2014年 · 第37卷第06期

Off-label usage is also called unregistered usage. According to the author's understanding, the specific meaning should include super-indication, super-adapted population, over-dose, over-treatment course, and change of medication interval and application route.

Pulmonary function examination is an examination to explore the functional state of human respiratory system by using the knowledge of respiratory physiology and modern examination techniques. Commonly used clinical examinations include lung volume examination, pneumometry examination, bronchial challenge test, bronchodilation test, lung diffusion function examination, airway resistance examination and exercise cardiopulmonary function examination. Pulmonary function examination is an important examination method for the diagnosis, severity, treatment effect and prognosis evaluation of chest and lung diseases in clinic. At present, it has been widely used in respiratory medicine, surgery, anesthesiology, pediatrics, epidemiology, diving and aerospace medicine.

Pulmonary hypertension associated with respiratory diseases is an important comorbidity of chronic obstructive pulmonary disease (COPD) and an independent risk factor affecting the course of COPD patients. Smoking has been found to be one of the leading causes of COPD and associated pulmonary hypertension. In the past, it was believed that the pathogenesis of COPD combined with pulmonary hypertension was mainly due to pulmonary vasoconstriction and pulmonary vascular remodeling caused by hypoxia. However, recent research results show that the active ingredients of tobacco smoke can directly act on the pulmonary vascular system, eventually leading to abnormal vascular remodeling and vasoconstriction reactions. The specific mechanism by which tobacco smoke causes pulmonary hypertension is unknown. The imbalance of calcium concentration in pulmonary artery smooth muscle cells is a key link in the pathogenesis of pulmonary hypertension, and the calcium pool manipulated calcium channel (SOCC) composed of classical transient receptor protein (TRPC) is an important factor in the imbalance of intracellular calcium concentration. Tobacco smoke can upregulate the expression of TRPC protein in PASMCs, increasing [Ca^2＋]_i, worth exploring in depth.

China is the second-largest country with a high burden of tuberculosis in the world. It is estimated that there are about one million new cases of tuberculosis every year, accounting for 11% of the world. China began to attach importance to tuberculosis problem in 1990s, and gradually implemented the modern tuberculosis control strategy (DOTS strategy) recommended by the World Health Organization. This study systematically evaluated the effectiveness of the implementation of the DOTS strategy over the past 20 years by secondary analysis of data from three national surveys on the prevalence of tuberculosis in 1990, 2000 and 2010.

Hypoxic pulmonary hypertension is a common respiratory disease. At present, there is no ideal treatment and poor prognosis. Transgelin is an actin-binding protein. We used proteomics to analyze the protein expression profile of human pulmonary artery smooth muscle cells (hPASMC) after normoxia and hypoxia treatment. The results showed that the expression level of Transgelin was significantly increased after hypoxia treatment, and when the expression of Transgelin was inhibited by siRNA, the migration of hPASMC induced by hypoxia was significantly weakened, which suggested that Transgelin may be involved in the occurrence of hypoxic pulmonary vascular remodeling. At present, the regulatory mechanism of Transgelin in hypoxic state is not well understood. Hypoxia-inducible factor-1 α (HIF-1 α) and its homologue HIF-2 α are core transcriptional regulators of hypoxic response and may be involved in regulating Transgelin expression in hypoxic state. The results indicate that the transforming growth factor-β 1 (TGF-β 1) /smad signaling pathway is involved in the regulation of Transgelin. This study aimed to investigate the regulatory mechanism of Transgelin under hypoxia and its role in hypoxic pulmonary vascular remodeling.

Right heart thrombosis combined with pulmonary embolism is one of the rare emergencies with high fatality rate, and it is more common in patients with high risk of deep vein thrombosis of lower limbs, such as long-term bed rest, lower limb trauma or surgery. Or patients with impaired right ventricular function, such as right ventricular infarction, right atrioventricular valve replacement, etc. The movement of right heart thrombosis with the cardiac cycle is easy to block the right ventricular outflow tract, or cause tricuspid valve insufficiency, causing hemodynamic changes, and the shedding embolus can lead to acute massive pulmonary embolism, with a high mortality rate. The incidence of right heart thrombosis in patients with pulmonary embolism is about 5%, and the mortality rate is about 30% ~40%^[1]Early and appropriate treatment can significantly reduce the mortality rate. At present, the treatment of right heart thrombosis combined with pulmonary embolism is still controversial, and its clinical status is summarized as follows.

pulmonary alveolar proteinosis (PAP) is the result of Rosen et al.^[1]A rare lung disease first reported in 1958. The pathological characteristics of PAP are that the alveoli and bronchioles are filled with amorphous phospholipid protein-like substances with positive periodic acid-Schiff (PAS) staining. Excessive deposition of phospholipid protein-like substances leads to pulmonary ventilation and ventilation dysfunction, causing progressive dyspnea, etc. PAP is divided into three categories: congenital, secondary and immune, of which about 90% are immune. whole lung lavage (WLL) has been the main clinical treatment for a long time. However, with the further understanding of the pathogenesis of PAP in the medical community, some new methods have been gradually applied in clinical practice. The research progress of PAP treatment is summarized as follows.

Caspofungin, micafungin and anifungin are the main antifungal drugs of the echinocyanin class, which act through non-competitive inhibition of fungal 1,3 – β – D – glucan synthase^[1]Is a bacteriostatic agent of Aspergillus^[2], plays an important role in the treatment of invasive aspergillosis. In recent years, many in vitro studies have found that echinocyanin antifungal drugs have a paradoxical effect in Aspergillus, that is, Aspergillus is inhibited at low drug concentration, while colony growth occurs at high drug concentration^[3]。 At present, the mechanism of this phenomenon has not been elucidated, and its clinical correlation is still unclear. In this study, the "contradictory phenomenon" produced by different Aspergillus genera in the in vitro drug susceptibility test of caspofungin and micafungin was preliminarily discussed, and the report is as follows.

Excessive secretion of airway mucus leads to airway obstruction and bacterial colonization, which are common pathological features of many chronic airway inflammatory diseases. It is closely related to the occurrence, development and outcome of chronic airway inflammatory diseases such as bronchial asthma, bronchiectasis and chronic obstructive pulmonary disease, and has become an independent risk factor affecting their morbidity and mortality rate and a prominent problem in clinical treatment. However, there is no effective drug for treating hypersecretion of airway mucus. The results suggest that IL-13 can activate the expression of chlorine channel 1 by upregulating calcium^[1]Signal transduction and transcription activator 6 (STAT6) phosphorylation and inhibitory transcription factor Foxa2 upregulate Muc5ac expression^[2]It is the main factor that leads to goblet cell proliferation and excessive mucus secretion in airways. peroxisome proliferator activated receptor-γ (PPAR-γ) is a class of nuclear transcription factors composed of dense molecules, dependent on ligand activation and with various biological effects, which play an important role in glycolipid metabolism, anti-inflammatory and immune regulation. Recent studies have shown that IL-13 also regulates goblet cell proliferation and mucus secretion induced by acrolein and tobacco smoke. In this study, a mouse model of airway goblet cell proliferation was established by specifically upregulating the expression of IL-13 in airway epithelial cells, and the role of rosiglitazone, a high affinity specific agonist of PPAR-γ, in IL-13-induced airway goblet cell proliferation was investigated.

Bronchial asthma (asthma for short) is a recurrent chronic airway inflammatory disease with complex pathogenesis and still not fully understood. The results showed that excess nitric oxide was found in the airway exhalation of asthma patients and asthma animal models, and the concentration of nitric oxide was closely related to the degree of airway inflammation^[1,2]It is suggested that nitric oxide in exhaled breath can be used as a new non-interventional examination method for airway inflammation in asthma. New research results show that the intervention of nitric oxide synthase (NOS) can provide new prevention and treatment targets for chronic airway inflammatory diseases such as asthma^[3]Some scholars believe that early exposure to a small amount of lipopolysaccharide has a protective effect on asthma^[4]。 In this study, lipopolysaccharide intervention was given in the process of establishing asthma animal model to observe the effects of lipopolysaccharide on the expression of airway inducible NOS (iNOS) and airway hyperresponsiveness in asthma.

A 66-year-old female was admitted to hospital for "edema of both lower limbs for more than 1 month, aggravated with joint pain of both lower limbs, dyspnea, cough and sputum for more than 20 days". One month ago, the patient developed edema of both lower limbs without obvious triggers, accompanied by anorexia, upper abdominal distension and pain, without nausea, vomiting and acid reflux, so he went to the local town hospital and was diagnosed as "chronic superficial gastritis". Symptomatic treatment such as analgesia and protection of gastric mucosa was given, but the patient's symptoms were not significantly relieved. More than 20 days ago, the edema of both lower limbs of the patient was worse than before, accompanied by joint pain of both lower limbs, dyspnea, cough, cough of white sticky sputum, which was filamentous and difficult to cough up, without hemoptysis, chest pain, chest tightness, fever and night sweats, etc. For further diagnosis and treatment, the chest CT showed a mixed density mass shadow in the basal segment of the lower lobe of the right lung, about 9.4 cm ×7.9 cm in size, and a soft tissue density nodule shadow in the anterior and middle mediastinum (Figure 1，Figure 2)。 Blood routine: white blood cells were 11.54×10⁹/L, the ratio of neutrophils was 0.79, and no obvious abnormalities were found in routine coagulation and biochemical indexes. Symptomatic treatment was given, and the patient's cough, expectoration, dyspnea and edema of both lower limbs were relieved compared with before.

Strongyloides stercoralis (strongyloides stercoralis) is a facultative parasite with a complex life history, including autogenous and parasitic generations. In the parasitic generation, adults mainly parasitize the small intestine of their hosts (such as humans, dogs, cats, etc.), and the larvae can invade tissues and organs such as lungs, brain, liver and kidneys, causing Strongyloidiasis. Larvae in patients with severe Strongyloidiasis faecalis can enter the brain, liver, lung, kidney and other organs, resulting in diffuse tissue damage and even death. It is more common in patients with long-term use of glucocorticoids and immunosuppressants or AIDS^[1]。 Diffuse alveolar hemorrhage has complex causes, different manifestations, and different onset. Among them, pulmonary small blood vessel vasculitis, immune diseases, coagulation dysfunction and primary pulmonary hemosiderosis are more common. Other rare causes include infection, bone marrow transplantation, drugs and mitral stenosis^[2]。 At present, two cases of massive hemoptysis caused by pulmonary strongyloidiasis faecalis were reported in foreign literature, and one case died^[3,4]。 Pulmonary strongyloidiasis faecalis can cause acute respiratory distress syndrome, sepsis and multiple organ system failure, which requires mechanical assisted ventilation by tracheal intubation. The mortality rate is extremely high, and it is rarely successful to be rescued^[5]。 A case of pulmonary Strongyloidiasis faecalis with diffuse alveolar hemorrhage, acute respiratory distress syndrome, acute respiratory failure, sepsis and multiple organ system failure was reported and successfully rescued.

Congenital unilateral absence of pulmonary artery (UAPA) is a rare pulmonary vascular malformation. A case of right pulmonary artery absence combined with left pulmonary artery embolism recently admitted to the Second Hospital of Hebei Medical University is reported below.

In recent years, the development of new tuberculosis vaccines has been very rapid, according to the World Health Organization (WHO)^[1]In 2013, a total of 12 tuberculosis vaccines were in the clinical stage, including my country's acellular Mycobacterium vaccae preparation in the clinical stage III for the prevention of tuberculosis in latently infected peopleM.vaccaeVaccine (M.V vaccine). In addition, a variety of new biological products for tuberculosis immunoprophylaxis are under registration in China. Compared with other vaccines and reagents for detecting latent MTB infections that have entered the clinical trial stage in the world, the scale and progress of similar studies in China are not inferior. However, due to the lack of relevant literature, the public and even some tuberculosis vaccine researchers believe that China's tuberculosis vaccine research is very lagging behind and relatively backward^[2]。 Therefore, we report the research status of biological products for tuberculosis immunotherapy and new biological products under registration in China as follows, for peers' reference and criticism and suggestions, so as to promote the progress of research and development of tuberculosis-related biological products in China.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE), is a dangerous and fatal cardiopulmonary disease, which seriously threatens human health and even endangers life. In recent years, some large-scale clinical studies at home and abroad have obtained evidence-based medicine results for the diagnosis and treatment of PTE, and at the same time, some questions and thinking have been aroused. At present, risk stratification is used in the diagnosis of PTE, which provides a reasonable method for disease assessment and treatment plan. Risk stratification was first assessed according to the patient's hemodynamic profile, classifying patients into high-risk, medium-risk, and low-risk^[1]。 Lower extremity venous ultrasonography can be used as a means to confirm the diagnosis of DVT. Echocardiography (UCG) has important diagnostic and differential diagnostic significance for high-risk and medium-risk patients. Especially in emergency, critically ill patients and cardiopulmonary resuscitation.

The long-acting anticholinergic drug tiotropium dry powder (trade name: Silihua Suole, Boehringer Ingelheim, Germany), which is assisted by powder inhaler, has been widely used to treat patients with chronic obstructive pulmonary disease (COPD) since its registration in 2002. The reason is very simple. Previous clinical randomized controlled trials (RCT) have reached a consistent conclusion: tiotropium bromide can improve lung function, exercise endurance, quality of life and reduce the frequency of acute exacerbation in patients with COPD^[1]。 These findings were confirmed by a multicenter large-scale RCT, the understanding potential Long-Term impacts on function with tiotropium (UPLIFT) study^[2]All relevant guidelines or expert consensus unanimously recommend tiotropium bromide as the first-line treatment for COPD.

The patient is a 39-year-old female, an employee of the washing department of a supermarket. He was admitted to hospital on March 8, 2011 due to "fever for 3 weeks and cough for more than 1 week". The patient developed fever without obvious trigger 3 weeks before admission, and the body temperature was about 39 ℃, without obvious regularity. At that time, there was no cough, hemoptysis, chest tightness and other symptoms and discomfort. The local hospital gave anti-infective and symptomatic treatment (the specific medication is unknown), and the body temperature returned to normal. One week before admission, the patient had fever again, with a body temperature of 38~40 ℃, mainly in the afternoon, accompanied by night sweats and fatigue, paroxysmal cough, accompanied by a little white sticky sputum, no yellow sputum, no hemoptysis and other discomfort, so he went to a hospital in Shanghai. X-ray chest film showed left lung patch shadow (Figure 1), diagnosed as "left lung inflammation", and given anti-infective treatments such as levofloxacin, cefuroxime, azithromycin and cefotaxime successively, but the symptoms did not improve significantly and the fever did not subside. Blood test (1,3) -β-D-glucan (G test) in other hospital: 38.44 ng/L (cut off value is 20 ng/L). Considering pulmonary fungal infection, he still had fever after oral treatment with fluconazole, so he was transferred to our hospital. The patient was previously in good health and underwent surgical treatment for ovarian cyst in 1995 and ectopic pregnancy in 2010. Deny raising pigeons, pets, etc., and deny history of infectious diseases such as hepatitis. Family history of hereditary disease denied.

Positive pressure ventilation is the most commonly used respiratory support for patients with critical respiratory illness. As an anti-physiological means of respiratory support, improper use of positive pressure ventilation can also be accompanied by serious complications, especially the occurrence of ventilator associated lung injury (VALI). At present, a large number of studies have confirmed that VALI will not only further aggravate the deterioration of lung function, but even increase the mortality rate of critically ill patients. Therefore, it is of great clinical significance to clarify the mechanism of VALI and adopt targeted prevention and treatment strategies for improving the treatment level of critically ill patients.

At present, inhalation therapy is the main treatment for chronic obstructive pulmonary disease (COPD), bronchial asthma (asthma) and other respiratory diseases. Portable drug inhalation devices for long-term maintenance therapy mainly include pressure metered dose aerosol inhalation devices (pMDIs) and dry powder inhalers (DPIs). Among them, pMDIs have a fast administration speed and a short maintenance time, and have relatively high requirements for hand-mouth coordination. Some elderly and young children cannot effectively inhale drugs simultaneously; DPIs can not granulate ideally due to insufficient inspiratory flow rate or moisture, which affects the effective inhalation of drugs. A novel Respimat device can slowly release "soft mist" fine drug particles, thereby effectively addressing the above shortcomings and providing the possibility of reducing inhaled drug doses while maintaining the same efficacy. For example, in the treatment of COPD and asthma, the effective therapeutic dose of HandiHaler dry powder device is 18 μ g/d^[1,2,3,4]and thereafter the effective therapeutic dose with the Respimat spray device was downregulated to 5 μ g/d. This article focuses on the characteristics of Respimat inhalation device and the clinical application of tiotropium bromide spray 5 μ g/d.

The first activity of Beijing Young Respiratory Scholars Salon in 2014 was held on March 27th, 2014. This activity was hosted by Dr. Huang Hui of Department of Respiratory Medicine, Peking Union Medical College Hospital. Professor Xu Zuojun of Department of Respiratory Medicine, Professor Feng Rui'e of Department of Pathology, Associate Professor Wang Qian and attending doctor Zhou Jiaxin of Department of Rheumatology and Immunology, and Professor Dai Huaping of Department of Respiratory Medicine, Beijing Chaoyang Hospital participated in this activity as special guests. The topic of this issue is to discuss the related contents of connective tissue disease-associated interstitial lung disease (CTD-ILD) with rheumatologists and immunologists, mainly from the definition/designation of CTD-ILD, diagnostic measures, treatment options, etc.

Time flies, and in the blink of an eye, 2014 is halfway through, and early summer is approaching. The sixth issue of this magazine in 2014 has met with you readers.