Elastase/antielastase systems in pulmonary diseases

Levels of serum elastase 1 in a variety of respiratory diseases were studied. In patients with pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or pulmonary infections, including pneumonia and pulmonary tuberculosis, serum elastase 1 levels were greater than those of an age-matched control group. In lung cancer patients, however, the serum elastase 1 level was within normal limits. Although alpha 1-antitrypsin levels were significantly higher in patients with pulmonary infections and lung cancer than in the normal group, they were within normal limits in patients with pulmonary emphysema, pulmonary fibrosis, and bronchial asthma. Alpha 2-macroglobulin levels were slightly increased in patients with pulmonary emphysema and pneumonia. These results suggest that the increases in serum elastase 1 levels in these respiratory diseases may be mainly caused by an imbalance of elastase/antielastase system in the lung tissue and the bloodstream.     

Ex vivo evaluation of PPD-specific IFN-gamma or IL-5 secreting cells in the peripheral blood and lungs of patients with tuberculosis.

OBJECTIVES: To evaluate ex vivo purified protein derivative (PPD) specific Th1- and Th2-type functional responses in human tuberculosis (TB). DESIGN: IFN-gamma and IL-5 secreting cells were measured by a computer-assisted ELISPOT assay in the peripheral blood of patients with pulmonary TB, in patients with other respiratory diseases (control patients) and in tuberculin skin test negative or positive healthy controls. Moreover, the number of IFN-gamma or IL-5 spots was assessed in the bronchoalveolar lavage (BAL) cells of five patients with advanced TB and lung inflammation. RESULTS: The frequency of PPD-specific IFN-gamma secreting cells in TB patients was higher than in control patients and healthy subjects. Although the number of PPD-specific IL-5 spots was low, a trend towards a higher frequency was observed in the peripheral blood of TB patients. Patients with advanced TB and lung inflammation had an increased number of both PPD-specific IFN-gamma and IL-5 spots in BAL as compared to that in peripheral blood, but the IFN-gamma/IL-5 ratio was about two-fold lower. CONCLUSIONS: In human TB, the host response in the periphery is driven by a specific Th1-type cytokine response, whereas in the lungs of patients with advanced disease and lung inflammation, polarisation towards a Th2-like bias is observed.     

Pulmonary manifestations of endocrine and metabolic disorders

In summary, there are a number of important respiratory manifestations of endocrine diseases. Hypothyroidism may be associated with respiratory failure that can be caused by a reduction in central respiratory drive, upper airway obstruction, and associated restrictive pulmonary function from pleural effusions or an intrinsic decrease in lung volumes. Hyperthyroidism can present with dyspnea as a major clinical manifestation because of the increase in central respiratory drive associated with thyrotoxicosis. Cardiac dysfunction associated with hyperthyroidism may lead to pulmonary edema in some patients. Hypoparathyroidism may occur acutely, especially after thyroid surgery and be associated with hypocalcemia and acute tetany, laryngeal stridor, and muscle weakness. Ovarian tumors, both benign and malignant, may present with unilateral or bilateral effusions. Finally, patients with diabetes mellitus are at increased risk of developing a variety of pulmonary disorders. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes, although cardiogenic and noncardiogenic pulmonary edema can also be a complication of their disease.     

Does interferon-gamma improve pulmonary function in idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile. Recently, a preliminary study of long-term treatment with interferon (IFN)-gamma1b and low-dose prednisolone in patients with IPF suggested that IFN-gamma1b treatment may improve lung function parameters of patients with IPF. Ever since, specialists in respiratory medicine who treat patients with IPF, are called by patients demanding treatment with IFN-gamma1b. Therefore, the authors here present another prospective investigation of IFN-gamma1b in five patients with IPF. According to the previously published design, patients received 200 microg IFN-gamma1b subcutaneously three-times per week and 10 mg prednisolone orally for 12 months. Two patients stopped IFN-gamma1b treatment after 4 months due to side-effects and further lung function deterioration and one patient died 3 months after commencement of therapy. In total, pulmonary function improved in only one patient during IFN-gamma1b treatment, while four patients deteriorated. To conclude, this small series of idiopathic pulmonary fibrosis cases treated with interferon-gamma1b and corticosteroids does not support previous data that this treatment improves pulmonary function or alters the natural course of idiopathic pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of interferon-gamma1b treatment can significantly reduce patients' quality of life.     

Pulmonary manifestations of Crohn’s disease

Crohn’s disease(CD)is a systemic illness with a constellation of extraintestinal manifestations affecting various organs.Of these extraintestinal manifestations of CD,those involving the lung are relatively rare.However,there is a wide array of lung manifestations,ranging from subclinical alterations,airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases.The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis.Bronchoalveolar lavage findings show an increased percentage of neutrophils.Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine,mesalamine and methotrexate,and opportunistic lung infections due to immunosuppressive treatment.In most patients,the development of pulmonary disease parallels that of intestinal disease activity.Although infrequent,clinicians dealing with CD must be aware of these,sometimes life-threatening,conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment.The treatment of CD-related respiratory disorders depends on the specific pattern of involvement,and in most patients,steroids are required in the initial management.     

三氧化二砷在呼吸系统疾病的研究进展

三氧化二砷作为药物治疗多种疾病已有上千年历史,近年来研究发现其对急性早幼粒细胞白血病具有显著疗效,有关三氧化二砷在其他疾病的研究越来越多,其作用机制复杂,主要包括:诱导细胞凋亡、诱导细胞分化和抑制细胞增殖.该文简要的总结了近年来三氧化二砷在呼吸系统疾病中的研究进展,包括原发性支气管肺癌、支气管哮喘、肺纤维化、恶性胸腔积液等,以提出其在呼吸系统疾病应用的展望,为呼吸系统多种疾病提供治疗新思路.     

The role of immunity and inflammation in lung senescence and susceptibility to infection in the elderly

Advancing age is associated with a decline in the integrity of physical barriers and protection against invading pathogens, and age-related changes in the immune system are associated with increased susceptibility to the emergence of autoimmune phenomena, neoplasia, and infections. Respiratory tract infections can occur at any age, but the incidence of lower respiratory tract infections increases significantly with advanced age such that pneumonia is a leading cause of illness and death in the elderly. Changes in lung physiology and immune function coupled with inflammation induced by environmental exposures or endogenous factors such as predisposition to aspiration may, in part, account for the increase in susceptibility to respiratory infections. Additionally, age-associated alterations in immune regulation ("immunosenescence") with dysregulation of lung homeostasis may allow low-grade inflammatory changes that lead to anatomical and physiological changes that characterize the senescent lung. The presence of disease states in elderly populations, such as chronic obstructive pulmonary disease (COPD) or nonpulmonary organ system diseases, may increase the likelihood of developing severe respiratory infections. This article examines age-related changes in immune function that predispose elderly individuals to lung remodeling but focuses especially on lower respiratory tract infections. It will discuss risk factors, identify pathogens that typically lead to respiratory infections in the elderly, and review current approaches to treatment and prevention of respiratory infections in the elderly population.     

介入呼吸病学年度进展（2015-2016）

介入呼吸病学是现代呼吸病学的一个分支,在呼吸系统疾病的诊断和治疗方面发挥着越来越重要的作用。随着科学技术的发展,新的介入诊疗方法已经逐渐应用于一些传统疾病,如COPD、支气管哮喘、恶性肿瘤等。介入呼吸病学逐渐发展为一个成熟的亚专科,其对呼吸系统疾病的诊断范围和治疗有效性也跃上一个新的台阶。本文就2015-2016年介入呼吸病学在呼吸系统疾病临床诊疗方面的新进展和最新研究成果作一综述。     

Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the clinical diagnosis of lung cancer]

In recent years the use of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) has become a valuable tool in the detection of a variety of tumors including lung cancer. To determine its role in the diagnosis of patients with suspected lung cancer, we compared the results of FDG-PET with those of the other scintigraphic imaging techniques (67Ga-planar image, 201Tl-SPECT and 99mTc-bone scintigraphy) used worldwide in patients with lung cancer. The analysis group consists of 178 patients, 159 malignant pulmonary diseases and 19 benign pulmonary diseases. FDG-PET was performed in 65 patients (51 malignant pulmonary diseases, 14 benign pulmonary diseases). FDG-PET had a sensitivity, specificity and accuracy of 98.0%, 78.6% and 93.8%, respectively, in detecting malignant pulmonary nodules. In N staging, sensitivity, specificity and accuracy were 66.7%, 81.3% and 76.0%, respectively. In M staging, the accuracy was 100%. Thus, FDG-PET imaging was more accurate than the other types of scintigraphic imaging. In our observations, whole-body 18FDG-PET images improved diagnostic accuracy in the evaluation of lung lesions and the staging of lung cancer.     

Interventional pulmonology: Focus on pulmonary diagnostics

Interventional pulmonology (IP) allows comprehensive assessment of patients with benign and malignant airway, lung parenchymal and pleural disease. This relatively new branch of pulmonary medicine utilizes advanced diagnostic and therapeutic techniques to treat patients with pulmonary diseases. Endobronchial ultrasound revolutionized assessment of pulmonary nodules, mediastinal lymphadenopathy and lung cancer staging allowing minimally invasive, highly accurate assessment of lung parenchymal and mediastinal disease, with both macro‐ and microscopic tissue characterization including molecular signature analysis. High‐spatial resolution, new endobronchial imaging techniques including autofluorescence bronchoscopy, narrow‐band imaging, optical coherence tomography and confocal microscopy enable detailed evaluation of airways with increasing role in detection and treatment of malignancies arising in central airways. Precision in peripheral lesion localization has been increased through innovative navigational techniques including navigational bronchoscopy and electromagnetic navigation. Pleural diseases can be assessed with the use of non‐invasive pleural ultrasonography, with high sensitivity and specificity for malignant disease detection. Medical pleuroscopy is a minimally invasive technique improving diagnostic safety and precision of pleural disease and pleural effusion assessment. In this review, we discuss the newest advances in diagnostic modalities utilized in IP, indications for their use, their diagnostic accuracy, efficacy, safety and challenges in application of these technologies in assessment of thoracic diseases.     

Cellular senescence in normal and premature lung aging

The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.     

Pulmonary diseases and the heart

The complex nature of interactions between the pulmonary and cardiovascular systems is becoming increasingly appreciated. Pulmonary vascular abnormalities are frequently present in patients with respiratory disorders, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, sarcoidosis, neuromuscular or chest wall disorders, and disorders of ventilatory control including sleep apnea syndromes and obesity hypoventilation syndrome. Pulmonary hypertension, classified as group III in the World Health Organization classification scheme for pulmonary hypertension, may result in severe right ventricular dysfunction caused by lung disease, also known as cor pulmonale. The development of cor pulmonale is generally associated with poorer prognosis and increased death. Systemic manifestations of lung disease, particularly obstructive disorders, are also particularly relevant because they are associated with increased cardiac death and impaired health status. This article will discuss the most common pulmonary diseases and disorders of ventilatory control that cause pulmonary vascular abnormalities and cor pulmonale, with particular concentration on how treatment of these diseases may affect the heart. In addition, the complex nature of cardiac and lung disease will also be explored, particularly with respect to the relationship between chronic obstructive pulmonary disease, systemic inflammation, atherosclerosis, and cardiovascular death, which is currently a very active focus of research.     

Patienten mit interstitiellen Lungenerkrankungen auf der Intensivstation

Despite relevant advances in the treatment of interstitial lung diseases (ILD), morbidity and mortality in patients with ILD are high. Patients receiving intensive care treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) exhibit increased mortality. Determination of the possible causes of the respiratory failure is crucial for further treatment and reasons include acute exacerbations, right heart failure in pulmonary hypertension, infection, pulmonary embolism, drug-associated complications, and aggravation of comorbidities. In patients with suspected AE-IPF, a HRCT (high-resolution computed tomography; obligate without contrast agent) should be performed immediately in addition to a medical history and physical examination, which should in particular take into account the differential diagnoses. The current therapeutic regimen for AE-IPF consists of high-dose corticosteroids with tapering, and possibly antibiotics and immunosuppressants. The mortality rate for patients who require mechanical ventilation in acute exacerbation is 87?%. Therefore, mechanical ventilation is discouraged in the German IPF guideline if the underlying cause of respiratory failure is due to IPF progression. Only in potentially reversible disease should invasive ventilation be considered. The use of noninvasive ventilation may be discussed. The use of extracorporeal membrane oxygenation (ECMO) as a bridging therapy can be a lifesaving option for patients with ILD and acute respiratory failure, if they are candidates for lung transplantation. The poor prognosis, however, can not be altered by this action if they are not suitable for a lung transplant.     

Clinicoradiological diagnosis of respiratory infections: estimate of pathogens by radiological findings and the strategy for treatment

This review discusses the clinicoradiological findings of community-acquired respiratory infections and the treatment strategy for respiratory infections. To make a differential diagnosis between bacterial pneumonia, pneumonia caused by atypical pathogens, and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal antomical structures. If clinicoradiological anlyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and respiratory bronchioles is very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures, estimation of causative pathogens could be possible. Especially, whether inflammatory exudates could pass Kohn's pores as well as Lambert's channel or not is very important factor to affect radiological findings of several pneumonia (as traditionally called "segmental" and "nonsegmental" distribution). To differentiate infections caused by Mycobacterium tuberculosis from nontuberculous mycobacteria, several important criteria have been demonstrated. Briefly, it has been suggested that Mycobacterium avium complex (MAC) respiratory infection is increasing especially in elderly women without underlying diseases. In MAC respiratory infection, right middle lobe and left lingula are frequently involved and centrilobular nodules and diffuse bronchiectases are characteristic radiological findings. Finally, the role of telithromycin in the treatment of respiratory infections is discussed.     

Clinicoradiological diagnosis of respiratory infections: estimate of pathogens by radiological findings and the strategy for treatment

This review discusses the clinicoradiological findings of pulmonary tuberculosis as well as non-tuberculous mycobacteria. To make a differential diagnosis between pneumonia and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal anatomical structures. If clinicoradiological analyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and respiratory bronchioles is very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures. estimation of causative pathogens could be possible. To differentiate infections caused by Mycobacterium tuberculosis from non-tuberculous mycobacteria, several important criteria have been demonstrated. Briefly, in MAC respiratory infection, right middle lobe and left lingula are frequently involved and centrilobular nodules and diffuse bronchiectases are characteristic radiological findings.     

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??Abstract??Interventional pulmonology is a newly developed medical discipline devoted to the performance of diagnosis and invasive therapy of respiratory diseases.The professional field of this discipline refers to diagnosis and staging of respiratory diseases??and focuses on treatment of pulmonary tumors??benign or malignant airway stenosis??pleural disease and pulmonary vascular diseases.So far??huge strides have been made in interventional pulmonology??and therefore some distinct features have been developed in China.Prevalent and common diseases??such as lung cancer??chronic obstructive pulmonary disease(COPD)and asthma??will hereafter be the focus of interventional pulmonary in China.     

Immune Dysregulation in the Pathogenesis of Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the α chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.     

Smoking-related interstitial lung diseases: a concise review.

Interstitial lung diseases (also known as diffuse infiltrative lung diseases) are a heterogeneous group of parenchymal lung disorders of known or unknown cause. These disorders are usually associated with dyspnoea, diffuse lung infiltrates, and impaired gas exchange. The majority of interstitial lung diseases are of unknown cause. Known causes of interstitial lung disease include inhalation of organic and inorganic dusts as well as gases or fumes, drugs, radiation, and infections. This review summarizes the clinical, radiological, and histopathological features of four interstitial lung disorders that have been linked to smoking. These disorders include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, pulmonary Langerhans' cell histiocytosis, and idiopathic pulmonary fibrosis. Available evidence suggests most cases of desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, and pulmonary Langerhans' cell histiocytosis are caused by cigarette smoking in susceptible individuals. Smoking cessation should be a main component in the initial therapeutic approach to smokers with these interstitial lung diseases. In addition, smoking appears to be a risk factor for the development of idiopathic pulmonary fibrosis.     

维生素D在肺部疾病中的作用

除了维持钙盐代谢和骨骼的稳态以外，研究发现维生素D还可调控包括机体防御，炎症，免疫，损伤修复等在内的多种生理和病理生理过程。流行病学资料表明，血清低水平的维生素D与肺功能受损、炎症反应和感染性疾病相关。因此，支气管哮喘、慢性阻塞性肺疾病和肺部感染性疾病都可能与维生素D水平有关，但具体的机制尚不明确。因此，本文通过文献回顾，概述维生素D在肺部疾病，包括支气管哮喘、慢性阻塞性肺疾病、肺结核和呼吸道感染中的作用。     

Other smoking-affected pulmonary diseases

Cigarette smoking is the leading cause of preventable death in the United States. Smoking adversely affects many organ systems, but especially the lung. Carcinoma of the lung and chronic obstructive pulmonary disease account for most smoking-associated respiratory morbidity and mortality, and their association with smoking is both well established and widely recognized. Cigarette smoking also is associated with differences in the incidence, severity, or natural history of a broad array of other respiratory illnesses, ranging from the common cold to pneumothorax, pulmonary hemorrhage, and various interstitial lung diseases. Interestingly, while the general effect of smoking on respiratory diseases is adverse, in the cases of sarcoidosis and hypersensitivity pneumonitis smoking may actually be associated with a decrease in the incidence of disease. In this article, the author briefly discusses some of the pulmonary and systemic effects of smoking that might mediate its effects on an array of lung diseases, then comprehensively reviews less common or less well-recognized smoking-affected lung diseases such as pulmonary infections, spontaneous pneumothorax, Goodpasture's syndrome, eosinophilic granuloma and other interstitial lung diseases, and pulmonary metastatic disease.