COPD lung function characteristics
1. Definition of COPD
The Global Guidelines for the Management of Chronic Obstructive Pulmonary Disease (GOLD) define COPD as a disease characterized by incomplete and reversible airway limitation. Airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to toxic particles or gases.
The diagnosis of COPD should be considered in those with symptoms of cough, sputum or shortness of breath and/or a history of exposure to risk factors, and can be clarified by pulmonary function tests. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has included pulmonary function tests as the gold standard for the diagnosis of COPD.
2. Pathophysiological characteristics
The pathology of COPD is characterized by chronic inflammation involving the airways, lung parenchyma, and pulmonary vasculature. Inhalation of harmful particles and gases (especially smoking) can cause inflammation of the lungs. Inflammatory cells such as macrophages, T-lymphocytes (mainly CD8+ cells) and neutrophils increase infiltration in different parts of the lung. Activated inflammatory cells release various inflammatory mediators, including leukotriene B4 (LTB 4) p interleukin 8 (IL8) p tumor necrosis factor a (TNF- a) and other cytokines that can cause lung tissue damage and/or maintain neutrophilic inflammation. In addition to inflammation, imbalance of pulmonary protease and anti-protease systems and oxidative stress are considered to be two other important pathways in the pathogenesis of COPD. Inhalation of harmful particles and gases can cause inflammation in the lungs. Smoking can cause inflammation and direct damage to lung tissue. Other risk factors for COPD may also trigger a similar inflammatory process in the lungs.
Pathophysiological changes in COPD include airway mucus hypersecretion, abnormal ciliary function, airflow limitation, lung hyperinflation, and abnormal gas exchange, which can progress to pulmonary hypertension and pulmonary heart disease in later stages. These pathophysiologic changes usually occur in the order described above during disease progression. Overproduction of mucus and abnormal cilia function lead to chronic cough and sputum. After many years of these symptoms, other symptoms or physiologic abnormalities may gradually appear. (preferably measured by spirometry) is the hallmark of the characteristic pathophysiological changes of COPD and is the key to the diagnosis of the disease. The main causes of airflow limitation are: spasmodic contraction and thickening of airway smooth muscle and hypertrophy, resulting in excessive bronchoconstriction; increased airway inflammation resulting in increased luminal secretions and blockage of the lumen by mucus; and destruction of the alveolar structure, which weakens the pulling effect on the surrounding small airways and reduces the ability to maintain small airways open, which is an important cause of irreversible airflow limitation in COPD patients.
In addition, hyperinflation of the lungs increases the demand for diaphragmatic downshift and lowering of respiratory performance, hypoxemia and acidosis decrease the central drive and diaphragmatic relaxation rate, and malnutrition affects the structure and function of respiratory muscles, resulting in decreased respiratory muscle strength; in addition, the structural destruction of the alveoli weakens the pulling effect on the airways and reduces the ability to maintain small airway opening. important reason for the irreversibility of airflow limitation in COPD patients. In advanced COPD, the obstruction of the peripheral airways, the derangement of the ventilation/blood flow ratio and the reduction of the gas diffusion area due to the destruction of the alveolar parenchyma and pulmonary vascular abnormalities reduce the gas exchange capacity of the lungs, leading to hypoxemia and the ensuing disruption of respiratory function due to hypercapnia.
Pulmonary function characteristics of COPD
(A) Ventilation function characteristics
Ventilation is the most common and important part of the respiratory function test, which is mainly measured by spirometry, including time-volume curve and flow-volume curve.
Patients with COPD show reduced expiratory flow, prolonged expiratory time, inability to reach expiratory plateau or time to reach plateau more than 6 seconds, significant decrease in FEV1 and its ratio to FVC FEV1/FVC, and significant decrease in MMEF and other indexes, FVC can be in normal range or decreased. The flow-volume curve shows typical features of obstructive ventilatory dysfunction. The depression of the expiratory phase descending branch toward the volume axis, the more obvious the depression, the more severe the airway obstruction. The more pronounced the depression, the more obstructed the airway. The expiratory flow indicators such as PEF, FEF 50%, FEF 75%, etc. decrease.
To determine the severity of COPD, GOLD considers FEV1/FVC<70% as a necessary condition for the diagnosis of COPD, and makes a severity rating based on FEV1. All FEV1 values refer to FEV1 after the use of bronchodilators.
(ii) Bronchial reactivity in COPD
1.Bronchodilator test
Although patients with bronchial asthma may also have the above-mentioned features of airway obstruction during exacerbation, the airway obstruction is often reversible, whereas in patients with COPD, the airway obstruction is irreversible or incompletely reversible, therefore, the two types of airway obstructive diseases can be differentiated by bronchodilator test.
The commonly used inhaled drug is a beta 2 agonist (e.g., Ventolin aerosol 400 μg). The change in FEV1 before and after inhalation (15 min) was compared and the rate of change was calculated. FEV1 change rate (%) = ( post-inhalation FEV1 – pre-inhalation FEV1) / pre-inhalation FEV1 × 100%]. A positive criterion was defined as a change in FEV1 of ≥ 15% and an increase in absolute value of ≥ 0.2 L. The bronchodilator test is often negative in COPD patients.
2, Bronchial excitation test
The airway reactivity of COPD patients can also be higher than normal, especially in elderly patients, and there is a low negative correlation between the increased airway reactivity and the underlying lung function, suggesting that the airway reactivity is increased after the underlying lung function is impaired. However, airway hyperresponsiveness in COPD is often less pronounced than in hand-foot hyperhidrosis3.
(iii) Lung volume characteristics of COPD
In general, COPD can be differentiated from restrictive ventilatory dysfunction by measuring flow-volume and time-volume curves, but in some cases both can decrease lung volume VC (COPD by increasing residual air volume and restrictive lesions by decreasing total lung volume), which requires lung volume measurements. Pulmonary volumetry is required to differentiate.
The most commonly used methods for measuring lung volume are gas dilution and body tracing. In patients with severe obstructive or large alveoli, gas distribution is often uneven, and the gas dilution method is too short to achieve gas equilibrium, so the measured TLC values may be biased. The body tracing method is more accurate for COPD patients and is therefore recommended.
Patients with COPD have typical lung volume characteristics of obstructive disease: increased TLC, FVC, RV, decreased VC, and slowed flow rate. The severity grading is shown in Table 2. In addition, it has been pointed out in recent years that there is a high negative correlation between IC and FRC, and IC increases when FRC decreases. Therefore, IC can be a simple and reliable index for assessing FRC when TLC changes are not obvious. Moreover, IC is commonly used for clinical monitoring because it is easy to measure and can dynamically reflect the change of intrapulmonary gas volume and the effect of treatment.
(iv) Diffusion function characteristics
Diffusion of the lung refers to the process of gas exchange between oxygen and carbon dioxide through the alveoli and capillary walls of the lung. The pathways of diffusion include alveolar gas, alveolar membrane, intra-capillary plasma, red blood cells and hemoglobin. The factors that determine gas diffusion are: gas partial pressure difference between the two sides of the respiratory membrane, gas solubility, diffusion area, and diffusion distance. Changes in any of these factors can cause changes in the amount of diffusion. Patients with severe COPD may have reduced diffusion function due to structural destruction and fusion of the alveolar wall, resulting in reduced pulmonary vascular bed area, reduced gas exchange area, and imbalance in ventilation/blood flow ratio.
Diffusion volume testing is not very meaningful in determining the severity of COPD. Expiratory flow rate and spirometry are much more accurate and sensitive than diffusion function in assessing the severity of COPD. However, diffusion function is useful in the determination of emphysema. If diffusion function is near normal despite some degree of airway obstruction, the underlying pathology is chronic bronchitis, whereas the underlying pathology of decreased diffusion function is maxillary sinus cancer9.
(E) Airway resistance characteristics of COPD
Airway patency is usually reflected by breathing gas flow rate, which is directly proportional to the airway diameter. Conversely, if the airway is spastic, narrow or blocked, the airway diameter is small and the gas flow rate is slowed down. In general, the above reasoning is correct, but ignored an important factor, gas flow rate is still related to the driving pressure of gas flow. Under the same diameter, the higher the driving pressure, the faster the gas flow rate. Therefore, it is incomplete to reflect airway patency by gas flow rate alone. In addition, gas entering the lungs from outside the lungs requires respiratory work, and respiratory work needs to overcome the resistance consumed by the friction of gas flow through the airway (its physical characteristic is viscous resistance), in addition to the resistance consumed by the expansion of the thorax and lung tissue (its physical characteristic is elastic resistance, the inverse of which is the compliance of the thorax and lungs), as well as the resistance generated during the gas flow and thoracic expansion movement (its physical characteristic is inertial resistance). The sum of viscous resistance, elastic resistance and inertial resistance of the respiratory system is collectively referred to as total respiratory resistance (or total respiratory impedance). The most closely related to airway patency is viscous resistance, which is often referred to as airway resistance (Raw). Airway resistance is equal to the ratio of the pressure difference (S P) consumed to maintain a certain flow of breathing gas (V) to that flow, i.e., Raw = S P/V. Increased airway resistance is indicative of airway obstruction or stenosis and is much more sensitive than FEV1.
In recent years, the forced oscillation technique (IOS) has evolved rapidly in the determination of airway resistance. In IOS results, it is possible to distinguish between central and peripheral airway obstruction in the COPD pathology. Respiratory impedance is a sensitive indicator of airflow obstruction in COPD patients. In patients with COPD, R 5, R 20 and Fres are significantly higher than normal, X 5 is significantly lower, and there is a significant frequency dependence of viscous resistance and electrical resistance between 5 and 35 Hz. The mechanism for the decrease in electrical resistance is due to reduced respiratory compliance and/or a frequency-dependent increase in resistance due to increased peripheral airway resistance. Fres is a sensitive indicator for the diagnosis of COPD, and its sensitivity increases as the disease worsens, reflecting the degree of airflow obstruction in COPD patients.
(vi) Respiratory function and nutrient metabolism characteristics of COPD
In COPD patients, due to airway obstruction, the respiratory effort to overcome airway resistance increases with the increase of airway resistance, and therefore, the oxygen consumption of respiratory muscles also increases. Brown et al. showed that in patients with COPD, oxygen consumption can be up to 10 times higher than normal in order to maintain respiration. The increase in oxygen consumption of respiratory muscles inevitably leads to an increase in the basal oxygen consumption and basal energy expenditure of the body. Zheng Jinping’s study found that the oxygen consumption and basal energy consumption of COPD patients increased with the increase of airway obstruction.
(VII) Characteristics of exercise cardiopulmonary function (CPET)
CPET in COPD patients is characterized by an increased need for ventilation with increased exercise load, but reduced ventilation capacity. The increase in airflow obstruction is accompanied by a decrease in pulmonary elastic retraction, which leads to an imbalance in the V/Q ratio due to inadequate ventilation in some lung areas and hyperventilation in some lung areas, resulting in an increase in VD/VT, thus requiring increased ventilation to expel CO 2 and maintain a constant blood PCO 2. In the perfused lung units, hypoventilation causes hypoxia, which also increases pulmonary ventilation via carotid body chemoreceptors.
As alveolar ventilation decreases, oxygen exchange decreases, V/Q decreases, and PaO 2 decreases and P (A-a) O 2 increases with increasing power during exercise. During exercise, cardiac output increases, blood flow through the V/Q imbalance region increases, and small arteries contract due to hypoxia because of reduced alveolar ventilation. However, alveolar blood flow in the V/Q homogeneous region increases, reducing the occurrence of hypoxemia, and exercise load can continue to increase. If this mechanism fails, hypoxemia increases and P (A-a) O 2 widens. In addition, an increase in right atrial pressure, which leads to shunting, also increases P(A-a) O2. In addition, the tidal flow velocity volume loops of COPD patients are characteristically altered during exercise: during exercise, the tidal flow velocity volume loops gradually approach the total lung volume and overlap significantly with the expiratory phase of the maximum flow velocity volume loops.
In general, the characteristics of CPET in COPD patients can be summarized as follows: 1. low VO 2 max; 2. high VD/VT; 3. high P (a-et) CO 2; 4. high P (A-a) O 2; 5. low BR; 6. increased operative oxygen consumption, lactic acidosis at low power, and inability to compensate for respiration in metabolic acidosis; 7. high HRR; 8. abnormal (rectangular trapezoidal) expiratory flow; 9. high HRR; and 10. high HRR. Rectangular Trapezoidal) expiratory flow type.