2017年 · 第40卷第03期

Most of the scientific and technological cadres in the People's Liberation Army graduated from military academies, and a small number of them were "specially recruited" to join the army after graduating from local academies, but they are all relatively young. There are very few people like me who only put on military uniforms when they are nearly 40 years old, and it can also be said that they "joined the army halfway".

bronchial thermoplasty (BT) is a new non-drug treatment for bronchial asthma^[1]。 In 2010, the U.S. Food and Drug Administration (FDA) approved BT for the treatment of patients over 18 years old with severe persistent asthma who still cannot effectively control their symptoms with inhaled glucocorticoids and long-acting beta-agonists. In 2011, the clinical use of BT was approved in Europe. At the end of 2013, China's Food and Drug Administration (CFDA) also officially approved the application of this technology in clinical practice^[2]。

Initiated and led by Professor McEvoy of Australia, the 7-year international multicenter sleep apnea cardiovascular endpoints (SAVE) study was concluded in June 2016, and the research results were subsequently published in Issue 10 of 2016N Engl J MedUpper^[1]。 This is by far the largest, largest number of participating countries and centers, and longest observation time in the world. The multicenter clinical study on the effect of non-invasive continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA) on the prevention and treatment of cardiovascular diseases is also the first published inN Engl J MedStudies of the same kind. The SAVE study is a major international project in the field of sleep apnea and a major event in the field of sleep respiratory diseases in China, because 1,714 of the 2,717 patients included in the study were from China, accounting for about two-thirds of the number of cases. Under the direct organization and leadership of Academician Zhong Nanshan, researchers in the field of sleep respiration in China participated in the whole process of SAVE research, including topic design, scheme formulation, quality control, data collection, statistical processing and final paper writing. The publication of this research result once again proves that Chinese doctors have the ability to participate in high-level international multi-center clinical research, and have high clinical research quality and potential.

Issue 10, 2016N Engl J MedThe results of the study of cardiovascular events in patients with sleep apnea treated with continuous positive airway pressure (CPAP) (SAVE) and their corresponding expert reviews were published^[1,2]It has aroused great concern in the medical community. The SAVE study is an international multicenter, open, parallel, prospective randomized controlled trial. The purpose is to observe whether CPAP treatment can reduce the recurrence rate and mortality rate of cardiovascular and cerebrovascular diseases in patients with moderate to severe obstructive sleep apnea (OSA) complicated with cardiovascular and cerebrovascular diseases on the basis of conventional treatment. It is a landmark clinical study of sleep medicine. The enrolled patients came from 7 countries and 89 clinical centers in Asia, America and Europe. A total of 2 717 patients were enrolled, of which 63% were from China. After 8 years of clinical observation, the results showed that CPAP treatment could not effectively prevent the recurrence of cardiovascular and cerebrovascular events in OSA patients.

The results of the Obstructive Sleep Apnea (OSA) Cardiovascular Endpoint Event Study (SAVE) were published in Issue 10, 2016 inN Engl J MedPublication^[1]The study included 2 717 patients from 89 sites in 7 countries, of which nearly 60% of the subjects were from 47 hospitals in China. Eight of the top 10 sites with the most patients enrolled were from China, including the site with the most patients enrolled. Chinese scholars who participated in this research made great contributions and played a key role in the success of this project.

Bronchial asthma (asthma) is a common respiratory disease characterized by reversible airflow restriction. There are more than 300 million patients worldwide, and there are more than 30 million asthma patients in China, of whom about 5% to 10% are severe asthma. Currently, commonly used drugs for the treatment of asthma include glucocorticoids, beta₂-Receptor agonists, theophyllines, leukotriene modulators and anticholinergic drugs cannot reverse the airway remodeling caused by asthma, nor can they fundamentally prevent the prolongation and deterioration of severe asthma patients^[1,2]。

programmed death receptor 1 (PD-1) is a co-inhibitory receptor mainly expressed on the surface of activated T cells and B cells^[1]。 programmed death ligand-1 (PD-L1) is the most dominant ligand of PD-1, and its expression is upregulated in many solid tumors^[2,3,4]。 The combination of PD-1 and PD-L1 can mediate negative immunomodulatory response, which is one of the important ways for tumors to evade autoimmunity^[5]。 Mounting evidence suggests that PD-L1 expression is associated with mutations in oncogenes^[6]。 epidermal growth factor receptor (EGFR) belongs to the tyrosine kinase receptor family and is one of the most common mutant genes in non-small cell lung cancer (NSCLC). When EGFR binds to its ligand, it can autophosphorylate tyrosine residues by dimerization^[7]。 The results showed that EGFR plays an important role in tumor proliferation, invasion and metastasis^[8]。 The correlation between PD-1/PD-L1 and EGFR in NSCLC is reviewed as follows.

Pulmonary hypertension, defined as mean pulmonary arterial pressure ≥25 mmHg (1 mmHg =0.133 kPa) measured at sea level, resting, right cardiac catheter, is a hemodynamic abnormal condition characterized by progressive increases in pulmonary vascular resistance^[1]。 pulmonary artery hypertension (PAH) is the first major type of pulmonary artery hypertension. It has a characteristic pulmonary artery disease, involving pulmonary arterioles. The main pathophysiological changes include intima proliferation and fibrosis, media hypertrophy, adventitia thickening, etc^[2]Causing increased pulmonary vascular resistance and restricted blood flow, which eventually leads to right ventricular insufficiency or even death.

obstructive sleep apnea syndrome (OSA) is a sleep disorder respiratory disease characterized by recurrent upper airway collapse leading to disappearance of oral and nasal airflow, namely apnea, decreased oxygen saturation and disordered sleep structure. The clinical manifestations of OSA patients are mainly daytime sleepiness, inability to concentrate, headache in the morning, snoring during sleep and arrest of sleep breathing airflow. The key pathophysiological mechanism of its pathogenesis is the recurrent episodes of intermittent hypoxia caused by apnea. The results indicate that OSA can lead to multiple systemic complications, such as cardiovascular diseases, endocrine and metabolic disorders, urogenital dysfunction and cognitive dysfunction^{[1,2,3,4,5,6,7,8]}Therefore, it has been recognized as a systemic disease at present. In recent years, the association between OSA and tumor has entered the field of vision of domestic and foreign researchers. Since 2012, many epidemiological studies on OSA and tumors have emerged. These studies have shown that OSA patients are more likely to suffer from tumors than normal people, and the mortality rate of OSA patients is also higher than that of patients with simple tumors. At the same time, a large number of studies based on OSA model intermittent hypoxia animal models also confirmed that OSA can improve the proliferation and invasion ability of various types of solid tumors. So what is the relationship between OSA and tumor and the occurrence and development of tumor, and what mechanism affects the occurrence and development of tumor. This article will explain the influence of epidemiology and related mechanisms on the development of OSA and tumor.

Aspergillus is widely distributed in nature, and Aspergillus fumigatus, Aspergillus flavus, Aspergillus terrestris and Aspergillus niger can infect humans and animals. Aspergillus spores are only 2~3 μ m in diameter and can spread in the air and enter the terminal airway. After human inhalation of Aspergillus spores, Aspergillus can cause sensitization and infection and colonize the airways. Invasive pulmonary aspergillosis (IPA) can be caused when the body's immune function is low^[1]。

Inhaled glucocorticoids can quickly and effectively alleviate the acute onset of bronchial asthma (asthma), but the specific mechanism has not been fully elucidated. In recent years, a large number of studies have shown that osteopontin, as a new pro-inflammatory factor, mediates the occurrence and development of chronic airway inflammation and is involved in early airway remodeling in asthma. vascular endothelial growth factor (VEGF) is involved in the regulation of angiogenesis. During asthma attack, VEGF mediates airway inflammation and remodeling by regulating the production of adhesion protein in airway smooth muscle cells and the regeneration of blood vessels, and the two promote each other, accelerating the process of airway remodeling in respiratory inflammation^[1,2]。 The purpose of this study was to investigate whether budesonide can alleviate early inflammation and airway remodeling in asthma by reducing the expression of osteopontin and VEGF in lung tissue of asthmatic mouse models.

Airway remodeling plays an important role in the disease outcome of bronchial asthma (asthma) and is therefore receiving increasing attention. The phenomenon of epithelial-mesenchymal transition (EMT) exists in the airway tissue of asthmatic patients, that is, epithelial cells lose epithelial cell characteristics (such as E-cadherin), and acquire mesenchymal cell characteristics such as vimentin and α-smooth muscle actin (α-SMA)^[1]。 The change of EMT in airway epithelial cells is an early change of airway remodeling, so exploring the related mechanism of EMT in asthmatic airway epithelial cells is beneficial to early prevention and treatment of airway remodeling. The results of animal experiments show that house dust mite extracets (HDM) can cause EMT in airway epithelium and participate in airway remodeling in asthma^[2]However, due to the influence of environmental receptor nerve, humoral regulation and other factors in vivo, it is impossible to clarify the direct relationship between HDM and epithelial EMT. In this paper, the effects of allergens on the EMT process of asthma were observed by stimulating human bronchial epithelial cells 16-HBE with HDM in vitro.

Recently, the problems of an asthmatic patient and a respiratory doctor have attracted the author's attention.

The "Guidelines for the Diagnosis and Treatment of Cough (2015)" was published in May 2016. The new version of the guidelines revises the 2009 version of the guidelines and uses an evidence-based medicine approach to grade the quality of evidence and strength of recommendations. In studying the new version of the guidelines, we noticed that the recommended diagnostic criteria for cough variant asthma (CVA) are: (1) chronic cough, often accompanied by significant nocturnal irritating cough; (2) positive bronchial challenge test, or peak expiratory flow (PEF) mean variation rate>10%, or positive bronchodilation test; (3) Anti-bronchial asthma (asthma) treatment is effective. Recommended Level 1A^[1]。 In the 2009 edition of the guidelines, the diagnostic criteria of CVA are as follows: (1) chronic cough, often accompanied by obvious nocturnal irritating cough; (2) Positive bronchial challenge test, or PEF day-to-day variation rate>20%, or positive bronchodilation test; (3) Bronchodilator therapy is effective^[2]。 As a special type of asthma, the diagnostic criteria of CVA should be consistent with those of asthma. China's asthma prevention and treatment guidelines have not been revised in recent years, and the Global Asthma Prevention and Treatment Initiative (GINA) is updated every year. Among them, the change of PEF variation rate, which is a diagnostic criterion for asthma, from 20% to 10%, occurred three years ago. GINA clearly pointed out that this revision was based on the "ATS/ERS Asthma Clinical Trial Standards" published in 2009, which pointed out that the upper limit of the average PEF variation rate in healthy adults is 9%^[3]。

"Guidelines for the Diagnosis and Treatment of Cough (2015)" was officially released in the Chinese Journal of Tuberculosis and Respiration, Volume 39, Issue 5, 2016. Dr. Wu Wei raised questions about the adjustment of peak expiratory flow variation rate in the diagnostic criteria of cough variant asthma. The letter raised questions about the basis and application of adjusting peak expiratory flow (PEF) variation rate in the cough guidelines. We greatly appreciate readers' interest in this guide and respond to relevant questions below.

A 50-year-old female was admitted to the hospital on January 22, 2016 due to "chronic cough and sputum for 2 years, aggravated for 2 weeks". The patient has intermittently coughed and coughed up sputum for 2 years, coughed up white sputum and was easy to cough up. Two weeks ago, due to the aggravation of cough and expectoration after "cold", it was still white phlegm, without fever and dyspnea. CT of the chest in the outer hospital showed stenosis of the bronchial opening in the left upper lobe, increased transparency of the left upper lung, and atelectasis in the lower tongue segment of the left lower lobe (Figure 1、Figure 2、Figure 3)。 Bronchoscopy showed that the granulation tissue in the left upper lobe bronchial opening proliferated and blocked most of the lumen. After cleaning the granulation, a foreign body was seen in the inferior tongue segment of the left lingual lobe. The attempt to remove it failed, so it was transferred to our hospital for further treatment. The patient denied history of foreign body inhalation. Has had allergic rhinitis for 4 years in the past, does not smoke, denies history of chest surgery. Physical examination: No abnormalities in heart and lung.

A 60-year-old female was admitted to the hospital on 3 December 2015 due to "dry cough for 15 d, aggravated for 2 d". The patient developed paroxysmal cough without obvious trigger 15 days ago, no expectoration, no chest tightness and shortness of breath, no low fever and night sweats, no hemoptysis and chest pain, no nausea and vomiting, no dizziness and headache, which was not paid attention to at that time and was not diagnosed and treated. 2 days ago, the cough was aggravated, so I came to our hospital for treatment. Chest CT showed: multiple nodules in both lungs, with clear boundaries, no burrs and lobes, with a diameter of 2~25 mm, mainly distributed in the upper lobes of both lungs, and a thin-walled cavity was seen in the nodule in the medial segment of the middle lobe of the right lung (Figure 1，Figure 2), was admitted to the hospital with "Multiple nodules in both lungs: metastases?" The patient had a history of uterine fibroid surgery 20 years ago. History of type 2 diabetes for 7 years. Physical examination: body temperature 36.3 ℃, pulse 72 beats/min, blood pressure 126/90 mmHg (1 mmHg =0.133 kPa), respiratory rate 18 beats/min, oxygen saturation (natural state) 98%, unpalpable swelling of cervical and supraclavicular lymph nodes, coarse respiratory sounds in both lungs, and no dry and wet rales. Confident and nervous system examination was negative. Auxiliary examination after admission: Blood routine showed that white blood cells were 6.4×10⁹/L, 0.45 for neutrophils, 153 g/L for hemoglobin and 145×10 for platelets⁹/L. C-reactive protein was 17.1 mg/L. The ESR was 53 mm/1 h. Antinuclear antibody (ANA), anti-dsDNA, and anti-neutrophil cytoplasmic antibody (ANCA) were negative. Sputum bacterial smear culture, fungal smear culture and acid-fast bacilli staining were all negative. The liver and kidney function and blood lipids were normal, fasting blood glucose was 9.83 mmol/L, and neuron specific enolase (NSE) was 65.75 μ g/L (normal reference value: ≤17 μ g/L). PPD test negative. The quantitative detection of β-D-glucan in peripheral blood (G test) was 30.93 ng/L (normal reference value: 0-60 ng/L), and the latex agglutination test of Cryptococcus capsular polysaccharide antigen was negative. Enhanced chest CT showed nodular high-density shadows of different sizes in both lungs, and small patches of low-density shadows were seen in the nodules in the medial segment of the middle lobe of the right lung. After enhancement, the nodules were slightly enhanced, and no enlarged lymph nodes were seen. PET-CT showed multiple nodules of different sizes scattered in both lungs (Figure 3，Figure 4), some nodules showed cavity and slightly increased FDG metabolism (SUVmax 0.95-1.23). No obvious abnormalities were found in gastroscopy and colonoscopy. Ultrasound bronchoscopy + virtual navigation (EBUS-GS) detected a 12.5 mm ×11.9 mm hypoechoic nodule in the medial segment of the right middle lobe, with slightly uneven internal echo. Pathology of transbronchoscopic lung biopsy (TBLB): a few chronic inflammation of the lung tissue.

In this issue, please focus on the "Bronchial Thermoplasty Operation and Perioperative Management Standards" published in the "Diagnosis and Treatment Plan" column. Bronchial thermoplasty (BT) is a new non-pharmacological treatment for bronchial asthma (asthma). At the end of 2013, my country's Food and Drug Administration (CFDA) officially approved the clinical application of this technology. After more than two years, dozens of medical institutions in China have carried out BT projects, accumulating nearly 300 cases. Judging from the number of operations alone, China has ranked second in the world, and the growth rate of cases ranks first in the world.