2016年 · 第39卷第11期

Glucocorticoids (hormones) are very important clinical drugs, and their value in the treatment of autoimmune diseases and so on is irreplaceable. Respiratory doctors also often use hormones to treat bronchial asthma, acute COPD, eosinophilic pulmonary infiltration, certain vasculitis, and cryptogenic organizing pneumonia (COP). On the other hand, long-term and large-scale use of hormones will also bring many serious adverse reactions, such as hypertension, hyperglycemia, electrolyte disorder and secondary conditional pathogenic infection.

In recent years, with the rapid development of the field of oncology, the concept of anti-angiogenesis therapy has been introduced into the treatment of advanced lung cancer. Results of multiple clinical studies confirm that anti-angiogenic therapy can significantly prolong the survival time of lung cancer patients^[1,2,3,4,5]。 At present, anti-angiogenic therapy has gradually become the standard treatment for advanced non-small cell lung cancer (NSCLC) worldwide, but there is no guideline or expert consensus on the use of anti-angiogenic therapeutic drugs specifically for lung cancer in China. Therefore, the Lung Cancer Group of Respiratory Disease Branch of Chinese Medical Association and China Lung Cancer Prevention and Control Alliance jointly organized nearly 150 lung cancer experts in the domestic respiratory field to write the "Expert Consensus of Anti-angiogenic Drugs for Advanced Non-small Cell Lung Cancer in China's Respiratory Field (2016 Edition)" (hereinafter referred to as the "Consensus"), so as to promote the rational use of anti-angiogenic therapeutic drugs for lung cancer in China and promote the treatment level of lung cancer to synchronize with the international level.

According to the latest edition of the International Classification of Sleep-Related Respiratory Diseases, congenital central hypoventilation syndrome (CCHS) is further divided into CCHS and late onset central hypoventilation syndrome (LO-CHS), both of which are rare diseases of ventilatory central regulatory dysfunction, with the difference that there is a PHOX2B gene mutation in CCHS and no LO-CHS. LO-CHS may be associated with endocrine abnormalities of hypothalamic origin, severe emotional or behavioral abnormalities, or the presence of neural crest tumors^[1,2], is a rare disease associated with hypothalamic dysfunction. The first symptom is often the rapid onset of obesity, and hypopnea usually occurs about 18 months after the onset of obesity symptoms^[3,4,5]。 Current prognosis of LO-CHS is poor, and early diagnosis can help improve the treatment of ventilatory and metabolic disorders^[6]。 LO-CHS has a predisposition to tumor origin, and up to 40% of LO-CHS patients have concomitant tumors. These sympathetic nervous system tumors are typically well differentiated and do not significantly deteriorate patient prognosis^[7,8]。

The traditional treatment methods for advanced non-small cell lung cancer (NSCLC) are mainly chemotherapy and radiotherapy. In recent years, the commonly used first-line chemotherapy regimens have similar curative effects, although they are still the cornerstone, they have reached the bottleneck of curative effect^[1]Therefore, it becomes more urgent to seek new therapeutic drugs and means. The emergence of small molecule targeted drugs in recent years has greatly improved the survival time and quality of life of driver-positive advanced NSCLC patients, but the treatment of driver-negative patients is still very limited. Unlike chemotherapy and small molecule targeted drugs acting on tumor cells themselves, anti-angiogenesis therapy acts on the tumor microenvironment, which can degenerate existing tumor blood vessels and inhibit tumor neovascularization at the same time. By combining chemotherapy or small molecule targeted drugs, it can exert a better anti-tumor effect. In recent years, the concept and drug of anti-tumor angiogenesis therapy have been used in the treatment of advanced NSCLC, and it has been regarded as one of the standard treatment options for advanced NSCLC internationally.

Continuous oral administration of cyclophosphamide for 12 months can delay the progression of scleroderma-associated interstitial lung disease compared with placebo; However, the toxic side effects of long-term oral cyclophosphamide need to be taken into account, and the effect will disappear after 24 months of stopping the drug. Therefore, clinical trials comparing the efficacy of oral mycophenolate mofetil for 2 years with oral cyclophosphamide for 1 year for this type of disease have been carried out. Methods: This study was a 24-month randomized, double-blind, parallel-controlled clinical trial divided into oral mycophenolate mofetil (1.5 g, twice/d, 24 months) and oral cyclophosphamide (2 mg · kg^－1• d^－112 months, followed by oral placebo for the following 12 months) in both groups; The primary endpoint was the magnitude of the decrease in % FVC. Patients from 14 clinical medical centers in the United States were defined as scleroderma-associated interstitial lung disease by symptoms (dyspnea), lung function, and high-resolution CT. Results: From September 28, 2009 to January 14, 2013, a total of 142 patients were enrolled, randomly divided into 69 cases in mycophenolate mofetil group and 73 cases in cyclophosphamide group; The final cases available for analysis were 126 (63 in each group). (1) Change of FVC%: The corrected improvement of FVC% was 2.19% (0.53-3.84) in mycophenolate mofetil group and 2.88% (1.19-4.58) in cyclophosphamide group; There was no significant difference in the improvement of FVC% between the two groups (P=0.24), although both groups showed a significant improvement in FVC% from baseline FVC% at endpoint. (2) 16 (11%) patients died [5 (7%) in the mycophenolate mofetil group and 11 (15%) in the cyclophosphamide group]; The cyclophosphamide group was more likely to influence the blood routine results than the mycophenolate mofetil group: peripheral blood leukopenia (30 cases in the mycophenolate mofetil group, 4 cases in the cyclophosphamide group,P<0.05), thrombocytopenia (4 cases in mycophenolate mofetil group, 0 cases in cyclophosphamide group,P<0.05)。 (3) Early termination of clinical trials (20 cases) or treatment failure (0 cases) were fewer in the mycophenolate mofetil group, 32 cases and 4 cases in the cyclophosphamide group, respectively; Patients in the cyclophosphamide group experienced treatment discontinuation events earlier (P＝0.019)。 Conclusion: Oral mycophenolate mofetil for 2 years or oral cyclophosphamide for 1 year in the treatment of scleroderma-associated interstitial lung disease can improve their lung function, and the efficacy of both is similar, that is, the mycophenolate mofetil group is not superior to the cyclophosphamide group; However, patients in the mycophenolate mofetil group tolerated it better and had fewer toxic side effects.

Frequent acute exacerbations in patients with chronic obstructive pulmonary disease (COPD) can lead to decreased lung function^[1]Causing a decline in quality of life and a shortening of survival life. The common causes of acute exacerbation are tracheobronchial tree infection and air pollution, but about 1/3 of the severe acute exacerbation can not find the exact cause^[2]。 This study adopted¹H NMR (¹H NMR) technique was used to screen the characteristic metabolites in serum of acute exacerbation of COPD, and to explore the formation mechanism of acute exacerbation of COPD from the metabolic level.

Chronic obstructive pulmonary disease (COPD) is a pulmonary disease in which restricted airflow is not completely reversible and progressively developed, which can be prevented and treated^[1]Now ranks third in the world as a cause of death^[2]。 Study findings suggest that about 60% of COPD patients are malnourished^[3]Body mass index is the "gold standard" for evaluating nutritional status. However, for the bedbed patients, the current medical conditions in China cannot complete the measurement of body weight in bed, which makes its application greatly limited. nutritional risk screening (NRS 2002) is a nutritional risk screening tool recommended by the European Society for Enteral and Parenteral Nutrition for inpatients. Compared with other tools, it can be evaluated for patients who cannot measure their body weight. It is a simple, safe and time-consuming method^[4]It can better assess the nutritional status of patients with COPD and respiratory failure, and analyze the impact of nutritional risk on patients' clinical outcomes.

diffuse lung disease (DLD) is a kind of disease that is difficult to diagnose in respiratory clinic, and the definite diagnosis generally requires histopathology. At present, the main methods for obtaining tissue specimens are transbronchial forceps biopsy (TBFB), percutaneous lung biopsy and surgical lung biopsy (SLB). TBFB is difficult to meet the pathological needs and has low diagnostic efficiency because of its small and poor quality tissue specimens obtained; Percutaneous lung biopsy also has the problem that small specimens are often difficult to meet the pathological needs, and there is a risk of pneumothorax and hemopneumothorax. SLB is limited by cardiopulmonary function because of its large trauma, high cost, and less clinical application. In order to solve the problem of satisfactory acquisition of lung tissue specimens for diagnosis of DLD, we carried out transbronchial cryobiopsy (TBCB) of 2 cases of DLD, and achieved good results, which are reported below.

Hypercapnia usually refers to the blood PaCO₂>45 mmHg (normal values 35-45 mmHg, 1 mmHg =0.133 kPa), severe hypercapnia can develop into respiratory acidosis. Patients with mild hypercapnia may have no obvious symptoms, while patients with severe hypercapnia may develop apathy, drowsiness, restlessness, and further progress to convulsion, coma or even death. Patients with chronic obstructive pulmonary disease (COPD) are prone to type II respiratory failure, and hypercapnia can be used as a reference for the severity of COPD patients. Non-COPD patients can also develop potential hypercapnia, but currently for non-COPD patients with blood PaCO₂Not much is known about elevation, and the manifestations of chronic hypercapnia are insidious, progressing slowly, and easily overlooked. Most patients have developed to increased hemoglobin, pulmonary hypertension, pulmonary embolism and cerebral embolism when they see a doctor with symptoms. The related diseases of non-COPD that currently cause hypercapnia and how to judge hypercapnia are summarized below.

community-acquired pneumonia (CAP) is a common infectious disease of the lower respiratory tract in clinic. Mild patients only need outpatient treatment, while severe patients need hospitalization or even admission to ICU for rescue. Delaying treatment of critically ill patients significantly increases their mortality^[1]。 Therefore, it is particularly important to comprehensively evaluate the condition of CAP patients in the early stage and formulate a reasonable treatment plan. In the past, the assessment of the condition of CAP patients mostly relied on the subjective judgment of clinicians and lacked objective standards. In recent years, respiratory disease societies and infectious disease societies in many countries have put forward their own scoring standards, among which pneumonia severity index (PSI) and CURB-65 score are the most widely used^[2,3]。 In this regard, although PSI and CURB-65 scores are more accurate, they are less effective in assessing whether patients need to be admitted to ICU^{[4,5,6,7,8,9,10,11]}。 In clinical work, timely admission of severe pneumonia patients to ICU for intensive treatment is one of the key factors to reduce the mortality rate. Subsequent evaluations of the severe pneumonia score (SCAP score) and the severe pneumonia modified criteria (M-ATS criteria) focused on whether the patient needed to be admitted to the ICU^[12,13]。 While the SMART-COP score in 2008^[14]It concentrates the advantages of the aforementioned various scoring standards, which achieves a good balance in ease of use and accuracy, and also has unique advantages in the classification of risk degree. Several CAP severity scoring systems widely used at present are introduced below.

The human genome is only about 2×10⁴Protein-encoding genes, accounting for less than 2% of the whole genome, and the rest of the genes do not encode proteins. This part of the nucleic acid sequence was once considered "junk sequence". In recent years, large-scale gene sequencing has made people have a deeper understanding of genome structure, revealing that the action of multiple molecules and links in cells leads to the occurrence and development of diseases, and some non-coding genes also play an important role in it. In recent years, it has been found that long noncoding RNA (lncRNA) plays a role in the occurrence and development of various respiratory diseases. This paper briefly introduces the basic concept, mechanism of action and research methods of lncRNA, and summarizes the related research progress as follows.

The patient was a 54-year-old female. The main cause was "cough for 1 month, aggravated with dyspnea for 1 week" and was admitted to hospital on November 26, 2015. The patient developed dry cough and low fever after exposure to pigeons 1 month ago, with a maximum body temperature of 37.5 ℃. No abnormalities were found in routine blood routine and X-ray chest radiographs in other hospitals (Figure 1), oral azithromycin and cough syrup, the symptoms did not improve significantly. 1 week ago, the cough gradually worsened, with a small amount of white phlegm, accompanied by dyspnea, which was obvious after activity. There were no hemoptysis, chest pain, emaciation, etc. Chest CT performed in an external hospital showed diffuse ground glass shadows in both lungs, accompanied by "mosaic sign" and "frozen skin sign" (Figure 2，Figure 3), was admitted for further diagnosis and treatment. Past physical health, denied smoking history. Three months ago, I lived in a relative's house, and I kept pigeons at home. Physical examination: Superficial lymph nodes were not palpable and swollen, and dry and wet rales were not heard in both lower lungs. No abnormalities were seen in the confidant. No pestle fingers/toes. Initial diagnosis of admission: diffuse parenchymal lung disease, allergic pneumonia?

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that are not only effective in lowering total cholesterol and low-density lipoprotein-cholesterol (LDL-C), but also mildly lowering triglycerides and mildly elevating high-density lipoprotein cholesterol (HDL-C)^[1]It is currently the most widely used lipid-lowering drug in clinical practice. The existing statins in China are lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin and pitavastatin. Because of its wide clinical application, its safety has also attracted much attention. Generally, statins have good safety and tolerability. In recent years, more attention has been paid to the safety of statins in liver, muscle, kidney, new-onset diabetes and cognitive function changes and nervous system damage^[2]。 Clinicians have found that there may be a correlation between statins and the occurrence of interstitial lung disease (ILD). Although there is no conclusive evidence, clinical attention should be paid to it.

According to the World Health Organization (WHO), chronic obstructive pulmonary disease (COPD) ranked the third leading fatal disease in the world in 2012, with 3.1 million deaths from COPD every year, second only to ischemic heart disease and stroke^[1]。 In China, about 1 million people die of COPD every year, ranking second in China's burden of disease (DALY)^[2]。

Bronchial asthma (asthma) is a heterogeneous inflammatory disease of the airway, which is mainly characterized by airway hyperresponsiveness and variable airflow restriction. Allergen-induced TH2 lymphocyte activation and IL-5-mediated eosinophil exudation play an important role in the pathogenesis of asthma. In recent years, it has been found that more than 50% of asthma patients do not have elevated eosinophil levels in the airways, and this subtype has been defined as non-eosinophil asthma. Some of these patients presented with obvious increase of neutrophils in the airway, which was called neutrophilic asthma. In our previous study, four inflammatory subtypes, namely neutrophil asthma (NA), eosinophil asthma (EA), mixed granulocytic (MA) and agranulocytosis asthma (PA), were described based on the classification of induced sputum inflammatory cells. In recent years, it has been found that different subtypes have different pathogenesis and different therapeutic responses. For eosinophilic asthma, inflammatory markers can predict hormone therapy sensitivity, but for non-eosinophilic asthma, it is also necessary to clarify the mechanism of chronic airway inflammation and the mechanism of inflammatory cell infiltration in order to provide effective and individualized targeted therapy strategies, and discover new markers to guide subtype classification and potential therapeutic response.

At the end of the year, the 11th issue of this magazine in 2016 met with you readers!