2011年 · 第34卷第04期

In my first year of college, I was lucky enough to know what respiratory pericardial frication is under the guidance of my teacher. Although it has been more than 30 years, it is still fresh in my memory and deeply impressed. I would like to introduce its experience and share it with readers, and express my opinions on the relationship between laying basic skills and mastering modern laboratory inspection methods.

Three doctors, Claude Bernard in 1846, Chauveau and Marey in 1861, successively put catheters into the right side of the heart in animal experiments, but it was not yet clear whether this technology could be safely used in humans. It was not until 1929 that a young surgeon in Germany, Werner Forssman, risked his life and bravely inserted a urinary catheter into his own right atrium to implement this technique on the human body for the first time, but this successful venture was not recognized and popularized by the medical community at the time. It was not until 1940s that Kurnand, Richards and others obtained mixed venous blood with the help of right cardiac catheterization technology, and applied Fick's principle to measure cardiac output. The feasibility and value of this technology were widely recognized. Right heart catheterization not only pioneered the accurate measurement of cardiac output, but also opened the way for in-depth exploration of the heart and lungs through clinical application in various cardiopulmonary diseases. As a result, Werner Forsman, Kurnand, and Richards jointly won the Nobel Prize in Medicine in 1956.

Hypersecretion of airway mucus is one of the important pathophysiological characteristics of chronic airway inflammatory diseases represented by COPD, and the main clinical manifestations are repeated cough and expectoration. For a long time, there is a misunderstanding in the understanding of airway mucus hypersecretion. It is believed that cough and expectoration caused by airway mucus hypersecretion are only a clinical symptom, and have little relationship with pulmonary function deterioration and acute exacerbation of COPD patients. Therefore, there is a lack of relatively holistic and objective understanding of airway mucus hypersecretion and expectorant treatment based on airway mucus hypersecretion. With the deepening of research on airway mucus hypersecretion, it is known that it far exceeds the scope of simple clinical symptoms. Besides symptomatic treatment, expectorant also plays a more important role in the treatment of COPD. Therefore, exploring the important role of airway mucus hypersecretion in the pathogenesis of COPD, developing new expectorants and carrying out clinical research on expectorants have become current research hotspots.

COPD is a common and frequently occurring disease, and ranks among the top causes of human death. The incidence of COPD is as high as 8.2% among people over 40 years old in China^[1]That is to say, there may be tens of millions of COPD patients in China's 1.3 billion people. Obviously, this huge patient population is bound to cause a heavy burden on people's health and hygiene resources. The most common and serious complications of COPD are pulmonary hypertension and pulmonary heart disease. Traditionally, COPD → pulmonary hypertension → pulmonary heart disease is regarded as an inevitable formula for the progressive aggravation of the same disease process, and the clinical manifestation is that the initial respiratory symptoms eventually progress to right heart failure. In recent years, with the progress of basic and clinical research, this formula seems to be beginning to be suspected^[2,3,4,5]。 This article reviews recent developments in relevant areas, focusing on new understanding of the concept of COPD.

In the past, when mentioning the pulmonary vascular changes in COPD, we considered that the main cause was pulmonary hypertension, which was related to hypoxia, and belonged to the main lesions in the late stage of COPD. This concept has long guided our clinical thinking in the treatment of COPD, that is, the main treatment was to correct hypoxia and dilate the pulmonary artery, but the clinical efficacy was minimal. In recent years, with the deepening of research on pulmonary and systemic inflammatory response and its related mechanisms in COPD, people's understanding of the nature, characteristics and related mechanisms of pulmonary vascular changes in COPD has changed greatly, and will have a profound impact on the prevention and treatment of COPD.

COPD is a chronic inflammatory reactive disease characterized by incomplete reversibility of restricted airflow, accompanied by systemic multi-system damage. skeletal muscle dysfunction (SMD) or weakness is one of the prominent manifestations of systemic effects (i.e. extrapulmonary effects) of COPD, which is closely related to the quality of life and the exacerbation of the disease^[1]。 SMD often starts with early COPD and has a high incidence. Therefore, the research on the prevention and treatment of SMD in COPD patients may provide a new way for the prevention and treatment of COPD.

In recent years, clinical studies on COPD-related drugs have gradually increased. Bronchodilators are the basic drugs for the treatment of COPD at present, among which the therapeutic effect of anticholinergic drugs on COPD is one of the hot research topics. Results from the understanding potential Long-Term impacts on function with tiotropium (UPLIFT) study up to 4 years suggest that^[1]Tiotropium bromide has significant significance in reducing the number and degree of acute exacerbations in COPD patients, and improving the health-related quality of life of patients, and this effect was always present during the 4-year study period. During the study period, patients in the tiotropium group had significantly better lung function than those in the placebo group, and the risk of death was significantly reduced. In particular, in recent years, many scholars have conducted in-depth research on the mechanism of action of anticholinergic drugs on COPD, and the results suggest that cholinergic nerves and receptors may play a more extensive role in the pathogenesis of COPD.

BACKGROUND AND OBJECTIVE: Grading COPD according to airflow restriction severity does not reflect the heterogeneity of COPD phenotypes. The study is intended to determine the COPD phenotype through a number of clinical variables. Methods: A multicenter cohort study of COPD patients was conducted according to uniform criteria grouping. Eight variables associated with COPD were selected: age, smoking index, FEV₁% of the predicted value, body mass index, frequency of acute exacerbations, dyspnea score, health status (St. George's Respiratory Questionnaire score) and depressive symptoms, and the patients were grouped using cluster analysis on the basis of principal component analysis. Results: 322 patients with COPD were classified into 4 clinical phenotypes: young/severe (44 cases, 13.7%), old/mild (89 cases, 27.6%), young/moderate (93 cases, 28.9%) and old/severe (96 cases, 29.8%). Dyspnea, health-related quality of life, frequency of acute exacerbations, and comorbidities (chronic cardiac insufficiency and depression) are consistent in the same phenotype, but there are significant differences in the same GOLD grade, suggesting that the above variables may represent independent COPD phenotypes, while FEV₁Based GOLD grading does not distinguish between different clinical phenotypes. FEV₁There were significant differences in age, symptoms, comorbidities, and predicted mortality among COPD patients with similar outcomes and different phenotypes. Conclusion: To improve the level of diagnosis and treatment of COPD and the quality of clinical trials, new multiple COPD classification criteria are needed. The prognostic value of the above phenotypes still needs to be validated in longitudinal studies.

BACKGROUND AND OBJECTIVES: Airway lesions and emphysema are two different components of COPD, and genetic variability in patients may influence the extent of airway disease and emphysema. The study aimed to clarify candidate gene single nucleotide polymorphisms (SNPs) associated with susceptibility to COPD, with emphysema severity and tracheal wall thickness as shown by chest CT. Methods: Polymorphisms of 6 candidate genes in 379 patients with COPD were detected. The percentage of lung low impairment areas below-950 HU, tracheal wall thickness and the square root of the bronchial wall area derived from this with an internal diameter of 10 mm were measured by lung CT. Multivariate regression analysis was used to evaluate the correlation between candidate genes and CT measurements. Results: Three SNPs of EPHX1 (rs2854450, rs3738042 and rs1009668), five SNPs of SERPINE2 (rs6734100, rs729631, rs975278, rs6436449 and rs7608941) and one SNP of GSTP1 (rs11227844) were significantly correlated with emphysema. Correlations with tracheal wall thickness in patients with COPD were 5 SNPs of TGFB1 (rs1800469, rs1800480, rs1800471, rs11083616 and rs11466321), 2 SNPs of EPHX1 (rs2854450 and rs3753658), 1 SNP of SERPINE2 (rs6436459) and 2 SNPs of ADRB2 (rs1042717 and rs1042718). Conclusion: Some candidate genes in patients with severe COPD are correlated with the thickness of tracheal wall and the severity of emphysema showed by CT, suggesting that further research on the genetic correlation between emphysema phenotype and airway phenotype is necessary.

In the mechanism of bacterial resistance, pumping out transporters can expel antimicrobial drugs out of the cell before they act on the target, thereby enhancing resistance. The results showed that the high expression of AcrAB-TolC pump plays an important role in the mutation selection of drug-resistant Gram-negative bacteria. Therefore, the development of composite formulations of antimicrobial drugs and pump-out inhibitors has broad promise.

BACKGROUND AND OBJECTIVE: Mutations in the human gene encoding transmembrane conduction regulator (CFTR) of cystic fibrosis can cause cystic fibrosis. There are more than 1,000 mutations, and the most common mutation type Δ F508 accounts for 90%, which can lead to CFTR synthesis disorder; Another mutation, G551D, accounts for 4% ~5%, which can make the transmembrane ion channel CFTR difficult to open. The CFTR enhancer VX-770 can increase the in vitro activity of cell surface CFTR. The primary objective of this study was to evaluate the safety of VX-770 in patients with cystic fibrosis with the G551D mutation. Methods: Thirty-nine patients with cystic fibrosis with G551D-CFTR mutation were randomly divided into two parts: (1) a total of 4 groups, orally administered VX-770 25, 75, 150 mg or placebo, once in 12 hours, for 14 days; (2) A total of 3 groups were orally administered VX-770 150, 250 mg or placebo, once in 12 hours, for 28 days. Results: No subjects withdrew from the study at 28 days. In the group of subjects treated with 150 mg VX-770, the median change in nasal potential difference was-3.5 mV (P=0.02) and the median change in sweat chloride concentration was-59.5 mmol/L (P=0.008), FVE₁The median change from baseline was 8.7% (P＝0.008)。 Six adverse events occurred in 2 patients, one with diffuse macular rash and one with diabetes mellitus with 5 increases in blood and urine glucose. All adverse events resolved without discontinuation of VX-770. Conclusions: VX-770 was associated with CFTR and improved pulmonary function in subjects, suggesting that CFTR enhancers could treat some patients with cystic fibrosis.

BACKGROUND AND OBJECTIVES: A subpopulation of patients with non-small cell lung cancer (NSCLC) has an epidermal growth factor receptor gene mutation against which tyrosine kinase inhibitors (EGFR-TKI) are effective; Another subset of NSCLC has an oncogenic fusion gene consisting of EML4 and anaplastic lymphoma kinase (ALK) gene rearrangement, for which the efficacy of ALK-TKI is unclear. An early clinical trial of the ALK-TKI drug crizotinib explored the efficacy of inhibiting ALK in this subset of NSCLC. Methods: Nearly 1500 NSCLC specimens were screened for gene rearrangement, and 82 patients with advanced ALK-positive patients met the inclusion criteria and were included in the extended cohort study. Most of these patients had previous treatment. The recommended dose of crizotinib was 250 mg twice daily for a cycle of 28 days as determined by the Phase 1 dose escalation study, and patients were evaluated for adverse events and efficacy. Results: Patients with ALK gene rearrangement were younger than those without rearrangement, and all of them were adenocarcinoma, with almost no history of tobacco exposure. The average treatment was 6.4 months, the total effective rate was 57% (47/82), 46 cases had partial remission and 1 case had complete remission; 27 cases were in stable condition. Sixty-three patients continued to take crizotinib at the time of final data examination, and the estimated probability of 6-month progression-free survival was 72%. The drug caused only mild (grade 1 or 2) gastrointestinal adverse reactions. Conclusion: In NSCLC with ALK gene rearrangement, inhibition of ALK can shrink or stabilize the disease in most patients.

You will find it ridiculous when you see this question. Who doesn't know Professor Mu Kuijin, of course his surname is Mu. Actually, I asked Elder Mu this question before he was alive, and he told me that his surname was not Mu! Professor Mu Kuijin is a Manchu, the son of Tie Liang, an outstanding Manchu military talent (Minister of War). He belongs to the Xiangbai Banner of Manchuria, and his surname is "Murcha". After the Manchu people united China, the Manchu culture was quickly merged and assimilated by the Han culture. Many Manchu people changed their surnames to single surnames of Han nationality, and Professor Mu's ancestors changed their surnames to Mu. Of course, some Manchu people still retain their original surnames, such as Aixinjueluo Puyi, Aixinjueluo Pujie, etc.

In recent years, COPD has been paid attention by the global academic community of respiratory diseases, and many achievements have been made in the research of COPD in China. By consulting the literature published in major related journals at home and abroad in 2010, the author summarized the new progress of COPD in 2010 as follows.

COPD is a pulmonary inflammatory disease characterized by progressive airflow restriction and decreased pulmonary function. Due to impaired lung function, the ability of daily living in COPD patients decreased, and the hospitalization rate and mortality rate increased^[1]。 The incidence of COPD is increasing year by year, and it is expected that COPD will become the third cause of death in the world in 2020^[2]。 Long-term oxygen therapy and smoking cessation can improve the natural course of COPD and delay the decline of lung function^[3]However, bronchodilators and glucocorticoids commonly used in clinic cannot improve the long-term prognosis of COPD patients. Therefore, seeking effective therapeutic drugs for COPD has become the focus of respiratory disease research. Recent studies have shown that statins have anti-inflammatory, antioxidant, immunomodulatory and thrombosis inhibitory effects in addition to lipid-lowering effects, which can make them play an important role in the treatment of COPD patients^[4]。 The authors reviewed the clinical effectiveness and mechanism of action of statins in the treatment of COPD.

Bronchial asthma (abbreviated as asthma) is a chronic airway inflammatory disease, which is formed by the combination of genetic and environmental factors. The heritability of asthma is as high as 36% ~75%^[1]。 The global incidence of asthma is increasing year by year, especially among children. About 15 million people in China suffer from asthma. The prevalence rate of asthma among children in urban areas is 0.12% ~3.34%, and the national average is 1.54%^[2]。 Global costs for asthma exceed those for tuberculosis and AIDS combined^[3]。 Report on the Global Asthma Burden under the Global Asthma Initiative (GINA)^[4]Studies on the etiology of asthma and the efficacy of primary and secondary asthma interventions are two priority areas in the field of asthma research. At present, more than 100 candidate genes for asthma have been found through localization cloning, linkage analysis and genome-wide association studies, but less than 50% of the candidate genes have been associated in multiple ethnic groups^[5]。 Serum orosomucoid 1-like protein 3 (ORMDL3) was developed in 2007 by Moffatt et al^[6]A novel candidate gene for asthma has been identified for the first time in a genome-wide association study, and its association with asthma has been confirmed in multiple ethnic groups^{[7,8,9,10,11,12,13,14,15,16,17]}。 Understanding the relationship between ORMDL3 and asthma and its mechanism may provide a new direction for early diagnosis, treatment and primary prevention of asthma. The research progress of asthma susceptibility gene ORMDL3 is summarized as follows.

Smoking is a risk factor for many chronic diseases, and the harm of cigarette smoke to some chronic diseases (such as COPD, lung cancer and coronary heart disease) has been paid more and more attention^[1,2]Quitting smoking will become a primary preventive measure for certain diseases. Most smokers have nicotine dependence, and withdrawal symptoms such as irritability, dizziness, headache, insomnia and inattention can occur after quitting smoking^[3], resulting in a low success rate of smoking cessation. Therefore, we conducted a survey on the willingness and cognition of smokers to quit smoking in the respiratory specialist clinic of a large general hospital in Beijing, and studied the degree of nicotine dependence and attitude of smokers to quit smoking, so as to adopt more effective methods to quit smoking, reduce the occurrence of some diseases and achieve the purpose of primary prevention.

The occurrence of pulmonary tuberculosis is related to the imbalance of cellular immune function, and the balance of Th1/Th2 cellular response plays a decisive role in the progression, exacerbation, control and prevention of tuberculosis^[1]。 Vasoactive intestinal peptide (VIP) is involved in the regulation of immune self-stabilization by regulating Th cell differentiation and influencing the production of cytokines. This study aimed to investigate the expression of VIP in serum of pulmonary tuberculosis patients and its correlation with Th1-type cytokine gamma-interferon and Th2-type cytokine interleukin (IL) -4.

Germline mutations in serine/threonine kinase 11 (LKB1) can cause Peutz-Jeghers syndrome (PJS)^[1]。 PJS is an autosomal dominant disease, and the incidence of tumors is 10-18 times that of the general population^[2]。 The results show that LKB1 mutations are rare in sporadic tumors, but in non-small cell lung cancer (NSCLC), the mutation rate of LKB1 can reach 30%^[3,4,5]。 It has been reported in the literature that LKB1 can phosphorylate threonine at site 172 on the activation loop of AMP-activated protein kinase (AMPK) α subunit, thereby activating AMPK, and then activating its downstream target protein, finally inhibiting the activity of mammalian target of rapamycin (mTOR), inhibiting cell proliferation and inducing apoptosis^[6]。 It has been reported that the function of LKB1 in inducing apoptosis in fibrosarcoma cell line HT1080 and other cells is related to the function of P53 protein^[7]However, the relationship between P53 and LKB1 and AMPK is still unclear, so we have conducted a preliminary discussion on this problem, and the results are reported below.

Pleural effusion is more common in patients with lung cancer after pleural metastasis. The occurrence of malignant pleural effusion seriously affects the quality of life of patients and suggests poor prognosis^[1]。 The infiltration of tumor cells into pleura is the main cause of pleural effusion formation. matrix metalloproteinase-9 (MMP-9) is a proteolytic enzyme involved in angiogenesis, which can promote the migration and angiogenesis of endothelial cells, and plays an important role in the invasive growth and metastasis of tumors^[2]。 Endostatin is an endogenous anti-angiogenic substance, which can specifically act on microvascular endothelial cells, inhibit angiogenesis and tumor growth, and is considered to be one of the most effective endogenous angiogenic inhibitors^[3]。 They play different roles in the formation of malignant pleural effusion because they play antagonistic roles in tumor growth. In this study, the contents of MMP-9 and endostatin in 176 cases of pleural effusion caused by different causes were measured, and the results are reported below.

Bronchial pigmentation (anthracofibrosis) originally refers to coal silicosis, once known as "coal silicosis". It is a lung disease caused by long-term inhalation of coal dust and free silica rock dust. It is more common in miners with a long-term history of exposure to coal dust and rock dust. The earliest in China by Cai Hourong and others^[1]Translated as "bronchial anthracofibrosis", the patient has no clear history of dust exposure and smoking, which is more common in elderly women, and only a few cases have been reported in China. The disease was named by Chung et al. abroad, and it was suggested that it has unique clinical manifestations, pathological and imaging features and bronchoscopic manifestations; However, some scholars believe that this is a clinical syndrome related to endobronchial tuberculosis and active tuberculosis infection^[2]。 A typical case admitted to Wujiang First People's Hospital is reported to accumulate experience for the clinical manifestations, treatment and prognosis of such cases.

Since the 1960s, β-blockers have been widely used in various fields of clinical medicine, especially in the prevention and treatment of cardiovascular diseases^[1]。 However, because β-blockers may cause bronchospasm, they have been rarely used to treat bronchial asthma (asthma for short) and COPD patients for a long time, and even considered as contraindications for asthma and COPD. At present, this view has been questioned. Some scholars believe that β-blockers are safe for COPD patients, especially beneficial for COPD patients with cardiovascular diseases. Some scholars even believe that beta-blockers are not only contraindicated for asthma patients, but may also have therapeutic effects. Whether β-blockers can be used for airway obstructive diseases such as asthma and COPD has gradually become a hot topic and the focus of debate among respiratory doctors.

According to the 2008 report of the World Health Organization (WHO), the total number of smokers worldwide is about 1.3 billion, accounting for about a quarter of the world's population, and more than 5 million people die from smoking-related diseases every year^[1]。 Six of the world's top 8 fatal diseases (ischemic heart disease, cerebrovascular disease, lower respiratory tract infection, COPD, tuberculosis and lung cancer) are associated with smoking^[1]。 Clinicians should integrate the treatment of tobacco use and dependence into their daily clinical practice, so that every smoker can receive effective smoking cessation treatment at the time of consultation^[2]。 Doctors should realize that smoking addiction is not a behavioral habit but a chronic disease that requires repeated intervention and repeated attempts to quit smoking^[2]。

The 10th Beijing Young Respiratory Scholars Salon was held on December 30th, 2010. The theme of this salon was "ICU-Challenges Faced by Respiratory Physicians". It was hosted by Dr. Shen Ning from the Department of Respiratory Sciences of Peking University Third Hospital.

In this editor-in-chief's essay column, editor-in-chief Liu Youning told young doctors the importance of laying basic skills by learning to recognize respiratory pericardial friction sounds when he was a resident. Professor Liu has been a resident doctor for 10 years and has rotated in several departments. This seemingly time-wasting experience has benefited him a lot. He told us with decades of insight: "Only when the foundation is played big and firmly can we have greater development"; "Medical history collection, physical examination and medical record writing should never be underestimated or vague, which is an important basic skill to reflect and evaluate the quality of doctors". The ancients said: If you don't accumulate small steps, you can't reach a thousand miles; If you don't accumulate small streams, you can't make rivers and seas. This article also enlightens us: we should be down-to-earth when looking up at the stars. Only by laying a solid foundation can we climb to the top of medicine step by step.