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。     

危重型毛细支气管炎抢救体会：附31例分析

231例毛细支气管炎,危重型38例占16.4％,抢救成功31例占81.6％。本文讨论了危重型毛细支气管炎并多器官功能衰竭的发生与预后及平喘药物的合理选用。认为早期应用免疫疗法、迅速平喘、保护重要器官功能及合理治疗并存症是抢救成功的关键。     

二丙酸倍氯米松联合酮替芬防治毛细支气管炎后婴幼儿哮喘的研究

目的　观察低剂量二丙酸倍氯米松和酮替芬联合应用能否降低毛细支气管炎后支气管哮喘患病率。方法　 5 6例毛细支气管炎患儿为治疗组 ,采用低剂量二丙酸倍氯米松局部吸入 ,口服酮替芬 ,疗程 6～ 9个月 ;32例毛细支气管炎患儿不用药作为对照组。临床随访≥ 1年 ,观察两组患儿哮喘发生率。同时检测治疗前、后患儿肺功能及骨密度。结果　完成随访 1年以上者 ,治疗组 5 2例中仅 3例 (5 77% )发生哮喘 ,而对照组 30例中有 14例 (4 6 6 7% )发生哮喘 ,两组比较有显著性差异 (P <0 0 1)。治疗组患儿肺功能与治疗前比较亦有显著性差异。两组骨密度检测治疗前、后比较无显著差异。结论　低剂量二丙酸倍氯米松局部吸入与酮替芬联合应用可降低毛细支气管炎后婴幼儿哮喘患病率     

Broncho-alveolar Lavage Matrix Metalloproteases as a Sensitive Measure of Bronchiolitis Obliterans

Bronchiolitis obliterans (BO) is a survival-limiting factor in lung transplantation. There are no common BO markers in use. Since BO is associated with extracellular matrix remodeling, we asked whether matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) could serve as BO markers. In 72 lung transplant patients (34 BO syndrome (BOS) 0, 15 BOS 0-p, and 23 BOS 1) serum and broncho-alveolar lavage (BAL) MMP and TIMP levels were examined by ELISA. The BAL cell counts were additionally analyzed. The serum MMP-2, MMP-8, MMP-9 and TIMP-2 levels were not different in all groups. In contrast, the BAL MMP-8, -9 and TIMP-1 levels were significantly elevated in BOS 0-p (p = 0.003; p = 0.007; p = 0.0003, respectively) and BOS 1 (p = 0.003; p = 0.001; p = 0.0004, respectively) as compared to BOS 0 patients. The BAL MMP-8, -9 and TIMP-1 levels were significant predictors of BOS 0-p (p = 0.01; p = 0.01; p = 0.01, respectively) and BOS-1 (p = 0.007; p = 0.01; p = 0.006, respectively) in receiver operating characteristic analysis. Except for BAL macrophages that were significantly decreased in BOS 0-p versus BOS 0 patients; other cell counts were not different between the groups. BAL MMP-8, -9 and TIMP-1 might be useful markers to detect BO in lung transplant patients.     

Clinical Impact of Community-Acquired Respiratory Viruses on Bronchiolitis Obliterans After Lung Transplant

Community-acquired viral respiratory tract infections (RTI) in lung transplant recipients may have a high rate of progression to pneumonia and can be a trigger for immunologically mediated detrimental effects on lung function. A cohort of 100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and throat swabs taken for respiratory virus antigen detection, culture and RT-PCR. All patients had pulmonary function tests at regular intervals for 12 months. Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and bacterial and fungal superinfection were compared at the 3-month primary endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33 of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI patients (p=0.006). The number of patients experiencing a 20% or more decline in FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p=0.003). In six of these nine patients, the decline in FEV-1 was sustained over a 1-year period consistent with bronchiolitis obliterans syndrome (BOS). Community-acquired respiratory viruses may be associated with the development of acute rejection and BOS.     

Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and >or=A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from >or=A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection.     

Wheezing at 8 and 13 years: changing importance of bronchiolitis and passive smoking

A group of 153 children (51 with a history of bronchiolitis and 102 matched controls) were evaluated in a historical cohort study at a mean age of 8 years and again at 13 years to test the primary hypothesis that mild bronchiolitis, far more common than severe (hospitalized) bronchiolitis, predicts wheezing. A secondary hypothesis was that passive smoking also predicts wheezing. Many potentially confounding variables such as family history of asthma were controlled in analyses. Analysis at 13 years produced results that were not anticipated from previous analysis of interviews at age 8. Although mild bronchiolitis was a powerful predictor of wheezing at age 8 years, it was no longer a strong predictor of wheezing at age 13 in either bivariate or multivariate analysis. Although epidemiologic studies, by their nature, cannot prove causality, findings are consistent with the hypothesis that sequelae often follow mild bronchiolitis but diminish during childhood. Maternal smoking was a powerful predictor of wheezing at age 13 in bivariate analysis (Kendall's Tau B = 0.19, P less than 0.01) and in multivariate analysis (odds ratio = 2.67, P less than 0.01). In children at highest risk for wheezing, males with a family history of asthma, multivariate analysis suggested that maternal smoking is associated with an increase in wheezing from 36% to 60%. We conclude that passive smoking, previously identified as a risk factor in this population for both bronchiolitis in infancy and wheezing at age 8, is a risk factor for wheezing-associated morbidity throughout the childhood years.     

Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases

 We identified eight patients with bronchiolitis obliterans (BO) in the autopsies of 81 bone marrow transplant (BMT) recipients. Rapidly progressive dyspnoea and cough were the main presenting symptoms in all eight patients, associated with overinflation and/or infiltrative opacity seen on chest X-ray and obstructive disorder revealed by pulmonary function tests. Early lesions were characterized by epithelial loss and an inflammatory infiltrate containing foamy histiocytes with mild luminal narrowing. Partial or total occlusion of the bronchiolar lumina by fibrous connective tissue was the feature of late lesions. Both changes were coexistent in all cases. In one case, small bronchi with cartilage were also affected by the obstructive process, showing bronchitis obliterans. All eight patients showed non-obstructive broncho-bronchiolitis characterized by denuding of respiratory epithelium, mural oedema and an inflammatory infiltrate in addition to BO, and these changes were also seen in 18 patients without BO. The submucosal glands of large bronchi and the trachea showed mucous retention and a mild inflammatory infiltrate in four of the eight patients. Coexistent infectious processes were seen in all cases, cytomegalovirus and Aspergillus being the most frequent organisms. BO probably develops as an immunopathological event related to graft-versus-host disease (GVHD) during the impaired immune status phase of the post-BMT period, possibly initiated by infection. Bronchial gland involvement in chronic GVHD is one of the factors responsible for this abnormal immune status. Received: 14 January 1997 / Accepted: 5 March 1997     

重组人干扰素α2b雾化吸入联合远红外止咳贴治疗小儿毛细支气管炎的临床效果

目的观察重组人干扰素α2b雾化吸入联合远红外止咳贴治疗毛细支气管炎的效果。方法选取2018年3月至2020年3月玉林市妇幼保健院收治的80例毛细支气管炎患儿,采用随机数字表法分为观察组与对照组,每组各40例。对照组给予常规综合治疗,观察组在常规综合治疗的基础上给予氧气驱动雾化吸入α2b干扰素联合远红外止咳贴治疗。比较两组治疗后的临床疗效、临床症状消失时间、住院时间以及肺部功能。结果观察组临床总有效率高于对照组,差异有统计学意义(P<0.05);观察组喘憋消失时间、咳嗽消失时间、肺部啰音消失时间、体温恢复正常时间、住院时间均短于对照组,差异有统计学意义(P<0.05);观察组治疗后潮气量、达峰时间比、达峰容积比均高于对照组,差异有统计学意义(P<0.05)。结论雾化吸入干扰素α2b联合远红外止咳贴治疗毛细支气管炎对提高治疗有效率,缩短临床症状消失时间、住院时间,改善肺功能具有重要作用,值得临床推广使用。     

自拟清肺平湍汤治疗毛细支气管炎120例临床研究

目的：了解中药佐治毛细支气管炎的疗效。方法：我料对1996年12月－1999年12月收往的毛细支气管炎的婴儿分组治疗。对照组给予抗菌素、抗病毒、平湍、纠酸及糖皮质激素等药物应用,治疗组在此基础上加用中药“清肺平湍汤”服用3－5日。结果：加用清肺平湍汤,可使患儿的症状及体征消失时间缩短、明显优于对照组（P＜0．01）。结论：说明中药清肺平湍汤佐治毛细支气管炎可达到尽快缓解症状、减少并发症、缩短病程、降低病死率的作用。