“三伏贴”对慢性阻塞性肺病系统炎症的影响

目的：观察“三伏贴”对稳定期慢性阻塞性肺疾病（COPD）患者系统炎症的影响,并评价其有效性。方法：收集稳定期慢性阻塞性肺疾病患者60 例,按随机数字表随机分为“三伏贴”治疗组与安慰剂治疗组,每组30 例;在常规西医治疗的基础上,分别给予“三伏贴”和安慰剂贴敷治疗,分别在入伏、初伏、中伏及末伏进行4 次穴位贴敷,完成1 疗程治疗者共56 例。观察治疗前、1 个疗程结束时、治疗后3 个月、治疗后6 个月血清炎症因子的变化。应用酶联免疫吸附试验（ELISA）检测血清白细胞介素-8（IL-8）,免疫比浊法测定血清CRP,比较治疗前后两组间的炎症因子变化趋势,同时比较治疗前后两组间CAT 评分（COPD assessment test,CAT）、呼吸困难评分（MRC）及生存质量评分。结果：“三伏贴”组、安慰剂组血清IL-8、CRP随时间变化趋势不同;其中试验组血清炎症因子随时间呈逐渐下降趋势,但治疗后6 个月时炎症因子略有升高,而安慰剂组炎症因子水平呈逐渐升高趋势,治疗前试验组与安慰剂组炎症因子水平差异无统计学意义,治疗3个月后,两组患者IL-8、CRP水平差异即有统计学意义（P〈0.05）。试验组患者治疗后CAT 评分、MRC 评分较治疗前下降,生存质量评分升高,差异有统计学意义（P〈0.05）,而安慰剂组患者在治疗后CAT 评分、MRC评分较治疗前升高,差异有统计学意义（P〈0.05）,生存质量评分下降,差异有统计学意义（P〈0.05）。同一时间点,试验组较安慰剂组CAT 评分、MRC评分下降,生存质量评分明显升高,差异有统计学意义（P〈0.05）。结论：冬病夏治穴位敷帖可以改善COPD 患者生存质量,缓解症状,其作用机理可能与降低系统炎症相关因子有关。     

"三伏贴"对慢性阻塞性肺病系统炎症的影响

目的:观察"三伏贴"对稳定期慢性阻塞性肺疾病(COPD)患者系统炎症的影响,并评价其有效性。方法:收集稳定期慢性阻塞性肺疾病患者60例,按随机数字表随机分为"三伏贴"治疗组与安慰剂治疗组,每组30例;在常规西医治疗的基础上,分别给予"三伏贴"和安慰剂贴敷治疗,分别在入伏、初伏、中伏及末伏进行4次穴位贴敷,完成1疗程治疗者共56例。观察治疗前、1个疗程结束时、治疗后3个月、治疗后6个月血清炎症因子的变化。应用酶联免疫吸附试验(ELISA)检测血清白细胞介素-8(IL-8),免疫比浊法测定血清CRP,比较治疗前后两组间的炎症因子变化趋势,同时比较治疗前后两组间CAT评分(COPD assessment test,CAT)、呼吸困难评分(MRC)及生存质量评分。结果:"三伏贴"组、安慰剂组血清IL-8、CRP随时间变化趋势不同;其中试验组血清炎症因子随时间呈逐渐下降趋势,但治疗后6个月时炎症因子略有升高,而安慰剂组炎症因子水平呈逐渐升高趋势,治疗前试验组与安慰剂组炎症因子水平差异无统计学意义,治疗3个月后,两组患者IL-8、CRP水平差异即有统计学意义(P0.05)。试验组患者治疗后CAT评分、MRC评分较治疗前下降,生存质量评分升高,差异有统计学意义(P0.05),而安慰剂组患者在治疗后CAT评分、MRC评分较治疗前升高,差异有统计学意义(P0.05),生存质量评分下降,差异有统计学意义(P0.05)。同一时间点,试验组较安慰剂组CAT评分、MRC评分下降,生存质量评分明显升高,差异有统计学意义(P0.05)。结论:冬病夏治穴位敷帖可以改善COPD患者生存质量,缓解症状,其作用机理可能与降低系统炎症相关因子有关。     

Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

Background

Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure.

Methods

Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria.

Results

Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality.

Conclusions

In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures.     

Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study

Background

The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.

Methods

Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162). Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).

Results

Expression of CD11b was increased on circulating neutrophils from smokers with COPD. It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05). In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).

Conclusions

Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers.     

经鼻高流量湿化氧疗与无创正压通气在改善AECOPD患者二氧化碳潴留临床疗效的比较

目的:经鼻高流量氧疗(HFNC)已广泛应用于缺氧性呼吸衰竭患者的治疗.本研究分析了HFNC治疗对慢性阻塞性肺疾病急性加重(AECOPD)合并Ⅱ型呼吸衰竭的治疗效果.方法:本研究前瞻性观察分析了2017年1月至2019年1月入住我院呼吸科和重症医学科,诊断为AECOPD且合并有中度Ⅱ型呼吸衰竭(血气分析PaO2/FiO2...     

阿托伐他汀对慢性阻塞性肺疾病合并肺动脉高压患者外周血ROCK2激酶活性及肺动脉压力的影响

目的：探讨口服阿托伐他汀片对慢性阻塞性肺疾病（chronic obstructive pulmonary Disease,COPD）合并肺动脉高压（pul-monary hypertension,PH）患者外周血ROCK2激酶活性及肺动脉压力的影响。方法：选取COPD合并PH患者60例为研究对象,并将其随机分为对照组（给予吸氧、抗感染、化痰、平喘等基础治疗）和阿托伐他汀治疗组（在基础治疗的基础上给予阿托伐他汀片20mg／d治疗）;随访观察周期12周,于试验开始前和结束后检测外周血ROCK2的活性,利用彩色多普勒检测肺动脉压力的变化,肺功能变化（测定FEV1,FVC）。结果：与对照组比较,阿托伐他汀治疗可显著降低患者血浆中ROCK2的水平（P〈0．01）;降低患者的肺动脉压力,改善患者的肺功能（FEV1,FVC）,P均〈0．05。结论：在常规吸氧、抗感染等治疗的基础上,联合应用阿托伐他汀可显著降低ROCK2激酶的活性和肺动脉压力,从而改善肺功能。     

COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

Background

There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.

Methods

Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.

Results

Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.

Conclusions

Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.

Trial Registration

SCO104960, clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00292552","term_id":"NCT00292552"}}NCT00292552     

AMPK调控内质网应激抵抗COPD大鼠肺泡上皮细胞凋亡的实验研究

目的:初步探讨AMPK在内质网应激所致COPD大鼠肺泡上皮细胞凋亡中所起的作用及机制。方法:实验分三组:对照组,COPD模型组,AICAR干预组,以香烟烟雾烟熏加气管内滴注脂多糖方法构建COPD大鼠模型,取大鼠肺组织行HE染色病理观察,免疫组化,western blot检测p-AMPK/AMPK,ORP150,caspase-3及CHOP表达,TUNEL法检测各组凋亡情况。结果:病理HE染色提示模型组大量炎症细胞浸润,肺大疱形成,支气管壁发生狭窄;AICAR干预组炎症细胞较模型组减少。与正常对照组相比,免疫组化及western blot均提示模型组中p-AMPK和ORP150蛋白表达含量增强,差异有统计学意义(P0.05)。而AICAR干预组中p-AMPK/AMPK及ORP150蛋白表达较模型组明显上升,差异有统计学意义(P0.05)。内质网应激相关凋亡指标CHOP及caspase-3的表达在模型组明显增强,较正常组比较差异有显著性(P0.05),而AICAR组中凋亡指标较模型组明显下调。结论:AMPK可以保护肺泡上皮细胞免于香烟烟雾所致内质网应激凋亡,且有可能通过增加ORP150来实现其保护作用。     

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background

Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.

Methods

A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV₁, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.

Results

IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.

Conclusions

The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.

Trial registration

No.:{"type":"clinical-trial","attrs":{"text":"NCT00605540","term_id":"NCT00605540"}}NCT00605540     

急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物和病情严重程度的相关性CSCD

目的 探讨急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。方法 选择2018年3月至2019年9月我院收治的122例急性加重期慢性阻塞性肺疾病患者,根据其痰色评分分为1~2分组(n=30)与3~4分组(n=92),比较两组患者肺部微生物分布、病情严重程度分布、慢性阻塞性肺疾病评估测试(CAT)评分、白细胞(WBC)水平、C反应蛋白(CRP)水平,分析急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。结果 3~4分组患者肺部肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率与1~2分组比较差异无统计学意义(均P>0.05)。3~4分组患者鲍曼不动杆菌检出率显著高于1~2分组(P<0.05)。3~4分组患者病情严重程度分布与1~2分组比较差异有统计学意义(P<0.05)。3~4分组患者CAT评分、WBC水平、CRP水平均显著高于1~2分组(均P<0.05)。急性加重期慢性阻塞性肺疾病患者痰色评分与肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率无显著相关性(均P>0.05),而与鲍曼不动杆菌检出率、CAT评分、WBC水平、CRP水平、病情严重程度呈显著相关性(均P<0.05)。结论 痰色评分与急性加重期慢性阻塞性肺疾病患者肺部微生物和病情严重程度关系密切,有望成为临床评价该类患者肺部微生物分布及病情严重程度的方法之一。     

CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.

Methods

Bronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects. Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8. In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.

Results

IL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (P < 0.0001). In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (P < 0.0001). After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (P < 0.0001) and IL-17F (P < 0.0001) in COPD patients compared to controls. The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR. The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.

Conclusion

These findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches.     

盐酸莫西沙星治疗慢性阻塞性肺疾病急性加重期的疗效及安全性

目的 探讨盐酸莫西沙星序贯疗法治疗慢性阻塞性肺疾病急性加重期的临床疗效及安全性。方法 选取200例慢性阻塞性肺疾病急性加重期的患者,随机分为对照组和观察组,对照组静脉给予盐酸莫西沙星氯化钠注射液治疗,观察组采用莫西沙星序贯疗法进行治疗,前5日静脉给予盐酸莫西沙星氯化钠注射液,病情好转后口服盐酸莫西沙星片,考察两组治疗前、后肺功能指标参数及血液中IL-8、TNF-α水平,比较两组的临床疗效和安全性。结果 经治疗后,观察组临床总有效率为94.0%,与对照组的95.0%比较,差异无统计学意义（χ2=0.0481,P>0.05）;两组患者的肺功能指标参数与治疗前比较,差异有统计学意义（P＜0.05）,但观察组改善程度与对照组比较,差异有统计学意义（P＜0.05）;两组患者血液中IL-8、TNF-α水平与治疗前比较,差异有统计学意义（P＜0.05）,观察组与对照组比较,差异无统计学意义（P>0.05）;观察组不良反应发生率8.0%与对照组17.0%比较,差异有统计学意义（χ2=1.8514,P＜0.05）。结论 采用序贯疗法治疗慢性阻塞性肺疾病,具有安全、有效等优点,有较大的临床推广意义。     

Acute effects of cigarette smoking on inflammation in healthy intermittent smokers

Background

Chronic smoking is the main risk factor for chronic obstructive pulmonary disease. Knowledge on the response to the initial smoke exposures might enhance the understanding of changes due to chronic smoking, since repetitive acute smoke effects may cumulate and lead to irreversible lung damage.

Methods

We investigated acute effects of smoking on inflammation in 16 healthy intermittent smokers in an open randomised cross-over study. We compared effects of smoking of two cigarettes on inflammatory markers in exhaled air, induced sputum, blood and urine at 0, 1, 3, 6, 12, 24, 48, 96 and 192 hours and outcomes without smoking. All sputum and blood parameters were log transformed and analysed using a linear mixed effect model.

Results

Significant findings were: Smoking increased exhaled carbon monoxide between 0 and 1 hour, and induced a greater decrease in blood eosinophils and sputum lymphocytes between 0 and 3 hours compared to non-smoking. Compared to non-smoking, smoking induced a greater interleukin-8 release from stimulated blood cells between 0 and 3 hours, and a greater increase in sputum lymphocytes and neutrophils between 3 and 12 hours.

Conclusion

We conclude that besides an increase in inflammation, as known from chronic smoking, there is also a suppressive effect of smoking two cigarettes on particular inflammatory parameters.     

慢性阻塞性肺疾病患者外周血CD4~＋CD25~＋CD127~（（Low/-））调节性T细胞的检测及临床意义

目的：研究CD4＋CD25＋CD127（Low/-）调节性T细胞在慢性阻塞性肺疾病（COPD）急性发作期外周血中的比例改变及其临床意义。方法：以25例COPD急性发作期患者外周血为研究组,20名正常人外周血作为对照组,采用三色直接荧光素标记法和多参数流式细胞仪检测外周血CD4＋CD25＋CD127（Low/-）调节性T细胞的比例,同时检测外周血C-反应蛋白（CRP）、血沉（ESR）、免疫球蛋白（Ig）等水平。结果：COPD急性发作期患者外周血CD4＋CD25＋CD127（Low/-）调节性T细胞占外周血CD4＋T淋巴细胞的比例明显低于健康对照组（P〈0.01）。而COPD急性发作期患者外周血CRP、ESR、Ig等水平明显高于健康对照组（P〈0.05）。COPD患者外周血调节T细胞下降与CRP和IgG升高成负相关。结论：COPD患者外周血CD4＋CD25＋CD127（Low/-）调节性T细胞在CD4＋T淋巴细胞的比例明显减少,调节性T细胞等免疫调节因素可能在COPD的发病机制发挥重要作用。     

Accelerated extracellular matrix turnover during exacerbations of COPD

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.

Methods

69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up. Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).

Results

Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001). Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001). Pro-C3 levels were unchanged. At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

Conclusions

Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression.     

情绪调节自我效能感对慢性阻塞性肺疾病患者治疗的影响

目的:本研究探讨心理干预对患者情绪调节自我效能感的影响,分析情绪调节自我效能感对慢性阻塞性肺疾病患者治疗和康复的影响.方法:1)实验分为干预组(实验组)和非干预组(对照).2)情绪调节自我效能感量表评定患者干预前后的情绪调节自我效能感.3)对心理干预组进行随访,使用理性情绪化疗法、支持疗法、情绪宣泄法、康复指导及疾病意外应对指导进行干预.结果:1)为其1年心理干预有效降低疾病复发率、住院时间和住院频率.但对急性发作治疗期的治疗影响不显著.2)心理干预有效提高患者的情绪调节自我效能感.结论:心理干预有效提高患者的情绪调节自我效能感,促进缓解期的慢性阻塞性肺疾病患者的康复,并有效降低复发率.     

Roles of bioavailable iron and calcium in coal dust-induced oxidative stress: possible implications in coal workers' lung disease

Marked regional differences in prevalence of pneumoconiosis are apparent in the US despite comparable dust exposure. In the present study, we examined the ability of 28 coal samples to release bioavailable iron (BAI) and calcium, as well as other metals such as Cr, Ni, Cu, and Co, from three coalmine regions in Utah (UT), West Virginia (WV), and Pennsylvania (PA), respectively. BAI is defined as iron (both Fe 2+ and Fe 3+ ) released by the coals in 10 mM phosphate solution, pH 4.5, which mimics conditions of the phagolysosomes in cells. We found that coals from the UT, WV, and PA regions released average levels of BAI of 9.6, 4658.8, and 12149 parts per million (ppm, w/w), respectively, which correlated well with the prevalence of pneumoconiosis from that region (correlation coefficient r =0.92 ). The low levels of BAI in the UT coals were due to the presence of calcite (CaCO 3 ), which was shown to be preferentially acid solubilized before iron compounds. Release of iron by two coal samples from the PA and UT regions was further examined in vitro in human lung epithelial A549 cells. We found that the coal from PA, with a high prevalence of pneumoconiosis, released BAI in a dose-dependent manner, both in tissue culture media and in A549 cells. At 2 μg/cm 2 , levels of lipid peroxidation induced by the PA coal were increased 112% over control cells at 24 h treatment, and were sustained at this level for 3 days. The coal from UT, with a low prevalence of pneumoconiosis, induced a marginal increase in cellular iron at 5 and 10 μg/cm 2 treatments and had no effect on lipid peroxidation. Calcium levels in the cells treated with the PA and UT coals were 8.6 and 11.5 μmoles/10 6 cells, respectively, and were significantly higher than that in the controls (53 μmoles/10 6 cells). Our results suggest that the differences in the BAI content in the coals may be responsible for the observed regional differences in the prevalence of pneumoconiosis. Therefore, BAI may be a useful characteristic of coal for predicting coal's toxicity.     

Importance of Mast Cell Prss31/Transmembrane Tryptase/Tryptase-γ in Lung Function and Experimental Chronic Obstructive Pulmonary Disease and Colitis

Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-γ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31^−/− C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases.     

HFNC与NIV治疗合并Ⅱ型呼衰的COPD患者的临床疗效对比

摘要 目的：探讨高流量湿化治疗仪（HFNC）治疗合并Ⅱ型呼吸衰竭的慢性阻塞性肺疾病患者的临床效果及安全性。方法：选择2020 年 4 月至 2022 年 3 月就诊于我院的合并Ⅱ型呼吸衰竭的慢性阻塞性肺疾病的患者共151名。随机分为接受 HFNC治疗组和NIV治疗组（HFNC组77名,NIV组74名）。分别评估患者治疗前和治疗后1小时、24小时以及治疗结束前心率（heart rate,HR）、呼吸频率（respiratory rate,RR）、氧合指数（Oxygenation index,PaO₂/FiO₂）、CO₂分压（arterial partial pressure of CO₂,PaCO₂）的变化、治疗不耐受和失败、有气管插管需求的情况、住院时间以及住院死亡率。结果：治疗后,两组各有6名患者死亡,死亡率分别为HFNC组7.8%,NIV组8.2%,组间比较差异无统计学意义（P=0.94）。两组患者治疗前后HR、RR、平均动脉压、白细胞计数、中性粒细胞百分比、C-反应蛋白、降钙素原及PaO₂/FiO₂、PaCO₂、动脉血酸碱度均无明显统计学差异。与NIV组相比,HFNC组气道护理干预次数明显减少（4±1 vs 8±2,P<0.05）,皮肤破损发生率明显降低（5.2% vs 20.3%,P<0.05）,住院天数明显缩短（6±2 vs 8±2,P<0.05）。结论：HFNC治疗合并Ⅱ型呼吸衰竭的COPD 患者效果并不亚于NIV,且HFNC的安全性更高,可作为该类患者的首选通气支持治疗方式。     

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Chronic obstructive pulmonary disease affects 64 million people and is currently the fourth leading cause of death worldwide. Chronic obstructive pulmonary disease includes both emphysema and chronic bronchitis, and in the case of chronic bronchitis represents an inflammatory response of the airways that is associated with mucus hypersecretion and obstruction of small airways. Recently, it has emerged that exposure to cigarette smoke (CS) leads to an inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, causing airway surface liquid dehydration, which may play a role in the development of chronic bronchitis. CS rapidly clears CFTR from the plasma membrane and causes it to be deposited into aggresome-like compartments. However, little is known about the mechanism(s) responsible for the internalization of CFTR following CS exposure. Our studies revealed that CS triggered a rise in cytoplasmic Ca²⁺ that may have emanated from lysosomes. Furthermore, chelation of cytoplasmic Ca²⁺, but not inhibition of protein kinases/phosphatases, prevented CS-induced CFTR internalization. The macrolide antibiotic bafilomycin A1 inhibited CS-induced Ca²⁺ release and prevented CFTR clearance from the plasma membrane, further linking cytoplasmic Ca²⁺ and CFTR internalization. We hypothesize that CS-induced Ca²⁺ release prevents normal sorting/degradation of CFTR and causes internalized CFTR to reroute to aggresomes. Our data provide mechanistic insight into the potentially deleterious effects of CS on airway epithelia and outline a hitherto unrecognized signaling event triggered by CS that may affect the long term transition of the lung into a hyper-inflammatory/dehydrated environment.