicotine dependence (including smoking age, daily smoking volume, etc.) and whether they use e-cigarettes and other tobacco products according to the nicotine dependence scale. Actively do a good job in promoting smoking cessation, encourage and guide patients to quit smoking, guide them to visit smoking cessation clinics when necessary, and assist in supervising smoking cessation treatment.

Treatment for smoking cessation includes pharmacological interventions (nicotine replacement therapy, bupropion, varenicline), psychological interventions, a combination of pharmacological and psychological interventions, and other interventions [47]. The combination of cognitive-behavioral interventions and smoking cessation medications can increase sustained smoking cessation rates and improve lung function. The usage, dosage, contraindications, adverse reactions, and precautions of commonly used smoking cessation drugs are shown in Table 15 [48].

3. Nutritional Status Assessment and Intervention:

(1) Nutritional assessment: patients with COPD suffer from malnutrition due to excessive energy consumption and reduced digestion and absorption due to long-term cough and dyspnea. Malnutrition is a risk factor for poor prognosis independent of lung function [49]. Primary doctors should strengthen the nutritional management of patients with COPD, regularly investigate the daily dietary intake habits of patients, and comprehensively evaluate the nutritional status of patients by measuring body mass index (BMI), fat thickness, and serum albumin. Individualized nutrition guidance was formulated for patients to guide them to strengthen high-quality protein diet, consume high-calorie foods in a timely manner, improve patients' nutritional level, and enhance immunity. Commonly used nutritional evaluation indicators include BMI, fat-free mass (FFM), fat-free mass index (FFMI), subcutaneous fat thickness, albumin, prealbumin, etc., and commonly used screening scales include malnutrition universal screening tool (MUST), Nutritional risk screening scale 2002 (NRS2002), mini-nutritional assessment (MNA), etc.

(2) Nutritional interventions: including general interventions and intensive interventions. General intervention: According to the results of the patient's nutritional assessment, the daily energy supply demand and ratio, combined with personal dietary habits, a reasonable and scientific diet is formulated for the patient, and the patients who cannot meet the nutritional needs can be appropriately given oral nutrition supplements and corresponding dietary education. Intensive intervention: For those with high nutritional risk, it is recommended to consult a dietitian or refer to the nutrition department of a higher-level medical institution for intensive nutritional intervention, and continue to monitor, follow-up, evaluate and adjust the treatment plan. Qualified primary medical institutions can cooperate with higher-level medical institutions to explore the establishment of a hospital-community-home (HCH) nutrition management model.

4. Rehabilitation assessment and intervention: In order to improve the physical fitness, activity endurance and quality of life of patients with COPD, it is necessary to carry out targeted respiratory rehabilitation training and individualized, multidisciplinary and comprehensive intervention, so as to reduce the symptoms and signs of patients and improve exercise endurance and quality of life (A, strongly recommended). Respiratory rehabilitation training has a significant effect on patients in the stable stage, and grassroots doctors should strengthen respiratory rehabilitation education and guide patients to carry out effective respiratory rehabilitation training [50].

(1) Rehabilitation assessment: The classification, content and methods of commonly used pulmonary rehabilitation assessment are shown in Table 16.

(2) Common rehabilitation training methods: Commonly used respiratory rehabilitation training includes aerobic exercise, resistance training, respiratory muscle training, coughing, and airway clearance techniques [51] (Tables 17 and 18). Most patients with COPD are elderly, and they are often sedentary and inactive due to factors such as worsening dyspnea after activity. The amount of physical activity in this group of people should reach the recommended amount of WHO (150~300 min of moderate-intensity aerobic exercise per week, 2 times of resistance exercise per week). Older people should gradually increase the amount of exercise, which is beneficial. Older adults are encouraged to participate in a combination of exercises that include aerobic exercise, resistance training, balance (fall prevention) and flexibility exercises, at least twice a week, and can incorporate them into their lives. Aerobic exercise should start from a low starting point, advance slowly, and change less, and be gradual under the premise of subjective will and objective ability tolerance; resistance training is very important to prevent rapid decline in muscle strength, and people with sarcopenia should strengthen muscle strength and muscle endurance exercises.

5. Psychological State Assessment and Intervention:

(1) Assessment of psychological status: With the progression and recurrence of the disease, patients with COPD often experience symptoms such as insomnia, sleep disorders, anxiety, irritability, and depression, and some studies have shown that the prevalence of anxiety and depression in COPD patients is nearly one-third [52]. Adverse psychological reactions have a significant impact on patients' treatment compliance, quality of life, mortality and other aspects, and patients' psychological state should be actively evaluated and targeted interventions should be given.

基层常用的心理评估量表包括焦虑自评量表（self-rating anxiety scale，SAS，50~59分为轻度焦虑，60~69分为中度焦虑，70分以上为重度焦虑），抑郁自评量表（self-rating depression scale，SDS，53~62分为轻度抑郁，63~72分为中度抑郁，73分以上为重度抑郁），可对患者进行评分，判断其焦虑、抑郁程度。

(2) Psychological intervention methods: Individualized psychological intervention measures are implemented according to the severity of the patient's condition, economic conditions, family background, education level, family and social support, etc. For anxiety and depression caused by lack or insufficient cognition of COPD, medical staff should carry out health education on COPD knowledge and health to improve their understanding of the disease, and actively do a good job in the work of the patient's family, so that the family can give sufficient support from the economic and psychological aspects, so that the patient can actively cooperate with the treatment and nursing.

Relaxation exercises can be used to reduce anxiety and depression. Deep breathing relaxation method: Ask the patient to quietly close their eyes and take deep breaths regularly and slowly, 15 min/time, 3 times/day. Imagination relaxation method: let the patient close his eyes, relax, and imagine on his own under the language guidance of the medical staff, so that the patient can achieve the most comfortable and comfortable situation, 5 min/time, 3 times/d. Music Appreciation Therapy: Select the soothing music that the patient likes to listen to and play it on time, 15~30 min/time, 3 times/day.

We attach importance to the role of social support and implement "peer education". Patients with successful experience in COPD psychological rehabilitation are encouraged to serve as volunteer propagandists, teach by word and deed once a week, educate and help patients through their personal experiences, let patients understand the positive effects of psychotherapy, improve their awareness of psychological rehabilitation, and actively cooperate with psychological intervention [53].

6. End-of-life care: Patients with COPD suffer greatly in the end-stage of their illness and should be strengthened in palliative care and end-of-life care [54].

(1) Palliative care: Palliative care is an extension of the traditional disease treatment model, with the aim of preventing and alleviating patients' suffering as much as possible and supporting patients to achieve the best quality of life. Palliative care can improve the quality of life, reduce symptoms, and even prolong the survival of some patients in advanced disease. The family doctor team should take steps to relieve physical discomfort such as dyspnea, fatigue, and pain, while providing emotional and emotional support to the patient and family. Specific methods include nebulized bronchodilators, self-management education and pulmonary rehabilitation including exercise training, oxygen therapy, non-invasive ventilation, analgesia, psychological interventions, etc.

(2) Hospice care: The starting point of hospice care is to guide the patient's final stage of life, improve the patient's psychological negative emotion, reduce the incidence of accidents, and at the same time enlighten the patient's family to face this fact correctly [55]. In the specific implementation, patients and their families should be communicated more to inform them of various critical situations that may occur, the corresponding treatment measures, and the financial burden, and help patients and their families make informed choices consistent with the patient's values [36], including discussing with patients and their families their views on invasive rescue measures. It allows patients and their families to face death with peace of mind, and relieves physical and psychological suffering.

2. Primary self-management of COPD patients

Under the guidance of medical staff, patients with COPD can correctly understand the dangers of COPD, understand the importance of quitting smoking, learn to master a healthy lifestyle and standardized rehabilitation skills, standardize treatment, identify acute exacerbations in a timely manner, interact closely with grassroots doctors, and carry out their own disease management according to the formulated management plan. The details are as follows:

(1) In accordance with the principle of individualization, work with patients and their caregivers to formulate plans and plans, formulate short-term and long-term goals according to the patient's condition, and the management content that needs to be completed by the patient himself. The content and key points of self-management are shown in Table 19.

(2) Doctors and patients make joint decisions, and have regular follow-up visits at least once every 3 months to assess their own conditions and revise their self-management plans and goals. Correctly grasp the use of inhaled drugs and precautions, effectively carry out pulmonary rehabilitation training suitable for themselves, enhance compliance with drug treatment, and seek medical help in a timely manner in case of emergency.

(3) Actively select general practitioners with respiratory expertise to carry out contracted management of family doctors, and carry out one-to-one health management services through face-to-face or WeChat and other forms.

Expert Group for the Development of Guidelines for Primary Diagnosis and Treatment and Management of Respiratory Diseases in China

Consultants: Wang Chen, Qu Jieming, Chen Rongchang, Shen Huahao

Team Leader: Chi Chunhua Yang Ting

Deputy team leader: Wu Hao, Lai Kefang, Zhao Jianping, Chen Yahong, Huang Kewu, Wang Wei, Jiezhijun struggled

Secretary-General: Liu Lan

Members (in alphabetical order):

Respiratory Specialists: An Li (Beijing Chaoyang Hospital, Capital Medical University), Bao Wuping (The First People's Hospital of Shanghai Jiao Tong University School of Medicine), Cao Bin (China-Japan Friendship Hospital), Chen Yahong (Peking University Third Hospital), Chen Yan (Second Xiangya Hospital, Central South University), Feng Queling (Peking University People's Hospital), He Yuanzhou (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Hu Yan (Peking University First Hospital), Hua Wen (The Second Affiliated Hospital of Zhejiang University School of Medicine), Huang Kewu (Beijing Chaoyang Hospital, Capital Medical University), Jie Zhijun (Shanghai Fifth People's Hospital), Jin Meiling (Zhongshan Hospital, Fudan University) Lai Kefang (The First Affiliated Hospital of Guangzhou Medical University), Li Guangxi (Guang'anmen Hospital, Beijing University of Chinese Medicine), Li Yanming (Beijing Hospital), Liu Huiguo (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Liu Kui (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Liu Xiaoju (The First Hospital of Lanzhou University), Luo Fengming (West China Hospital, Sichuan University), Luo Wei (The First Affiliated Hospital of Guangzhou Medical University), Qiu Zhongmin (Tongji Hospital, Tongji University), Song Yuanlin (Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University), Tang Wei (Ruijin Hospital, Shanghai Jiaotong University School of Medicine), Wang Wei (The First Affiliated Hospital of China Medical University), Xia Lixia (The Second Affiliated Hospital of Zhejiang University School of Medicine), Xie Jiaxing (The First Affiliated Hospital of Guangzhou Medical University), Xu Jihuai (Tongji Hospital, Tongji University), Yang Ting (China-Japan Friendship Hospital), Yin Yan (The First Affiliated Hospital of China Medical University) Li Yu (Tongji Hospital, Tongji University), Jing Zhang (Zhongshan Hospital, Fudan University), Min Zhang (The First People's Hospital of Shanghai Jiao Tong University School of Medicine), Jianping Zhao (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Yumin Zhou (The First Affiliated Hospital of Guangzhou Medical University)

General Medicine Specialists: Cao Zhaolong (Peking University People's Hospital), Chen Haiying (Fengpu Community Health Service Center, Fengxian District, Shanghai), Chen Hong (Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital), Chi Chunhua (Peking University First Hospital), Cui Liping (Ningxia Medical University General Hospital), Ding Jing (Yuetan Community Health Service Center, Xicheng District, Beijing), Dong Aimei (Peking University First Hospital), Duan Yingwei (Shichahai Community Health Service Center, Xicheng District, Beijing), Fang Lili (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine), Feng Mei (Shanxi Bethune Hospital), Hu Fang (Hangzhou Sijiqing Street Community Health Service Center), Huan Hongmei (Shanghai Minhang District Gumei Community Health Service Center), Huang Min (Suzhou Municipal Hospital), Kong Min (Fangzhuang Community Health Service Center, Fengtai District, Beijing) Zhigang PAN (Zhongshan Hospital, Fudan University), Ling Shi (Health Affairs Management Center, Putuo District, Shanghai), Qiaoli SU (West China Hospital, Sichuan University), Wei TAN (The Second Affiliated Hospital of Wuhan University of Science and Technology), Jianjing Tong (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine), Shuang Wang (The First Affiliated Hospital of China Medical University), Xuejuan Wei (Fangzhuang Community Health Service Center, Fengtai District, Beijing), Hao Wu (College of General Medicine and Continuing Education, Capital Medical University), Xue Xiao (Affiliated Hospital of Zunyi Medical University), Yi Chuntao (Health Supervision Institute of Xuhui District, Shanghai), Zhu Lan (Xietu Community Health Service Center, Xuhui District, Shanghai) Zhu Weiguo (Peking Union Medical College Hospital)

Methodology: Yali Liu (Beijing Children's Hospital, Capital Medical University) and Xiaoxia Peng (Beijing Children's Hospital, Capital Medical University)

Grassroots network review experts: Chen Jing (Xinxing Street Community Health Service Center, Heping District, Tianjin), Gan Jingwen (Liyuan Community Health Service Center, Liyuan Town, Tongzhou District, Beijing), Li Yongjin (Jinsong Community Health Service Center, Chaoyang District, Beijing), Liang Xingyu (Qianhu Hospital, Yinzhou District, Ningbo), Lu Chongjun (Loujiang Community Health Service Center, Suzhou), Sheng Fei (Community Health Service Center Affiliated to Tongji University School of Medicine, Shanghai), Wang Le (Yuhe Community Health Service Center, Caoshi, Qingyang District, Chengdu), Xi Sen (Huairou Town Community Health Service Center, Huairou District, Beijing), Zhang Juanhui (Yizhou Community Health Service Center, Taijiang District, Fuzhou City)

Guideline Guide: Rongchang Chen (Shenzhen People's Hospital) and Jian Kang (The First Affiliated Hospital of China Medical University)

Experts: Yan Chen (Second Xiangya Hospital, Central South University), Yingwei Duan (Shichahai Community Health Service Center, Xicheng District, Beijing), Ke Huang (China-Japan Friendship Hospital), Kong Min (Fangzhuang Community Health Service Center, Fengtai District, Beijing), Li Demin (China-Japan Friendship Hospital), Tong Jianjing (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine), Yang Ting (China-Japan Friendship Hospital), Yin Yan (The First Affiliated Hospital of China Medical University), Zhang Jing (Zhongshan Hospital, Fudan University), Zhou Yumin (The First Affiliated Hospital of Guangzhou Medical University), Zhu Weiguo (Peking Union Medical College Hospital)

External reviewers: Cao Jie (Tianjin Medical University General Hospital), Liu Xiaoju (The First Hospital of Lanzhou University), Ran Pixin (The First Affiliated Hospital of Guangzhou Medical University), Sun Dejun (Inner Mongolia Autonomous Region People's Hospital), Sun Yongchang (Peking University Third Hospital), Wen Fuqiang (West China Hospital, Sichuan University), Xiao Wei (Qilu Hospital of Shandong University), Xu Jianying (Shanxi Bethune Hospital), Yang Lan (The First Affiliated Hospital of Xi'an Jiaotong University)

References (omitted) Conflicts of interestAll authors declare no conflicts of interest

Please click the link to view the full text of the previous guide↓↓↓

Guidelines for primary care of bronchial asthma (2018)

Guidelines for Primary Care of Bronchial Asthma (Practice Edition·2018)

Guidelines for Primary Care of Chronic Obstructive Pulmonary Disease (2018)Guidelines for Primary Care of Chronic Obstructive Pulmonary Disease (2018)Guidelines for Primary Care of Chronic Cor Pulmonary Heart Disease (2018)Guidelines for Primary Care of Chronic Cor Pulmonary Heart Disease (Practice Version·2018)Guidelines for Primary Care of Adults with Obstructive Sleep Apnea (2018)Guidelines for Primary Care of Adults with Obstructive Sleep Apnea (Practice Version·2018)

Guidelines for primary care of adults with community-acquired pneumonia (2018)

Guidelines for Primary Care of Community-Acquired Pneumonia in Adults (Practice Edition, 2018)

Guidelines for primary diagnosis and treatment of cough (2018)Guidelines for primary diagnosis and treatment of cough (practice version·2018)Guidelines for primary diagnosis and treatment of hypertension (2019)Guidelines for primary diagnosis and treatment of acute tracheo-bronchitis (2018)Guidelines for primary diagnosis and treatment of acute tracheo-bronchitis (practice version·2018)Guidelines for primary diagnosis and treatment of dyslipidemia (2019)Guidelines for primary diagnosis and treatment of dyslipidemia (practice version· 2019) Guidelines for the primary diagnosis and treatment of acute upper respiratory tract infection (2018)Guidelines for the primary diagnosis and treatment of acute upper respiratory tract infection (practice version, 2018)Guidelines for the primary diagnosis and treatment of routine pulmonary function tests (2018)Guidelines for the primary diagnosis and treatment of chronic abdominal pain (2019)Guidelines for the primary diagnosis and treatment of chronic abdominal pain (practice version, 2019)Guidelines for the primary diagnosis and treatment of gastroesophageal reflux disease (2019)Guidelines for the primary diagnosis and treatment of gastroesophageal reflux disease (practice version·2019)Guidelines for the primary diagnosis and treatment of hypertension (practice version· 2019) Guidelines for the Primary Care of Tuberculosis (2018)Guidelines for the Primary Care of Type 2 Diabetes Mellitus (Practice Version·2019)Guidelines for the Primary Care of Acute Pancreatitis (2019)Guidelines for the Primary Care of Acute Pancreatitis (Practice Version·2019)Guidelines for the Primary Care of Chest Pain (2019)Guidelines for the Primary Care of Chest Pain (Practice Version·2019)Guidelines for the Primary Care of Acute Heart Failure (2019)Guidelines for the Primary Care of Acute Heart Failure (Practice Version· 2019) Guidelines for Primary Care of Chronic Heart Failure (2019)Guidelines for Primary Care of Chronic Heart Failure (Practice Version·2019)Guidelines for Primary Care of Hypothyroidism (2019)Guidelines for Primary Care of Hypothyroidism (Practice Version·2019)

Guidelines for primary care of cardiac arrest (2019)Guidelines for primary care of cardiac arrest (Practice Version·2019)Guidelines for Primary Care of Ventricular Tachycardia (2019)Guidelines for Primary Care of Ventricular Tachycardia (Practice Version·2019)Guidelines for Primary Care of Hyperthyroidism (2019)Guidelines for Primary Care of Hyperthyroidism (Practice Version·2019)Guidelines for Primary Care of Parkinson's Disease (Practice Version· 2019) Guidelines for Primary Diagnosis and Treatment of Helicobacter Pylori Infection (2019)Guidelines for Primary Care of Helicobacter Pylori Infection (Practice Version·2019)Guidelines for Primary Care of Atrial Fibrillation (2019)Guidelines for Primary Care of Atrial Fibrillation (Practice Version·2019)Guidelines for Primary Care for Pre-excitation Syndrome (2019)Guidelines for Primary Care for Drug-induced Liver Injury (2019)

Guidelines for Primary Diagnosis and Treatment of Drug-induced Liver Injury (Practice Edition·2019)

Guidelines for Primary Care of Alcoholic Liver Disease (2019)

Guidelines for Primary Care of Alcoholic Liver Disease (Practice Edition·2019)

Guidelines for Primary Care of Chronic Gastritis (2019)

Guidelines for Primary Care of Chronic Gastritis (Practice Edition·2019)

Guidelines for Primary Care of Chronic Constipation (2019)

Guidelines for Primary Care of Chronic Constipation (Practice Edition, 2019)

Guidelines for Primary Care of Chronic Diarrhoea (2019)

Guidelines for Primary Care of Chronic Diarrhea (Practice Edition, 2019)

Guidelines for the primary care of ST-elevation myocardial infarction (2019)

Guidelines for the primary diagnosis and treatment of ST-segment elevation myocardial infarction (practice version, 2019)Guidelines for the primary diagnosis and treatment of non-ST-segment elevation acute coronary syndrome (2019)Guidelines for the primary diagnosis and treatment of non-ST-segment elevation acute coronary syndrome (practice version·2019)Guidelines for the rational use of primary medication for hypertension, guidelines for the rational use of primary medication for dyslipidemia, guidelines for the primary diagnosis and treatment of chronic hepatitis B (2020)Guidelines for the primary diagnosis and treatment of stable coronary heart disease (2020)Guidelines for the primary diagnosis and treatment of stable coronary heart disease (practice version· 2020）

Guidelines for primary care of ischemic stroke (2021)

Guidelines for Primary Care of Ischemic Stroke (Practice Edition·2021)

Guidelines for primary care of essential tremor (2021)

Guidelines for Primary Care of Essential Tremor (Practice Edition·2021)

Guidelines for Primary Care of Generalized Anxiety Disorder (2021)

Guidelines for Primary Care of Depression (2021)

Guidelines for Primary Care of Generalized Anxiety Disorder (Practice Edition, 2021)Guidelines for Primary Care of Atopic Dermatitis (2022)

Guidelines for Primary Care of Psoriasis (2022)Guidelines for Primary Care of Drug Eruption (2022)

Guidelines for Primary Care of Atopic Dermatitis in Children (2023)

Guidelines for Primary Care of Sunburn (2023)

Guidelines for Primary Care of Bacterial Folliculitis, Boils, and Carbuncles (2023)

Consensus on Primary Diagnosis and Treatment of Stable Coronary Heart Disease Complicated with Psychological Problems (2023)

Chinese Expert Consensus on Early Screening and Primary Prevention of Heart Failure (2024)

Chinese Expert Consensus on Lipid Management in Community Adults (2024)

Guidelines for the primary diagnosis and treatment of heart failure in China (2024)

Chinese Expert Consensus on Public Education on Cough (1st Edition)