High Expression of Cathepsin E is Associated with the Severity of Airflow Limitation in Patients with COPD.

BACKGROUND: It was reported that Cathepsin E (Cat E) plays a critical role in antigen processing and in the development of pulmonary emphysema. The aim of this study was to investigate the role of Cat E and airflow limitation in the pathogenesis of COPD. METHODS: Sixty-five patients with COPD, 20 smoking control subjects without COPD and 15 non-smoking healthy control subjects were enrolled. Cat E and EIC (Elastase inhibitory capacity) expressions were measured by ELISA in sputum and serum samples and compared according to different subgroups. RESULTS: Cat E concentrations were significantly higher in patients with COPD than smoking control and non-smoking control subjects (P < 0.01). The levels of CatE were inversely correlated with FEV1% predicted in COPD patients (r = -0.95, P < 0.01). The levels of EIC were inversely positively correlated with FEV1% predicted in COPD patients (r = 0.926, P < 0.01). Levels of Cat E were also inversely correlated with the levels of EIC (r = -0.922, P < 0.01). CONCLUSIONS: Cat E contributes to the severity of airflow limitation during progression of COPD.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

PM2.5 compromises antiviral immunity in influenza infection by inhibiting activation of NLRP3 inflammasome and expression of interferon-ß.

PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.5 index is closely associated with severity of influenza A virus (IAV) infection. However, the underlying mechanisms have not been addressed. NLRP3 inflammasome and type I interferon signaling regulate host defense against influenza infection. The present study investigated the potential effects of air pollutants on host defense against influenza infection in vitro and in vivo. In this study, different concentrations of PM2.5 were pre-exposed to macrophages and mice before IAV infection to assess the negative effects of air pollutants in virus infection. We found that exposure to PM2.5 deteriorated influenza virus infection via compromising innate immune responses manifested by a decrease IL-1ß and IFN-ß production in vitro. Meanwhile, mice exposed with PM2.5 were susceptible to PR8 virus infection due to down-regulation of IL-1ß and IFN-ß. Mechanistically, PM 2.5 exposure suppressed the NLRP3 inflammasome activation and the AHR-TIPARP signaling pathway, by which compromised the anti-influenza immunity. Thus, our study revealed that PM2.5 could alter macrophage inflammatory responses by suppressing LPS-induced activation of NLRP3 inflammasome and expression of IFN-ß during influenza infection. These findings provided us new insights in understanding that PM2.5 combining with influenza infection could enhance the severity of pneumonia.

Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China.

OBJECTIVES: Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China. METHODS: Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement. RESULTS: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05). CONCLUSIONS: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.

Beneficial effects of Omalizumab therapy in allergic bronchopulmonary aspergillosis: A synthesis review of published literature.

Omalizumab, a humanized mAb that binds to IgE, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of Omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA) except some case reports. To assess the clinical and immunological effects of Omalizumab in ABPA patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of Omalizumab therapy in ABPA and conducted subgroup analyses to determine factors that influenced the therapy endpoints. We found that Omalizumab treatment not only provided a clinically important reduction in serum IgE, exacerbation rates and steroid requirement, but also showed attenuated asthma symptoms and improved pulmonary function parameters in patients with ABPA. Moreover, further discussion was made when interpretating the results. Double-blind, randomized, placebo-controlled trials are necessary to establish the efficacy and safety of this novel therapeutic intervention for ABPA patients.

Immunity status of invasive pulmonary aspergillosis patients with structural lung diseases in Chinese adults.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a fungal infection frequently observed in patients with immune dysfunction, such as those suffering from structural lung diseases. Nevertheless, studies assessing IPA combined with other common respiratory diseases remain scarce, particularly those regarding the immune status of its patients. Different structural lung diseases are known to differently affect patient immune status; however, the mechanisms by which this is conferred have yet to be determined. Thus, our study aims to compare the immune status of IPA patients with the structural lung diseases chronic obstructive pulmonary diseases (COPD), interstitial lung disease (ILD) and non-cystic fibrosis bronchiectasis (NCFB). METHODS: This study was performed retrospectively with data collected over the years 2004 to 2013 at Shanghai Pulmonary Hospital, Tongji University, and included 77 patients whose lower respiratory tract (LRT) samples tested positive for. Our analysis considered blood examinations of CD3+, CD4+, CD8+, CD4+/CD8+, IgG, IgA and IgM levels. RESULTS: CD4+/CD8+ double positive cells, representing cell-mediated immunity, were less abundant in IPA patients with COPD than those with ILD and NCFB (0.81±0.09 vs. 1.39±0.25 and 0.81±0.09 vs. 1.57±0.06, respectively, P<0.001). In agreement with this result, corticosteroid and broad-spectrum antibiotic use were most common in individuals with COPD (57%). IgA levels, which indicate humoral immunity, were lower in IPA patients with NCFB than those with COPD or ILD (0.95±0.28 vs. 1.64±0.40 g/L and 0.95±0.28 vs. 3.16±0.83 g/L, respectively, P<0.001). CONCLUSIONS: Immunity status differs between IPA patients with different structural lung diseases. Among IPA patients with COPD, ILD and NCFB, those with COPD have the lowest cell-mediated immunity, while those with NCFB have the lowest humoral immunity.

Pulmonary Langerhans cell histiocytosis: analysis of 14 patients and literature review.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an orphan disease in respiratory medicine, which most affects adult smokers. The purpose of this article was to discuss the clinical features, especially the radiologic features of PLCH patients during their hospitalization through a retrospective analysis on clinical data. Furthermore, the current literature was also reviewed. METHODS: Between December 2008 and June 2012, 14 patients with PLCH were assessed at Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Among these patients, seven patients were diagnosed through tissue biopsy from the lung and one patient from enlarged cervical lymph nodes; the rest of six patients were diagnosed based on the clinical-radiological data. The data consisting of demographics, clinical presentation, smoking habits, pulmonary function tests (PFTs) and radiographic image from the medical records was analyzed retrospectively. RESULTS: The average age of patients (11 males and 3 females) was 42.79 (±13.71) years old. All male patients and one female patient had a long smoking history. The common manifestations were cough and exertional dyspnea. Spontaneous pneumothorax was found in three patients. Varieties of pulmonary shadows such as nodular, cystic, patch-like and cord-like were revealed by chest computed tomography (CT) examination. Large Langerhans cells (LCs) were discovered in biopsy tissue by immunohistochemical stains. CONCLUSIONS: PLCH is still an orphan disease and maybe related to smoking. Clinical symptoms such as cough and exertional dyspnea are non-specific. We shall pay attention to recurrent pneumothorax as clinically it is associated with PLCH. The characteristic radiological manifestation is cystic or nodular shadow in the lungs, which plays crucial roles in diagnosing PLCH.

Short-term Exposure to Ambient Fine Particulate Matter Increases Hospitalizations and Mortality in COPD: A Systematic Review and Meta-analysis.

BACKGROUND: Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide. METHODS: Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.5 µm (PM2.5) and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using a random effects model and a fixed effects model in COPD hospitalizations and mortality, respectively. RESULTS: The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies suitable for the mortality meta-analysis until April 15, 2015. A 10-µg/m(3) increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI, 1.6%-4.6%) increase in COPD hospitalizations and a 2.5% (95% CI, 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality. CONCLUSIONS: Our combined analysis indicated that short-term exposure to a 10-µg/m(3) increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to what extent this relationship is causal, together with other factors, and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations.

The existence of bronchiectasis predicts worse prognosis in patients with COPD.

Bronchiectasis is prevalent in patients with COPD. The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China. Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed. SPSS statistical software was used to analyze the data. Data from 896 patients with COPD were analyzed. Bronchiectasis was present in 311 patients. The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35-6.37; P = 0.007). During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group. The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02-3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD. These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum. Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD.

Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers.

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.