Chronic Obstructive Pulmonary Disease (COPD) is a common respiratory disease that seriously endangers the physical and mental health of patients. Standardized treatment for COPD patients can stop the development of the disease, delay the acute exacerbation, improve the quality of life, reduce the rate of disability and death, and reduce the burden of disease.
I. Definition
COPD is a preventable and treatable disease characterized by airflow limitation. COPD is a preventable and treatable disease characterized by airflow limitation, which is not completely reversible, progressive, and associated with an abnormal inflammatory response of the lungs to inhalation of harmful gases or particles such as tobacco smoke, etc. COPD primarily involves the lungs, but can also cause systemic (or extrapulmonary) adverse effects. Pulmonary function tests are important to clarify the presence of airflow limitation. After inhalation of bronchodilators, if the exertional expiratory volume in one second as a percentage of the exertional lung volume (FEV1/FVC%) is <70%, it indicates the presence of incomplete reversible airflow limitation. Wang Haifeng, Department of Pulmonary Diseases, The First Affiliated Hospital of Henan College of Traditional Chinese Medicine
II. Risk factors
The onset of COPD is the result of a combination of genetic and environmental pathogenic factors.
(a) Genetic factors.
Certain genetic factors can increase the risk of COPD development. The known genetic factor is α1-antitrypsin deficiency. European and American studies have shown that severe α1-antitrypsin deficiency is associated with emphysema formation. The role of α1-antitrypsin deficiency in the development of emphysema in our population remains to be clarified. Gene polymorphisms have a role in the pathogenesis of COPD.
(B) Environmental factors.
1. smoking: smoking is the most common risk factor for the development of COPD. Smokers have significantly higher respiratory symptoms, impaired lung function and death rates than non-smokers. Passive smoking can also cause the occurrence of COPD.
2. Occupational dust and chemical substances: COPD can occur when the concentration of inhaled occupational dust, organic and inorganic dust, chemicals and other harmful fumes is too large or the exposure time is too long.
3. Indoor and outdoor air pollution: Indoor air pollution caused by cooking and heating with biofuels in poorly ventilated dwellings is one of the risk factors for the development of COPD. The relationship between outdoor air pollution and the development of COPD is yet to be clarified.
4. Infection: Severe respiratory infections in childhood are associated with decreased lung function and respiratory symptoms in adulthood. A previous history of tuberculosis is associated with airflow limitation in adults over 40 years of age.
5. Socioeconomic status: The onset of COPD is associated with socioeconomic status. This may be related to the presence of indoor and outdoor air pollution exposure, crowded living conditions, and poor nutrition in low socioeconomic classes.
III. Pathogenesis
COPD can involve the airways, lung parenchyma, and pulmonary vasculature and is characterized by a chronic inflammatory response dominated by neutrophil, macrophage, and lymphocyte infiltration. These cells release inflammatory mediators that interact with structural cells in the airways and lung parenchyma, which in turn contribute to the accumulation of T lymphocytes (especially CD+8) and neutrophils and eosinophils in the lung tissue, releasing various mediators such as leukotriene B4 (LTB4), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α), causing destruction of lung structures. Oxidative and antioxidant imbalances and protease and anti-protease imbalances as well as autonomic nervous system dysfunction and increased cholinergic tone further aggravate COPD pulmonary inflammation and airflow limitation. Genetic predisposition plays a role in the pathogenesis.
IV. Pathology
COPD involves the central airways, peripheral airways, lung parenchyma, and pulmonary vasculature. The central airways (trachea, bronchi and fine bronchi with an inner diameter greater than 2-4 mm) are infiltrated by superficial epithelial inflammatory cells, with increased mucus secretion due to enlarged mucus-secreting glands and increased cupped cells. In the peripheral airways (small bronchi and fine bronchi with an internal diameter of less than 2 mm), chronic inflammation leads to recurrent airway wall damage and repair processes. During the repair process structural remodeling of the airway wall occurs, with increased collagen content and scar tissue formation, and these changes cause narrowing of the airway and result in fixed airway obstruction.
Pulmonary parenchymal involvement in COPD manifests as lobar central emphysema, involving the respiratory fine bronchi, with luminal dilatation and destruction. In milder cases, the lesions often occur in the upper regions of the lungs, and when the disease progresses, it can involve the entire lung with destruction of the pulmonary capillary bed.
Pulmonary vascular changes in COPD are characterized by thickening of the vessel wall, which can appear early. They are characterized by intimal thickening, smooth muscle hyperplasia and inflammatory cell infiltration of the vessel wall. In the acute exacerbation of COPD, deep vein thrombosis and pulmonary thromboembolism are easily combined.
V. Pathophysiology
The pathophysiological changes of COPD include increased mucus secretion, cilia dysfunction, airflow limitation, hyperinflation, abnormal gas exchange, pulmonary hypertension and pulmonary heart disease and systemic adverse effects due to chronic inflammation of airways and lung parenchyma. Increased mucus secretion and ciliary dysfunction lead to chronic cough and sputum. Small airway inflammation, fibrosis and increased luminal secretion cause decreased FEV1, FEV1/FVC. Gas trapping occurs after small airway obstruction, which can lead to alveolar hyperinflation. Hyperinflation increases functional residual air volume and decreases inspiratory volume, causing dyspnea and limited exercise capacity. It is now believed that hyperinflation occurs early in the disease and is the main cause of shortness of breath after activity. As the disease progresses, airway obstruction and damage to the lung parenchyma and pulmonary vascular bed increase, causing a further decrease in pulmonary ventilation and gas exchange capacity, leading to hypoxemia and hypercapnia. Long-term chronic hypoxia can cause extensive pulmonary vasoconstriction and pulmonary hypertension. Pulmonary intimal hyperplasia, fibrosis and occlusion cause pulmonary circulation remodeling, and pulmonary hypertension occurs in the later stages of COPD, leading to chronic pulmonary heart disease and right heart insufficiency.
The inflammatory response of COPD is not limited to the lungs, but also has systemic adverse effects. The systemic adverse effects of COPD are clinically important and can affect the quality of life and prognosis of patients.
VI. Clinical manifestations
(A) Symptoms.
1. Chronic cough: often the first symptom. Initially, the cough is intermittent, heavier in the morning, and later it can be present in the morning and evening or throughout the day, and the cough is often not significant at night. A small number of patients have no cough symptoms, but lung function shows significant airflow restriction.
2. Coughing sputum: small amount of mucus sputum, more in the early morning. In case of co-infection, the sputum volume increases and may be purulent. In a few patients, cough is not accompanied by sputum.
3. Shortness of breath or dyspnea: This is a typical manifestation of COPD. In the early stage, it only appears after activity, and then gradually worsens, and in severe cases, shortness of breath is felt even during daily activities and even at rest.
4. Wheezing: Some patients, especially the severe ones, may have wheezing symptoms.
5. Systemic symptoms: weight loss, loss of appetite, peripheral muscle atrophy and dysfunction, mental depression and/or anxiety, etc.
(ii) Physical signs.
The early signs of COPD are not obvious. As the disease progresses the following signs may appear.
1. General: mucous membrane and skin cyanosis, anterior sitting in severe cases, bulbar conjunctival edema, jugular vein filling or anger.
2. Respiratory system: shallow and rapid respiration, auxiliary respiratory muscles involved in respiratory movement, in severe cases may be thoracoabdominal contradictory respiration; barrel-shaped chest, increased anterior and posterior diameter of the thorax, widening of the rib space, widening of the inferior angle of the sternum under the saber; bilateral diminished fibrillation; lung percussion may be over clear sound, lung and liver boundary downward shift; both lung breath sounds are reduced, prolonged expiratory phase, sometimes can be heard dry sternal stop woven grass
3. Heart: subxiphoid apical pulsation; narrowing of the turbid border of the heart; distant heart sounds, with clearer and louder heart sounds in the saber, P2 > A2 in the presence of pulmonary hypertension and pulmonary heart disease, and systolic murmurs in the tricuspid region.
4. abdomen: the hepatic border is shifted downward, the hepatic neck regurgitation sign is positive in the presence of right heart insufficiency, and the ascites mobile turbid sound is positive.
5. Other: pestle-shaped fingers/toes may be seen in cases of chronic hypoxia, and concave edema of both lower extremities may be seen in cases of hypercapnia or right heart failure.
(iii) Pulmonary function tests.
Pulmonary function tests, especially ventilation function tests, are important for the diagnosis of COPD and the assessment of the severity of the disease.
1. First second expiratory volume as a percentage of forceful lung volume (FEV1/FVC%) is a sensitive indicator to evaluate airflow limitation. The first second expiratory volume as a percentage of the expected value (FEV1% expected value) is often used for grading the severity of COPD with little variability and is easy to perform. An FEV1/FVC <70% after inhalation of bronchodilators is indicative of incomplete reversible airflow limitation.
2. Increased total lung volume (TLC), functional residual air volume (FRC), residual air volume (RV) and decreased lung volume (VC) suggest hyperinflation. Since the increase in TLC is not as pronounced as the increase in RV, the RV/TLC is increased.
3. Decreased carbon monoxide diffusion volume (DLco) and DLco to alveolar ventilation volume (VA) ratio (DLco/VA) indicate impaired pulmonary diffusion function, suggesting disruption of alveolar septa and loss of pulmonary capillary beds.
4. Bronchodilator test: The improvement rate of FEV1 ≥ 12% and the increase of FEV1 absolute value over 200 ml after inhalation of short-acting bronchodilator is used as the judgment criterion of positive bronchodilator test. Its clinical significance is that: (1) it helps to differentiate COPD from bronchial asthma or suggests the possible coexistence of the two; (2) it cannot reliably predict the patient’s response to bronchodilator or glucocorticoid therapy and disease progression; (3) it is affected by factors such as drug therapy and has poor sensitivity and reproducibility.
(iv) Chest X-ray imaging.
1. X-ray chest radiography: early onset of chest radiography may not be abnormal, and later appear non-specific changes such as increased lung texture and disorder; when emphysema occurs, related manifestations can be seen: lung volume increases, anterior and posterior diameter of the thorax grows, ribs flatten, lung field translucency increases, diaphragm position is low and flat, heart overhang is narrow, peripheral lung field texture is slender and sparse, etc.; when pulmonary hypertension and pulmonary heart disease are complicated, in addition to the enlarged right heart In the case of pulmonary hypertension and pulmonary heart disease, in addition to the enlarged right heart, there may be conical bulging of the pulmonary artery, enlargement of the hilar vascular shadow, widening of the right lower pulmonary artery and the appearance of the residual root sign. Chest X-ray is important to determine the presence of pulmonary complications and to differentiate from other diseases (such as pneumothorax, pneumomediastinum, pneumonia, tuberculosis, interstitial fibrosis, etc.).
2. Chest CT examination: High-resolution CT (HRCT) has high sensitivity and specificity for identifying lobar-centered or total lobar emphysema and determining the size and number of pulmonary blisters, which is helpful for the phenotypic analysis of COPD and has important value for determining the indications of pulmonary blister resection or surgical reduction surgery, and is more helpful for the differential diagnosis of COPD and other diseases.
(E) Blood gas analysis.
It can be used to diagnose hypoxemia, hypercapnia, acid-base imbalance, respiratory failure and their types.
(F) Other laboratory tests.
Hemoglobin, red blood cell count and red blood cell pressure may be increased. Leukocytes may be elevated and the percentage of neutrophils may increase in the presence of bacterial infection.
Sputum smear and sputum culture can help diagnose bacterial, fungal, viral and other atypical pathogenic microbial infections; blood pathogenic microbial nucleic acid and antibody tests and blood culture can be positive; positive pathogenic culture and drug sensitivity tests can help rationalize the selection of anti-infective drugs.
Other relevant tests may be performed to help diagnose pathophysiology and comorbidities.
VII. Diagnosis
The diagnosis is based on a comprehensive analysis of risk factors such as smoking, clinical symptoms, signs and lung function tests. Incomplete reversible airflow limitation is a necessary condition for the diagnosis of COPD. Incomplete reversible airflow limitation can be determined by FEV1/FVC <70% after inhalation of bronchodilators.
In a few patients, there is no cough, sputum or shortness of breath, but only FEV1/FVC<70% is found in the pulmonary function test, which can be diagnosed as COPD after excluding other diseases.
Eight, severity grading and disease stage
(A) COPD severity grading.
According to FEV1/FVC, FEV1% expected value and clinical performance, the severity of COPD can be graded by clinical severity (Table 1).
Table 1 Clinical severity grading of COPD
Grading
Clinical characteristics
Grade I (mild)
・ FEV1/FVC <70%
・ FEV1 ≥ 80% of expected value
・ With or without chronic symptoms (cough, sputum)
Grade II (moderate)
・ FEV1/FVC <70%
・ 50% ≤ FEV1 < 80% expected value
・ Often with chronic symptoms (cough, sputum, dyspnea after activity)
Grade III (severe)
・ FEV1/FVC <70%
・ 30% ≤ FEV1 < 50% of expected value
・ Mostly with chronic symptoms (cough, sputum, dyspnea), recurrent acute exacerbations
Grade IV (very severe)
・ FEV1/FVC <70%
・ FEV1 <30% of the expected value or FEV1 <50% of the expected value
・ With chronic respiratory failure, may be combined with pulmonary heart disease and right heart insufficiency or failure
(ii) COPD disease course staging.
1. Stable stage: Patients with stable or mild symptoms such as cough, sputum and shortness of breath.
2. Acute exacerbation stage: In the course of the disease, there is a continuous deterioration of the disease beyond the daily condition, and the daily basic medication of COPD needs to be changed. It usually refers to the patient’s short-term aggravation of cough, sputum, shortness of breath and/or wheezing, increased sputum volume, purulent or mucopurulent, and may be accompanied by fever and other manifestations of significantly increased inflammation.
IX. Differential diagnosis
Some diseases with known etiology or characteristic pathological manifestations of airflow limitation, such as bronchial asthma, bronchiectasis, tuberculosis fibrosis, pulmonary cystic fibrosis, diffuse panbronchitis and occlusive bronchitis, have their own specific pathogenesis, clinical characteristics and treatment methods, which do not belong to the category of COPD and must be clinically differentiated.
The airflow limitation in bronchial asthma is mostly reversible, but in some patients, the persistence of airway inflammation leads to airway remodeling, which can develop into fixed airflow limitation, showing the clinical and pathological characteristics of both asthma and COPD, which is now considered as one of the clinical phenotypes of COPD.
X. Complications
Spontaneous pneumothorax, pulmonary hypertension, chronic pulmonary heart disease, venous thromboembolism, respiratory insufficiency or failure are common complications of COPD. respiratory insufficiency and failure due to COPD are mainly characterized by ventilatory respiratory impairment, respiratory muscle fatigue, hypoxemia and/or hypercapnia, and the course of the disease is characterized by chronic respiratory insufficiency or failure, with intermittent acute exacerbations.
XI. Treatment
(A) Stable phase treatment.
1. Education and management.
Educate and supervise smoking cessation in COPD patients who smoke and avoid exposure to secondhand smoke. Smoking cessation has been clearly shown to be effective in delaying progressive decline in lung function.
Advise patients to avoid or prevent inhalation of dust, smoke and noxious gases; help patients to master the basics of COPD and learn the key points and methods of self-management; let patients know when to go to the hospital.
2. Drug treatment.
(1) Bronchodilators.
Bronchodilators are important therapeutic drugs to control COPD symptoms, mainly including β2 agonists and anticholinergics. Inhalation therapy is preferred. Short-acting agents are suitable for patients with all levels of COPD and are used as needed to relieve symptoms; long-acting agents are suitable for patients with moderate or higher levels to prevent and reduce symptoms and increase exercise endurance. Methylxanthines also have bronchodilatory effects. The rational combination of drugs with different mechanisms and duration of action can enhance the bronchodilator effect and reduce adverse reactions.
(1) β2 agonists: short-acting β2 agonists (SABA) mainly include salbutamol, terbutaline and other quantitative nebulized inhalers, which take effect within a few minutes and last for 4-5 hours, 100-200μg (1-2 sprays) each time, no more than 8-12 sprays in 24 hours; long-acting β2 agonists (LABA) mainly include salmeterol and terbutaline. LABA) mainly salmeterol (Salmeterol), formoterol (Arformoterol), etc., the effect lasts for more than 12 hours, inhaled twice a day.
(2) Anticholinergics: Short-acting anticholinergics (SAMA) mainly include Ipratropium bromide, which is a quantitative nebulized inhaler with a slower onset of action than salbutamol, with an effect lasting 6-8 hours, 40-80μg each time, 3-4 times daily; Long-acting anticholinergics (LAMA) mainly include Tiotropium bromide, with an effect lasting more than 24 hours, and 40-80μg each time, 3-4 times daily. Long-acting anticholinergics (LAMA) include Tiotropium bromide, which has an action time of more than 24 hours, with an inhalation dose of 18μg once a day.
(3) Methylxanthines: including short-acting and long-acting dosage forms. Short-acting dosage form such as Aminophylline, commonly used dose is 100-200mg per time, 3 times a day; long-acting dosage form such as Theophylline SR, commonly used dose is 200-300mg per time, 1 time every 12 hours. High-dose theophylline is not recommended for routine application due to its potential toxic side effects. Smoking, drinking alcohol, taking anticonvulsants, rifampin, etc. can cause liver enzyme impairment and shorten theophylline half-life, reducing the efficacy; advanced age, persistent fever, heart failure and significant liver dysfunction, concomitant application of cimetidine, macrolides, fluoroquinolones and oral contraceptives may increase theophylline blood concentrations. Since the therapeutic and toxic concentrations of such drugs are similar, it is recommended that the blood concentration of theophylline be monitored in hospitals with conditions.
(2) Glucocorticoids.
Long-term regular inhaled glucocorticosteroids are suitable for patients with severe and very severe recurrent acute exacerbations, which can reduce the number of acute exacerbations, increase exercise tolerance and improve quality of life, but cannot stop the decreasing trend of FEV1. The combination of inhaled glucocorticoids and long-acting β2 agonists is more effective than single agents. Long-term oral, intramuscular or intravenous glucocorticoid therapy is not recommended.
(3) Other drugs.
(1) Expectorants: commonly used drugs include aminoglutethimide hydrochloride, acetylcysteine, carboxymethylstilbestrol, standard myrtle oil, etc.
(2) Antioxidants: limited evidence suggests that antioxidants such as carboxymethylstilbestrol and N-acetylcysteine may reduce the number of acute exacerbations of the disease.
3) Vaccine: mainly refers to influenza vaccine and pneumonia vaccine. Influenza vaccination can prevent influenza and avoid acute exacerbations caused by influenza, and is suitable for COPD patients of all levels of clinical severity; it is recommended that patients over 65 years of age and those below this age but with FEV1 <40% of the expected value can receive pneumococcal polysaccharide vaccine, etc. to prevent respiratory bacterial infections.
(4) Chinese medicine treatment: certain herbs have the effect of regulating the body condition, and can be treated with evidence.
3. Non-pharmacological treatment.
(1) Oxygen therapy.
Long-term oxygen therapy has beneficial effects on the hemodynamics, respiratory physiology, exercise endurance and mental status of patients with COPD combined with chronic respiratory failure, which can improve the quality of life and survival rate of patients. Long-term home oxygen therapy (LTOT) is recommended to be administered under the guidance of a physician.
1) Indications for oxygen therapy (with any of the following).
①PaO2≤55mmHg or SaO2<88% at rest, with or without hypercapnia.
②56mmHg≤PaO2<60mmHg, SaO2<89% with one of the following: secondary erythrocytosis (red blood cell pressure >55%); pulmonary hypertension (mean pulmonary artery pressure ≥25mmHg); edema due to right heart insufficiency.
(2) Oxygen therapy method: Generally, nasal catheter oxygen is used, oxygen flow rate is 1.0-2.0L/min, oxygen duration > 15h/d, so that the patient can achieve PaO2 ≥ 60mmHg and/or make SaO2 rise to more than 90% in the resting state.
(2) Rehabilitation therapy.
Rehabilitation therapy is applicable to patients with moderate COPD or above. Among them, respiratory physiological treatment includes correct coughing, sputum excretion methods and lip retraction breathing, etc.; muscle training includes whole body exercise and respiratory muscle exercise, such as walking, biking, abdominal breathing exercise, etc.; scientific nutritional support and strengthening health education are also important aspects of rehabilitation treatment.
(3) Surgical treatment.
For example, pulmonary herniotomy, pulmonary decompression and lung transplantation, please refer to the relevant guidelines.
Treatment should be graded according to the clinical severity of COPD (see Table 2).
Table 2 Graded treatment options for stable COPD
Grade I (mild) Grade II (moderate) Grade III (severe) Grade IV (very severe)
Avoidance of risk factors, influenza vaccination; use of short-acting bronchodilators as needed
Regular application of one or more long-acting bronchodilators; supplement with rehabilitation
Repeated acute exacerbations, inhaled glucocorticoids
Respiratory failure, long-term oxygen therapy
Surgical treatment may be considered
Note: Short-acting bronchodilators refer to short-acting β2 agonists, short-acting anticholinergics and aminophylline; long-acting bronchodilators refer to long-acting β2 agonists, long-acting anticholinergics and slow-release theophylline; inhaled bronchodilators are recommended as the first choice for treatment.
(ii) Acute exacerbation treatment.
1. Determine the cause of acute exacerbation of COPD.
The most common cause of acute exacerbation of COPD is respiratory tract infection, with viral and bacterial infections being the most common. The cause of acute exacerbation in some patients is difficult to determine, and changes in environmental physical and chemical factors may also be involved. The factors that cause acute exacerbation of COPD should be avoided, removed or controlled as much as possible.
2. Assessment of the severity of acute exacerbations of COPD.
The severity of this acute exacerbation can be determined by comparing the patient’s history, symptoms, signs, pulmonary function measurements, arterial blood gas analysis and other laboratory tests before the acute exacerbation.
(1) Pulmonary function measurement: FEV1 <1L indicates a severe exacerbation. However, it is often difficult for patients to cooperate with pulmonary function tests during exacerbations.
(2) Arterial blood gas analysis: PaO2 <50 mmHg, PaCO2 >70 mmHg, pH <7.30 indicates critical condition and requires close monitoring and respiratory support therapy. If available, the patient should be transferred to internal medicine or respiratory intensive care treatment unit (MICU or RICU).
(3) Chest imaging and electrocardiogram (ECG): Chest imaging can help distinguish COPD exacerbations from other diseases with similar symptoms. If PaO2 cannot rise above 60 mmHg after hypotension or high-flow oxygenation, be alert to the possibility of pulmonary thromboembolism and arrange CT pulmonary angiography (CTPA) and other related examinations. ECG can help to diagnose arrhythmia, myocardial ischemia and right heart enlargement and/or hypertrophy.
(4) Other laboratory tests: blood picture (blood leukocytes, red blood cell count, red blood cell pressure, platelet count, etc.), blood biochemical indexes and pathogenic tests are helpful to determine the condition of acute exacerbation of COPD and guide the diagnosis and treatment.
3. Out-of-hospital treatment of acute exacerbations of COPD.
Patients with relatively mild acute exacerbations can be treated out of hospital, but close observation of changes in the condition is needed to decide whether to send them to hospital for treatment in a timely manner.
(1) Bronchodilators: Outpatient treatment for acute exacerbations of COPD includes increasing the dose and frequency of bronchodilators used in the past as appropriate. If anticholinergic drugs have not been used, they may be added. In more severe cases, higher doses of nebulized therapy such as salbutamol, ipratropium bromide, or salbutamol combined with ipratropium bromide nebulized inhalation may be given for several days. Bronchodilators can also be combined with glucocorticoids for nebulized inhalation treatment.
(2) Glucocorticosteroids: Systemic use of glucocorticosteroids is beneficial for patients with acute exacerbations in terms of remission and improvement of lung function. If the patient’s basal FEV1 is less than 50% of the expected value, in addition to the application of bronchodilators, oral glucocorticoids, such as prednisolone 30-40 mg daily for 7-10 d, can be considered.
(3) Antibacterial drugs: Antibacterial drugs should be given when COPD symptoms worsen and sputum volume increases especially when it is purulent. Sensitive antimicrobial drugs should be selected as early as possible according to the severity of the disease, combined with the type of common local pathogenic bacteria, drug resistance trends and drug sensitivity (see Table 3).
4. Hospitalization for acute exacerbation of COPD.
(1) Indications for inpatient treatment.
(1) Significant exacerbation of symptoms, such as short-term emergence of dyspnea in resting conditions.
(2) The appearance of new signs or aggravation of existing signs, such as cyanosis, peripheral edema, etc.
3) new onset of cardiac arrhythmias.
4) The presence of severe concomitant disease.
5) failure of the initial treatment regimen.
6) advanced age.
7) unclear diagnosis.
(8) Poor outcome of out-of-hospital treatment.
(2) Indications for ICU admission.
1) Severe respiratory distress and poor response to initial treatment.
(2) presence of mental disturbance, such as drowsiness, coma
(3) Severe hypoxemia (PaO2 < 50 mmHg) and/or severe hypercapnia (PaCO2 > 70 mmHg) and/or severe respiratory acidosis (PH < 7.30) without remission or worsening after oxygen therapy and non-invasive positive pressure ventilation (NIPPV) treatment.
(3) Therapeutic management of acute exacerbation of COPD hospitalization.
(1) Assess the severity of the disease based on symptoms, blood gas analysis, and X-ray chest radiograph.
(2) Controlled oxygen therapy.
Oxygen therapy is the basic treatment for COPD inpatients. Patients without serious comorbidities can easily achieve satisfactory oxygenation level (PaO2>60mmHg or pulse oximetry SpO2>90%) after oxygen therapy. Controlled low-concentration oxygen therapy should be administered to avoid sudden large increases in PaO2 causing respiratory depression leading to CO2 retention and respiratory acidosis. After 30 minutes of oxygen therapy, arterial blood gas should be rechecked to understand the effect of oxygen therapy.
3) Antimicrobial drugs.
Antimicrobial drug therapy plays an important role in the inpatient treatment of COPD patients. When patients have increased dyspnea, cough with increased sputum and purulent sputum, sensitive drugs should be selected as early as possible according to the severity of the disease, combined with the type of common local pathogenic bacteria, drug resistance trends and drug sensitivity.
In mild or moderate COPD, the main causative agents are often Streptococcus pneumoniae, Haemophilus influenzae and Catamorax, etc. In severe or very severe COPD, in addition to the above common causative agents, there are often Enterobacteriaceae, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infections. Risk factors for the occurrence of P. aeruginosa infection include recent hospitalization, frequent application of antimicrobial drugs, and previous isolation or colonization of P. aeruginosa. Appropriate antimicrobial drug therapy was used according to the spectrum of possible bacterial infections (see Table 3). Long-term application of broad-spectrum antimicrobials and glucocorticoids is prone to secondary deep fungal infections; clinical signs of fungal infections should be closely observed and appropriate measures should be taken.
Table 3 Reference table of antimicrobial drug application during acute exacerbation of COPD
Disease
Possible pathogenic bacteria
Antibiotics to be used
Mild and moderate COPD acute exacerbation
Haemophilus influenzae, Streptococcus pneumoniae, Catamorphosis
Penicillin, β-lactam/enzyme inhibitors (amoxicillin/clavulanic acid, etc.), macrolides (azithromycin, clarithromycin, roxithromycin, etc.), 1st or 2nd generation cephalosporins (cefuroxime, cefaclor, etc.), doxycycline, levofloxacin, etc., usually given orally
Acute exacerbation of severe and very severe COPD
No risk factors for Pseudomonas aeruginosa infection
Haemophilus influenzae, Streptococcus pneumoniae, Catamorax, Klebsiella pneumoniae, Escherichia coli, Enterobacter spp.
β-lactam/enzyme inhibitors, second-generation cephalosporins (cefuroxime, etc.), fluoroquinolones (levofloxacin, moxifloxacin, gatifloxacin, etc.), third-generation cephalosporins (ceftriaxone, cefotaxime, etc.)
Acute exacerbation of severe and very severe COPD
Risk factors for Pseudomonas aeruginosa infection
Above bacteria and Pseudomonas aeruginosa
Third-generation cephalosporins (ceftazidime), cefoperazone/sulbactam, piperacillin/tazobactam, imipenem, meropenem, etc.
Aminoglycosides, quinolones (ciprofloxacin, etc.) can also be applied in combination
4) Bronchodilators. Short-acting β2 agonists are more suitable for the treatment of acute exacerbations of COPD. If the effect is not significant, it is recommended to add anticholinergic drugs (ipratropium bromide, tiotropium bromide, etc.). For more severe acute exacerbation of COPD, intravenous theophylline can be considered, but be alert to cardiovascular and neurological side effects. β2 agonists, anticholinergic drugs and theophylline can be reasonably combined to obtain synergistic effects.
(5) Glucocorticoids: Patients hospitalized with acute exacerbation of COPD can receive oral or intravenous glucocorticoids on the basis of bronchodilators. The use of glucocorticosteroids should be weighed against the efficacy and safety. It is recommended that oral prednisolone be given at 30-40 mg daily for 7-10 d and then reduced and stopped. Methylprednisolone can also be given intravenously at 40mg once daily and then switched to oral after 3-5d. Prolonging the course of glucocorticoid administration does not increase the efficacy, but rather increases the risk of side effects.
(6) diuretics. diuretics can be used in acute exacerbation of COPD combined with right heart failure. diuretics should not be used in excess and in haste to avoid blood concentration, thick sputum that is not easily coughed out and electrolyte disturbance.
7）Cardiotonic agents can be used in acute exacerbation of COPD combined with left ventricular insufficiency; for those whose right heart function has not improved after diuretic treatment even though the infection has been controlled and respiratory function has improved, cardiotonic agents can also be used appropriately. Cardiac stimulants should be applied with caution because COPD patients are in long-term hypoxia and have low tolerance to digitalis, and the amount of digitalis treatment is close to the amount of poisoning, which is prone to toxic reactions and arrhythmias.
(8) vasodilators. in acute exacerbation of COPD combined with pulmonary hypertension and right heart insufficiency, vasodilators can be applied under the premise of improving respiratory function.
(9) anticoagulant drugs, COPD patients have a tendency to hypercoagulation. For patients who are bedridden, have erythrocytosis or have difficulty in correcting dehydration, heparin or low molecular heparin can be considered if there is no contraindication. anticoagulant therapy should be given when COPD acute exacerbation combined with deep vein thrombosis and pulmonary thromboembolism, and thrombolytic therapy can be given when large or high-risk pulmonary thromboembolism occurs.
10) Respiratory stimulants. In critically ill patients with markedly elevated PaCO2, blurred consciousness and significantly weakened cough reflex, if they are not in a position to use or do not agree to use mechanical ventilation, they can be treated with respiratory stimulants under the premise of trying to keep the airway open to maintain respiration and wakefulness. Currently, the commonly used drugs in China are niclosamide (kolamine), santoprene (Lopressor) and morphine pyrone. Because of the limited effect of central respiratory stimulants, and easy to produce tolerance, at the same time, there are side effects such as convulsions, elevated blood pressure, increased systemic oxygen consumption, should be used with caution for patients who have respiratory muscle fatigue.
(11) Mechanical ventilation.
Severely ill patients can choose non-invasive or invasive mechanical ventilation according to the needs of their condition. Arterial blood gas status should be monitored at the same time.
(1) Non-invasive mechanical ventilation: The application of non-invasive positive pressure ventilation (NIPPV) can reduce PaCO2, relieve respiratory muscle fatigue and reduce dyspnea, thus reducing the use of tracheal intubation and invasive ventilator and shortening the number of hospital days. The use of NIPPV should pay attention to the mastery of reasonable operation methods and improve patient compliance in order to achieve satisfactory results.
Indications for the use of NIPPV.
Indications (meeting at least 2 of the following) are moderate to severe dyspnea; with participation of auxiliary respiratory muscles in breathing and paradoxical chest and abdominal movements; moderate to severe acidosis (pH 7.30-7.35) and hypercapnia (PaCO2 45-60 mmHg); respiratory rate >25 breaths/min.
Contraindications (meeting one of the following conditions) are respiratory depression or arrest; unstable cardiovascular system function (intractable hypotension, severe arrhythmias, myocardial infarction); drowsy, unconscious or uncooperative individuals; individuals prone to aspiration (abnormal gag reflex, severe upper gastrointestinal bleeding); viscous sputum or large airway secretions; recent facial or gastroesophageal surgery; head and facial trauma; inherent nasopharyngeal abnormalities. Extreme obesity; severe gastrointestinal distention.
②Invasive mechanical ventilation: Invasive mechanical ventilation is appropriate when the patient’s respiratory failure is progressively worsening despite active pharmacological and NIPPV treatment conditions, with life-threatening acid-base imbalance and/or altered mental status.
Specific indications for the use of invasive mechanical ventilation: severe respiratory distress with involvement of supplementary respiratory muscles and paradoxical thoracoabdominal movements; respiratory rate >35 breaths/min; life-threatening hypoxemia (PaO2 <40 mmHg or PaO2/FiO2 <200 mmHg); severe respiratory acidosis (pH <7.25) and hypercapnia; respiratory depression or arrest; drowsiness. impaired consciousness; severe cardiovascular complications (hypotension, shock, heart failure); other complications (metabolic disorders, sepsis, pneumonia, pulmonary thromboembolism, pneumatic injuries, massive pleural effusions); failure of NIPPV therapy or the presence of contraindications to the use of NIPPV.
For acute exacerbations of COPD treated with invasive mechanical ventilation in combination with severe respiratory failure, invasive-noninvasive sequential ventilation therapy is usually appropriate. In cases of acute exacerbation and respiratory failure induced by pulmonary infection, invasive-noninvasive sequential ventilation can be implemented using the pulmonary infection control window as the time switch point for conversion from invasive to noninvasive mechanical ventilation.
12) Other inpatient treatment measures.
Pay attention to maintaining fluid and electrolyte balance, replenish fluids and electrolytes under volume and blood electrolyte monitoring; pay attention to supplementation of nutrition, gastrointestinal supplementation of elemental diet or intravenous nutrition for those who cannot eat; pay attention to sputum drainage, actively give sputum drainage treatment (such as stimulation of cough, percussion of chest, postural drainage, etc.); pay attention to identification and management of concomitant diseases (coronary heart disease, diabetes, hypertension, etc.) and comorbidities ( Shock, diffuse intravascular coagulation, upper gastrointestinal bleeding, gastric insufficiency, etc.).