Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation

BACKGROUND:Early withdrawal of invasive mechanical ventilation(IMV) followed by noninvasive MV(NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD) with acute respiratory failure(ARF).Using pulmonary infection control window(PIC window) as the switch point for transferring from invasive to noninvasive MV,the time for early extubation can be more accurately judged,and therapy efficacy can be improved.This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy(FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV.METHODS:Since July 2006 to January 2011,106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization.Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used(group A,n=54) or not(group B,n=52) during sequential weaning from invasive to noninvasive MV.In group A,for sputum suction and bronchoalveolar lavage(BAL),a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube,which was accompanied with uninterrupted use of a ventilator.After achieving PIC window,patients of both groups changed to NIMV mode,and weaned from ventilation.The following listed indices were used to compare between the groups after treatment:1) the occurrence time of PIC,the duration of MV,the length of ICU stay,the success rate of weaning from MV for the first time,the rate of reventilatJon and the occurrence rate of ventilator-associated pneumonia(VAP);2) the convenience and safety of FOB manipulation.The results were compared using Student's f test and the Chi-square test.RESULTS:The occurrence time of PIC was(5.01 ±1.49) d,(5.87±1.87) d in groups A and B,respectively(P<0.05);the duration of MV was(6.98±1.84) d,(8.69±2.41) d in groups A and B,respectively(P<0.01);the length of ICU stay was(9.25±1.84) d,(11.10±2.63) d in groups A and B,respectively(P<0.01);the success rate of weaning for the first time was 96.30%,76.92%in groups A and B,respectively(P<0.01);the rate of reventilation was 5.56%,19.23%in groups A and B,respectively(P<0.05);and the occurrence rate of VAP was 3.70%,23.07%in groups A and B,respectively(P<0.01).Moreover,it was easy and safe to manipulate FOB,and no side effect was observed.CONCLUSIONS:The application of FOB in patients with AECOPD during sequential weaning of invasive-noninvasive MV is effective in ICU.It can decrease the duration of MV and the length of ICU stay,increase the success rate from weaning MV for the first time,reduce the rate of reventilation and the occurrence rate of VAP.In addition,such a method is convenient and safe in patients of this kind.

Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis:In vitro and in vivo study

Objective:To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice.Methods:GC/MS was used for analysis of active constituents of Calotropis gigantea extract.Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus.Neutropenic mice were randomly assigned into 5 groups:group 1 was neutropenic(control);group 2 was infected with Aspergillus fumigatus;group 3 was infected with Aspergillus fumigatus,and treated with Calotropis gigantea extract;group 4 was infected with Aspergillus fumigatus and treated with amphotericin B;group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B.Fresh lung tissues were histopathologically examined.Fungal burden and gliotoxin concentration were evaluated in lung tissues.Catalase,superoxide dismutase,and malondialdehyde content were determined in lung tissues.Myeloperoxidase,tumor necrosis factor-alpha,interleukin-1,and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay.Results:Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160μg/mL,respectively,for Aspergillus fumigatus.Additionally,Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95%and inhibited production of gliotoxin in lung tissues from 6320 to 1350μg/g lung.Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation.Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced.Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated Aspergillus fumigatus and leak of cellular components after damage of the cell wall.In vivo study revealed the suppression of lung tissue damage in mice of invasive pulmonary aspergillosis,which was improved with Calotropis gigantea/amphotericin B compared to the control group.Conclusions:Calotropis gigantea/amphotericin B is a promising treatment to reduce lung fungal burden and to improve the drugs’therapeutic effect against invasive pulmonary aspergillosis.

The Effect Analysis of Different Experimental Methods for the Diagnosis of Invasive Pulmonary Aspergillosis in a Rat Model

Background: Consensus on the most reliable assays to detect invasive aspergillosis from minimally or noninvasive samples has not been reached. In this study, we compared the efficacy of an enzyme-linked immunosorbent assay (ELISA) for galactomannan (GM) detection and quantitative real-time PCR assay (qRT-PCR) for the diagnosis of invasive pulmonary aspergillosis in a rat model. Methods: Neutropenic, male Sprague-Dawley rats (specific pathogen free;8 weeks old;weight, 200 ± 20 g) were immunosuppressed with cyclophosphamide and infected with Aspergillus fumigatus intratracheally. Tissue and whole blood samples were harvested on days 1, 3, 5, and 7 post-infection and examined with GM ELISA and qRT-PCR. Results: On day 7, A. fumigatus DNA was amplified from 14 of 48 whole blood samples from immunosuppressed infected rats: day 1 (0/12), day 3 (0/12), day 5 (6/12), day 7 (8/12) post infection. The sensitivity and specificity of the qRT-PCR assay were 29.2% and 100%, respectively. Receiver operating characteristic curve (ROC) analysis indicated a Ct cut-off value of 15.35, and the area under the curve (AUC) was 0.627. The GM assay detected antigen in sera obtained on day 1 (5/12), day 3 (9/12), day 5 (12/12), and day 7 (12/12) post-infection, and thus had a sensitivity of 79.2% and a specificity of 100%. The ROC of the GM assay indicated that the optimal cut-off value was 1.40 (specificity, 100%;AUC, 0.919). Conclusions: The GM assay was more sensitive than qRT-PCR assay in diagnosing invasive pulmonary aspergillosis in rats.

A Case of Invasive Pulmonary Aspergillosis Resulted from the Treatment of Chronic Eczema

This was an advanced male(87-year-old)with refractory chronic eczema for over 40 years,based on his allergic constitution,accompanied with chronic kidney disease due to primary hypertension(CKD,phase 3).It was so difficult to tolerate the severe itching that the glucocorticoids(GC)had to be applied to it,but some new-onset respiratory symptoms,such as cough,dyspnea after exertion etc.,occurred to this patient.Some classical IPA images were found on his pulmonary CT scanning,which were further comfirmed by the positive findings of GM-test,and then a final diagno­sis of IPA was accordingly established.Unfortunately,a persistent fever emerged after starting an antifungal therapy to the patient,and his IL-2 level was detected to be superhigh.As a response to allergic fever,GC was carefully given intravenously again to treat it,and it turned out to be totally improved since then;suggesting that systemic thinking(integrated with the other clinical evidences)is essential to diagnose IPA,and GC can also be used to improve its symptoms with the existence of antifungal therapy.

临床药师参与1例大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染治疗的药学实践

目的为大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染患者的抗菌药物方案调整、不良反应识别和个体化药学监护提供参考。方法临床药师参与1例大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染患者的治疗全过程,结合循证证据协助临床遴选初期抗皮疽诺卡菌感染的联合治疗方案,并及时沟通微生物室以提供早期药敏数据;在患者出现癫痫时甄别可疑药物,并提醒临床亚胺培南西司他丁钠会影响丙戊酸钠疗效,建议将丙戊酸钠换为左乙拉西坦抗癫痫治疗,并停用亚胺培南西司他丁钠;治疗期间,建议临床对伏立康唑、利奈唑胺进行血药浓度监测,并根据监测结果协助临床及时调整用药剂量。结果医生采纳临床药师建议。患者病情好转,带药出院。结论临床药师基于循证医学证据、药敏试验结果和血药浓度监测数据,协助临床为患者选择敏感的抗感染方案;及时识别不良反应并调整治疗方案,并为患者提供全程用药监护,保证了临床药物治疗的安全性和有效性。

重症患者侵袭性肺曲霉病的抗真菌治疗用药方案对比研究

目的对比分析不同抗真菌药物治疗方案用于ICU侵袭性肺曲霉病(Invasive pulmonary aspergillosis,IPA)患者的疗效和安全性。方法应用HIS系统回顾性收集2020年1月至2022年1月入住陕西省人民医院ICU并确诊为IPA患者的相关临床资料,比较伏立康唑单药、卡泊芬净单药或伏立康唑+卡泊芬净联合治疗等不同抗真菌治疗之间的临床疗效、ADR发生率和出院时的全因死亡率。结果共纳入40例患者,其中单药治疗组34例(伏立康唑组22例,卡泊芬净组12例),伏立康唑+卡泊芬净组6例。烟曲霉菌是IPA患者最常见的致病菌,其次为黄曲霉菌。临床疗效方面,单药治疗组与联合治疗组有效率差异无统计学意义(P=0.564),单用伏立康唑或卡泊芬净与伏立康唑联合卡泊芬净有效率比较,差异亦无统计学意义(P=0.280)。安全性方面,联合用药组的总ADR发生率略高于单药治疗组,但差异无统计学意义(P>0.05),联合用药组肾功能异常、肝功能异常、视觉异常及低钾血症例数与单药治疗组比较,差异无统计学意义,但联合用药组全血细胞减少的发生率高于单药治疗组(P<0.01)。全因死亡率方面,联合用药组高于两个单药治疗组(P<0.05)。结论伏立康唑仍是危重症IPA患者的首选治疗药物,卡泊芬净具有较好的临床疗效和安全性,可有效替代伏立康唑用于该类患者,而伏立康唑与卡泊芬净的联合治疗不会改善危重症IPA患者全因死亡率,并不推荐作为该类患者的初始治疗方案。

Prognostic value of serum galactomannan index in critically ill patients with chronic obstructive pulmonary disease at risk of invasive pulmonary aspergillosis

Background Critically ill chronic obstructive pulmonary disease （COPD） patients admitted to an intensive care unit （ICU） due to respiratory failure are at particularly high risk of Aspergillus infection.The serum galactomannan index （GMI） has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis （IPA） in classical immunocompromised patients.However,the prognostic value of serum GMI in critically ill COPD patients needs evaluation.The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.Methods In this single-center prospective cohort study,serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients＇ discharge or death.Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission.Univariate analysis and survival analysis were tested in these two groups.Results One hundred and fifty-three critically ill COPD patients were included and were divided into survival group （106 cases） and non-survival group （47 cases） according to their outcome.Univariate analysis showed that the highest GMI level during the first week after admission （GMI-high 1st week） was statistically different between the two groups.Independent prognostic factors for poor outcome in severe COPD patients were：GMI-high 1st week ＞0.5 （RR：4.04,95％ CI：2.17-7.51） combined with accumulative dosage of corticosteroids ＞216 mg before the RICU admission （RR：2.25,95％ CI：1.11-4.56） and clearance of creatinine （Ccr） ＜64.31 ml/min （RR：2.48,95％ CI：1.22-5.07）.Conclusions The positive GMI-high 1st week （＞0.5） combined with an accumulative dosage of corticosteroids ＞216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

Altered CD8＋ T-cell counts as an early predictor of prognosis in critically ill immunocompromised patients with invasive pulmonary aspergillosis

Background The number of critically ill immunocompromised （CIIC） patients has increased dramatically in recent years,and they represent a high risk population for invasive pulmonary aspergillosis （IPA） infection.Host immunity should play a major role in determining the outcome and recovery of these patients.The purpose of this study was to evaluate the dynamic changes in host immune status and its potential influence on prognosis in CIIC patients with IPA.Methods We monitored the evolution of a number of key cellular and humoral parameters on days 1,3,and 10 （D1,D3 and D10） following ICU admission in sixty-two CIIC patients with microbiological evidence of IPA.We included immunoglobulins IgG,IgA and IgM,complement factors C3 and C4,and lymphocyte subgroups CD3＋,CD4＋,CD8＋,CD28＋CD4＋,and CD28＋CD8＋ T cells,CD19＋B cells,and CD3-CD16＋CD56＋ natural killer cells （NK）.Results The primary outcome was 28-day mortality.Thirty-eight （61.3％） patients died within the 28 days following ICU admission.Compared to patients who died,CD3＋,CD8＋,CD28＋CD8＋ T-cell counts on D1,D3,and D10,CD28＋CD4＋ T-cell counts on D3 and D10,and NK counts on D3 and D10 were significantly higher in survivors.Receiver operating characteristic （ROC） analysis of immune parameters predicting 28-day mortality revealed area under the curve （AUC） values of 0.82 （95％ CI 0.71-0.92）,0.94 （95％ CI 0.87-0.99）,and 0.94 （95％ CI 0.85-0.99） for CD8＋ T-cell counts for D1,D3,and D10 respectively,and 0.84 （95％ CI 0.75-0.94）,0.92 （95％ CI 0.85-0.99）,and 0.90 （95％ CI 0.79-0.99） for CD28＋CD8＋ T-cell counts for D1,D3,and D10 respectively.Kaplan-Meier survival analysis showed that CD8＋ T-cell counts ＜149.5×106 cells/L and CD28＋CD8＋ T-cell counts ＜75×106 cells/L at ICU admission were associated with lower survival probabilities in CIIC patients with IPA （both Log rank：P＜0.001）.Conclusions Low CD8＋ and CD28＋CD8＋ T-cell counts were associated with high mortality in CIIC patients with IPA.Early counts of CD8＋ and CD28＋CD8＋ T cells in CIIC patients with IPA may be valuable for predicting outcome.

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis

Background:The incidence of chronic obstructive pulmonary disease(COPD)complicated with invasive pulmonary aspergillosis(IPA)has increased in the last two decades.The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear,and the role of T helper cells 17(Th17 cells)in the compound disease remains unknown.Therefore,this study aimed to assess the function of Th17 cells in COPD combined with IPA.Methods:COPD,IPA,and COPD+IPA mouse models were established in male wild type C57/BL6 mice.The amounts of Th17 cells and retinoic acid-related orphan receptorsγt(RORyt)were tested by flow cytometry.Then,serum interleukin(IL)-17 and IL-23.levels were detected by enzyme-linked immunosorbent assay(ELISA)in the control,COPD,IPA and COPD+IPA groups.In addition,COPD+IPA was induced in IL-17 knockout(KO)mice,for determining the role of Th17 cells in COPD+IPA.Results:Compared with the COPD group,the COPD+IPA group showed higher amounts of blood RORyt([35.09±16.12]%vs.[17.92±4.91]%,P=0.02)and serum IL-17(17.96±9.59 pg/mL vs.8.05±4.44 pg/mL,P=0.02),but blood([5.18±1.09]%vs.[4.15±0.87]%,P=0.28)and lung levels of Th17 cells(1.98±0.83]%vs.[2.03±0.98]%,P=0.91),lung levels of RORyt([9.58±6.93]%vs.[9.63±5.98]%,P=0.49)and serum IL-23(51.55±27.82 pg/mL us.68.70±15.20 pg/mL,P=0.15)showed no significant differences.Compared with the IPA group,the COPD+IPA group displayed lower amounts of blood([5.18±1.09]%vs.[9.21±3.56]%,P=0.01)and lung Th17 cells([1.98±0.83]%vs.[6.29±1.11]%,P=0.01)and serum IL-23(51.55±27.82 pg/mL vs.154.90±64.60 pg/mL,P=0.01)and IL-17(17.96±9.59 pg/mL uUs.39.81±2.37 pg/mL,P=0.02),while comparable blood([35.09±16.12]%Vs.[29.86±15.42]%,P=0.25)and lung levels of RORγt(9.58±6.93]%VUS,[15.10±2.95]%,P=0.18)were found in these two groups.Finally,Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice(1,851,687.69±944,480.43"vs.892,958.10±686,808.80,t=2.32,P=0.02).Conclusion:These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA,with L-17 likely playing an antifungal role.

气道侵袭性肺曲霉病21例CT征象分析

目的探讨气道侵袭性曲霉病(invasive pulmonary aspergillosis,IPA)的计算机断层扫描(computed tomography,CT)表现特点,旨在加强医师对气道IPA的认识并提高诊断水平。方法选取2018年8月—2023年6月在我院就诊的21例气道IPA,根据CT征象,分为3型,Ⅰ型累及小叶及段支气管,表现为支气管壁增厚;Ⅱ型病灶进一步发展,表现为小叶及段支气管扩张及周围实变;Ⅲ型累及细支气管及肺实质,细支气管壁增厚、周围树芽征及腺泡结节。详细分析3种类型的CT征象及鉴别诊断。结果21例气道IPA患者,Ⅰ型3例(14.3%),表现为段及小叶支气管管壁增厚,部分有树芽征及腺泡结节;Ⅱ型11例(52.4%),表现为段及小叶支气管扩张、周围实变;Ⅲ型7例(33.3%),表现为细支气管管壁增厚,周围树芽征、腺泡结节及斑片状模糊影。结论气道IPA具有特定的CT表现,掌握其CT分型及特征性征象,有助于临床早期诊断及治疗。

大鼠侵袭性肺曲霉菌病模型的建立

目的探讨正常SD大鼠侵袭性肺曲霉菌病(IPA)模型的建立方法。方法选择9只正常SD大鼠随机分为3组,A、B组经气管内滴注不同量曲霉菌孢子悬液,C组滴注生理盐水。结果A组接种后体重较接种前显著下降(P<0.05),B组接种后体重呈下降趋势但无差异显著性(P>0.05),C组接种后体重较接种前显著增加(P<0.05)。A组接种后第5、8天外周血白细胞数较接种前显著升高(P<0.05),B组白细胞数呈升高趋势但差异无显著性(P>0.05),C组白细胞数变化无显著性(P>0.05)。A、B组肺组织培养烟曲霉阳性且病理学表现为强烈的急性炎症反应,C组肺组织培养阴性且病理无急性炎症反应和曲霉菌丝及孢子。结论单次气道内滴注烟曲霉分生孢子悬液(浓度1×10^(9)cfu/mL,孢子量2×10^(8)/个)的方式可在正常免疫大鼠中稳定建立IPA模型。

非粒细胞缺乏的慢阻肺合并侵袭性肺曲霉菌病诊断及预后分析

目的 探究非粒细胞缺乏的COPD患侵袭性肺曲霉菌病的危险因素及实验室检查相关指标对其的诊断预测价值。方法 根据欧洲癌症/真菌病研究组织的标准收集了108例非粒细胞缺乏的COPD患者,并将他们分为非IPA组(n=76)、IPA组(n=32),其中临床诊断IPA组(n=14)和确诊IPA组(n=18),将IPA组分为存活组(n=22),死亡组(n=10),并进行回顾性分析。结果 IPA组和非IPA组年龄、性别方面没有显著差异。与非IPA组相比,IPA组糖尿病发生率更高,差异存在统计学意义(P<0.05)。IPA组的肺功能分级更高,差异存在统计学意义(P<0.05)。IPA组外周血淋巴细胞计数、白蛋白水平显著低于非IPA组,差异有统计学意义(P<0.05)。与非IPA组相比,IPA组血清IL-8、BALF IL-8和BALF半乳甘露聚糖水平显著升高(P<0.05),而两组间血清半乳甘露聚糖水平无明显差异(P>0.05)。单因素Cox回归分析示存活组与死亡组在淋巴细胞计数、白蛋白水平、血红蛋白、C-反应蛋白、降钙素原、白蛋白、血IL-8、BALF IL-8水平之间存在统计学差异(P<0.05),多因素Cox回归分析提示存活组与死亡组白蛋白水平存在统计学差异(P<0.05)。结论 当患者同时存在外周血淋巴细胞计数下降、BALF IL-8及BALF GM试验水平升高时更加提示COPD可能合并IPA。低白蛋白水平可能是非粒细胞缺乏的COPD患IPA的不良预后的独立危险因素。

CYP2C19 Genotyping Plus Therapeutic Drug Monitoring Dependent Voriconazole Treatment for Invasive Pulmonary Aspergillosis in a Patient with Liver Failure

Invasive pulmonary aspergillosis(IPA)is a lethal infectious disease with high mortality in patients with liver failure.Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes.Voriconazole is recommended as the first-line drug for IPA,but hepatotoxicity limits its use in the context of liver diseases.We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure.The polymorphism of cytochrome P450(CYP)isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole.However,the patient developed side effects such as skin rash,vomiting,hyperbilirubinemia,and alteration of consciousness,even if she received half of the recommended dosage for voriconazole.Therapeutic drug monitoring(TDM)was applied to guide the dosage adjustment of voriconazole in this patient,and consequently,the patient presented a favorable outcome.In conclusion,genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.

莫西沙星溶液雾化吸入配合无创呼吸机治疗慢性阻塞性肺疾病急性加重合并肺部感染的效果

目的 探讨莫西沙星溶液雾化吸入配合无创呼吸机治疗慢性阻塞性肺疾病急性加重(acute exacerbation of chronic obstructive pulmonary disease, AECOPD)合并肺部感染的效果。方法 选取2020年1月-2023年1月收治的AECOPD合并肺部感染120例,采用随机数字表法分为观察组和对照组各60例。2组均予以常规治疗,于此基础上,对照组予以无创呼吸机治疗,观察组予以莫西沙星溶液雾化吸入配合无创呼吸机治疗。2组均治疗2周。比较2组临床疗效及治疗前、治疗3 d后、治疗7 d后辅助呼吸肌评分、急性生理学和慢性健康状况评价Ⅱ(acute physiological and chronic health statusⅡ, APACHEⅡ)评分、血气分析[动脉血二氧化碳分压(partial pressure of carbon dioxide, PaCO_(2))、动脉血氧分压(arterial oxygen partial pressure, PaO2)、动脉血氧饱和度(arterial oxygen saturation, SaO2)]、血清炎性因子[肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白细胞介素-6(interleukin-6, IL-6)、C反应蛋白(C response protein, CRP)]、NOD样受体蛋白3(NOD-like receptor protein 3, NLRP3)/半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)/白细胞介素-1β(IL-1β)炎症免疫信号通路相关mRNA表达。结果 观察组总有效率[96.67%(58/60)]较对照组[85.00%(51/60)]高(P<0.05);治疗3 d、7 d后,观察组辅助呼吸肌评分、APACHEⅡ评分及TNF-α、IL-6、CRP水平、NLRP3、Caspase-1、IL-1β mRNA低于对照组(P<0.05);治疗3 d、7 d后,观察组PaO_(2)、SaO_(2)较对照组升高,PaCO_(2)较对照组降低(P<0.05)。观察组不良反应发生率[13.33%(8/60)]与对照组[8.33%(5/60)]比较差异无统计学意义(P>0.05)。结论 莫西沙星溶液雾化吸入配合无创呼吸机能改善AECOPD合并肺部感染患者血气指标,降低血清炎性因子,改善患者健康状况,疗效显著,可能与调节NLRP3/Caspase-1/IL-1β炎症免疫信号通路有关。

伏立康唑治疗肺部侵袭性真菌感染患者对肺功能指标及药学效果的影响分析

目的分析伏立康唑对肺部侵袭性真菌感染(Invasive Pulmonary Fungal Infections,IPFI)患者的治疗效果。方法方便选取于2021年10月—2023年10月江苏省无锡凯宜医院收治的102例IPFI患者为研究对象,以随机数表法划分为氟康唑治疗的对照组和伏立康唑治疗的研究组,各51例。比较两组肺功能指标、临床症状改善情况、不良反应发生率。结果治疗后,研究组1 s用力呼气容积占预计值百分比(Forced Expiratory Volume in One Second,FEV1)为(73.63±4.47)%、用力肺活量占预计值百分比(Forcedvital Capacity,FVC)为(75.17±7.42)%、FEV1/FVC为(90.04±6.12),均高于对照组,差异有统计学意义(t=6.843、3.481、6.175,P均<0.05);研究组发热、全身疼痛、咳嗽咳痰、肺部湿啰音改善时间均短于对照组,差异有统计学意义(P均<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论将氟康唑、伏立康唑用于IPFI患者,伏立康唑对患者的肺功能、临床症状改善效果明显优于氟康唑,并且具有一定安全性。

狼疮性肾炎继发侵袭性肺曲霉病的临床特征及预后

目的:回顾性分析狼疮性肾炎(LN)患者合并侵袭性肺曲霉病(IPA)的临床特征及预后。方法:选取2008年9月至2022年1月国家肾脏疾病临床医学研究中心收治的LN合并IPA的22例患者,分析其临床资料及预后。结果:22例LN患者发病年龄35.6±15.6岁,LN病程4.5(3,51)月,诊断IPA前6月内平均接受3种免疫抑制剂。IPA首发症状多为发热、咳嗽、咳痰(72.7%),以烟曲霉最为常见。7例(31.8%)患者在IPA起病3月内死亡,死亡组患者IPA起病前6月内24 h尿蛋白定量、IPA感染时乳酸脱氢酶及狼疮活动性指标显著高于存活组,CD20+B细胞计数显著低于存活组,治疗期间出现混合感染、入住ICU、需要丙种球蛋白/升白细胞药物、气管插管机械通气、连续性肾脏替代治疗(CRRT)的比例更高(P<0.05)。5例患者在随访中进入终末期肾病。结论:LN患者继发IPA的危险因素复杂,狼疮活动及免疫功能低下者预后更差。

免疫抑制介导大鼠侵袭性黑曲霉菌肺病模型的构建与评价

目的 本研究建立免疫抑制大鼠侵袭性黑曲霉菌肺病模型,为抗侵袭性肺曲霉病药物药效学评价及机制研究提供理论支持。方法 将60只SD大鼠随机分为正常对照组、环磷酰胺对照组、环磷酰胺+真菌感染低、中、高剂量组,每组12只动物。每天进行一般临床观察,分别于造模第3、7天采用ELISA法检测血清中免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、血清半乳甘露聚糖(GM)水平,并检测外周血CD4^(+)、CD8^(+)细胞比例及白细胞(WBC)、中性粒细胞(Neu)含量,同时观察肺泡灌洗液黑曲霉菌负荷和大鼠肺组织形态学变化。结果 环磷酰胺对照组、环磷酰胺+真菌感染低、中、高剂量组大鼠造模后均出现自主活动减少及竖毛,且环磷酰胺+真菌感染低、中、高剂量组大鼠伴有呼吸急促,可闻及肺部湿音;与正常对照组比较,环磷酰胺对照组大鼠血中CD4^(+)、WBC、Neu、IgG、IgM水平均显著减少,CD8^(+)比例显著增加(P<0.05,P<0.01);与环磷酰胺对照组比较,环磷酰胺+真菌感染中、高剂量组大鼠血中IgG、IgM、CD4^(+)水平均显著减少(P<0.05,P<0.01),环磷酰胺+真菌感染低、中、高剂量组大鼠血中WBC、Neu水平均显著减少(P<0.05,P<0.01),环磷酰胺+真菌感染中、高剂量组大鼠血中CD8^(+)水平显著升高(P<0.05,P<0.01),环磷酰胺+真菌感染低、中、高剂量组大鼠血中GM水平及肺泡灌洗液黑曲霉菌负荷均显著增加(P<0.05,P<0.01);环磷酰胺+真菌感染低、中、高剂量组大鼠肺组织出现菌丝分布和肺泡上皮破坏、肺泡内支气管上皮杯状细胞增多、炎症细胞浸润,其病变程度与造模剂量呈正相关。结论 本研究采用黑曲霉菌联合环磷酰胺免疫抑制剂构建侵袭性黑曲霉菌肺病模型,病程与菌液浓度和造模时间呈正相关,证实细胞免疫在该病发病机制方面中发挥重要作用,同时免疫球蛋白也可影响侵袭性肺曲霉病疾病的发展过程,推测侵袭性肺曲霉病发病机制可能与体液免疫中免疫球蛋白水平有关。

老年肺癌患者肺部侵袭性真菌感染影像学CT特征与PBMCs中CLRs表达的关系

目的探究肺部侵袭性真菌感染老年肺癌患者影像学CT特征与外周血单个核细胞(PBMCs)中C型凝集素受体(CLRs)表达的关系。方法选取100例老年肺癌患者,按有无肺部侵袭性真菌感染分为感染组和无感染组。比较两组影像学CT特征和PBMCs中CLRs的表达。COX回归分析患者感染的影响因素,明确影像学CT特征与PBMCs中CLRs表达的关系。结果与无感染组比较,感染组年龄≥80岁、应用糖皮质激素、应用抗生素时间>14天、侵入性操作、影像学CT分型弥散型占比明显升高,而影像学CT分型结节型占比、CLRs表达明显降低(P<0.05)。COX回归分析提示,年龄、应用糖皮质激素、应用抗生素时间、侵入性操作、CLRs表达是患者感染的影响因素(P<0.05)。感染组影像学CT特征为弥散型的患者CLRs表达明显低于其他型患者(P<0.05)。结论老年肺癌合并肺部侵袭性真菌感染患者影像学CT特征与PBMCs中CLRs表达有关,严格控制抗菌药物和激素的使用、减少侵入性操作,对降低患者肺部侵袭性真菌感染的发生风险有积极作用。

侵袭性肺曲霉菌病发病危险因素的研究进展

侵袭性肺曲霉菌病(invasive pulmonary aspergillosis,IPA)是一种死亡率较高的深部真菌感染性疾病,近几年发病率有上升的趋势,早期诊断和治疗有助于降低死亡风险,改善疾病预后。目前针对IPA诊断技术及治疗方法的研究较多,但缺乏对该病发病危险因素的系统分析。本文综合近几年的研究文献对IPA发病的基因易感因素、环境因素、合并疾病等危险因素进行综述,旨在为该病的早期预防和诊治提供参考。

肺泡灌洗液GM、IL-8试验在侵袭性肺曲霉病的临床诊断价值和意义

目的:探索肺泡灌洗液的GM、IL-8水平在侵袭性肺曲霉病的临床诊断价值和意义。方法:选取2021年01月~2023年04月在洛阳市中心医院住院的52例肺曲霉菌病患者为研究对象(包括确诊组10例,临床诊断组42例)。选取同期住院的93例肺部细菌性感染患者为对照组。所有住院患者均于治疗前完成支气管检查,并完成血液GM、IL-8水平和肺泡灌洗液GM、IL-8水平测定,并进行比较和诊断效能分析。结果:血清GM、肺泡灌洗液GM、血清IL-8、肺泡灌洗液IL-8水平四项指标在IPA组和非IPA组对比,U值分别为3448.500、1320.000、3922.000、3796.500,P值均小于0.001,差异有统计学意义。血清GM水平在0.365时,曲线下面积为0.713(P<0.001)(95%置信区间0.616~0.810),诊断效能最高,灵敏度59.6%,特异度81.7%;肺泡灌洗液GM水平在1.0时,曲线下面积为0.728(P<0.001)(95%置信区间0.643~0.813),诊断效能最高,灵敏度38.5%,特异度96.8%;血清IL-8水平在55.0时,曲线下面积为0.811(P<0.001)(95%置信区间0.728~0.893),诊断效能最高,灵敏度73.1%,特异度84.9%;肺泡灌洗液IL-8水平在933.5时,曲线下面积为0.785(P<0.001)(95%置信区间0.705~0.865),诊断效能最高,灵敏度50%,特异度97.8%。血清GM、肺泡灌洗液GM、血清IL-8、肺泡灌洗液IL-8水平四项指标联合诊断,灵敏度90.4%,特异度71.0%,PPV63.5%,NPV93%,约登指数0.614。结论:肺泡灌洗液GM和IL-8在IPA的诊断中具有一定的临床诊断价值,两者联合有望成为新的诊断方式。