造血干细胞移植后肺孢子菌肺炎23例临床研究

目的:分析异基因造血干细胞移植（allo-HSCT）后肺部危重并发症-肺孢子菌肺炎（PCP）的高危因素、临床特点及预后转归。方法:回顾性收集并分析2016年1月至2021年1月在本院血液科接受HSCT后发生肺孢子菌肺炎的患者的临床特征、实验室资料、治疗及转归。结果:共纳入23例符合PCP临床诊断标准的患者,PCP中位发病时间为移植后221 d;影像CT以弥漫性磨玻璃样渗出影为主。血清β-1,3-D葡聚糖（BDG）中位数为894.25 ng/L,共有91.3%的患者大于60 ng/L;60.9%患者的淋巴细胞计数低于1×10 9/L;65.2%的CD4 +T淋巴细胞绝对值低于200/μL。21例患者在肺泡灌洗液mNGS中检测到肺孢子菌属序列,15例患者为混合感染。治疗上给予TMP-SMX抗肺孢子菌后18例患者好转出院,5例死亡。 结论:HSCT后患者并发PCP为肺部急症,进展较快,常合并混合感染,血清BDG升高对PCP诊断具有指导意义,肺泡灌洗液中二代测序（mNGS）对肺孢子菌敏感性高,及早进行肺泡灌洗,有助于早期诊治,明显降低病死率;PCP患者进展为需要机械通气及高流量吸氧提示预后不佳。     

肺炎支原体肺炎患儿肺泡灌洗液病菌量与临床特征相关性研究

目的研究肺炎支原体(MP)肺炎患儿肺泡灌洗液(BALF)中MP-DNA基因拷贝数和患儿病情严重程度的关系。方法选取河北省儿童医院2012年10月至2013年12月收治的82例MP肺炎患儿作为研究对象,行支气管镜下支气管肺泡灌洗(BAL),采用荧光实时定量聚合酶链反应(FQ-PCR)对肺泡灌洗液中MP-DNA定量检测,并根据检测结果的基因拷贝数分为低菌量组(MP-DNA的拷贝数103/mL的患儿),中等菌量组(MP-DNA的拷贝数为103~106/mL的患儿)和高菌量组(MP-DNA的拷贝数106/mL的患儿)。比较不同菌量组患儿的临床症状、实验室检查结果和影像学结果。结果高菌量组患儿总病程长,高热患儿和热程大于或等于7d的患儿数量均多于中、低菌量组,使用大环内酯类药物后退热时间也较其他两组更长,差异均具有统计学意义(P=0.027、P=0.025、P=0.029、P=0.003)。实验室检查中高菌量组C反应蛋白值升高明显,高于中低菌量组,差异有统计学意义(P=0.005)。影像学检查中高菌量组大片肺实变、肺不张者较、低菌量组多(P=0.002)。低菌量组未见双侧胸腔积液或大量胸腔积液患儿,中高菌量组此症状患儿较多,差异有统计学意义(P=0.033)。结论 MP肺炎患儿BALF病菌量和临床表现密切相关,高菌量组患儿病情更为严重。可能与患儿体内的肺炎支原体不易清除和存在较强的免疫反应有关,临床需延长抗菌药物治疗时间以及加强免疫治疗。     

Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice

Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.     

Comprehensive lipid profiling of bleomycin‐induced lung injury

Drug‐induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting‐edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug‐induced lung injury. We used a mouse model of bleomycin‐induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory‐to‐fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether‐type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D₂, were elevated on day 2, and those of 5‐ and 15‐lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12‐lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti‐inflammatory responses in the inflammatory phase, phospholipidosis and anti‐inflammatory responses in the inflammatory‐to‐fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug‐induced lung injury.     

Pulmonary and systemic effects of mononuclear leukapheresis

Background and Objectives There is increasing evidence that monocytes play a key role in the pathogenesis of acute lung inflammation. Mononuclear cell (MNC) leukapheresis can be used to remove large numbers of monocytes from circulating blood; however, the detailed characteristics of monocyte subpopulations removed by MNC leukapheresis, and the biological effects on the lung, remain incompletely defined. Material and Methods Six healthy male volunteers underwent MNC leukapheresis of four total blood volumes. Blood was collected at 0, 2, 4, 6, 8 and 24 h; bronchoscopy with bronchoalveolar lavage (BAL) was performed at 8–9 h. Multiparameter flow cytometry was used to identify subpopulations of monocytes in blood and monocyte‐like cells in BAL fluid. Results A median of 5·57 × 10⁹ monocytes were retrieved. Blood monocyte counts indicated that the circulating blood monocyte pool was actively replenished during leukapheresis and subsequently contained a greater proportion of classical (CD14⁺⁺ CD16^?) monocytes. A particular subpopulation of monocyte‐like cells, reminiscent of classical monocytes, was also prominent in BAL fluid after leukapheresis. Conclusion Mononuclear cell leukapheresis was safe. The greater proportion of classical monocytes present in blood after MNC leukapheresis may be clinically significant. MNC leukapheresis also appears to affect the proportion of monocyte‐like cells in the lung; however, we found no evidence that leukapheresis has a clinically important pro‐inflammatory effect in the human lung.     

盐酸氨溴索注射液治疗脑外伤气管切开术后呼吸道感染的疗效观察

目的探讨盐酸氨溴索注射对脑外伤气管切开术后患者呼吸道感染的疗效。方法将2008年4月—2013年12月来上海中医药大学附属曙光医院就诊的76例接受气管切开术的颅脑外伤患者随机分为治疗组(38例)和对照组(38例)。对照组接受支气管肺泡灌洗,治疗组在对照组的基础上于气管切开第1天起iv盐酸氨溴索30 mg+18 mL生理盐水,3次/d,每次间隔8 h,连续使用1周。对比分析两组患者气管切开后呼吸道的感染及控制情况。结果第5、7天,治疗组肺泡灌洗液中白细胞个数明显少于对照组,两组比较差异有统计学意义(P<0.05)。第3、5、7天,治疗组肺泡灌洗液中多形核细胞数明显少于对照组,两组比较差异有统计学意义(P<0.05)。气管切开1个月后,治疗组和对照组呼吸道感染发生率分别为60.5%、92.1%,两组比较差异有统计学意义(P<0.05)。两组感染控制率分别为82.6%、57.1%,两组比较差异有统计学意义(P<0.05)。结论盐酸氨溴索注射液联合肺泡灌洗对脑外伤气管切开术后患者呼吸道感染的疗效显著,值得推广。     

Expression of Th1 markers by lung accumulated T cells in pulmonary sarcoidosis

OBJECTIVES: The balance between Th1 and Th2 T cells, classified by virtue of their cytokine production can in an immune response influence the phenotype and progression of several clinical diseases. In this study, we examined the expression of Th1 associated chemokine and cytokine receptors CXCR3, CCR5, and interleukin (IL)-12R, IL-18R, respectively, as well as of the Th2 associated chemokine receptors CCR4 and CXCR4 on CD4+ and CD8+ T cells. SUBJECTS: Eighteen patients with untreated pulmonary sarcoidosis. MATERIALS AND METHODS: We used monoclonal antibodies and flow cytometry to analyse the expression of chemokine receptors CXCR3, CXCR4, CCR4 CCR5 and cytokine receptors IL-12R, IL-18R in combination with anti-CD4 and anti-CD8 mAbs in bronchoalveolar lavage fluid (BAL) and peripheral blood lymphocytes (PBL) from sarcoidosis patients. RESULTS: There were significantly more BAL CD4+ T cells expressing CXCR3, CCR5, IL-12R and IL-18R compared with paired PBL CD4+ T cells. In contrast, the Th2 associated chemokine receptors CXCR4 and CCR4 were expressed by a fewer percentage of BAL CD4+ compared with PBL CD4+ T cells. There was a positive correlation between the percentage of BAL lymphocytes and the number of CXCR3 and CCR5 expressing CD4+ BAL T cells. Also, the number of CD4+ IL-18R+ BAL fluid cells correlated negatively with disease duration. CONCLUSIONS: The lung accumulation of CXCR3, CCR5, IL-12R and IL-18R expressing T cells is in line with previous reports showing elevated levels in the lung of the corresponding ligands in sarcodosis. Blocking such ligands and/or receptors may develop into a future immunomodulatory therapy.