Showing papers by "Huahao Shen published in 2017"

Reference values for spirometry in Chinese aged 4-80 years.

Abstract: Background Although there are over 1.34 billion Chinese in the world, nationwide spirometric reference values for Chinese are unavailable, which is usually based on Caucasian conversion. The aim of this study was to establish spirometric reference values for Chinese with a national wide sample. Methods We enrolled healthy non-smokers in 24 centers in Northeast, North, Northwest, Southwest, South, East and Central China from January 2007 to June 2010. Spirometry was performed according to American Thoracic Society and European Respiratory Society guidelines. Reference equations were established using the Lambda-Mu-Sigma (LMS) method for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF) and maximal midexpiratory flow (MMEF). Popular Caucasian reference values adjusted with ethnic conversion factors were validated with Chinese measured spirometry data. The present study also compared with other published Chinese equations for spirometry. Results A total of 7,115 eligible individuals aged 4 to 80 years (50.9% females) were recruited. Reference equations against age and height by gender were established, including predicted values and lower limits of normal (LLNs). Validated with Chinese data, the mean percentage differences of Caucasian reference values adjusted with ethnic conversion factors were -10.2% to 1.8%, and the percentages of total subjects under LLNs were 0.1% to 8.9%. Compared with this study, the percentage differences of previous Chinese studies ranged from -17.8% to 11.4%, which were found to significantly overestimate or underestimate lung function. Conclusions This study established new reference values for better interpretation of spirometry in Chinese aged 4 to 80 years, while Caucasian references with adjustment were inappropriate for Chinese.

Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis.

Abstract: // Xiaohui Wang 1,2,* , Zhengqiang Bao 1,2,* , Xiaoju Zhang 3,* , Fei Li 1 , Tianwen Lai 1 , Chao Cao 1 , Zhihua Chen 1 , Wen Li 1 , Huahao Shen 1,4 and Songmin Ying 1,2 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China 2 Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China 3 Department of Respiratory Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, China 4 State Key Laboratory of Respiratory Diseases, Guangzhou, China * These authors have contributed equally to this manuscript Correspondence to: Songmin Ying, email: // Huahao Shen, email: // Keywords : PD-1, PD-L1, nivolumab, pembrolizumab, cancer Received : August 12, 2016 Accepted : March 01, 2017 Published : May 31, 2017 Abstract Background: PD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors Methods: We searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews Eligible RCTs that compared PD-1/PD-L1 inhibitors with other chemotherapy agents or placebo in solid tumor patients were included For each RCT, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), stable disease rate (SDR), progressive disease rate (PDR), and adverse events (AEs) were pooled for meta-analysis Findings: Based on an analysis of 10 eligible RCTs, PD-1/PD-L1 inhibitors were found to significantly improve PFS (Hazard ratio (HR), 065; 95% confidence interval (CI) 053 to 079, P <0001), OS (HR, 069; 95%CI 062 to 076, P <0001), and ORR (Risk Ratio (RR) 2 92; 95% confidence interval (CI) 206 to 415, P <000001) in all populations, including melanoma and NSCLC subgroups However, they failed to increase the DCR of cancer patients (RR 115; 95%CI 091 to 145, P =025) Furthermore, less AEs were observed in the PD-1/PD-L1 inhibitor groups than the control groups Interpretation: PD-1 inhibitors are more effective for improving the PFS, OS, and ORR of cancer patients with little toxicity, despite having little effect on increasing of the DCR

Bcl-2 Inhibitors Reduce Steroid-insensitive Airway Inflammation.

Abstract: Background Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies. Objective We sought to explore the underlying mechanisms of airway inflammation persistence, as well as corticosteroid resistance, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma. Methods Mouse models of either eosinophil-dominated or neutrophil-dominated airway inflammation were used in this study to test corticosteroid sensitivity in vivo and in vitro . We also used vav–Bcl-2 transgenic mice to confirm the importance of granulocytes apoptosis in the clearance of airway inflammation. Finally, the Bcl-2 inhibitors ABT-737 or ABT-199 were tested for their therapeutic effects against eosinophilic or neutrophilic airway inflammation and airway hyperresponsiveness. Results Overexpression of Bcl-2 protein was found to be responsible for persistence of granulocytes in bronchoalveolar lavage fluid after allergic challenge. This was important because allergen-induced airway inflammation aggravated and persisted in vav–Bcl-2 transgenic mice, in which nucleated hematopoietic cells were overexpressed with Bcl-2 and resistant to apoptosis. The Bcl-2 inhibitors ABT-737 or ABT-199 play efficient roles in alleviation of either eosinophilic or corticosteroid-resistant neutrophilic airway inflammation by inducing apoptosis of immune cells, such as eosinophils, neutrophils, T H 2 cells, T H 17 cells, and dendritic cells. Moreover, these inhibitors were found to be more efficient than steroids to induce granulocyte apoptosis ex vivo from patients with severe asthma. Conclusion Apoptosis of inflammatory cells is essential for clearance of allergen-induced airway inflammation. The Bcl-2 inhibitors ABT-737 or ABT-199 might be promising drugs for the treatment of airway inflammation, especially for corticosteroid-insensitive neutrophilic airway inflammation.

Autophagy as a double-edged sword in pulmonary epithelial injury: a review and perspective

Abstract: Pulmonary epithelial cells form the first line of defense of human airways against foreign irritants and also represent as the primary injury target of these pathogenic assaults. Autophagy is a rev...

A new antagonist for CCR4 attenuates allergic lung inflammation in a mouse model of asthma.

Abstract: CCR4 is highly expressed on Th2 cells. CCR4 ligands include CCL22 and CCL17. Chemokine-like factor 1 can also mediate chemotaxis via CCR4. We designed and synthetized novel CCR4 antagonists, which were piperazinyl pyridine derivatives, for disrupting the interaction between three ligands and CCR4. We also determined whether these novel CCR4 antagonists could alleviate allergic asthma in a mouse. For identifying the potent compounds in vitro, we used chemotaxis inhibition and competition binding assays induced by CCL22, CCL17 and one of CKLF1’s C-terminal peptides, C27. We found compound 8a which showed excellent potency in blocking the interaction of CCR4 and its three ligands. For studying the specificity of compounds, we chose chemotaxis inhibition assays with different receptors and ligands. We found compound 8a had excellent receptor specificity and exerted few influence on the interaction of other receptors and their ligands. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, compound 8a had no obvious cytotoxicity till the higher concentration (16 μM). For determining the potency of compounds in blocking the interaction of CCR4 in vivo, we used the ovalbumin induced allergic asthma model in mice. Our study demonstrated that CCR4 blockaded by compound 8a effectively attenuated airway hyperresponsiveness, airway eosinophilia and Th2 cytokines.

Neutrophilic Inflammation in the Immune Responses of Chronic Obstructive Pulmonary Disease: Lessons from Animal Models.

Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide, which is characterized by chronic bronchitis, destruction of small airways, and enlargement/disorganization of alveoli. It is generally accepted that the neutrophilic airway inflammation observed in the lungs of COPD patients is intrinsically linked to the tissue destruction and alveolar airspace enlargement, leading to disease progression. Animal models play an important role in studying the underlying mechanisms of COPD as they address questions involving integrated whole body responses. This review aims to summarize the current animal models of COPD, focusing on their advantages and disadvantages on immune responses and neutrophilic inflammation. Also, we propose a potential new animal model of COPD, which may mimic the most characteristics of human COPD pathogenesis, including persistent moderate-to-high levels of neutrophilic inflammation.

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

Abstract: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221)

Efficacy and safety of bronchoscopic lung volume reduction therapy in patients with severe emphysema: a meta-analysis of randomized controlled trials

Abstract: // Yong Wang 1 , Tian-Wen Lai 1 , Feng Xu 1 , Jie-Sen Zhou 1 , Zhou-Yang Li 1 , Xu-Chen Xu 1 , Hai-Pin Chen 1 , Song-Min Ying 1 , Wen Li 1 , Hua-Hao Shen 1, 2 and Zhi-Hua Chen 1 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China 2 State Key Lab of Respiratory Disease, Guangzhou, China Correspondence to: Zhi-Hua Chen, email: zhihuachen@zju.edu.cn Hua-Hao Shen, email: huahaoshen@zju.edu.cn Keywords: bronchoscopic lung volume reduction therapy, severe emphysema, meta-analysis, endobronchial coils, endobronchial valves Received: February 27, 2017 Accepted: June 29, 2017 Published: July 18, 2017 ABSTRACT BACKGROUND: Increasing randomized controlled trials (RCTs) indicate that bronchoscopic lung volume reduction (BLVR) is effective for severe emphysema. In this meta-analysis, we investigated the efficacy and safety of BLVR in patients with severe emphysema. METHODS: PubMed, Embase and the Cochrane Library and reference lists of related articles were searched, and RCTs that evaluated BLVR therapy VS conventional therapy were included. Meta-analysis was performed only when included RCTs ≥ 2 trials. RESULTS: In total, 3 RCTs for endobronchial coils, 6 RCTs for endobronchial valves (EBV) and 2 RCTs for intrabronchial valves (IBV) were included. Compared with conventional therapy, endobronchial coils showed better response in minimal clinically important difference (MCID) for forced expiratory volume in 1s (FEV1) (RR = 2.37, 95% CI = 1.61 – 3.48, p < 0.0001), for 6-min walk test (6MWT) (RR = 2.05, 95% CI = 1.18 – 3.53, p = 0.01), and for St. George’s Respiratory Questionnaire (SGRQ) (RR = 2.32, 95% CI = 1.77 – 3.03, p < 0.00001). EBV therapy also reached clinically significant improvement in FEV1 (RR = 2.96, 95% CI = 1.49 – 5.87, p = 0.002), in 6MWT (RR = 2.90, 95% CI = 1.24 – 6.79, p = 0.01), and in SGRQ (RR = 1.53, 95% CI = 1.22 – 1.92, p = 0.0002). Both coils and EBV treatment achieved statistically significant absolute change in FEV1, 6MWT, and SGRQ from baseline, also accompanied by serious adverse effects. Furthermore, subgroup analysis showed there was no difference between homogeneous and heterogeneous emphysema in coils group. However, IBV group failed to show superior to conventional group. CONCLUSIONS: Current meta-analysis indicates that coils or EBV treatment could significantly improve pulmonary function, exercise capacity, and quality of life compared with conventional therapy. Coils treatment could be applied in homogeneous emphysema, but further trials are needed.

Comparison of the roles of house dust mite allergens, ovalbumin and lipopolysaccharides in the sensitization of mice to establish a model of severe neutrophilic asthma

Abstract: Neutrophilic asthma (NA) is associated with a severe disease course and poor response to corticosteroids. The present study aimed to compare the effects of various concentrations of house dust mite (HDM) allergens, ovalbumin (OVA), the major egg allergen, and lipopolysaccharide (LPS) in combination on the onset of severe NA. Female C57BL/6 mice were grouped according to a random number table and intranasally sensitized with HDM/LPS/OVA extracts on days 0, 1 and 2 of the study. In group 1, mice received 50 µg HDM + 50 µg OVA + 15 µg LPS, mice in group 2 received 50 µg HDM + 100 µg OVA + 15 µg LPS, mice in group 3 received 100 µg HDM + 50 µg OVA + 15 µg LPS and those in group 4 received 100 µg HDM + 100 µg OVA + 15 µg LPS, while mice in the control group received saline only. The mice were then challenged by OVA solution with atomized excitation on days 14, 15, 18, 19 and 20 for 30 min each. Ethology, airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and specific cytokines interleukin 17A (IL-17A) and IL-4 in serum were assessed. Histological examination of inflammation by hematoxylin and eosin staining and immunohistochemical assessment of neutrophils (NEU), eosinophils (EOS), IL-17A and IL-4 were also performed. Compared with the control group, the HDM/OVA/LPS-sensitized groups 1-4 had markedly increased BALF cells, serum interleukin IL-17A and IL-4, inflammatory cell infiltration, EOS as well as IL-17A and IL-4 by immunohistochemical staining (all P<0.05). Among the four HDM/OVA/LPS-sensitized groups, mice of group 4 had higher AHR, a significantly higher total cell number, NEU and EOS in BALF as well as significantly higher NEU and NEU/EOS ratios according to immunohistochemical staining when compared to groups 1-3 (P<0.05 for all). In conclusion, sensitization with 100 µg HDM + 100 µg OVA + 15 µg LPS successfully established a severe asthma model with a predominantly neutrophilic inflammatory phenotype.

CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA-damaging therapeutic agents

Abstract: Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability. Moreover, we show that compromised CDK1 activity dramatically increases the efficacy of chemotherapeutic agents that kill cancer cells through perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor. Our study has revealed an important role for CDK1 in the DNA replication program, and suggests that the therapeutic targeting CDK1 may be a novel approach for combination chemotherapy.

Severe asthma and asthma-COPD overlap: a double agent or identical twins?

Abstract: Since the joint project of asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome first released by the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD), numerous debates have been triggered. However, the term asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) remained controversial. Furthermore, ACOS is replaced by asthma-COPD overlap (ACO) and the concept of a syndrome is no longer advised in GINA 2017. In 1961, “Dutch hypothesis” promulgated that the various forms of airway obstruction, including asthma, chronic bronchitis, and emphysema, should be considered as different expressions of one disease entity (1). Conversely, the opposing “British hypothesis” cited asthma and COPD as distinct clinical entities, with different inflammatory cells and mediators, in return, different responses to therapy (2).

The efficacy and safety of tivantinib in the treatment of solid tumors: a systematic review and meta-analysis.

Abstract: Background Tivantinib was designed to kill cancers by targeting the mesenchymal-epithelial transition (MET) protein. Although numerous tivantinib clinical trials are ongoing, tivantinib's efficacy and safety are still not clear. This meta-analysis was done to evaluate tivantinib's efficacy and safety in solid tumor treatment. Materials and methods PUBMED, EMBASE, and other databases were searched for eligible tivantinib clinical trials. The hazard ratio (HR) and 95% confidence interval (CI) of progression-free and overall survival (PFS and OS, respectively) were pooled and analyzed to evaluate tivantinib's efficacy. Data concerning adverse events (Grade ≥ 3) were pooled to calculate relative risks (RRs) with 95% CI for tivantinib-treated compared with control arms. Findings Patients (1824) from six randomized control trials (RCTs) were enrolled. Compared with controls, tivantinib produced a significant improvement in PFS (HR, 0.73; 95% CI 0.65-0.83) but not in OS. In the non-small-cell lung cancer (NSCLC) subgroup, tivantinib combined with erlotinib prolonged patients' PFS when compared with controls (HR, 0.75; 95% CI, 0.65-0.86). In the white population, tivantinib also significantly improve PFS between treatment and control arms (HR, 0.75; 95% CI, 0.65-0.87). Tivantinib significantly improved OS in patients with high levels of MET expression. Tivantinib was shown to increase the risk of anemia and neutropenia. Interpretation Tivantinib was better in prolonging PFS (not OS) in patients with solid tumors. High MET expression cancers may benefit from tivantinib. Tivantinib appeared to be well-tolerated by patients.

Deletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo.

Abstract: Shp2 played an important role in cigarette-smoke-mediated inflammation, surfactant homeostasis and asthmatic airway remodeling. However, whether shp2 plays a key role in epithelium-associated allergic reaction is still unknown. In this study, LPS and OVA were observed to induce the production of IL-25 in bronchial epithelial cells in vitro via the activation of MAPK p38 and JNK. Furthermore, blockage of Shp2 by its specific inhibitor PHPS1 or by siRNA-mediated depletion was found to reduce the production of IL-25 in epithelial cells as well as the up-regulated LPS-triggered activation of JNK but not p38. To confirm the role of intra-bronchial epithelial Shp2 in OVA-induced allergic reaction, we generated CC10-rtTA/(tetO)7-Cre/Shp2f/f mice, where Shp2 was conditionally knocked out in bronchial epithelial cells. Surprisingly, specific deletion of Shp2 in bronchial epithelial cells showed a mild but insignificant effect on the expressions of epithelium-derived cytokines as well as TH2 and TH17 polarization following allergen-induced murine airway inflammation. Collectively, our data suggested that deletion of Shp2 impaired IL-25 production in bronchial epithelial cells in vitro, but might yet have minor influence on OVA-induced allergic reaction in vivo.

The REACH study, a randomized controlled trial assessing the safety and effectiveness of the Spiration Valve System endobronchial therapy for severe emphysema: 12 month follow-up results

Abstract: The REACH study is the first multicenter randomized controlled trial conducted in China assessing the safety and effectiveness of endobronchial valve treatment for severe emphysema patients with complete fissures. The study objectives were target lobe volume reduction (TLVR) and significant improvement in lung function. 101 subjects, 66 treatment and 35 control, were enrolled at 12 study sites. Target lobe selection, based on visual HRCT identified an upper lobe in 55% and a lower lobe in 45% of patients. Treatment consisted of target lobe occlusion utilizing the Spiration Valve System (Olympus, USA). The control group received optimal medical management. 64.6% of patients at 12 months showed evidence of significant (TLVR at 350 ml MCID). Mean TLVR in treatment patients was 781 ml at 12 months. Compared to control, the treatment group achieved a significant and clinically meaningful improvement in FEV1 at the 1, 3, 6 and 12 month visits (16.8%, 14.2%, 20.7%, 22.8%) with a responder rate of approximately 39.8% at 12 months. Significant improvements were also observed for quality of life measures and 6MWT. Between the 6 and 12 month follow-up visits, there were 8 serious adverse events in the treatment group consisting primarily of acute COPD exacerbations (6), lung abscess (1) and pneumothorax (1). There was one control and no treatment group deaths. In conclusion, this is the first multicenter study comparing endobronchial valve therapy to medical arm control that has demonstrated 12 month sustained clinically meaningful benefit with acceptable adverse events for severe emphysema patients selected only by HRCT.

Breaking through Restricting Bottleneck for Better Asthma Control.

Abstract: Asthma is characterized by chronic bronchial inflammation, airway hyperresponsiveness induced by specific and nonspecific stimuli, reversible bronchial obstruction, and airway remodeling. Although standard asthma medications were applied, there are approximately 55% of patients with asthma still suffer from poorly or uncontrolled disease.[1,2] Uncontrolled asthma is associated with a worse life quality and a higher risk of asthma-related hospitalization and mortality, which results in heavy health care and socioeconomic burden.[3,4] Various factors contribute to the low control rates, such as less responsiveness to pharmacologic therapy, complications of other diseases, incorrect use of inhaler devices, poor medication compliance, and smoking.[5,6] In recent years, a lot of researchers have focused on making new exploratory interventions to improve asthma management and control.

Activating Transcription Factor 3 Is Essential for Cigarette Smoke-Induced Mucin Expression via Interaction with Activator Protein-1.

Abstract: Mucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction. This study aimed to investigate the role and molecular mechanisms of ATF3 in CS-induced Mucin 5AC (MUC5AC) expression. ATF3 was elevated in lung tissues of mice exposed to CS for 12 weeks. Treatment with CS extract significantly induced ATF3 expression and MUC5AC production in human bronchial epithelial cells, NCI-H292, and mouse tracheal epithelial cells. Interference of ATF3 significantly attenuated CS-induced MUC5AC expression in NCI-H292 and human bronchial epithelial cells. Mouse tracheal epithelial cells isolated from Atf3−/− mice also exhibited less MUC5AC production in response to CS extract treatment. In vivo, the Atf3−/− mice also displayed a significantly reduced mucus production relative to wild-type controls in response to chronic CS exposure. Furthermore, a chromatin immunoprecipitation assay revealed increased ATF3 binding to the MUC5AC promoter after CS treatment, and this transcriptional binding was significantly inhibited by knockdown of JUN, a subunit of activator protein-1. These results demonstrate that ATF3 may be involved in activator protein-1 signaling and transcriptional promotion of CS-induced MUC5AC expression in airway epithelial cells.

Anti-IgE therapy as novel target for asthma-COPD overlap syndrome: More questions before celebration

Abstract: To the editor,We read the pioneer work by Tat and colleagues [1] with great interest. The authors reviewed their experience of treating asthma-COPD overlap syndrome (ACOS) patients with the anti-Ig...

Cellular Mechanisms of the Adverse Respiratory Health Effects Induced By Ambient Particulate Matter: A Review and Perspective

Abstract: Environmental particulate matter (PM) pollution causes adverse respiratory health effects. Accumulating evidence suggests that exposure to high levels of PM, either acutely or chronically, is associated with increased loss of lung function, exacerbation, hospitalization, disease incidence, and/or mortality of certain chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease, and lung cancer. However, the detailed cellular mechanisms how PM induces the airway injury remain largely unknown. In this short review, we summarize recent advances on the fundamental mechanisms of PM-induced adverse respiratory health effects, with emphases on the damages in airway epithelial cells and the responses from the immune system. We further discuss the inadequacy of current studies and give a perspective on this burgeoning field.