微创性肺表面活性物质治疗新生儿呼吸窘迫综合征的疗效及肺部影像学表现

目的探讨微创性肺表面活性物质(LISA)治疗新生儿呼吸窘迫综合征(NRDS)的疗效及肺部影像学表现。方法择取郑州市第二人民医院于2018年3月至2021年2月收治的70例NRDS患儿,随机分为两组。对照组实行INSURE治疗方案,观察组采用LISA治疗方案,比较两组临床治疗情况、血气分析指标、不良反应事件及肺部影像学表现。结果两组二次PS使用率、给药成功率、NAPAP时间及住院时间比较,差异无统计学意义(P>0.05);而观察组72h内MV率为8.57%,低于对照组(28.57%,P<0.05);于T₂、T₃、T₄及T₅时点,两组PaO₂水平较T1时点均上升,PaCO₂、FiO₂水平则下降(P<0.05);于T₄、T₅时点,观察组FiO2水平低于对照组(P<0.05);两组不良反应及并发症发生率比较,差异均无统计学意义(P>0.05);经影像学特征分析,两组共计7例重度病症(“雪花征”样肺实变,已累及所有分区)、48例中度病症(“雪花征”样肺实变,尚未累及全部肺野)及15例轻度病症(呈“磨玻璃征”样肺实变,累计范围不限),经PS治疗6h、12h及24h后,给予LUS复查,两组NRDS患儿肺脏影像学评分均低于治疗前(P<0.05)。结论LISA及INSURE治疗NRDS均可起到较好疗效,但LISA整体获益更高,血气指标有一定改善,可降低72h内MV使用率,且不增加不良反应事件风险。     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

Prenatal exposure to perfluoroalkyl substances,immune-related outcomes,and lung function in children from a Spanish birth cohort study

BackgroundPrenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study.MethodsWe assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003–2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests.ResultsThe most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): −0.17 (−0.34, −0.01) and −0.13 (−0.29, 0.03), respectively], but not at 7 years.ConclusionThis longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.     

低分子肝素钙治疗肺心病并呼吸衰竭的临床价值研究

目的探讨肺源性心脏病(肺心病)并呼吸衰竭患者运用低分子肝素钙进行治疗的临床应用价值。方法72例肺心病并呼吸衰竭患者,应用随机数字表法分为观察组和对照组,每组36例。对照组患者采取常规治疗,观察组患者在对照组上采用低分子肝素钙治疗。对比两组患者治疗前后动脉血气指标[氧分压(PaO2)、二氧化碳分压(PaCO2)及酸碱度(pH)值]及治疗效果。结果治疗前,两组患者的PaO2、PaCO2、pH值水平比较,差异无统计学意义(P>0.05);治疗后,观察组患者的PaO2(9.36±1.02)kPa明显高于对照组的(7.78±0.98)kPa,PaCO2(6.33±0.97)kPa明显低于对照组的(7.65±1.28)kPa,差异均具有统计学意义(P<0.05);两组患者pH值比较差异无统计学意义(P>0.05)。观察组患者总有效率为97.22%,显著高于对照组的83.33%,差异具有统计学意义(P<0.05)。结论针对肺心病并呼吸衰竭患者运用低分子肝素钙进行治疗,可有效改善患者的血气指标,提高治疗效果,具有较高的临床价值。     

射干麻黄汤治疗呼吸道感染后咳嗽的临床疗效及对免疫球蛋白指标的影响

目的:探讨射干麻黄汤治疗呼吸道感染后咳嗽的临床疗效。方法:将92例呼吸道感染后咳嗽患者按照随机对照法将患者分为治疗组和对照组,每组46例。比较两组治疗疗效、治疗前后中医证候积分、日间和夜间咳嗽症状积分,比较两组治疗前后免疫球蛋白指标水平。结果:治疗组治疗总有效率高于对照组(P<0.05);治疗组治疗后中医证候积分、日间和夜间咳嗽症状积分低于对照组(P<0.05);治疗组治疗后免疫球蛋白(Immunoglobulin,Ig)G、IgA和IgM指标高于对照组(P<0.05)。结论:在呼吸道感染后咳嗽风寒恋肺型患者西医治疗的基础上加用射干麻黄汤治疗,可有效减轻临床症状,提高机体免疫力和治疗疗效,值得推广应用。     

Relationship Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Etiology of Acute Kidney Injury (AKI)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first recognized in December 2019, it has resulted in the ongoing worldwide pandemic. Although acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are the main features of the disease, the involvement of other organs needs to be explored. There has been a growing concern regarding the association between acute kidney injury (AKI) and poor outcomes in SARS-CoV-2 patients. Based on current observational data, AKI is the 2^nd most common cause of morbidity and mortality behind ARDS in SARS-CoV-2 patients. Angiotensin-converting enzyme 2 (ACE2) receptor has been shown to be the cornerstone of SARS-CoV-2 infection and possibly plays a significant role in the occurrence of renal injury. The pathogenesis of AKI is likely multifactorial that involves not only direct viral invasion but also dysregulated immune response in the form of cytokine storm, ischemia to kidneys, hypercoagulable state, and rhabdomyolysis, among others. We performed a literature search of the Pubmed and Google Scholar database from 1996 to 2020 using the following keywords: severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, angiotensin-converting enzyme 2 receptor, and acute kidney injury to find the most pertinent and highest-quality of evidence. Any cited references were reviewed to identify relevant literature. The purpose of this review is to discuss, explore, and summarize the relationship between AKI in SARS-CoV-2 patients, with a focus on its epidemiology, association with ACE2 receptors, and pathophysiology of AKI.