ObjectiveTo investigate the protecting effect of rosiglitazone for lung in airway-instillation- lipopolysaccharides and smoke-induced chronic obstructive pulmonary disease (COPD) rat models.MethodsFifty male Wistar rats with the SPF standard were randomly divided into 5 groups (n=10). The rats were treated by airway-instillation-lipopolysaccharides and exposing to smoking to establish COPD rat models excepted normal group, and the treatment groups were received gavage rosiglitazone of 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg rosiglitazone daily for 30 days, and the normal group or model group was received gavage normal saline. All rats were sacrificed after 30 days' treatment, and the lung tissue section was stained by hematoxylin and eosin. The mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured in all groups. In addition, the protein levels of p-Stat3 and p-NF-κB were detected by immunohistochemistry.ResultsCompared with normal group, the inflammation and emphysema were observed in the lung of rats in model group, and the symptoms of the group treated with rosiglitazone were lighter than normal group. The lungs of rats treated with highest dose of rosiglitazone (0.2 mg/kg) were evaluated with lowest pathology assessment score among three treatment groups, but there was no significant difference of MLI or MAN among three treatment groups. Compared with normal group, the protein levels of p-Stat3 and p-NF-κB were increased in the lung and tracheal epithelium and lymphoid tissue of rats in model group, while the protein levels of p-NF-κB were decreased in these tissues and the protein levels of p-Stat3 were decreased in the lymphoid tissue after treatment with rosiglitazone, but the protein levels of p-Stat3 were not changed in the lung and tracheal epithelium.ConclusionRosiglitazone has a protective effect on the COPD rat models by inhibiting NF-κB pathway to reduce the inflammation of the lung parenchyma.
Objective Using a simple management strategy to investigate the etiologic spectrum of chronic cough in Chengdu city and its suburbs. Methods Chronic cough patients were randomly recruited fromthe outpatient clinic of Sichuan Provincial People ’s Hospital between July 2011 to May 2012. A conception of “Chronic Airway Inflammatory Cough Syndrome, CAICS”was established including several common causes of cough such as cough variant asthma ( CVA) , eosinophilic bronchitis ( EB) , atopic cough ( AC) , and atypical chronic bronchitis. Based on CAICS, a simplified suspected diagnosis procedure of chronic cough was conducted. Patients were empirically treated. Etiology and efficiency of chronic cough was analyzed. Results A total of 148 patients of chronic cough were recruited. The mean age was ( 43. 0 ±13. 0) years old. There were 72 male and 76 female patients with mean ages of ( 39. 7 ±10. 7) and ( 45. 0 ± 14. 2) years old respectively. The males were younger than the females ( P lt; 0. 05) . There was 96. 6% ( 143/148) of patients suspectedly diagnosed and 3.4% ( 5/148) patients were undiagnosed. The suspected causes of these chronic cough patients were as follows, ie. CAICS ( 57. 5% ) , upper airway cough syndrome ( UACS, 21. 5%) , gastroesophageal reflux cough ( GERC, 9. 1% ) , and others ( 8. 4% ) . A single possible cause was found in 95 patients ( 64.1% ) , two possible causes in 41 patients ( 27. 7% ) , and three possible causes in 3 patients( 2. 0% ) . 12.2% of chronic cough patients were combined with allergic rhinitis ( AR) . Among the diseases, CVA, CAICS and UACS were disposed to coexist with AR. The overall efficiency of empiric management strategy of chronic cough was 83. 7% .Conclusions The etiological spectrum of chronic cough in Chengdu acquired by this strategy was generally consistent with previous findings in China.The three most important causes of chronic cough in Chengdu were CAICS, UACS and GERC. This strategy was simple, effective, economic and feasible. It could be a primary management for chronic cough in some hospital.
ObjectiveThrough measuring fractional exhaled nitric oxide (FeNO) and eosinophil levels of peripheral blood in chronic obstructive pulmonary disease (COPD) patients with different phenotype of acute exacerbation frequency, to predict the therapeutic effect of glucocorticoid therapy and guide the clinical treatment of different subtypes patients with acute exacerbations of COPD.MethodsA total of 127 patients with acute exacerbation of COPD in Suining Central Hospital from February 2017 to October 2019 were recruited. They were divided four groups according to the number of acute exacerbations in the past one year and the treatment scheme, ie. a frequent acute exacerbation with glucocorticoid treatment group (34 cases), a frequent acute exacerbation with non-glucocorticoid treatment group (31 cases), a non-frequent acute exacerbation with glucocorticoid treatment group (30 cases), and a non-frequent acute exacerbation with non-glucocorticoid treatment group (32 cases). FeNO value, eosinophil ratio in peripheral blood, COPD assessment test (CAT) score, and interleukin-8 (IL-8) concentration were measured before and on the 10th day of treatment, and the differences within group and between groups before and after treatment were compared.ResultsCAT score, FeNO, eosinophil ratio and IL-8 level in the four groups were significantly improved on the 10th day after treatment (all P<0.05). The declines of FeNO value, eosinophil ratio, and IL-8 level on the 10th day of treatment compared with those before treatment in the frequent acute exacerbation with glucocorticoid treatment group and the frequent acute exacerbations with non-glucocorticoid treatment group were larger than those in the non-frequent acute exacerbation with glucocorticoid treatment group and the non-frequent acute exacerbation with non-glucocorticoid treatment group (all P<0.05). The declines of FeNO value, blood eosinophil ratio and IL-8 level in the frequent acute exacerbation with glucocorticoid treatment group were also statistically significantly larger than those in the frequent acute exacerbations with non-glucocorticoid treatment group (all P<0.05). The improvement of CAT score in the frequent acute exacerbation with glucocorticoid treatment group was greater than that in other three groups (all P<0.05). There was no significant difference in CAT score between the non-frequent acute exacerbation with glucocorticoid treatment group and the non-frequent acute exacerbation with non-glucocorticoid treatment group (P>0.05).ConclusionsThe degree of airway inflammation is more obvious in patients with frequent acute exacerbation phenotype of COPD. FeNO value can reflect the level of airway inflammation in patients with frequent acute exacerbation of COPD and evaluate the response to glucocorticoid therapy.
ObjectiveTo investigate the synergistic effect of cold stress plus particulate matter 2.5 (PM2.5) co-exposure on the occurrence of respiratory inflammation and the possible post-transcriptional regulation mechanism of cold inducible RNA-binding protein (CIRP).MethodsIn vivo and in vitro experiments were carried out, and the lung tissue specimens from human surgical resection were observed. The rat model and cultured airway epithelial cells 16HBE were respectively divided into four groups (n=8), namely blank control group, 5 °C/18 °C group, PM2.5 group and 5 °C/18 °C+PM2.5 group. The expression of mRNA and protein of representative inflammatory cytokines and CIRP of cultured airway epithelial cells and rat bronchial/pulmonary tissues were respectively detected by ELISA, qPCR, and Western blot. Furthermore, the temporal dynamics of CIRP distribution were observed by cellular immunofluorescence. Finally, immunohistochemical method was used to observe the localization and expression of CIRP in rat and human bronchial/pulmonary tissues at the same time.ResultsIn vivo experiments, the mRNA and protein expression levels of CIRP, interleukin-6, and tumor necrosis factor-α in 5 °C group and PM2.5 group were significantly higher than those in the control group (all P<0.05), while the expression level of mRNA and protein in 5 °C+PM2.5 group were increased most obviously (all P<0.01). The same rule also appeared in the experimental results of each group in the vitro experiment. In addition, CIRP was mainly located in the cell nucleus; compared with the control group, the intracellular shift of CIRP appeared in 18 °C group and PM2.5 group, while the migration phenomenon was most obvious in the 18 °C+PM2.5 group. In the immunohistochemistry of rat bronchus/pulmonary tissue, the expressions of CIRP in the 5 °C group and in the PM2.5 group were significantly higher than those in the control group, and the CIRP expression in 5 °C+PM2.5 group was increased most evidently. Moreover, CIRP was expressed in the bronchial epithelial mucosa of normal people and patients with chronic obstructive respiratory disease (COPD), and it is mainly located in the nucleus of airway mucosal epithelial cells. The CIRP expression of COPD patients was significantly higher than that in the normal population.ConclusionCold stress has a sensitizing effect on airway epithelial inflammatory response induced by PM2.5, and post-transcriptional regulation of CIRP translocation from nucleus to cytoplasm may be an important mechanism.
Objective To observe the effects of astaxanthin (AST) on the airway inflammation and remodeling in the asthmatic rats. Methods Fifty male Wistar rats were randomly divided into five groups (n=10 for each group): saline-sensitized and-saline-challenged group (the control group), bronchial asthma group (the asthma group), bronchial asthma+astaxanthin 5 mg/kg gavage treatment group (the AST 5 mg/kg group), bronchial asthma+10 mg/kg gavage treatment group (the AST 10 mg/kg group), and bronchial asthma+50 mg/kg gavage treatment group (the AST 50 mg/kg group). The level of interleukin-5(IL-5), interleukin-13(IL-13), interferon-γ(IFN-γ), tansforming growth factor-β (TGF-β), malondialdehyde (MDA) and superoxide dismutase (SOD) in the bronchoalveolar lavage fluid (BALF) and the total IgE level in the serum were measured using enzyme linked immunosorbent assay (ELISA).The infiltration of airway inflammatory cells and the degree of airway epithelial cells detachment, the extent of goblet cell hyperplasia and the severity of subepithelial collagen deposition were evaluated on the hematoxylin eosin (HE), periodic acid Schiff (PAS) and Masson trichrome stained lung sections. reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of mucin 5A and C (MUC5AC) messenger ribonucleic acid(mRNA) in lung tissue; Immunohistochemical staining was used to determine the expression of MUC5AC protein in the rat airway epithelium. Results The level of IL-5, IL-13, TGF-β, MDA and the total IgE in the serum respectively [(36.73±2.29), (53.99±2.70), (60.89±2.54)ng/mL,(18.65±0.76)umol/L, (54.50±2.91)ng/mL], the extent of inflammatory cells infiltration (46.24 ± 4.26), the extent of eosinophils infiltration (2.09± 0.13), the extent of epithelial cells detachment [(6.09±0.45)%], the extent of goblet cell hyperplasia [(13.65±1.90)%], the extent of subepithelial collagen deposition [(17.58±2.14)%], the MUC5AC mRNA expression level, and the lung tissue MUC5AC protein expression IOD value (187±12) in the asthma group were all higher than those in the control group (P<0.01 or P<0.001), the level of IFN-γ and SOD in the BALF[(26.38±1.70) ng/mL], [(16.37±1.22) U/L], was lower than that in the control group (P<0.001); The level of IL-5, IL-13, total IgE, TGF-β, MDA, the inflammatory cells infiltration in the airway epithelial, the degree of epithelial cell damage and detachment, the degree of goblet cell hyperplasia, the degree of subepithelial collagen deposition, the MUC5AC mRNA expression in lung tissue,and the MUC5AC protein expression in airway epithelial cells in the AST treated groups were all lower than those in the asthma group (P<0.05 or P<0.01 or P<0.001),the level of IFN-γ, SOD in the BALF was higher than that in the asthma group (P<0.05 or P<0.01). Conclusion Astaxanthin can inhibit airway inflammation, downregulate airway MUC5AC expression, inhibit goblet cell proliferation, and alleviate airway remodeling in rats with bronchial asthma.
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To explore the effects of dioscin (Dio) on airway inflammation and microRNA-155 (miR-155)/cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathways in asthmatic mice. Methods Seventy mice were randomly divided into control group, model group, inhibitor negative control group (inhibitor-NC group), miR-155 inhibitor group, and Dio group, Dio+miR-155 mimic negative control group (Dio+mimic-NC group), Dio+miR-155 mimic group, with 10 mice in each group. Using house dust mite to induce the preparation of asthma mouse models; enzyme linked immunosorbent assay was used to detect the levels of PGE2, tumor necrosis factor α (TNF-α), cysteyl leukotrienes (CysLTs), cysteyl leukotriene receptor 1 (CysLTR1) and interleukin (IL)-4, IL-5, IL-13 in mouse bronchoalveolar lavage fluid (BALF); hematoxylin-eosin and periodic acid-Schiff staining were used to observe the infiltration of inflammatory cells around the airway and the secretion of mucus by goblet cells; quantitative real-time PCR was used to detect the expression levels of miR-155 and COX-2 mRNA in mouse lung tissue; Western blot was used detect the expression of COX-2 protein in mouse lung tissue. Results MiR-155 inhibitor and Dio could reduce the levels of PGE2, TNF-α, CysLTs, CysLTR1 and IL-4, IL-5, IL-13 in BALF of asthmatic mice, reduce lung tissue inflammatory cell infiltration and goblet cell mucus secretion, and reduce lung tissue miR-155, COX-2 mRNA and protein expression; and miR-155 mimic could significantly weaken the anti-asthma effect of Dio. Conclusion The anti-asthma effect of Dio may be related to the inhibition of miR-155/COX-2/PGE2 pathway to reduce airway inflammation in asthmatic mice.
Objective To explore the effects of prolonged Aspergillus fumigatus spores inhalation on airway inflammation and remodeling in rats with chronic obstructive pulmonary disease（COPD）.Methods Fifty Wistar rats were randomly divided into group A，B，C，D and E，(n=10 in each group) and group E was served as normal control.In group A，B，C and D，COPD models were established by intratracheal administration of lipopolysaccharide (LPS) combined with cigarette smoke exposure.The rats in group A，B and C were given intranasal inhalation of 1×106cfu spores，1×103cfu spores and 100 mL saline twice a week for consecutive 5 weeks，respectively，while the rats in group D were given no treatment.Bronchoalveolar lavage fluid(BALF) were collected for total and differential cell count，and interleukin-8（IL-8） and transforming growth factor-b(TGF-b) concentration measurement.The pathologic changes of lung tissue were observed by HE，PAS and Masson stainings.Results Pathological changes characteristic of COPD were found in group D.The total cell count，the percentage of neutrophile and lymphocyte in BALF in group A and B were higher than those in group C and D(all Plt;0.01).IL-8 and TGF-b in BALF in group A and B were higher than those in group C and D(all Plt;0.01).The pathologic score of airway inflammation in group A was higher than those in group B，C and D(all Plt;0.01)：The thickness of airway wall(WAt/Pbm) and airway smooth muscles(WAm/Pbm)，the collagen deposition in the total airway wall(WCt/Pbm) and in the outer airway wall(WCo/Pbm) and the percentage of goblet cells to epithelial cells in group A and B were higher than those in group C and D(all Plt;0.01).In group A and B，IL-8 was positively correlated with the percentage of neutrophile(r=0.856，Plt;0.01)，the pathologic score of airway inflammation(r＝0.884，Plt;0.01)，and the percentage of goblet cells to epithelial cells (r=0.702，Plt;0.05)，respectively.TGF-b was positively correlated with WAt/Pbm，WCt/Pbm，WCo/Pbm and the ratio of goblet cells to epithelial cells (r=0.706，Plt;0.05：r=0.802，Plt;0.01：r=0.876，Plt;0.01：r=0.713，Plt;0.05).Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate the airway inflammation and remodeling in rats with COPD.
0bjective To study the effect of bacterial infection on acute exacerbation of chronic obstructive pulmonary disease(AECOPD)，and to compare the airway inflammation caused by different isolated bacteria．Methods A total of 159 sputum samples were collected from AECOPD patients diagnosed according to GOLD 2004 standard，in which conventional culture and identification of bacteria was conducted．The patients with purulent sputa were divided into different groups according to bacteria separated．Levels of IL-6．IL-8 and TNF-α in sputum supernatant were assayed and compared in different bacteria groups．the purulent sputum without isolated bacteria group(NG)and normal control group(NC)． Results One hundred and twenty-nine strains of bacteria were isolated in 159 qualified sputa，including 26 strains of Klebsiella pneumoniae(KB)，21 strains of Hemophilus influenza(Hi)，17 strains of Pseudomonas aeruginosa(PA)，37 strains of Haemophilus parainflb~enzae(HP)(mixed infection not included)and 28 strains of other bacteria．Among of all samples，20 were double infection of Haernophilus parainfluenzae with another bacterium．Ninety-seven purulent sputa were collected．According to bacteria isolated，these sputa were divided into five groups，named HP(24 samples)，Hi(20 samples)，PA(16 samples)，KB(19 samples)and NG(18 samples)．Contrast to NC，concentration of IL-8 and TNF-α rose in sputa from which PA，Hi，KB were isolated(Plt;0．05)．The level increased much more in sputa from which PA and Hi were isolated compared with KB(Plt;0．05)．Concentration of IL-6 rose in sputa of each group collected from AECOPD patients contrast to sputa collected from NC(Plt;0．05)，without significant differences among all other group except for NC．Conclusions Bacterial infection plays an important role in AECOPD characterized with high level of inflammatory factors especially when PA，Hi，KB were infected bacteria．This study provides evidence for antibacterial therapy in AECOPD patients．
ObjectiveExploring the potential causal effects and directions of insulin resistance (IR) and chronic airway inflammatory diseases, including asthma and chronic obstructive pulmonary disease (COPD), through two sample Mendelian randomization (MR). MethodsA total of 53 validated single nucleotide polymorphisms (SNPs) associated with IR were selected as instrumental variables. The inverse variance-weighted (IVW) method was used to model the causal association, and sensitivity analyses through leave-one-out analysis and pleiotropy testing were conducted to assess the relationship between IR and asthma and COPD. ResultsMR analysis revealed no significant causal effect of IR on asthma (IVW: OR=1.067, 95%CI 0.871 to 1.306, P=0.531) or COPD (IVW: OR=0.906, 95%CI 0.686 to 1.196, P=0.557). The results were consistent across sensitivity analyses and multiple pleiotropy tests, with no evidence of horizontal pleiotropy detected. ConclusionNo causal association was found between IR and the development of asthma or COPD. The relationship between these conditions may be influenced indirectly through complex interactions between metabolic and inflammatory pathways affecting disease progression.