Chronic Obstructive Pulmonary Disease (COPD) is a common, frequent, disabling and fatal chronic respiratory disease. 9.40%. The prevalence of COPD in the population over 40 years of age in Tianjin is 9.42%, which is close to the recent prevalence rates of 9.1% and 8.5% in the same age group in Europe and Japan, and compared with the results of the 1992 survey in China, the prevalence of COPD has increased three times.
The mortality rate of cardiovascular diseases in the United States has decreased by 35%-64% since 1965-1998, while the mortality rate of COPD has increased by 163%. The World Health Organization estimates that COPD is the fourth or fifth deadliest disease worldwide, comparable to the death rate of AIDS.
1, COPD concept, etiology and pathology
The traditional COPD includes chronic bronchitis, obstructive pulmonary emphysema and irreversible bronchial asthma with partial airway obstruction, and is a combination and overlap of these three chronic respiratory diseases. The new concept of COPD in the 2004 edition of the Global Strategy for the Diagnosis and Prevention of COPD (GOLD), developed by the National Heart, Lung, and Blood Institute, the American Thoracic Society, the European Society of Respiratory Diseases, and the World Health Organization, no longer emphasizes or even uses the term “chronic bronchitis and obstructive pulmonary disease”. COPD is defined as a preventable and treatable chronic inflammatory disease of the airways that progresses with incomplete reversible airflow limitation.
The pathology of airflow limitation is based on an abnormal inflammatory response of the airways to different noxious particles and gas stimuli. The pathological changes of incomplete reversible airflow limitation include reversible and irreversible components. The reversible part is the accumulation of inflammatory cells, mucus and plasma exudates in the bronchi, the contraction of smooth muscles of the peripheral and central airways, and the hyperinflation of the airways during exercise; the irreversible part is the fibrosis and narrowing of the airways, the loss of alveolar support that keeps the small airways open, and the destruction of the alveolar structure that makes the lung elastic contractility decrease.
Restriction of expiratory flow rate, a hallmark of pathophysiological changes in COPD, is mainly caused by fixed airway obstruction and the consequent increase in airway resistance. Disruption of alveolar attachment impairs the ability of small airways to remain open, but plays a smaller role in airflow limitation.
As COPD progresses, peripheral airway obstruction, lung parenchymal destruction, and pulmonary vascular abnormalities reduce pulmonary gas exchange capacity, producing hypoxemia and later hypercapnia. The development of pulmonary hypertension in the late stages of COPD (grade III: severe COPD) is an important complication of COPD and is associated with the formation of pulmonary heart disease, suggesting a poor prognosis.
Altered bronchial and pulmonary anatomy in the elderly is more likely to exacerbate the pathophysiological changes of COPD. During the aging process, although the number of alveoli does not decrease significantly, the alveoli become significantly thinner, the alveolar cavity becomes larger, the elasticity decreases, the microvasculature of the alveolar wall gradually decreases or even partially loses, the intima becomes fibrotic to varying degrees, the collagen component increases, and the fine bronchi expand, resulting in a gradual increase in residual lung volume (RV) and a gradual decrease in lung vital capacity (VC). The RV increases nearly 1-fold in older adults over 60 years of age compared to younger adults in their 30s, and further affects anatomical dead space, alveolar dead space, and gas exchange. The anatomic dead space was approximately 130 cm3 and VD/VT was approximately 0.25-0.30 in healthy young adults, compared with 150-160 cm3 and 0.3-0.4, respectively, in older adults.
The partial pressure of arterial oxygen in healthy 30 year olds is about 95-100 mmHg, while it decreases to 75 mmHg by the age of 60. In addition, the elderly also have reduced sensitivity of respiratory chemoreceptors and neuroreceptors, resulting in a reduced response to hypoxic and carbon dioxide ventilation stimuli, which predisposes them to alveolar hypoventilation, or more likely to manifest as hypoxia and carbon dioxide retention. The above factors contribute to the more severe pathophysiological changes that occur in older adults with COPD.
COPD is characterized by chronic inflammation of the airways, lung parenchyma and pulmonary vasculature, with an increase in macrophages, T lymphocytes (especially CD8+) and neutrophils in different parts of the lung. Activated inflammatory cells release a variety of mediators, including leukotriene B4 (LTB4), interleukin (IL)-8, tumor necrosis factor (TNF) alpha, and others. These mediators can disrupt the structure of the lung and/or promote the neutrophil inflammatory response. In addition to inflammation, protease and anti-protease imbalances and oxidation in the lung play an important role in COPD pathogenesis. Inhalation of toxic particles or gases can lead to inflammation in the lungs. Smoking induces inflammation and directly damages the lungs.
Smoking, respiratory infections and air pollution are the three main causes of COPD. In the 1960s, Pitot, a professor at Oxford University, recorded the habits of smokers and traced their deaths among 40,000 practicing physicians. It was found that those who smoked 15 to 24 cigarettes a day were 12 times more likely to die than nonsmokers, and those who smoked more than 25 cigarettes a day were 20 times more likely to die than nonsmokers. A simple lung function (ventilation) test yielded a smoking index as the product of the number of cigarettes smoked per day and the number of years of smoking (e.g., if one smokes 20 cigarettes per day and continuously for 20 years, the smoking index is 20 × 20 = 400).
Infection:Upper respiratory tract infections can be caused by viruses, mycoplasma, chlamydia and bacteria. There are many types of viruses, of which more than 10 viral infections are associated with chronic bronchitis. Air pollution:Air pollution refers to ambient air pollution, workplace air pollution and home air pollution can all cause the onset of chronic bronchitis.
Other than smoking, infection and air pollution, malnutrition, allergy, reduced immune function and autonomic dysfunction are all related to the onset of chronic bronchitis.
2. Diagnosis and clinical evaluation of COPD
COPD diagnosis should be considered in patients with the following characteristics: cough, sputum, dyspnea, and a history of exposure to COPD risk factors. Confirmation of the diagnosis requires pulmonary function tests, and the presence of irreversible airflow limitation can be confirmed by an FEV1/FVC force spirometry <0.7 after the use of bronchodilators. Functional classification is based on FEV1 as a percentage of the expected value.
Severity staging In a slight departure from the GOLD view, the new guidelines suggest that FEV1 does not fully reflect the complex clinical consequences of COPD, but that pulmonary function grading is still useful for predicting health status and morbidity and mortality. The new guidelines emphasize the prognostic role of body mass index BMI and dyspnea classification and recommend that both be evaluated in all patients, with an increased rate of death in patients with a BMI <21 kg/m2.
Symptoms that should be primarily evaluated in the clinical assessment include chronic cough, sputum production, and shortness of breath. Past history and systematic review should be noted for the presence of asthma, allergic diseases, infections, and other respiratory diseases (e.g., tuberculosis) during childhood, history of smoking (in pack-years) and exposure to occupational and environmental hazards, family history of COPD and respiratory disease, and other diseases with the same risk factors (smoking) such as heart disease, peripheral vascular disease, and neurological disease. Vital signs examination included respiratory rate, weight and height, and BMI was calculated.
All patients with suspected COPD should have the following tests: pulmonary ventilation tests to clarify the diagnosis and to evaluate the severity of the disease; reversibility tests to exclude not only asthma, but also to understand the patient’s optimal lung function and to evaluate the prognosis; and X-ray chest radiographs to help exclude other diseases (pneumonia, tumors, heart failure, pleural effusion and pneumothorax) and to detect pulmonary alveoli.
Some patients should complete the following tests: α1 antitrypsin level, static lung volume such as total lung volume, residual air volume, functional residual air volume and total residual ratio, carbon monoxide diffusion volume, blood gas analysis, exercise test, respiratory muscle function, pulmonary circulation pressure and right ventricular function, chest CT, polysomnography monitoring, etc.
3.Prevention and treatment of COPD
3.1 Early interventions
Smoking cessation is of great benefit in reducing many secondary complications such as COPD. The widely accepted smoking cessation guidelines were published by the U.S. Department of Health and Human Services in 2000 and are based on evidence-based medicine. Studies have demonstrated that cessation of smoking in patients of any age or duration is effective in slowing the rate of FEV1 decline and progression of disease. Treatment of smoking dependence in smokers includes social support and nicotine replacement therapy. Treatment needs to be a long-term process, and anyone who fails to quit smoking needs to be re-educated and re-treated, and physicians should not forgo any opportunity to promote education and treatment.
3.2 Stable COPD treatment
Stable phase treatment includes pharmacotherapy, oxygen therapy, respiratory rehabilitation, and surgical treatment of the lungs.
Pharmacological treatment: Available pharmacological treatments can reduce or eliminate patients’ symptoms, improve activity tolerance, reduce the number and severity of acute exacerbations, and improve health status, but there are no drugs that can change the rate of lung function decline.
Inhalation therapy is preferred over oral therapy. Inhalation therapy is administered in smaller doses, can have the same or greater effect as oral therapy, and has fewer side effects. Patients must be educated on the proper use of various inhalers. A significant number of patients who cannot breathe effectively with MDI, a quantitative nebulizer inhaler, can use DPI, a dry powder inhaler, or a nebulizer reservoir, the latter of which is useful when inhaling corticosteroids to reduce local side effects such as drug deposition in the oropharynx.
Explaining the purpose and effects of treatment to patients helps them to adhere to treatment. Although pulmonary ventilation function tests are necessary to clarify the diagnosis, the results of reversible tests are not useful in predicting their clinical prognosis. Studies have confirmed that patients with a negative reversible test also benefit from receiving treatment.
Bronchodilators: There are three types of bronchodilators commonly used in clinical practice: beta agonists, anticholinergics, and methylxanthines. The most important effect of bronchodilators is to relax smooth muscle and improve lung emptying during respiration. Therefore, the increase in FEV1 may be small, but the lung volume is often improved, and the residual air volume is reduced, slowing down the onset of dynamic hyperinflation during exercise and thus reducing the symptoms of dyspnea.
In general, the more severe the COPD, the more important the change in lung volume relative to the change in FEV1. Improvements in FVC and spirometry are significantly associated with improvements in activity tolerance. Other factors such as nutritional status, cardiopulmonary function and peripheral muscle strength also affect activity tolerance and may influence the efficacy of bronchodilator therapy.
Inhalation of a mixture of long-acting beta agonists and glucocorticoids is a convenient treatment. In patients with FEV1 < 50% of predicted values, the combination improves acute exacerbations and health status significantly better than single agents.
Long-term oxygen therapy LTOT: LTOT improves patient survival and improves mobility, sleep and cognition. The presence or absence of carbon dioxide retention should be noted after correction of hypoxemia. Arterial blood gas analysis is the preferred test, which should include indicators of acid-base balance. Arterial oxygen saturation SpO2 measured by finger oximetry can be used to observe trends. The physiological indication for oxygen therapy is an arterial partial pressure of oxygen PaO2 < 7.3 kPa (55 mmHg). The therapeutic goal is to maintain SpO2 >90% during rest, sleep and activity. Discontinuation of oxygen in patients who meet the oxygen therapy indication due to improved PaO2 may be harmful. Increased patient education may improve compliance.
Nutritional therapy: Patients with stable COPD may experience weight loss and decreased fat-free weight FFM, the latter two being independent of the degree of airflow limitation but associated with an increased risk of death. Nutritional interventions themselves should focus on early prevention and early treatment of weight loss to prevent energy imbalance. Nutritional therapy should be considered when the patient meets one or more of the following conditions: BMI < 21 kg/m2, weight loss > 10% within 6 months or > 5% within 1 month , FFM loss, FFM index < 16 kg/m2 in men and < 15 kg/m2 in women . Nutritional therapy should initially be followed by a change in the patient's diet, followed by high-energy supplements, and should be given in several doses over the course of a day to avoid decreased appetite and increased ventilation needs due to high caloric load.
Surgery: COPD is not an absolute contraindication to any surgical procedure, but patients have a 2.7 to 3.7-fold increased risk of postoperative pulmonary complications. The further the surgery is from the diaphragm, the lower the rate of pulmonary complications. Postoperative complications can be reduced by quitting smoking for at least 4 to 8 weeks prior to surgery and by keeping lung function in optimal condition. Early activity, deep breathing, intermittent positive pressure breathing, and effective pain relief may reduce postoperative complications. Surgical treatment of COPD should be strictly patient-selected, and alveolar resection and lung volume reduction may improve dynamic lung function, lung volume, mobility, dyspnea, health-related quality of life, and perhaps survival. Lung transplantation may be considered in a small number of patients.
Sleep COPD patients can sleep with reduced oxygen saturation, which is primarily due to the disease itself rather than sleep apnea. The decrease in oxygen saturation is more pronounced during sleep than during heavy exercise, and the incidence of sleep apnea in COPD patients is approximately the same as in the general population of the same age, but the decrease in oxygen saturation during sleep is more pronounced when the two conditions coexist. Not all patients with COPD require sleep monitoring, the latter being indicated when there is clinical suspicion of sleep apnea or the presence of hypoxemia that contradicts arterial oxygen levels during waking hours.
3.3 Treatment of acute exacerbations of COPD
The new guidelines define an acute exacerbation of COPD as an acute worsening of dyspnea, cough, and sputum symptoms from baseline levels in patients with COPD that requires adjustment of the treatment regimen. There is no consensus on the severity grading, but the following criteria can be referred to: Grade I, treated at home; Grade II, requiring hospitalization; Grade III, acute respiratory failure. Treatment includes the application of bronchodilators, glucocorticoids, antibiotics and oxygen therapy.
Oxygen therapy for hospitalized patients: The goal is to maintain PaO2 > 8 kPa (60 mmHg) or SpaO2 > 90% to avoid tissue hypoxia. Arterial blood gas analysis, including PaO2, PaCO2 and PH should be monitored. finger oximetry measurement of SpaO2 can be used to observe trends and adjust oxygenation settings. Prevention of tissue hypoxia should be accompanied by attention to carbon dioxide retention. If carbon dioxide retention occurs, monitor blood pH. If acidosis is present, consider mechanical ventilation.
Adjunctive ventilation: Patients with acute exacerbation who have respiratory acidosis PH < 7.36 and/or persistent severe dyspnea after optimal drug therapy and oxygen therapy should be ventilated with non-invasive positive pressure ventilation NPPV. arterial blood gas analysis should be checked in all patients before considering mechanical ventilation. while NPPV, if PH < 7.25, one should be prepared for intubation. The combination of continuous positive airway pressure CPAP, e.g., at 4-8 cmH2O, and pressure support ventilation PSV, e.g., at 10-15 cmH2O, is the most effective mode of NPPV for COPD. Patients with contraindications to NPPV should be considered for immediate intubation and admission to the monitoring unit.
4. Advances in pharmacological treatment of COPD
Despite the high prevalence and mortality of COPD, research on its basic and specific treatment is far from adequate. The drugs currently used are mainly adrenergic agonists, anticholinergics, theophylline, glucocorticoids, and mucodynamic or phlegmolytic agents as well as long-term oxygen therapy. All of these treatments have limited effectiveness, have little impact on preventing their progression and disease progression, and can help only a small percentage of people. For example, oral or inhaled glucocorticoids are effective in only 20-30% of COPD patients. Recent studies have shown that there are several molecular targets for possible therapeutic use, and the most exciting new compounds are selective muscarinic receptor antagonists and phosphodiesterase 4 inhibitors, representing important advances in respiratory pathology in recent years.
4.1 Selective muscarinic receptor antagonists
There are three muscarinic receptor subtypes in the lung that regulate airway tone and secretion. m 1 receptors are in the parasympathetic ganglia and accelerate conduction; m 2 receptors are located in presynaptic cholinergic nerve endings and inhibit acetylcholine release; m 3 receptors are present in smooth muscle and cause smooth muscle contraction. The ideal choice for maximum control of cholinergic input is to antagonize M 1 and M 3 receptors rather than M 2 receptors. Ipratropium bromide has been used for many years in COPD as a non-selective muscarinic receptor antagonist. Selective muscarinic receptor antagonists that are longer acting and more potent than ipratropium bromide, such as cetropium, oxitropium, revatˉropate, or darifenacin, are being explored, and there is evidence that cetropium may have additional clinical effects by reducing acute exacerbations in patients.
Revatropate is a selective M 1 /M 3 muscarinic receptor antagonist that inhibits acetylcholine-induced bronchoconstriction. In the initial COPD clinical trials, inhaled Revatropate produced a similar increase in FEV1 as ipratropium bromide. However it remains to be determined whether more selective compounds such as revatropate or drafenacin, have more clinical benefit than ipratropium bromide.
4.2 Phosphodiesterase 4 inhibitors
Phosphodiesterase 4 (PDE4) is a member of the growth protein family. phosphodiesterase (PDE) metabolizes intracellular messenger 2, cAMP and cGMP. PDE4 specifically metabolizes cAMP and is the major PDE isoenzyme in the lung and also in immune and inflammatory cells present in airway smooth muscle. pDE4 is the most abundant of the PDEs in neutrophils, CD8+ T cells, and macrophages. The most expressed, suggesting that PDE4 inhibitors would be effective in controlling COPD inflammation, potentially providing a more comprehensive and effective treatment for COPD. However, an obvious challenge is to screen for potent PDE4 inhibitors without the side effects of the first generation compound rolipram . Such molecules include SB207499 (Ariflo), CDP804, V11294A, CP-220, 629, and roflumilast. these compounds have demonstrated significant preclinical effects, i.e., maintaining the anti-inflammatory activity and bronchodilatory effects of rolipram while significantly reducing gastrointestinal side effects, including vomiting.
Clinical studies of PDE4 inhibitors for pulmonary disease are still limited, however, of particular note is the initial clinical validation with Ariflo, which showed significant improvement in lung function and quality of life in patients with difficult-to-reverse COPD at tolerable oral doses.
4.3 P38 kinase inhibitors
P38 is a member of a unique family of stress-induced mitogen-activated protein kinases. It is a highly conserved proline-directed serine threonine protein kinase. p38 kinase is an important component of signaling pathways and should be responsible for the release and action of different proinflammatory signals, such as TNFα and IL1β . Regarding the expected role of inflammatory cytokines in airway inflammation, P38 inhibition may represent an appropriate pathway to control several key cells and processes affecting the pathophysiology of lung disease and COPD. Potent and selective P38 inhibitors, including SB239063, have been identified and have produced a range of potent effects in animal studies, including inhibitory effects on airway neutrophils, cytokine production, MMP activity and fibrosis.
4.4 Protease inhibitors
The imbalance between proteases and their natural levels of inhibition constitutes some of the features of COPD. Neutrophil elastase, a serine protein kinase is hypothesized to play a role in the destruction of lung parenchyma in emphysema. Due to its potent mucus pro-secretory activity, it promotes lentive-specific mucus hypersecretion. Several potent and selective elastase inhibitors have been identified, including ONO-5046, ICI200, 355 and MR899 and TEI-8362. these compounds prevented elastase-mediated lung damage and inhibited mucus hypersecretion in animal models. However, clinical studies have shown that administration of MR899 to COPD patients for four weeks did not affect the 2 markers of lung damage, plasma elastin-derived peptide or urinary lock-linked lysine.
There are also many other potentially relevant proteases, including cysteine protein kinases in alveolar macrophages, such as Cathepsin S and Cathepsin L, and MMPs released from activated neutrophils and macrophages, which are 15 members of a family of secreted or membrane-bound enzymes that degrade most extracellular matrix components. The role of MMP9 in the pathogenesis of COPD has been demonstrated.
4.5 Chemokine antagonists
A possible strategy for the treatment of COPD is to target receptors involved in the recruitment or activation of the most important inflammatory cells, such as neutrophils, CD8+ T cells and macrophages. Chemokines are a family of proteins about 8 to 12 kDa in size that regulate the chemotaxis and activation of inflammatory cells. Currently, more than 30 different chemokines are known, classified as CXC, CC, CX3C and C families. Chemokines stimulate G protein-coupled specific members of the seven transmembrane superfamily receptors.
IL-8, the prototype CXC chemokine, activates neutrophils by interacting with CXCR1 and/or CXˉCR2 and is elevated in bronchoalveolar lavage fluid from COPD patients. Application of CXCR2 knockout mouse experiments and studies with a non-peptide-selective CXCR2 antagonist, SB225002, suggest that CXCR2 is necessary for neutrophil recruitment and that activation of CXCR1 increases elastase release and peroxide production. These initial observations support the potential application of selective CXCR1 and/or CXCR2 antagonists for the treatment of COPD.
4.6 Endothelin modulators
Endothelin (ET)-1 is a 21-amino acid peptide first isolated from cultured endothelial cells in 1988.The polybiological actions of ET-1 are regulated by ETA and ETB2 receptors, belonging to the G protein-coupled superfamily of seven transmembrane receptors. Pulmonary hypertension is a common and serious complication of COPD. In vitro studies have shown that ET-1 produces 2 features of pulmonary hypertension, pulmonary vasoconstriction and vascular remodeling, directing strong constriction of isolated human pulmonary vessels and increasing human pulmonary artery cell proliferation. The contractile effects are mainly produced by activation of ETA receptors, with evidence also for a contribution of ETB receptors, while mitogenic effects are ETA receptor-mediated. in addition to possible effects on vascular components of COPD, other potentially pathophysiologically relevant in vitro effects of ET-1 include increased mucus secretion, recruitment and activation of neutrophils and macrophages and enhanced neuroinduced responses. There have been numerous reports of increased ET-1 levels or expression in children or adults with pulmonary hypertension, or when animals and humans are exposed to hypoxia.
Several potent selective non-peptide receptor antagonists have now been identified, such as ETA receptor-selective compounds, ETB receptor-selective compounds, or mixed ETA/ETB receptor-selective antagonists. Many compounds have been subjected to extensive preclinical trials, including animal models of pulmonary hypertension. For example, Bosentan and SB217242 reversed or prevented pulmonary artery pressure elevation and vascular remodeling induced by acute or chronic hypoxia or monocrotaline action in rats or guinea pigs. However, to date, reports on the role of ET receptor antagonists in pulmonary diseases, including COPD, are lacking. A key question that remains to be clinically clarified is what is the most desirable and optimal selective compound for COPD.
4.7 Tachykinin receptor antagonists
Tachykinins are small molecular peptides found in the central or peripheral nervous system, including substance P, neurokinin (NK) A and B. Possible pulmonary systemic effects associated with tachykinins include neurogenic inflammation, plasma exudation, mucus secretion, bronchoconstriction, and inflammatory chemotaxis and activation. substance P levels are elevated in sputum specimens from COPD patients.
The multiple actions of tachykinins are mediated by three known receptors, NK-1, NK-2, and NK-3, which belong to the G-protein-coupled superfamily of seven transmembrane receptors. activation of NK-1 receptors induces mucus secretion, microvascular exudation, inflammatory cell recruitment and activation, and bronchoconstriction. Intrapulmonary NK-2 receptor activation produces bronchospasm, activation of alveolar macrophages, neurogenic inflammation and enhanced neurally mediated responses. The role of pulmonary NK-3 receptors has not been extensively studied, however electrophysiological analysis suggests the presence of NK-3 receptors in the bronchial parasympathetic ganglion of the guinea pig, which have a modulatory neural afferent role.
The first non-peptide tachykinin receptor antagonist was CP-96,345 which was identified as an NK-1 receptor antagonist by high channel screening. Since this first discovery, several potent and selective nonpeptide NK-1 receptor antagonists have been identified from different structural classes of drugs.
In 1992, Sanofi reported the potent selective nonpeptide NK-2 receptor antagonist, SR48968. potent members of this class of compounds were subsequently reported, including GR159897 and SR144190. NK-2 receptor antagonists such as SR48968 are effective in animal models of airway hyperresponsiveness and cough. Potent selective NK-3 receptor antagonists were also identified, such as SR142801 and SB223412. SR142801 was effective in guinea pig models of cough and bronchial hyperresponsiveness. Looking at the diverse potential pathophysiological effects of tachykinins in the lung, compounds that can produce interactions by stimulating three receptors rather than one may have greater clinical effects than selecting a single tachykinin receptor, for example, the non-peptide NK-1/NK-2 receptor antagonist MDL105212A.
4.8 Epidermal growth factor receptor antagonists
Epidermal growth factor (EGF) was discovered by Cohen and his colleagues, and the mechanism of action of EGF and epidermal growth factor receptor (EGFR) was subsequently investigated in depth. EGFR is a 170 kDa membrane glycoprotein that can be activated by ligands such as EGF, TGFα, heparin-binding EGF, bimodulin, betacellulin and epiregˉ ulin. These proteins are synthesized as transmembrane precursors and then hydrolyzed and cleaved by metalloproteinase proteins to release mature growth factors before they can interact with EGFR and perform their functions.
Many chronic airway disorders (e.g. asthma, COPD, nasal polyps and cystic fibrosis) are combined with mucus overproduction. Many stimuli, such as allergens, bacteria, mechanical injury, smoking, as well as cytokines and activated neutrophils, can cause airway epithelial differentiation into mucin-producing cells via activation of the EGFR waterfall. richter et al. demonstrated that cigarettes induce the release of IL-8 from bronchial epithelial cells, causing neutrophil recruitment.
This process is mediated by TGF-α hydrolysis release and EGFR activation. a positive correlation between EGFR expression and MUC5AC production suggests the importance of EGFR for airway mucus production. The result causes mucus overproduction that is difficult to treat and even affects gas exchange. Recent studies suggest that several pathways involving EGFR expression and activation have the potential to provide new therapeutic approaches for mucus hypersecretion. Clinical collaboration is needed to study the role of EGFR in COPD patients.