scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals FSTL1 aggravates Cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2020 ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Copd Patients ◽  
Tnf Α ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for COPD. Follistatin-like protein 1(FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulaton, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1+/- mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA) ,an inhibitor of autophagy, were applied in CS exposed WT mice. The lung tissue and serum from patients and murine models were tested for FSTL1 and autophagy associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed by Electron Microscope Technology(EMT). LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined by ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS exposed WT mice. Autophagy activation was upregulated in CS exposed mice accompanied by airway remodeling and airway inflammation. FSTL1+/- mice showed a lower level of CS-induced autophagy compared with control mice. FSTL1+/- mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS exposed WT mice with 3-MA pretreatment have a similar manifestation with CS exposed FSTL1+/- mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke induced COPD.

scholarly journals Baicalin Exerts Anti-Airway Inflammation and Anti-Remodelling Effects in Severe Stage Rat Model of Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Genfa Wang ◽  
Nabijan Mohammadtursun ◽  
Yubao Lv ◽  
Hongying Zhang ◽  
Jing Sun ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Bronchoalveolar Lavage ◽  
Cigarette Smoke ◽  
Rat Model ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Airway Remodelling ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic. Current approaches are disappointing due to limited improvement of the disease development. The present study established 36-week side stream cigarette smoke induced rat model of COPD with advanced stage feature and evaluted the effects of baicalin on the model. Fifty-four Sprague–Dawley rats were randomly divided into six groups including room air control, cigarette smoke exposure, baicalin (40 mg/kg, 80 mg/kg, and 160 mg/kg), and budesonide used as a positive control. Rats were exposed to cigarette smoke from 3R4F research cigarettes. Pulmonary function was evaluated and pathological changes were also observed. Cytokine level related to airway inflammation and remodelling in blood serum, bronchoalveolar lavage fluid, and lung tissue was determined. Blood gases and HPA axis function were also examined, and antioxidant levels were quantified. Results showed that, after treatment with baicalin, lung function was improved and histopathological changes were ameliorated. Baicalin also regulated proinflammatory and anti-inflammatory balance and also airway remodelling and anti-airway remodelling factors in blood serum, bronchoalveolar lavage fluid, and lung tissue. Antioxidant capacity was also increased after treatment with baicalin in COPD rat model. HPA axis function was improved in baicalin treated groups as compared to model group. Therefore, baicalin exerts lung function protection, proinflammatory and anti-inflammatory cytokine regulation, anti-airway remodelling, and antioxidant role in long term CS induced COPD model.

scholarly journals Immunomodulatory Effects of Hydrolyzed Seawater Pearl Tablet (HSPT) on Th1/Th2 Functionality in a Mice Model of Chronic Obstructive Pulmonary Disease (COPD) Induced by Cigarette Smoke

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Zhenxing Chen ◽  
Qiangqiang Yan ◽  
Zhongmin Zhang ◽  
Taijin Lan ◽  
Peng Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
High Performance ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Mice Model ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death around the world. The present study is designed to investigate whether hydrolyzed seawater pearl tablet (HSPT) has immunoregulatory effects on the Th1/Th2 functionality in cigarette smoke-induced COPD model mice. The determination of the amino acid composition of HSPT was carried out by high-performance liquid chromatography (HPLC) with precolumn phenylisothiocyanate (PITC) derivatization. COPD model mice were constructed by cigarette smoking (CS) treatment and HSPT was administered. HSPT inhibited the infiltration of inflammation in the airway of the lung, reduced influx of eosinophils (EOSs), lymphocytes (LYMs), neutrophils (NEUs), and macrophages (MACs) in the bronchoalveolar lavage fluid (BALF), decreased the levels of IFN-γ, IL-2, IL-4, and IL-10 in the serum and lung, and decreased the expression of aforementioned cytokines in the spleen and lung in CS-treated mice. Besides, HSPT also had the ability to reduce the amount of CD3+CD4+ T cells and modulate the Th1/Th2 balance. Taken together, this study supports the consensus that CS is a critical factor to induce and aggravate COPD. HSPT could regulate the balance of Th1/Th2 in CS-induced COPD model mice, indicating its effects on inhibiting the development of COPD.

scholarly journals α1-Antichymotrypsin Mutations In Patients With Chronic Obstructive Pulmonary Disease

1998 ◽  
Vol 13 (4) ◽  
pp. 257-260 ◽  
Author(s):  
Andrew J. Sandford ◽  
Tabassum Chagani ◽  
Tracey D. Weir ◽  
Peter D. Parè
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Mutations in the α1-antichymotrypsin gene have been described which result in reduced levels of α1-antichymotrypsin in the serum. Previous studies have suggested that two of these mutations (Pro227→Ala and Leu55→Pro) predispose to chronic obstructive pulmonary disease (COPD). We have investigated the prevalence of these mutations in 168 COPD patients and 61 controls without airflow obstruction. The prevalence of the Pro227→Ala mutation was 0.9% and it was not associated with impaired lung function. None of the subjects had the Leu55→Pro mutation.

Screening of High-risk Patients for Chronic Obstructive Pulmonary Disease in Primary Care: A Narrative Review (Preprint)

2020 ◽  
Author(s):  
Ponrathi Athilingam ◽  
Andrew Bugajski ◽  
Usha Menon
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Current Knowledge ◽  
Screening Tools ◽  
Chronic Obstructive ◽  
Early Screening ◽  
Obstructive Pulmonary Disease ◽  
Impaired Lung Function ◽  
Risk Patients

UNSTRUCTURED Chronic obstructive pulmonary disease (COPD) predominantly affects older adults, and claimed 3 million lives in 2016, making it the third leading cause of death worldwide. Over 35 million Americans aged 40 or older have lung function consistent with diagnosable COPD. COPD and cardiovascular disease (CVD) have a bidirectional relationship, in that one is a risk factor for developing the other. National and international consortiums recommend early screening of adults at risk of COPD, such as those with CVD. Recommended screening strategies include screening tools to assess symptoms, medical history, and handheld spirometry. Handheld spirometry has high diagnostic accuracy and if impaired lung function is indicated, these patients are referred for pulmonary function testing (PFT), the diagnostic gold standard for COPD. However, there is no clinical consensus for pulmonary screening in people with CVD. Current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence is key in combating the global burden of COPD.

scholarly journals Classification of COPD patients and compliance to recommended treatment in Greece according to GOLD 2017 report: the RELICO study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nikolaos Tzanakis ◽  
Nikolaos Koulouris ◽  
Katerina Dimakou ◽  
Konstantinos Gourgoulianis ◽  
Epameinondas Kosmas ◽  
...  
Keyword(s):  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Medical Practitioners ◽  
Recommended Treatment ◽  
Copd Patients ◽  
Assessment Approach ◽  
Impaired Lung Function ◽  
Group B

Abstract Background Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece. Methods This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece). Results The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A. Conclusion Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.

scholarly journals Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary Inflammation via IκBα/NF-κB Signaling

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2489 ◽  
Author(s):  
Na-Rae Shin ◽  
Chul Kim ◽  
Chang-Seob Seo ◽  
Je-Won Ko ◽  
Young-Kwon Cho ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Pulmonary Inflammation ◽  
Water Extract ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Obstructive Pulmonary Disease ◽  
Cell Counts ◽  
Oxide Synthase

Galgeun-tang water extract (GGWE) is used to treat various diseases such as the common cold, eczema and asthma in China and Korea. In this study, we investigated the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The mice were exposed to CS for a total of seven days (eight cigarettes per day for 1 h) and LPS was administered intranasally to mice on day 4. GGWE was administered by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE decreased inflammatory cell counts, and expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha (IκBα) and nuclear factor kappa-B (NF-κB) in CS- and LPS-exposed mice. Histological examinations revealed that GGWE suppressed inflammatory cell infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary inflammation. Our results indicate that GGWE may be used as a protective drug to control pulmonary inflammation diseases such as chronic obstructive pulmonary disease.

Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

2020 ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Heat Shock ◽  
Lung Function ◽  
Heat Shock Protein ◽  
Disease Severity ◽  
Heat Shock Protein 70 ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Abstract Background: Extracellular heat shock protein 70 (eHsp70) acts like a damage-associated molecular pattern (DAMP) and it might modulate immune responses in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore plasma eHsp70 concentration in patients with stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment.Methods: Blood samples were collected from 137 COPD patients and 95 healthy individuals. COPD patients were subdivided into GOLD 2-4 stages based on airflow obstruction severity and GOLD A-D groups regarding symptoms and exacerbations. Concentration of eHsp70 was assessed in EDTA plasma by the commercially available ELISA kit. Statistic analysis was performed by MedCalc statistical software.Results: eHsp70 concentration was increased in COPD patients when compared to controls and was increasing with the severity of airflow limitation as well as symptoms burden and exacerbation history. There were no differences in eHsp70 concentrations among COPD patients based on smoking status, yet eHsp70 was increased in healthy smokers compared to healthy non-smokers. Interestingly, healthy smokers had similar eHsp70 level as COPD patients in GOLD 2 stage and those in GOLD A group. In addition, eHsp70 showed significant negative correlation with lung function parameters FEV1 and FEV1/FVC and positive correlation with COPD multicomponent indices BODCAT, BODEx, CODEx and DOSE. Finally, eHsp70 showed great predictive value (OR=7.63) and correctly classified 76% of cases.Conclusions: Plasma eHsp70 is associated with COPD prediction and disease severity and might have a potential of becoming an additional biomarker in COPD assessment.

scholarly journals Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 157 ◽  
Author(s):  
Eitan Halper-Stromberg ◽  
Lucas Gillenwater ◽  
Charmion Cruickshank-Quinn ◽  
Wanda Kay O’Neal ◽  
Nichole Reisdorph ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Cell Metabolism ◽  
Lavage Fluid ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
False Discovery ◽  
Copd Patients ◽  
Clinical Covariates

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography–mass spectrometry (LC–MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10−4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

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