Small airway immunoglobulin A profile in emphysema-predominant chronic obstructive pulmonary disease / 中华医学杂志(英文版)

BACKGROUND@#Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with "emphysema phenotype." The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.@*METHODS@#Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats.@*RESULTS@#Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15 ± 1.53 vs. 6.03 ± 0.85; 1.94 ± 0.66 vs. 1.67 ± 0.04; 41.69 ± 21.02 vs. 28.44 ± 9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89 ± 24.81 vs. 31.49 ± 9.28, P = 0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r = 0.45, P = 0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P > 0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P  0.05).@*CONCLUSION@#Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with "emphysema phenotype" preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.

Distribution of pathogenic bacteria and drug resistance analysis in patients with acute exacerbation of chronic obstructive pulmonary disease / 中国实用内科杂志

OBJECTIVE: To investigate the distribution of pathogenic bacteria and drug resistance analysis in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD), so as to guide clinical medication. METHODS: A retrospective study was conducted in Shanxi Dayi Hospital. Totally 1173 cases of AECOPD patients, hospitalized with infection from September 2013 to August 2018, were included. Then relevant laboratory data was collected, including sputum culture, drug sensitivity test, and some commonly used laboratory results. The data was analyzed. RESULTS: A total of 231 strains were isolated in 1173 AECOPD patients,the mian pathogenic bacteria were Gram-negative bacteria(115, 49.7%), fungi(66, 28.6%), Gram-positive bacteria(48, 20.8%),other bacteria(2, 0.9%). Drug-resistant strains of producing ESBLs mainly included Acinetobacter(88.9%), Escherichia coli(87.5%),Pseudomonas aeruginosa(70.6%) and Klebsiella pneumoniae(19.4%). The drug-resistance of Acinetobacter to carbapenems and quinolones was more than 70%. The drug-resistance of Escherichia coli to quinolones was 87.5%. The drug-resistance of Streptococcus pneumoniae to penicillin and first and second generation cephalosporins was 66.7%. The drug-resistance of Staphylococcus to penicillin and first and second generation cephalosporins, quinolones and methicillin was 92.3%, 76.9% and 46.2%, respectively. In all Gram-positive bacteria, drug-resistant strains for Vancomycin and linezolid can't be found. The positive rate of bacteria in the group of PaO_2≤60 mmHg(37.3%) was higher than that in the group of PaO_2> 60 mmHg(8.8%). The detection rate of bacteria in the WBC≥10×10~9/L group(18.7%), NLR≥7.3 group(19.7%)and PCT>0.5 ng/mL group(50.7%),which in turn was higher than that in the WBC90% group was 10.6%, 16.9% and 30.1%, respectively. The results of trend chi-square test showed that the detection rate of bacteria increased with the decrease of PaO_2 and the increase of WBC, Neu%, NLR and PCT. CONCLUSION: The distribution and drug resistance of pathogenic bacteria in sputum culture of AECOPD are serious, and the distribution of pathogens in AECOPD patients with different levels of PaO_2, WBC, Neu%, NLR and PCT was different. Therefore, we should pay more attention to sputum culture and some commonly used laboratory results in AECOPD patients, so as to provide the basis for the clinical medication.

Effects of L-borneol on chloride channel and cell volume in human umbilical vein endothelial cells / 中国药理学通报

Aim To study the effects of L-borneol on the chloride channel and cell volume of human umbili-cal vein endothelial cells (HUVECs). Methods Whole-cell patch-clamp technique was used to record chloride currents. The expression of ClC-3 protein was down-regulated by siRNA interference technique. The cell volume was measured by dynamic image analysis. Results 20 nmol·L-1L-borneol significantly activa-ted chloride current in HUVEC (79.59 ± 4.90) pA/pF, which could be inhibited by chloride channel blockers,NPPB and DIDS. The outward current inhib-itory rate of NPPB was (95.57 ± 2.57)%, while that of DIDS was (97.28 ± 6.36)%. The chloride current activated by L-borneol significantly decreased after the silence of ClC-3 (27.03 ± 3.89) pA/pF. Cell volume was markedly reduced by L-borneol (14.38 ± 1.58)%,which was inhibited after NPPB appliance. Conclusion L-borneol can activate ClC-3 chloride channel in HUVECs, which induces Cl- outflow then cell volume decrease.

Comparison of Serum Adiponectin in Smoke-induced Pulmonary Emphysema Rats Fed Different Diets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Smoking and body mass index (BMI) are the key risk factors for chronic obstructive pulmonary disease (COPD). Adiponectin with both anti-inflammatory and pro-inflammatory properties is a vital modulator of inflammatory processes, which is expressed in epithelial cells in the airway in COPD-emphysema. The aim of this study was to examine the effects of adiponectin on tobacco smoke-induced emphysema in rats, which were fed different diets.</p><p><b>METHODS</b>Seventy-six adult (6-8 weeks old) male Sprague-Dawley rats (average weight 220 ± 20 g) were exposed to smoke or smoke-free room atmosphere and fed different diets (regular, high-fat, or low-fat diets) for 6 months. The rats were randomly divided into six groups. They are nonsmoke-exposed regular diet (n = 10), nonsmoke-exposed high-fat diet (n = 14), nonsmoke-exposed low-fat diet (n = 14), smoke-exposed regular diet (n = 10), smoke-exposed high-fat diet (n = 14), and smoke-exposed low-fat diet groups (n = 14). A full 2 3 factorial design was used to evaluate the effect of independent variables on smoke exposure and different rearing methods. Serum adiponectin and inflammatory cytokines were measured by the enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Serum adiponectin levels in rats fed low-fat and regular diets exposed to smoke exposure were remarkably higher than that of rats exposed to room air while serum adiponectin levels of fat-rich diet rats exposed to tobacco smoke were lower than that of rats exposed to room air. Compared with regular diet or low-fat diet group, serum adiponectin levels in high-fat diet rats exposed to tobacco smoke were lower (t = 6.932, 11.026; all P < 0.001). BMI was inversely correlated with serum adiponectin levels (r = -0.751, P = 0.012). Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and 4-hydroxy 2-nonenal (HNE) levels in rats exposed to low-fat or fat-rich diets were remarkably higher than that of rats exposed to normal diets (IL-6, t = 4.196, 3.480; P < 0.01, P = 0.001; TNF-α, t = 4.286, 3.521; P < 0.01, P = 0.001; 4-HNE, t = 4.298, 4.316; all P < 0.001). In nonhigh-fat diet rats exposed to tobacco smoke, serum adiponectin levels correlated positively with serum IL-6, TNF-α, and 4-HNE, bronchoalveolar lavage cell count, and mean linear intercept. In contrast, in high-fat diet rats, serum adiponectin levels correlated inversely with these parameters.</p><p><b>CONCLUSIONS</b>In smoke-induced emphysema and fat-rich diet rat model, serum adiponectin level was decreased, and the anti-inflammatory effect was attenuated. By contrast, nonhigh-fat diet elevated serum adiponectin and enhanced the role of pro-inflammatory.</p>

Expression and significance of myeloid differentiation factor 88 in marrow dendritic cells in asthmatic rats with cigarette smoke exposure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Smoking causes frequent asthma attacks, leading to a rapid decline in lung function in patients with asthma, and it can also reduce the therapeutic effect of glucocorticoids in patients with asthma. Therefore, the present study aimed to investigate the effect of cigarette smoke on the expression of myeloid differentiation factor 88 (MyD88) in marrow dendritic cells (DCs) in asthmatic rats, and to explore the molecular mechanism of cigarette smoke exposure on asthma by DCs.</p><p><b>METHODS</b>Forty Wistar rats were randomly divided into the following groups: control, smoke exposure, asthma, and asthma combined with smoke exposure. The animal model was established, and then rat bone marrow-derived DCs were collected. Additionally, rat spleen lymphocytes and bone marrow-derived DCs were cultured together for mixed lymphocyte responses. Interferon (IFN)-gamma and interleukin (IL)-4, IL-10, and IL-12 expressions were determined by enzyme-linked immunosorbent assay (ELISA). MyD88 expression was determined by Western blotting. The proliferation of lymphocytes was examined with methyl thiazolyl tetrazolium (MTT) colorimetric assay.</p><p><b>RESULTS</b>MyD88 expression was decreased in the asthma combined with smoke exposure group compared to the asthma group (P < 0.01), and IL-10 and IL-12 expressions were decreased in the asthma combined with smoke exposure group compared to control group (P < 0.01). In addition, DCs stimulating activity on allogeneic lymphocytes were significantly decreased in the smoke exposure combined with asthma group compared to the control and asthma groups (P < 0.01). After allogeneic mixed lymphocyte responses, IL-4 expression was increased and IFN-gamma was decreased in the asthma group and the asthma combined with smoke exposure group compared to control group (P < 0.01). IL-4 expression was increased and IFN-gamma was decreased in the asthma combined with smoke exposure group compared to the asthma group (P < 0.01). The study also showed that MyD88 expression was positively correlated with IL-12 and IFN-gamma expressions and the activity of lymphocytes (P < 0.01), and negatively correlated with IL-4 expression (P < 0.01).</p><p><b>CONCLUSIONS</b>Smoking aggravates asthma by weankening immunological mechanism. MyD88-dependent pathways may play a role in the immunological balance and activation of lymphocytes.</p>

Effects of angiotensin II receptor antagonist on expression of collagen III, collagen V, and transforming growth factor beta1 in the airway walls of sensitized rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Repeated attacks of bronchial asthma lead to different degrees of airway remodeling, the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some growth promotion factors. Angiotensin II is a polypeptide that may be involved in airway remodeling. To evaluate its role in airway remodeling in asthma, we observed the effects of an angiotensin II type 1 receptor antagonist (valsartan) on the expression of collagen III, collagen V, and transforming growth factor beta1 (TGF-beta1) mRNA and protein in the airway walls of sensitized rats.</p><p><b>METHODS</b>Forty Wistar rats were randomly divided into 5 groups: control group, sensitized group, and valsartan groups 1, 2, and 3. The rats in the sensitized group and in valsartan groups 1, 2, and 3 were sensitized and challenged with ovalbumin. Rats in control group were sensitized and challenged with 0.9% NaCl. Rats from valsartan groups 1, 2, and 3 were drenched with valsartan (10 microg, 20 microg, or 30 microg, respectively) at the time of the ovalbumin challenges. The expression of collagen III, collagen V, and TGF-beta1 protein were detected using immunohistochemical method in combination with image analysis methods. The expression of TGF-beta1 mRNA was detected by in situ hybridization.</p><p><b>RESULTS</b>The expression in the airways of collagen III and collagen V was significantly higher in rats from the sensitized group (7.73 +/- 0.81, 1.34 +/- 0.28) and from valsartan groups 1, 2, and 3 (5.73 +/- 0.64, 1.13 +/- 0.15; 4.96 +/- 0.51, 0.98 +/- 0.08; 4.43 +/- 0.35, 0.93 +/- 0.06, respectively) than those in the control group (2.65 +/- 0.38, 0.67 +/- 0.08, P < 0.05). In addition, collagen levels were significantly lower in valsartan groups 1, 2, and 3 than those from the sensitized group (P < 0.05). The expression of TGF-beta1 mRNA and protein in the airways was significantly higher in rats from the sensitized group (20.49% +/- 3.46%, 29.73% +/- 3.25%) and from valsartan groups 1, 2, and 3 (16.47% +/- 1.94%, 19.41% +/- 1.87%; 14.38% +/- 1.58%, 18.29% +/- 1.43%; 12.96% +/- 1.73%, 18.63% +/- 1.11%, respectively) than that from the control group (7.84% +/- 1.61%, 5.63% +/- 1.07%, P < 0.05). TGF-beta1 mRNA and protein levels were significantly lower in valsartan groups 1, 2, and 3 than that in the sensitized group (P < 0.05).</p><p><b>CONCLUSIONS</b>Angiotensin II receptor antagonist valsartan can suppress synthesis of collagen III and collagen V by downregulating TGF-beta1 mRNA and protein expression. Valsartan can decrease airway remodeling and could play a role in asthma therapy.</p>