2016年 · 第39卷第08期

In this hot midsummer season, the 8th issue of this magazine in 2016 meets you readers!

I have a monograph in my hand signed by the writing group of "Differential Diagnosis of Internal Diseases" of Sun Yat-sen Medical College at that time, and published by People's Medical Publishing House in March 1976. This book has been with me for 40 years. Whenever I encounter problems related to differential diagnosis, I always consult it. Sometimes, even before being invited to a consultation, I will "arm" my mind with it. Worried that reading too much would turn the book "rotten", I also specially asked someone to make a cardboard cloth cover, which turned the simple cover into a "hardcover". The reason why I value and care for this book so much is that it has really helped me a lot and contributed greatly to the growth of my clinical knowledge. For 40 years since this book, I have not found a more practical book on differential diagnosis.

Sleep-related hypoventilation disorders (SRHD) are a series of respiratory diseases that mainly occur during sleep and have decreased alveolar ventilation function as pathophysiological changes. In 2014, SRHD was officially named as a new classification of sleep disorders and included in the 3rd edition of the International Classification of Sleep Disorders^[1]。 Although the clinical diagnosis and treatment of hypopnea has been carried out for many years, it is the first time that it is classified as an independent sleep respiratory disease, and the relevant concepts have not yet appeared in previously published respiratory monographs and textbooks. This new classification greatly expands the coverage of sleep respiratory diseases, making respiratory diseases and sleep respiratory diseases more systematic and perfect. The etiology of SRHD is complex and involves a variety of diseases including respiratory diseases and other systemic diseases. SRHD initially occurs only during sleep and can be an early stage of hypoventilatory disease, progressing to daytime hypoventilatory disease, or even chronic respiratory failure. Sleep hypopnea exists in all daytime hypopnea diseases, and rapid eye movement sleep phase CO₂Retention occurs earliest and is most severe. In the case of upper respiratory tract infection and/or surgical anesthesia, SRHD can rapidly exacerbate and progress to acute respiratory failure, even leading to coma and life-threatening patients. From this perspective, the development of clinical work of SRHD is also a advance in the diagnosis and treatment of respiratory failure, which can be detected and treated as soon as possible to avoid the progression of the disease and the occurrence of multiple complications. This kind of disease affects a large number of patients and is harmful to health, but it is still poorly understood. It is a kind of disease worthy of special attention by clinicians, especially those specializing in respiratory, critical care and sleep.

With the development of sleep medicine, sleep-related hypopnea disorders are getting more and more attention. In the newly released International Sleep Disorders 3rd Edition (ICSD-3) in 2014, sleep-related hypopnea diseases are divided into six categories: obesity hypopnea syndrome, congenital central alveolar hypopnea syndrome, delayed central hypopnea with hypothalamic dysfunction, idiopathic central alveolar hypopnea, drug or toxic sleep hypopnea, and disease-related sleep hypopnea, among which disease-related sleep hypopnea is the most common in respiratory and critical care departments, and refers to diseases with underlying diseases accompanied by hypopnea during sleep as clinical features, including obstructive ventilatory dysfunction, restrictive ventilatory dysfunction, and poor ventilation caused by neuromuscular diseases caused by different causes.

With the popularization of standardized treatment strategies for acute and chronic pain and the improvement of people's requirements for quality of life, the application of opioids and sedative and hypnotic drugs is increasingly widespread^[1]Related side effects are also valued, especially their effects on breathing during sleep. Long-term use of these drugs is associated with the incidence of sleep disorder of breathing (SDB) and related mortality^[2,3]And the increased risk of sudden sleep death was associated with the frequency and duration of application. Opioids and sedative and hypnotic drugs can cause obstructive sleep apnea (OSA) and drug-induced central sleep apnea (CSA)^[4]In addition, it can also cause hypopnea during sleep^[5]。 Sleep-related hypoventilation due to a medication or substance is defined as insufficient alveolar ventilation during sleep caused by drugs or substances, resulting in hypercapnia, but underlying diseases such as neuromuscular diseases and lung parenchymal lesions should be excluded.

Idiopathic alveolar hypoventilation is a rare disease, mainly manifested by the decrease of respiratory central drive, causing insufficient alveolar ventilation, causing hypoxia and CO in the body₂A series of pathophysiological changes such as retention. At present, most of the studies on idiopathic alveolar hypopnea at home and abroad are case reports, but there is a lack of systematic research, and there is a general problem of insufficient understanding of this disease^[1]。 The results show that the disease has certain genetic characteristics, and there have been reported cases of monozygotic twin, sister and sibling^[2]。 Although idiopathic alveolar hypopnea is common in infants and young children and leads to premature death, a small number of patients are not diagnosed until adulthood^[3,4]。 Diagnosis is often established by exclusion. Since all links involved in ventilation can lead to alveolar hypoventilation, cortex, brainstem, respiratory muscles and related neuropathies must be excluded. Respiratory and pulmonary diseases include chronic obstructive pulmonary disease (COPD), bronchial asthma (asthma) and thoracic disease. Some neuromuscular diseases that can involve respiratory muscles, such as myasthenia gravis and motor neuron diseases, should also be ruled out. Organic brainstem lesions can be diagnosed by CT and MRI. The abnormal function of respiratory muscle and its innervated nerves can be evaluated by respiratory muscle function examination, including maximum inspiratory pressure, transdiaphragmatic pressure, maximum diaphragmatic electromyography, and trembling transdiaphragmatic pressure induced by super-stimulation of phrenic nerve^[5,6,7]。 Chest X-ray or chest CT, lung function and other tests can help the diagnosis of lung diseases such as COPD and asthma and thoracic lesions. Long-term hypoxia can lead to polycythemia, pulmonary hypertension and pulmonary heart disease. Some patients may have sudden syncope and pulmonary hypertension as the main manifestations, and comprehensive examinations including cranial MRI, blood gas, respiratory muscle function examination and sleep multi-map examination should be performed to correctly diagnose this rare disease.

obesity hypoventilation syndrome (OHS) is one of the serious complications of morbid obesity. OHS is defined as obesity (BMI ≥30 kg/m²) and awake carbon dioxide retention (PaCO₂≥45 mmHg, 1 mmHg =0.133 kPa), and other diseases causing hypercapnia were excluded, such as severe obstructive airway disease, interstitial lung disease, chest wall disease, hypothyroidism, neuromuscular disease, and congenital central alveolar hypopnea syndrome. About 90% of patients with OHS also have obstructive sleep apnea (OSA).

In recent years, with the rapid development and popularization of respiratory endoscopic diagnosis and treatment technology in China, various new diagnosis and treatment technologies have emerged constantly, which has become an important diagnosis and treatment method in the diagnosis and treatment of respiratory diseases. With the increasing number of people receiving respiratory endoscopy and the extensive development of various treatment techniques, the incidence of massive hemorrhage related to bronchoscopy in clinical work also increases, and it has become the most important cause of death caused by bronchoscopy. At present, due to the differences in diagnosis and treatment facilities, operation level and clinical experience of various medical institutions, there are great differences in the degree of understanding and treatment ability of this problem. At the same time, there is still a lack of standardized treatment plans and guidelines for the prevention and treatment of massive hemorrhage related to bronchoscopy in the world.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases of respiratory system. In recent years, its morbidity and mortality are increasing year by year, and it has become a major public health problem that endangers human health and increases social and economic burden^[1,2]。 The pathogenesis of COPD is closely related to inflammation and oxidative stress. At present, it is generally believed that tobacco smoke exposure (including active smoking and passive smoking) is an important pathogenic factor of COPD, and harmful smoke particles and gases in tobacco smoke can lead to inflammation and oxidative stress in lung tissue^[3,4,5,6]。 However, inflammation and oxidative stress are closely related to the regulation of NF-κ B and MAPK^[7,8,9]。

When the body is stimulated, the sympathetic nerves that innervate the adrenal medulla are excited and release acetylcholine. acetylcholine activates nicotinic acetylcholine receptors (nAChRs) of adrenal medullary chromafiin cells (AMCCs), and then activates calcium channels, causing the increase of intracellular calcium ion concentration to trigger the release of catecholamines (epinephrine, norepinephrine, etc.). Compared with normal mice, the composition of nAChRs in the adrenal medulla of bronchial asthma (asthma) mice was altered, i.e., the expression of α 3, α 4, α 7 and β 4 subunit mRNA was increased. We hypothesized that the altered composition of nAChRs subunits in asthmatic mice may be involved in the regulation of adrenaline release from AMCCs.

unilateral absence of pulmonary artery (UAPA) is a very rare congenital pulmonary vascular malformation, which mostly occurs on the right side, and it is even rarer to occur on the left side. A case of left pulmonary artery absence combined with right pulmonary artery embolism and systemic lupus erythematosus admitted to our hospital is reported below.

A 37-year-old male was admitted to hospital in September 2015 due to "recurrent abdominal pain for 16 years, intermittent swelling of the right lower limb for 10 years, and hemoptysis for 2 years". In 1999, the patient suffered from periumbilical pain, and the gastrointestinal decompression drainage fluid was soy sauce color. He was considered "mesenteric venous thrombosis", and the abdominal pain was relieved after intravenous urokinase thrombolysis. In 2005, the patient's right lower limb was swollen, which was concave, and the swelling resolved spontaneously after 2 weeks. In April 2006, he had sudden dyspnea with transient syncope. Color Doppler ultrasound of blood vessels in both lower limbs showed "old thrombosis of femoral vein, popliteal vein and calf vein". He started warfarin treatment and stopped taking drugs on his own 2 years later. In September 2009, he suffered from sudden abdominal pain again. An exploratory laparotomy was performed in the emergency department, and necrosis of the small intestine was found. Part of the small intestine (about 1 m) was removed, and the abdominal pain was relieved after the operation and he was discharged. After discharge, the patient took aspirin 0.3 g/d intermittently for half a year. In November 2009, the patient had repeated ulcers and crusts in the right lower limb, which gradually spread from the pretibia to the entire right calf, and the skin color gradually changed: redness, swelling, red-purple, purple-black progressed to black crusts, without intermittent claudication, which was not paid attention to. In January 2013, the patient had sudden hemoptysis, which was 200-300 ml of brown liquid, blood pressure 130/80 mmHg (1 mmHg =0.133 kPa) and heart rate 90 beats/min. Hemoglobin 132 g/L, platelet count 71.0×10⁹/L, D-dimer 9.99 mg/L. Chest CT showed ground glass and flocculate density increased shadows of the right lung and the lower lobe of the left lung. CT pulmonary angiography (CTPA): The lumen of the trunk of the pulmonary artery was thickened, about 4.0 cm, and there was no obvious development in the branch of the right lower pulmonary artery, and a punctate filling defect was seen in the branch of the left lower pulmonary artery. Arteriovenous color Doppler ultrasound of both lower limbs: medium and low echoes can be seen in the deep veins of the right lower limb, considering thrombosis. Warfarin 3.75 mg/d was given and the patient spontaneously discontinued after 1 month. Hemoptysis occurred again in August 2015, volume approximately 600 ml, hemoglobin 163 g/L, platelet count 90.0×10⁹/L, D-dimer 0.722 mg/L. CTPA: The main pulmonary artery was widened, and a small filling defect was seen in the left lower pulmonary artery. Cardiac ultrasound: Widening of the aortopulmonary artery and reduced left ventricular compliance. He was diagnosed as pulmonary embolism and was given low molecular weight heparin 6 000 U, 12 h/time, subcutaneous injection, but the patient stopped the drug again and came to our hospital for treatment. Past history: fatty liver. Family history: denial of similar thrombus patients. One sister suffers from "varicose veins in both lower limbs". Physical examination at admission: blood pressure 137/93 mmHg, heart rate 90 beats/min, blood oxygen saturation 95% in natural state. The breathing sounds of both lungs were coarse, the heart rhythm was uniform, the abdomen was soft, no tenderness, the dorsal arteries of both feet pulsed symmetrically, the skin of the right calf became dark and hard, the circumference of the right calf was 41 cm, and the circumference of the left calf was 39 cm.

obstructive sleep apnea (OSA) is characterized by repeated upper airway collapse during sleep leading to apnea and/or hypopnea, resulting in intermittent hypoxia, manifested by decreased blood oxygen saturation and disordered sleep structure, resulting in relative sleep deprivation and daytime fatigue. It has become a prominent public health problem because of its high prevalence and easy complication of serious diseases such as diabetes, hypertension, coronary heart disease, stroke, cognitive function and metabolic dysfunction. On the other hand, bronchial asthma (asthma) is a complex syndrome with multiple clinical phenotypes. It is a chronic inflammatory disease of the airway involving a variety of cells (eosinophils, mast cells, lymphocytes, neutrophils, airway epithelial cells, etc.) and cellular components, causing recurrent symptoms such as wheezing, dyspnea, chest tightness, and cough. Both OSA and asthma are common diseases associated with airway obstruction, and in 1979 Hudgel and Shucard^[1]The coexistence of OSA and asthma was first proposed in the form of a case report. Subsequently, it has been reported in the literature that OSA and asthma are closely related in many aspects, and the pathophysiological mechanisms of these two diseases overlap to a great extent. For example, airway obstruction, inflammation, obesity, gastroesophageal reflux, allergic rhinitis and other factors are closely related to the development of the two diseases, and can promote the progression of the disease. Combined with OSA will make asthma difficult to control, and combined with asthma will lead to aggravation of OSA hypoxia, which is more likely to secondary cardiovascular and cerebrovascular diseases and pulmonary hypertension. Although the association between OSA and asthma is common, there are few systematic studies in this area, especially the epidemiological and pathophysiological mechanisms. The relationship between OSA and asthma and its clinical significance are reviewed.

Sarcoidosis is a granulomatous disease with unclear etiology and pathogenesis. Pulmonary involvement is the most common, followed by intrathoracic lymph nodes. The skin, heart and nervous system are also the most common sites^[1]。 Non-caseous necrotizing granuloma is a typical pathological change of sarcoidosis. It is formed by a large number of epithelial cells and polymorphonuclear giant cells surrounding lymphocytes. The etiology and pathogenesis of non-caseous necrotizing granuloma are unknown. In recent years, the literature has reported the presence of a locally active immune response in the affected organs of sarcoidosis patients, and CD has been found in patients with lung involvement BALF₄⁺/CD₈⁺The phenomenon of increased cell ratio suggests the important role of immune response in the pathogenesis of sarcoidosis. With the progress of molecular biology and clinical diagnosis and treatment, people have a deeper understanding of the immune response and immune regulation abnormalities in sarcoidosis. This article will summarize the research progress of immune aspects of sarcoidosis as follows.

epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a milestone in the field of lung cancer treatment. It prolongs the progression free survival (PFS) and improves the quality of life of non-small cell lung cancer (NSCLC) patients with EGFR-sensitive mutations. However, EGFR-TKI resistance is inevitable and mostly occurs around 10 months after medication^[1], drug resistance has become a bottleneck limiting the clinical application of TKI.

In recent years, the morbidity and mortality of bronchial asthma (asthma) have been increasing in different countries and regions^[1]Moreover, the incidence rate in urban areas is significantly higher than that in rural areas^[2]。 Asthma, characterized by chronic airway inflammation, is gradually becoming a major disease in most industrialized countries^[3]。 Asthma affects nearly 300 million people worldwide, and more than 100 million people are expected to be diagnosed by 2025^[1]。 At present, the results of studies have confirmed that the lower respiratory tract is not a completely sterile environment, and there are a large number of microbial flora in it^[4,5]。 When chronic airway inflammatory diseases, including asthma, appear, the species and quantity of lower respiratory flora can be greatly changed^[4]Airway microbiota may play an important role in the occurrence and development of asthma. Asthma is a heterogeneous disease, which often manifests in a series of different clinical phenotypes and inflammatory phenotypes. Recently, many studies have expounded the relationship between microbiota and inflammatory phenotype of asthma from different aspects. The role of microbiota in the inflammatory phenotype of asthma is reviewed below.

extravascular lung water (EVLW) refers to fluid distributed outside the pulmonary blood vessels (i.e., the amount of water contained in the lungs). EVLW can be increased by increased pulmonary vascular filtration (caused by factors such as intracapillary hydrostatic pressure, pulmonary interstitial hydrostatic pressure, intracapillary colloidal osmotic pressure and pulmonary interstitial colloidal osmotic pressure) or decreased fluid discharge. EVLW consists of intraalveolar fluid, intracellular fluid, and pulmonary interstitial fluid. During normal intrapulmonary tissue fluid circulation, due to less changes in intracellular fluid, pulmonary interstitial and intraalveolar fluid reflect the degree of extravascular pulmonary water^[1,2,3]。 Monitoring EVLW is the most direct and quantifiable index reflecting the degree of pulmonary edema. Under normal circumstances, EVLW should<7 ml/kg (3~7 ml/kg). If it exceeds 7 ml/kg, it indicates that the patient has pulmonary edema^[4,5]。

A 23-year-old female was admitted to the hospital mainly for "cough for 6 months, asthma for 4 months, and blood in sputum for 3 months". One month ago, the patient underwent chest CT examination in the local hospital and found tracheal and bronchial lesions with obvious enlargement and fusion of mediastinal lymph nodes, and the boundary with the esophageal wall was unclear, so he came to our hospital. Bronchoscopy in the outpatient clinic showed carina, bilateral main bronchial mass and stenosis. Admission physical examination: body temperature 36.6℃, pulse rate 80 beats/min, respiratory rate 20 beats/min, blood pressure 104/78 mmHg (1 mmHg =0.133 kPa), clear consciousness, weak spirit, no cyanosis of the lips, centered trachea, a small amount of wheezing sound in the larynx, reduced breathing sound in both lungs, snoring sound, strong heart sound, harmonic heart rhythm, heart rate 80 beats/min, no pathological murmur, flat and soft abdomen, no tenderness and rebound pain, and no edema in both lower limbs. Auxiliary examination: Except for chest CT and bronchoscopy, other examinations are not special.

The second activity of Beijing Young Respiratory Scholars Salon in 2016 was held in Chinese Medical Association on March 31, 2016. The clinical application of extracorporeal membrane oxygenation (ECMO) technology in severe respiratory failure was mainly discussed. This salon activity was hosted by Chief Physician Zhan Qingyuan of China-Japan Friendship Hospital.

The 15th Respiratory Week Conference and the 2nd China Respiratory Leadership Forum were grandly held in Shenzhen on May 21, 2016. With the theme of "Joint Efforts and Win-Win-Creating a New Model of Respiratory Chronic Disease Management", this conference aims to build a professional, cutting-edge and clinical practical international academic exchange platform for clinicians in the field of respiratory diseases in China, and at the same time, build a new model of respiratory chronic disease management based on cooperation, and jointly promote the process of "whole-process management" of respiratory diseases, so as to improve the prevention and treatment of respiratory diseases in China.