Chunxue Bai

The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a syndrome characterized by pulmonary edema and acute inflammation. Lipopolysaccharide (LPS), a major component in Gram-negative bacteria, has been used to induce ALI/ARDS. LPS-induced animal models highlight ways to explore mechanisms of multiple diseases and provide useful information on the discovery of novel biomarkers and drug targets. However, each model has its own merits and drawbacks. The goal of this article is to summarize and evaluate the results of experimental findings in LPS-induced ALI/ARDS, and the possible mechanisms and treatments elucidated. Advantages and disadvantages of such models in pulmonary research and new directions for future investigations are also discussed.

Role of airway epithelial cells in development of asthma and allergic rhinitis.

Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.

Potential significance of telocytes in the pathogenesis of lung diseases

Multiple cells play critical roles in the pathogenesis of lung diseases, even though the exact mechanisms are still not clear. Telocytes are characterized by telopodes, which are thin and long prolongations, and a small amount of cytoplasm rich with mitochondria, as shown by immune-positive staining against CD34, c-kit and vimentin. Telocytes have been found in many organs of mammals, including the trachea and lung. This report summarizes the latest findings associated with telocytes, with a special focus on the lung, and demonstrates that telocytes exist in the smooth muscle layer under cartilage and bronchiole in the lung, and also in the interstitial space of alveoli. Telocytes have a mediate connection with epithelial cells and direct connection with smooth muscle cells both in blood vessels and bronchiole in the lung. Telocytes also have a close relationship with other cell types, such as immune cells and stem cells. Telopodes appear with dichotomous branching and alternation of podom and podomer, forming a 3D network structure with complex homo- and hetero-cellular junctions. All characteristics of telocytes in lung tissue indicate that telocytes may play a potential, but important, role in the pathogenesis of lung diseases.

Proteomics-Based Biomarkers in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with progressive obstruction of airflow affecting peripheral airways. The proteomic analysis highlights ways to identify novel biomarkers for diagnosis, therapy, and prognosis in COPD. Human samples, for example, lung tissue, bronchoalveolar lavage, sputum, and serum, have been used for COPD proteomic research, each with its own merits and demerits. In the present review, we aimed at discussing the feasibility of clinical studies on COPD proteomics and the potential candidates for COPD biomarkers detected in human samples that are sensitive to the progress of COPD, disease-specific to COPD, and associated with the status of the patients. There is an increasing need to be able to perform proteomic studies on patients with COPD that describe the association with disease specificity, severity, progress, and prognosis as well as monitor the efficacy of therapies. There is an urgent need to establish and clarify the criteria for subjects including controls and data analysis and standardize the study design, methodology, and process as this is vital when designing prospective clinical studies on COPD. It is important to clarify the source of the samples, the efficiency, and quality when dealing with large amount of candidates and the specificity of biomarkers according to the severity, therapeutic effects, progress, and prognosis of the disease.

Involvement of Gax gene in hypoxia-induced pulmonary hypertension, proliferation, and apoptosis of arterial smooth muscle cells.

Hypoxia down-regulates the expression of the growth arrest-specific homeobox (Gax) in pulmonary arterial smooth muscle cells (PASMCs), resulting in increased cell proliferation and decreased apoptosis, but the mechanism for this response remains unclear. The present study investigated the role of Gax in the development of hypoxia-induced pulmonary hypertension (PH). We found that hypoxia suppressed the expression of endogenous Gax in rats, but not in those pretreated intratracheally with a Gax construct (Ad-Gax). Hypoxic rats pretreated with Ad-Gax were resistant to hypoxia-induced PH, right ventricular hypertrophy, increased wall thickness, and the muscularization of pulmonary arterioles. Hypoxia-induced PASMC proliferation and suppression of Gax expression were blocked by the Mitogen-activated protein kinase (MEK) inhibitor U0126. The PASMCs with Ad-Gax transfection exhibited hyperexpression of the Bcl-2-associated X protein (Bax) and hypoexpression of B-cell lymphoma 2 (Bcl-2), leading to cell apoptosis. Thus, our data indicate that the enhanced expression of Gax inhibits hypoxia-induced PASMC proliferation, probably via the extracellular-signal-regulated kinase (ERK) 1/2 pathway, and induces the apoptosis of hypoxic PASMCs via the Bcl-2/Bax pathway. Gax may be a potential new therapeutic target for pulmonary hypertension.

Airway epithelial dysfunction in the development of acute lung injury and acute respiratory distress syndrome.

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are common and important stages of both pulmonary and systemic critical illnesses. ALI/ARDS is categorized as primary or secondary based on the etiology of the disease. There is increasing evidence to suggest the involvement of airway epithelial cells in the pathogenesis of ALI/ARDS. The airway epithelial cell is a new candidate as a biological target responsible for development of the disease and the role of these cells in the pathogenesis of ALI/ARDS is under investigation. This review describes the importance of the airway epithelial cell in the development of ALI/ARDS, its role as the first line of lung defense facing local and primary challenges, its role as an important player in the development of airway inflammation and remodeling, as an inflammatory promoter for initiating both local and systemic inflammation and as an active producer of several inflammatory and anti-inflammatory mediators. It is hypothesized that airway epithelial cells may contribute to ALI/ARDS via Toll-like receptor-involved mediators, reactive oxygen species-involved reactions and an imbalance between protease and antiprotease activation. The airway epithelial cell may be a valuable therapeutic target for discovering and developing new drugs and/or new therapeutic strategies for ALI/ARDS.

Clinical analysis of patients with pulmonary lymphangioleiomyomatosis (PLAM) in mainland China

BACKGROUND AND OBJECTIVE There have been no clinical reports on pulmonary lymphangioleiomyomatosis (PLAM) based on large studies or epidemiological surveys in mainland China. The purpose of this study was to provide a retrospective analysis of PLAM patients in mainland China by reviewing the clinical data of PLAM cases reported. METHODS The China Academic Journals Full-text Database search engine was used to collect related cases in mainland China through the end of 2008. 120 cases met the studys inclusion criteria and were reviewed for this analysis. RESULTS The average age of the 120 patients upon confirmed diagnosis was 37.3+/-6.4 years. The average duration from onset of symptoms to a confirmed diagnosis was 29.6+/-35.8 months, with 80 person-time patients having experienced misdiagnosis before the confirmed diagnosis. The major clinical manifestations of PLAM included progressive dyspnea, recurrent pneumatothorax, refractory chylothorax. Pulmonary function abnormalities included obstructive pulmonary ventilation disorders and degenerated diffusing capacity. Ten patients were found to be complicated with renal angiomyolipoma and 17 with abdominal or pelvic lymphangioleiomyoma. Half of the patients had undergone antiestrogen therapies such as progesterone, and four patients received pulmonary transplantation. The average duration from the confirmed diagnosis to death was 36.4+/-48.9 months among the 28 cases of death. CONCLUSIONS Doctors in mainland China are becoming increasingly vigilant to PLAM, although misdiagnosis or missed diagnosis still exists. Provider attention to the correlation between PLAM and tuberous sclerosis complex, as well as to the possible involvement of multiple organs, is insufficient.

Serum chemokine network correlates with chemotherapy in non-small cell lung cancer.

OBJECTIVE Inflammation plays an important role in the microenvironment of lung cancer. The present study aimed to evaluate the association of inflammatory biomarker networks with chemotherapies for patients with non-small cell lung cancer (NSCLC). METHODS The sera of healthy non-smokers (n = 14) and patients with NSCLC (n = 50), 36 with adenocarcinoma and 14 with squamous cell carcinoma, were collected. Healthy patients were untreated, while those with NSCLC were either chemotherapy-naïve or had received one and two courses of chemotherapy. The cytokine concentrations were measured using multiplexed cytokine immunoassays. The clinical informatics was scored with a Digital Evaluation Score System (DESS) to assess the severity of the patients. All patients completed follow-up for up to 2 years. RESULTS Among the 40 mediators measured, 13 significantly differed between patients with lung cancer and healthy controls, while 18 differed between untreated patients and those with stage IV adenocarcinoma who had undergone the first and second chemotherapy courses. The protein network of cytokines in NSCLC after multiple courses of chemotherapy was similar to that of normal persons. MIP-3α is the most crucial biomarker for predicting survival rates in NSCLC patients. CONCLUSIONS Our data identify an NSCLC-specific profile of inflammatory mediators that may be useful for cancer sub-classification, as well as the evaluation of therapeutic effects and overall survival.

The implication of telehealthcare in COPD management of China.

Chronic obstructive pulmonary disease (COPD) is a very common disease all around the world and has become an increasing public health concern to the Chinese medical community. In the past decades, telehealthcare technology has become a good way to manage COPD but current evidence makes it hard to determine the effectiveness of this technology. Internet of things (Iot) is a recent breakthrough in communication technology, which links the virtual world to the real world through connection between sensors and working devices. It relates people and items in any ways so that data collection and management become more flexible. Our review concentrates on the effectiveness and potential application of telehealthcare in COPD management and how IoT technology may stimulate COPD healthcare delivery through telehealthcare technology.

COPD-associated vascular pathology: a future targeting area

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide, affecting the airways (i.e., chronic bronchitis and airway collapse), the parenchyma (i.e., hyperinflation, air trapping and emphysematous destruction) and the vasculature (i.e., hypoxic vasoconstriction, rarefaction and pulmonary arterial hypertension) with different severities [1]. Pharmacotherapy for COPD is still under development to show disease-specific efficacy on disease progression and has a great need to explore new and effective therapeutic areas [2,3]. Pathological angiogenesis has been suggested to be associated with the development and remodeling of COPD and tumor growth [4]. COPD can result in both pulmonary and extrapulmonary vascular pathology, including endothelial barrier dysfunction, wall thickening, smooth muscular cell hypertrophy, inflammation and remodeling [5]. The direct vascular changes and hyperinflation lead to the precapillary type of pulmonary hypertension, a fundamental alteration in the pulmonary vascular resistance. Vascular pathology is a critical part of the structural tissue remodeling that occurs in COPD. However, the reason for the lack of effective treatment in COPD-associated vascular pathology is that the attention and understanding of such pathology remains limited and neglected [6,7]. It has been proposed that endothelial dysfunction might be an initiating event, promoting vascular remodeling in COPD. The pathogenesis of vascular pathology in the development of COPD remains unclear, although a number of factors in COPD may involve atherosclerosis through vascular inflammation and oxidative stress [8,9]. Therefore, we call for special attention from respiratory physicians and scientists to COPD-associated vascular pathology, in order to highlight clinical evidence of the pathology, explore potential mechanisms and biomarkers and propose a future therapeutic area for COPD.