Chronic Obstructive Pulmonary Disease
Wu Dawei, Department of Respiratory Medicine, Qilu Hospital, Shandong University
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by incomplete and reversible airflow limitation. COPD mainly affects the lungs, but can also cause systemic (or extrapulmonary) adverse effects, which aggravate the severity of the disease. Wu Dawei, ICU Department, Qilu Hospital, Shandong University
COPD is an important public health problem with high prevalence and mortality rates and a high socioeconomic burden. According to the World Bank/World Health Organization (WHO), COPD will be the fifth largest economic burden of disease in the world by 2020. In the 1990s, a survey of 102,230 people in rural areas of northern and central China found that COPD accounted for about 3% of the population over 15 years of age; in a recent survey of 20,245 people in seven regions of China, the prevalence of COPD accounted for 8.2% of people over 40 years of age, which is a very alarmingly high prevalence.
In the past, COPD was classified into chronic bronchitis, obstructive emphysema and chronic pulmonary heart disease according to the characteristics of the developmental stages of the disease. The definition of chronic bronchitis is based on clinical symptoms and is usually defined as a patient with cough and sputum for more than 3 months per year for 2 years after excluding other known causes of chronic cough; emphysema is a pathological and anatomical term that refers to an abnormal and persistent dilatation of the distal air spaces of the terminal fine bronchi in the lungs with destruction of the alveolar wall and fine bronchi without significant pulmonary fibrosis. The main diagnostic criterion for COPD is abnormal pulmonary function. COPD is diagnosed only when there is airflow limitation on pulmonary function tests in patients with chronic bronchitis and emphysema, and when it is not fully reversible.
Chronic pulmonary heart disease is an important complication of COPD. Chronic pulmonary heart disease in China is mainly seen in patients with severe COPD, but can also be caused by a variety of other airway diseases, parenchymal or interstitial lung diseases, pulmonary vascular diseases or chronic lesions of the thorax
Bronchial asthma (asthma) is not COPD. although asthma and COPD are both chronic airway inflammatory diseases, the nature and pathogenesis of airway inflammation differ between the two, as do their clinical manifestations and responsiveness to treatment. Airflow limitation is significantly reversible in most asthma patients and is a key feature that distinguishes it from COPD. However, some patients with asthma may experience more pronounced airway reconstruction as the disease progresses, resulting in significantly less reversible airflow limitation, which is clinically difficult to distinguish from COPD. Asthma patients who smoke also develop chronic cough with sputum and symptoms of chronic bronchitis, and some COPD patients are also associated with airway hyperresponsiveness. Because COPD and asthma are both common and prevalent, both can occur in the same patient.
Some airflow limitation diseases with known etiology or characteristic pathological manifestations, such as bronchiectasis, tuberculosis fibrotic lesions, pulmonary cystic fibrosis, diffuse panbronchitis and occlusive bronchiectasis, are not COPD.
Etiology and pathogenesis
1) Etiology The factors that cause the development of COPD include individual susceptibility factors and environmental factors, both of which influence each other.
(1) Individual factors: mainly genetic factors. Some genetic factors can increase the risk of COPD. It is clear that severe α1-antitrypsin deficiency is associated with emphysema formation in non-smokers, but even in the world, COPD cases related to α1-antitrypsin deficiency are only very few, and emphysema caused by α1-antitrypsin deficiency has not been officially reported in China so far. COPD occurs in only 15% to 20% of the smoking population, suggesting that other genetic factors also influence host susceptibility to COPD. The susceptibility genes associated with COPD have been identified to include transforming growth factor beta 1 (TGF-β1), microsomal epoxide hydrolase 1 (mEPHX1), and tumor necrosis factor alpha (TNF). necrosis factor alpha (TNFα), etc.
In addition, prematurity and poor lung development in low birth weight infants may also be individual factors in the development of COPD in adulthood.
(2) Environmental factors
(1) Smoking: It is the main pathogenic factor of COPD. The tar, hydrocyanic acid and oxygen radicals contained in tobacco can damage airway epithelial cells, causing squamous epithelial hyperplasia of bronchial mucosa, cilia adhesion, inversion or even loss, loss of cilia function, so that the purification and clearance function of the airway is reduced; bronchial mucosa is congested and swollen, mucus glands are hypertrophied, cup cells are proliferated, too much mucus is produced, and airway infection easily occurs; parasympathetic excitability is increased, and bronchial smooth muscle Contraction. The annual rate of decline in the first second forceful expiratory volume (FEV1) of lung function is faster in smokers. The decline in FEV1 is about 25-30 ml/year in nonsmokers with normal lung function and up to 60 ml/year in smokers, and the rate of decline in FEV1 is even faster in patients who already have COPD if they continue to smoke. Passive smoking may also contribute to the development of COPD. Smoking during pregnancy may affect the growth and development of the fetal lung, and has an effect on fetal immune system function.
(2) Occupational dust and chemical substances: When the concentration of occupational dust and chemical substances (smoke, allergens, industrial waste gas and indoor air pollution, etc.) is too large or the exposure time is too long, it can lead to COPD that is not related to smoking. Exposure to certain irritants, organic dusts and allergens can increase airway reactivity.
(3) Air pollution: Chemical gases such as chlorine, nitrogen oxide, sulfur dioxide, etc., have an irritating and cytotoxic effect on the bronchial mucosa. There is a significant increase in acute COPD attacks when there is a significant increase in airborne soot or sulfur dioxide. Other dusts such as silica, coal dust, cotton dust, and cane dust also irritate bronchial mucosa, impair airway clearance, and create conditions for bacterial invasion. In China, indoor air pollution caused by soot from biofuels (firewood, animal manure and coal, etc.) and large amounts of grease smoke from cooking is associated with the onset of COPD in women from non-smoking households.
(4) Infections: Respiratory infections (viral, mycoplasma and bacterial infections) are an important factor in the onset and acute exacerbation of COPD. About 80% of acute exacerbations of COPD are related to respiratory infections, with Streptococcus pneumoniae and Haemophilus influenzae being the main pathogens of acute exacerbations, and respiratory viruses, chlamydia and mycoplasma infections playing an important role in acute exacerbations of COPD. Severe respiratory infections in childhood are associated with reduced lung function and the onset of respiratory symptoms in adulthood. Premature infants and low birth weight neonates have a higher susceptibility to respiratory viral infections.
5) Socioeconomic status: The onset of COPD is associated with the socioeconomic status of the patient. This may be intrinsically linked to living conditions, nutritional status, and other factors related to socioeconomic status.
2. Pathogenesis
(1) Pulmonary inflammation: The abnormal amplified inflammatory response of the airways to various physical and chemical stimuli is a key link in the pathogenesis of COPD, and almost all COPD-related damage is the result of airway and lung inflammation: airway reconstruction is the result of repeated abnormal repair of the airways to chronic inflammatory damage; lung parenchymal destruction (emphysema) caused by proteases released from inflammatory cells in the lungs; inflammatory cells COPD airway inflammation is characterized by an increase in neutrophils, macrophages and T-lymphocytes (especially CD8+ T-lymphocytes). Some patients present with an increase in eosinophils during acute exacerbations. pulmonary inflammation in COPD involves almost all structures of the lung, including the central airways, peripheral airways, lung parenchyma, and pulmonary vasculature.
Airway inflammation is regulated by a variety of inflammatory mediators released by alveolar macrophages stimulated by cigarette smoking and other inhaled physicochemical factors. The main inflammatory mediators released by alveolar macrophages are TNF-α, leukotriene B4 (LTB4), IL-1, IL-8, granulocyte-monocyte colony-stimulating factor (GM-CSF), macrophage chemotactic peptide (MCP-1), intercellular adhesion molecule (ICAM), platelet-activating factor (PAF), and various protein hydrolases. Vascular endothelial cells and neutrophils, under the action of TNF-α released by macrophages, through the interaction with adhesion molecules, cause neutrophils to transfer across the vascular endothelium to lung tissue, recruit and activate in bronchial and lung tissues under the chemotactic effect of IL-8 and LTB4, and prolong their survival by the action of GM-CSF, release a series of protein hydrolases, and proteases released by macrophages jointly digest and destroy lung tissues. Alveolar macrophages and their inflammatory mediators play an important regulatory role in the adhesion of various inflammatory cells to the vascular endothelium, chemotaxis to lung tissue, activation and amplification of the inflammatory response, and may be the key cells in COPD inflammation.
(2) Protease-anti-protease imbalance: A variety of inflammatory cells can release proteolytic enzymes to destroy the extracellular matrix, leading to emphysema. The major proteolytic enzymes include: neutrophil elastase (NE), neutrophil matrix metalloproteinases (N-MMPs), macrophage matrix metalloproteinase (M-MMPs), etc. As a result of various pathogenic factors, inflammatory cells synthesize and release proteases and concentrate them locally, resulting in a relatively high concentration of proteases in the local microenvironment and a protease-anti-protease imbalance, resulting in insufficient anti-proteases to counteract the digestive effect of proteases on tissues.
(3) Oxidation-antioxidation imbalance:Oxides in the lung come from respiratory bursts produced by the mitochondria of body cells and inflammatory cells, smoking and environmental pollution gases. Cigarette smoke contains large amounts of free radicals and nitrogen oxides (NO, NO2). Oxides can directly damage fatty acid chains of cell membranes and cellular DNA, and can also further amplify inflammation by activating nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), which initiate transcription of a series of inflammatory regulators such as TNFα, IL-1β, IL-8, IL-12, GM-CSF, ICAM-1, VCAM-1 and other genes. Oxidation inactivates protease inhibitors normally present in the body such as α1-protease inhibitor (α1-PT) and secretory leukocyte protease inhibitor (SLPI), aggravating the protease-anti-protease imbalance.
(4) Airway spasm and mucus overproduction: abnormal autonomic function, protein hydrolases and airway inflammation may play an important role in the process of airway spasm and mucus overproduction in COPD.
Pathology and pathophysiology
1. The pathology of COPD is mainly characterized by chronic airway inflammation and emphysema, and the inflammatory cells involved are mainly CD8+ T lymphocytes and macrophages.
(1) Airway inflammation: the peripheral airways (small airways) are small bronchi and fine bronchi with an inner diameter of less than 2 mm, which are non-chondrogenic airways and are the main sites of airway pathological changes in COPD. The pathological changes include lymphoid follicular hyperplasia of the duct wall; cupular cell hyperplasia, mucus gland hypertrophy; increased collagen content and scar tissue formation; smooth muscle hyperplasia; breakage of elastic fibers that pull the fine bronchi; thickening of the mucosa. Increased mucus in the lumen; narrowing and occlusion of the airway due to collapsed occlusion of the lumen resulting in folds in the mucosa. Chronic inflammatory damage and repair processes lead to structural reconstruction of the airway, resulting in a fixed airflow restriction. The main pathological changes in the central airway (large airway) are ciliated columnar epithelial cilia adhesion, inversion or even loss of cilia, loss of ciliary function, bronchial mucus gland hypertrophy, cupped cell hyperplasia, and airway epithelial squamous metaplasia. Pathological changes in the peripheral airways are the main cause of airflow limitation, while pathological changes in the central airways mainly lead to clinical cough and cough symptoms.
(2) Emphysema: It refers to persistent enlargement of the distal air spaces of the terminal fine bronchi (respiratory fine bronchi, alveolar ducts, alveolar sacs and alveoli) and destruction of the air space walls. Emphysema can be classified into three types according to the site of the affected alveoli (lung tissue distal to the terminal bronchioles): ① central lobar emphysema: cystic expansion starting from the respiratory bronchioles, with the enlarged air spaces located in the central part of the secondary lobules, i.e., the respiratory bronchioles, with the peripheral alveoli still intact. (ii) Total lobar emphysema: the entire lobule is involved, and the respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli are all dilated. (iii) Mixed emphysema: the first two are present in the same patient’s lungs at the same time. (iv) Distal alveolar emphysema (parietal septal or subpleural emphysema): occurs subpleurally or along the fibrous lobe septa, commonly in the apical lung, and can cause pulmonary maculopathy. Central lobar emphysema is the most common type of emphysema in smokers, with more severe lesions in the upper and anterior parts of the lung than in the base.
(3) Pulmonary vasculature: chronic inflammation of the small pulmonary vessels accompanying the fine bronchi, with edema, degeneration and necrosis of the walls. Vascular remodeling occurs when smooth muscle hypertrophy and fibrous tissue proliferation occur, leading to organomegaly narrowing. As a result of alveolar rupture and inflammatory erosion, the number of pulmonary capillary beds and their cross-sectional area are reduced. Severe patients develop right ventricular hypertrophy.
Figure 2-7-1
Figure 2-7-1 Central lobar and total lobar emphysema
TB: terminal bronchus; RB: respiratory bronchus; A: alveoli
2. Pathophysiology In the early stage, only small airway function is abnormal, and tests reflecting large airway function [e.g., the absolute value of the first second forceful expiratory volume (FEV1)] may be in the normal range. As the disease progresses, airflow limitation progressively worsens and FEV1, first second expiratory volume/exertional lung volume (FEV1/FVC) decreases, as does maximum ventilation volume (MVV). The residual air volume (RV), functional residual volume (FRC), and total lung volume (TLC) are increased in patients with obstructive emphysema, and the RV/TLC ratio is higher than normal due to dilatation of the distal lumen of the terminal fine bronchus, reduced alveolar elastic retraction, and reduced expiratory flow rate and airway trapping during exhalation, resulting in gas trapping. Among the many factors of airflow limitation, reduced alveolar elastic retraction due to lung structural damage reduces the drive to expiratory airflow and maintenance of small airway opening, and increased airflow resistance due to small airway remodeling are irreversible; airway inflammatory cell infiltration, mucus and plasma exudation, smooth muscle spasm, and dynamic lung hyperinflation during exercise can be reduced spontaneously or with treatment, and thus airflow limitation caused by these factors is The airflow limitation caused by these factors is reversible to varying degrees.
The respiratory muscle load is significantly increased due to increased airflow resistance; the diaphragm is flattened due to increased RV and FRC; and the respiratory muscle contraction and endurance are reduced due to hypoxia and inflammation. The above factors lead to insufficient ventilation, which can cause hypoxia and carbon dioxide retention, with varying degrees of hypoxemia and hypercarbia, and eventually respiratory failure.
Alveolar expansion and rupture, reduced alveolar area, and extensive damage to peri-alveolar capillaries can cause decreased diffusion function; uneven airway inflammation, mucosal congestion and edema, and mucus plugging can cause uneven ventilation distribution in different lung regions; and various factors such as destruction of the alveolar capillary network, vascular remodeling, hypoxic vasoconstriction, and increased intra-alveolar pressure can cause uneven perfusion in different lung regions. Different ventilation/blood flow ratio abnormalities can produce increased dead space ventilation or shunt-like effects in different regions of the lung and impaired ventilatory function.
Hypoxic small pulmonary artery constriction and pulmonary vascular remodeling increase pulmonary circulatory resistance and produce pulmonary hypertension, which can eventually lead to pulmonary heart disease and right heart failure.
COPD can lead to systemic adverse effects, where the inflammatory mediators produced by the lungs enter the circulation leading to systemic inflammatory effects, such as skeletal muscle dysfunction. the systemic adverse effects of COPD are clinically important, and it can further aggravate the patient’s limited mobility, resulting in reduced quality of life and poorer prognosis.
Clinical manifestations
The clinical manifestations of COPD differ greatly according to the different stages of disease development and the severity of the disease.
Chronic cough and sputum are the first and only symptoms in the early stage. The initial cough is intermittent, with a small amount of mucus sputum, and is heavier in the morning. In a few cases, the cough is not accompanied by sputum. In a few cases, the cough is not accompanied by sputum, although airflow restriction is obvious. When combined with infection, the sputum volume increases and may be purulent, and the lungs can be heard on auscultation as dry or wet woven woven woven 2 furrows.
2. manifestations of pulmonary hyperinflation and obstructive emphysema As the disease progresses, exertional dyspnea appears and gradually worsens, so that shortness of breath is felt even during daily activities and even at rest. In severe emphysema, the anteroposterior diameter of the thorax is enlarged and the chest is barrel-shaped; the percussion is hyperclear, and the turbid boundary is narrowed; the breath sounds are reduced on auscultation, the heart sounds are distant, and the heart sounds at the saber are clearer and louder.
3. The manifestations of chronic pulmonary heart disease See Chapter 11 of this article for details.
4. Systemic symptoms In more severe patients, there may be weight loss, loss of appetite, peripheral skeletal muscle atrophy and dysfunction, mental depression and/or anxiety, etc.
Laboratory and special tests
Pulmonary function test is the main objective index to determine airflow limitation, which is important to establish the diagnosis of COPD, evaluate the severity, progress, prognosis and response to treatment.
(1) Indicators of airflow limitation: FEVl/FVC is a sensitive indicator to diagnose the existence of airflow limitation, and can detect mild airflow limitation; FEVl as a percentage of the expected value is a good indicator to determine the severity of airflow limitation, with little variability and easy to operate. Those with FEVl/FVC% <70% and/or FEVl <80% of the expected value after inhalation of bronchodilators can be identified as having irreversible airflow limitation.
(2) Indicators of pulmonary hyperinflation or obstructive emphysema: increased TLC, FRC and RV. the increase in TLC is not as great as the increase in RV, so the RV/TLC is increased. Spirometry (VC) is also reduced in severe cases. Inspiratory volume (IC) is the sum of tidal volume and compensatory inspiratory volume, and IC/TLC increases.
(3) Impaired diffusion function: Alveolar septal destruction and loss of pulmonary capillary bed can impair diffusion function, and the diffusion volume of carbon monoxide (DLCO) is reduced, and the ratio of DLCO to alveolar ventilation (VA) (DLCO/VA) is more sensitive than simple DLCO.
2. Chest X-ray examination in the early stage of COPD may have no obvious changes, and later there are non-characteristic changes such as increased and disturbed lung texture. The main X-ray signs are hyperinflation of the lungs: lung volume increases, the anterior and posterior diameter of the thorax grows, the ribcage becomes flat, the lung field translucency increases, the diaphragm is low and flat, the heart overhangs narrowly, the vascular texture of the pulmonary hilum is stump-like, the vascular texture around the lung field is slender and sparse, and sometimes the formation of pulmonary vesicles is seen. In the case of pulmonary hypertension and pulmonary heart disease, in addition to the X-ray signs of right heart enlargement, there may also be conical bulging of the pulmonary artery, enlargement of the hilar vascular shadow and widening of the right lower pulmonary artery.
3. CT chest examination High-resolution CT (HRCT) has high sensitivity and specificity in identifying lobar-centered or total lobar emphysema and determining the size and number of pulmonary blisters, and is valuable in predicting the effect of resection of pulmonary blisters or surgical decompression surgery, etc.
4. Arterial blood gas analysis is important for determining hypoxemia, hypercapnia, acid-base imbalance and determining the type of respiratory failure.
5.Other long-term hypoxemia may appear erythrocytosis. In case of co-infection, a large number of neutrophils can be seen in sputum smear and various pathogenic bacteria can be detected in sputum culture, commonly Streptococcus pneumoniae, Haemophilus influenzae, Catamorax, Klebsiella pneumoniae, etc.
Diagnosis and severity classification
1. Chronic bronchitis The diagnosis of chronic bronchitis can be made after excluding other cardiac and pulmonary diseases (such as tuberculosis, pneumoconiosis, bronchial asthma, bronchiectasis, lung cancer, heart disease, etc.) based on symptoms of cough, cough or with wheezing, with onset lasting three months per year and for two consecutive years or more. If the patient’s respiratory function and chest imaging are normal, it is simple chronic bronchitis and does not belong to COPD; when the patient’s respiratory function test shows fixed airflow limitation, the diagnosis of COPD is made, and at this time chronic bronchitis is generally no longer used as a separate diagnosis.
2. The diagnosis of COPD is mainly determined by a comprehensive analysis of the history of smoking and other high-risk factors and pulmonary function tests. Irreversible airflow limitation is a necessary condition for the diagnosis of COPD. The diagnosis of COPD can be confirmed after FEV1/FVC <70% after inhalation of bronchodilators and exclusion of other cardiac and pulmonary diseases (e.g. tuberculosis, pneumoconiosis, bronchial asthma, bronchiectasis, lung cancer, heart disease, etc.).
The severity of COPD can be graded according to FEV1/FVC, FEV1% expected value and symptoms (Table 2-7-1).
Table 2-7-1 Severity grading of COPD and recommended treatment measures
Grading
Grading criteria
Recommended treatment measures
Grade I: Mild
FEV1/FVC<70%
FEV1≥80% of expected value
Add short-acting bronchodilators as needed
Grade II: Moderate
FEV1/FVC<70%
50%≤FEV1<80% expected
Increase: regular use of one or more long-acting bronchodilators
Grade III: Severe
FEV1/FVC<70%
30%≤FEV1<50% expected
Increase: regular use of ICS
Grade IV: Very severe
FEV1/FVC<70%
FEV1<30% predicted
or FEV1<50% predicted with chronic respiratory failure
Increase: Long-term home oxygen therapy according to the arterial oxygen status; consider surgical treatment
The acute exacerbation phase of COPD refers to a short-term increase in cough, sputum, shortness of breath and/or wheezing during the course of the disease that requires appropriate treatment or a change in the usual treatment plan. The stable stage refers to patients with stable or mild cough, sputum and shortness of breath.
Differential diagnosis
1. Bronchial asthma mostly starts in childhood or adolescence, characterized by episodic wheezing, with both lungs covered with croup during the attack, and the symptoms disappear after remission. The airflow limitation of asthma is mostly reversible and its bronchodilator test is positive. However, in some patients with long-standing asthma, airway remodeling has occurred and airflow limitation cannot be completely reversed.
2. Bronchodilation Repeated episodes of cough and sputum, often with recurrent hemoptysis. In case of co-infection, there is a large amount of purulent sputum. On examination, there is often fixed wet woven woven 2 bran in the lungs, and HRCT shows bronchial dilatation changes.
3. pulmonary tuberculosis There may be symptoms of tuberculosis poisoning such as afternoon hypothermia, malaise, night sweats, etc. Sputum examination may find Mycobacterium tuberculosis, and chest X-ray examination may find lesions.
4. Lung cancer has chronic cough and sputum, and blood in the sputum may occur repeatedly recently. Chest X-ray and CT may find occupying lesions, obstructive pulmonary atelectasis or pneumonia. Sputum cytology, fiberoptic bronchoscopy and even lung biopsy may help to make a clear diagnosis.
Emphysema is a pathological diagnostic term for enlargement of the respiratory airspace due to other causes. Although it does not meet the strict definition of emphysema, it is often customarily referred to as emphysema in clinical practice, such as compensatory emphysema, senile emphysema, and congenital emphysema in Down syndrome, when the respiratory air spaces are uniformly and regularly enlarged without destruction of the alveolar wall. Clinical manifestations can present with exertional dyspnea and emphysematous signs, but pulmonary function measurements are not altered by airflow limitation, i.e., FEV1/FVC ≥ 70%, unlike COPD.
[Treatment
（In addition to educating and urging patients to quit smoking, avoiding or preventing the inhalation of dust, smoke and harmful gases, the following therapeutic measures can be chosen clinically.
1. Drug treatment
(1) Bronchodilator: It can relieve airflow restriction and reduce lung hyperinflation, and is the main treatment measure to control COPD symptoms. Preferred inhalation dosage form.
(1) β2 adrenoceptor agonists (β2 agonists): salbutamol and terbutaline are short-acting β2 agonists (SABA), which are inhaled through a quantitative nebulized inhalation device (MDI) at a dose of 100-200 μg (100 μg per spray), usually no more than 8-12 sprays in 24 hours. It is mainly used for symptom relief and is administered on an as-needed basis. Salmeterol and f ormoterol are long-acting β2 agonists (LABA), which last for more than 12 hours and are more effective and convenient to use than SABA, but they are more expensive. The common dosage of salmeterol is 25-50μg twice a day. Formoterol is effective 1 to 3 minutes after inhalation, and the commonly used dose is 4.5 to 9 μg twice a day. Adverse reactions are mainly tachycardia, limb tremor, and arrhythmia can occur in serious cases.
(2) Anticholinergics: ipratropium aerosol, 40~80μg, 3~4 times a day. Tiotropium selectively acts on M3 and M1 receptors and is a long-acting anticholinergic. The effect of inhalation lasts for more than 24 hours and the inhalation dose is 18μg once a day. The bronchodilatory effect of tiotropium is superior to that of ipratropium or LABA, and long-term inhalation can increase deep inspiratory volume (IC) and reduce end-expiratory lung volume (EELV), thereby improving dyspnea, exercise tolerance and quality of life. Anticholinergics are well tolerated and safe, and the main adverse effect is dry mouth.
(3) Theophylline drugs: In addition to bronchodilatory effects, they also improve cardiac blood volume, diuresis, excite the central nervous system, improve respiratory muscle function and certain anti-inflammatory effects. Controlled-release or extended-release theophylline can be given orally once or twice a day to achieve stable plasma concentrations. In patients with COPD, theophylline decreases the number and proportion of induced sputum neutrophils, reduces IL-8 production, and decreases the neutrophil chemotactic response. Theophylline and glucocorticoids may exhibit synergistic anti-inflammatory effects.
(2) Glucocorticoids: mainly inhaled glucocorticoids (ICS) are recommended for long-term regular use only for COPD patients with FEV1 <50 % of expected value (grade III and IV) and clinical symptoms and recurrent exacerbations. The combination of budesonide/formoterol and fludrocortisone/salmeterol is available. COPD patients should not be treated with long-term oral glucocorticoids.
(3) Other drugs: Expectorants (mucolytics) such as ambroxol hydrochloride and N-acetylcysteine (NAC) are good for airway drainage and improve ventilation, and NAC also has antioxidant effects.
(4) Vaccine: Influenza vaccine can significantly reduce the number of acute exacerbations of COPD caused by influenza virus and reduce the mortality caused by acute exacerbations of COPD. Inactivated viral vaccines are more effective. The application of pneumococcal polysaccharide vaccine can reduce the incidence of community-acquired pneumonia in COPD patients.
2. long-term home oxygen therapy (LTOT) For patients with chronic respiratory failure, LTOT can stop the progression of pulmonary hypertension and prolong survival. specific indications for LTOT are: ①PaO2≤7.3 kPa (55 mmHg) or arterial oxygen saturation (SaO2)≤88% with or without hypercapnia. ② PaO27.3-8.0 kPa (55-60 mmHg) or SaO2 < 89% with pulmonary hypertension, heart failure, edema or erythrocytosis (hematocrit > 55%). The basic goal is to bring the patient to PaO2 ≥ 60 mmHg at rest and/or to raise SaO2 to at least 90%.
3. Rehabilitation includes various measures such as respiratory muscle and limb muscle strength and endurance training, nutritional support, psychiatric treatment and education. Reasonable rehabilitation program should be formulated according to the specific situation of each patient, paying attention to the combination of pathophysiology and psychotherapy.
4. Pulmonary decongestion is to reduce lung overinflation by removing part of the overinflated lung tissue (pulmonary bullae), improve respiratory muscle work, and improve exercise capacity and health status, but it cannot prolong the life span of patients.
The current recommendation is to grade the severity of COPD according to pulmonary ventilation function and to select the appropriate treatment plan (Table 2-7-1).
(ii) Treatment of acute exacerbations of COPD An acute exacerbation of COPD is a condition in which the patient’s cough, sputum and dyspnea symptoms worsen so acutely that further intensive therapeutic measures are required than usual. The most common causes of acute exacerbation are bacterial or viral infections of the lower respiratory tract. Atypical pathogens (such as Mycoplasma pneumoniae and Chlamydia pneumoniae) also play an important role, while other causes include pulmonary embolism, pneumothorax, chest trauma, irrational use of medications (sedatives, anesthetics, β2-blockers), heart failure or arrhythmias, etc.
1. Antibacterial drugs When patients have increased sputum volume and purulent sputum suggesting bacterial infection, the application of antibacterial drugs is more effective. The antimicrobial spectrum of the drug selected for patients with mild disease should cover Streptococcus pneumoniae, Haemophilus influenzae, and Catamobacter, and amoxicillin/clavulanic acid, levofloxacin, moxifloxacin, and second and third cephalosporins can be used; patients with severe degree of pulmonary impairment and increased number of acute exacerbations have increased chance of infection by Enterobacteriaceae and Pseudomonas aeruginosa, and ciprofloxacin, levofloxacin, ceftazidime , cefoperazone/sulbactam, piperacillin/tazobactam, carbapenems, etc. If the sputum volume does not increase or is non-purulent, it may not be necessary to apply antibacterial drugs, but the cause of the acute exacerbation should be carefully analyzed and the corresponding treatment should be given.
2. Bronchodilators The dose and/or frequency of short-acting bronchodilator therapy should be increased appropriately, with preference for β2 agonists. Combination of different types of bronchodilators increases the efficacy, such as β2 agonists combined with anticholinergic drugs, and theophylline can be added when necessary. With the increase of bronchodilators, the adverse effects can also increase significantly.
3. Glucocorticoids It has been proved that systemic application of glucocorticoids can reduce the clinical symptoms of patients with acute exacerbation of COPD, shorten the hospitalization time and delay the occurrence of re-acute exacerbation. Prednisone can be given 30~40mg/d for 7~10 days, without the process of gradual dose reduction, and can be stopped directly.
4. Other treatments Respiratory stimulants, non-invasive positive pressure ventilation (NIPPV) can be considered for those with respiratory failure.
Medication tips
The purpose and principles of COPD medication is to reduce the number and severity of acute exacerbations, improve health status and increase exercise capacity. Although existing medications have not yet been able to alter the long-term trend of declining lung function in COPD, the effectiveness of medication in reducing symptoms has been confirmed. Since the development of COPD is usually progressive, the selection of drug treatment regimens should follow the following principles: (i) the type of drug required should be increased accordingly according to the grading of disease severity (see Table 2-7-1); (ii) long-term, regular medication should be maintained; (iii) there is variability in the efficacy and adverse effects of different drugs in different individuals, and follow-up and evaluation should be strengthened over a certain period of time to develop a reasonable treatment regimen and We should strive for the best pharmacoeconomic effect.
2. Application of glucocorticoids Previous studies have led to more controversies about the application of hormones in COPD due to inconsistent observation methods, endpoint targets and evaluation criteria, but in recent years, there has been a gradual trend toward a positive attitude. reduce the number of hospitalization days, and reduce airway inflammation. Currently, it is believed that the dose of ICS should be higher in stable COPD than in general asthmatic patients.
Combination therapy For different aspects of COPD pathogenesis, the combination of multiple drugs can enhance the efficacy. For example, the combination of salmeterol and tiotropium improves FEV1 more significantly than both alone; the combination of ICS+LABA has better synergistic effect on airway inflammation; theophylline and LABA have stronger bronchodilator effect; theophylline enhances the anti-inflammatory effect of ICS. Combination therapy has become an important strategy for COPD treatment. The choice of drugs for combination therapy should also consider whether the adverse effects are additive, such as the risk of palpitations and skeletal muscle tremor may be increased when β2-adrenergic agonists and theophylline are combined.
4. Inhalation devices and techniques The main devices currently used for inhalation therapy are quantitative inhalers (MDI) and dry powder inhalers, the latter mainly include turbuhaler and disc inhalers. The survey proved that most of the uninstructed patients cannot correctly master the inhalation technique by reading the drug instructions. Therefore, patients must be instructed and trained in the inhalation technique at the time of first prescription, must be assured that the inhalation technique is correct, and should be rechecked at subsequent visits.
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