非囊性纤维化支气管扩张症的最新进展

支气管扩张症是气道多种病原菌清除不良与反复感染引起的慢性炎症与支气管壁破坏,导致气道永久性扩张.非囊性纤维化支气管扩张症(non-cystic fibrosis bronchiectasis,NCFB)是一种临床低估的疾病,诊断时要注意其基础病因,但大多数病因不清楚.治疗要强调个体化并注意随访,临床评价常用的工具是莱斯特咳嗽问卷与痰液颜色.要对细菌定植进行定期评价.NCFB的治疗研究很少,长期应用抗生素可改善临床症状,但不降低急性加重发生率,也不改善肺功能.有严重感染或出血危险性的1或2叶严重损害的患者可考虑手术治疗.本文重点为NCFB,指出了其处理及肺移植治疗,进一步研究其病理生理学机制与探索新的治疗方法是非常必要的.     

非囊性纤维化性支气管扩张症的免疫调节机制

支气管扩张症是慢性炎症性支气管疾病的一种,病理上表现为一个或多个支气管的永久性扩张。非囊性纤维化性支气管扩张症的发病往往与反复感染、免疫缺陷或自身免疫性疾病相关,也有相当一部分呈特发性。细菌定植、气道炎症和气道结构损伤这样一个恶性循环导致了支气管扩张症的发生,其中气道炎症承前启后,是整个恶性循环的关键,因此研究气道炎症的免疫调节机制对理解其发病机理具有重要意义,并可指导支气管扩张症的药物研发。本文着重讨论了与支气管扩张症的发病密切相关的细胞与分子免疫调节机理,并阐述了细菌慢性定植的机理,还结合免疫调节讨论了支气管扩张症的新药研发。     

成人非囊性纤维化性支气管扩张的诊治进展

支气管扩张是慢性气道损伤引起支气管管壁肌肉和弹力支撑组织破坏所导致的一组支气管不可逆性扩张.其发病率在3.9/10万到52/10万左右,不发达国家发病率相对较高.在我国,支气管扩张被当做气道的一般化脓性炎症来治疗,但其病因、发病机制、针对性的治疗手段均研究甚少.文中结合目前的文献及2010年英国胸科学会的支气管扩张诊治指南,对非囊性纤维化性支气管扩张的诊治最新进展作简要述评。     

Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe

BackgroundBronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020.MethodsWe retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made.ResultsA total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown “destroyed lobe” (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction.ConclusionsIn spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.     

Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis

Pseudomonas aeruginosa infection is associated with poorer outcomes in non-cystic fibrosis bronchiectasis. It is unknown whether early eradication improves outcomes. This retrospective study assessed clinical and microbiological outcomes of eradication therapy following initial Pseudomonas infection. All patients undergoing Pseudomonas eradication therapy from 2004 to 2010 were identified retrospectively and assessed for microbiological eradication, exacerbation frequency, hospital admissions, clinical symptoms and lung function. 30 patients were identified with median follow-up time 26.4 months. Eradication therapy involved intravenous antibiotics (n?=?12), intravenous antibiotics followed by oral ciprofloxacin (n?=?13) or ciprofloxacin alone (n?=?5), combined with 3 months of nebulised colistin. Pseudomonas was initially eradicated from sputum in 24 patients (80.0%). 13/24 patients remained Pseudomonas-free and 11/24 were subsequently reinfected (median time 6.2 months). Exacerbation frequency was significantly reduced from 3.93 per year pre-eradication and 2.09 post-eradication (p?=?0.002). Admission rates were similar, at 0.39 per year pre-eradication and 0.29 post-eradication (p?=?NS). 20/30 patients reported initial clinical improvement, whilst at one-year follow up, 19/21 had further improved or remained stable. Lung function was unchanged. This study demonstrates that Pseudomonas can be eradicated from a high proportion of patients, which may lead to prolonged clearance and reduced exacerbation rates. This important outcome requires confirmation in a prospective study.     

422例非囊性纤维化支气管扩张症临床特点分析

目的了解支气管扩张症的临床特点及不同类型支气管扩张症临床特点的差异。方法回顾性分析2014年10月至2016年10月期间在四川省人民医院(东院)呼吸内科住院治疗的422例非囊性纤维化支气管扩张症患者的临床资料,并比较不同影像学类型的患者的临床特点差异。结果422例患者中男性201例(47.6%),女性221例(52.4%),中位年龄60.87±12.66岁,中位患病时间16.63±15.81年,不同影像学类型的支气管扩张症分类:囊状型62例(14.7%),柱状型211例(50%),囊柱状型149例(35.3%)。分析三组数据:柱状型支气管扩张症患病时间最短,平均住院时间最短,咳痰、出现肺部湿啰音及哮鸣音较少,血清CRP水平、外周血中心粒细胞计数水平、动脉血PaCO 2水平较低,较少感染铜绿假单胞菌及较少并发慢性肺源性心脏病(P<0.0167)。结论不同影像类型的支气管扩张症,以柱状型最为常见,其病情较囊状型及囊柱状轻,根据影像学类型,可对支气管扩张症患者进行分类管理。     

Exacerbations in noncystic fibrosis bronchiectasis: Clinical features and investigations

Children with bronchiectasis have recurrent acute pulmonary exacerbations and many of these exacerbations require hospital admission when oral therapies fail. However there is no standardized definition and little published data is available about the features of an exacerbation. Our aim was to determine the clinical and investigational features of exacerbations in bronchiectasis, the proportion that fail to resolve on oral antibiotics and the factors associated with it.

Methods

A retrospective cohort study of 115 respiratory exacerbations from 30 children with noncystic fibrosis bronchiectasis diagnosed on HRCT chest. Clinical features, investigations and treatment related to the exacerbations were extracted and analysed.

Results

Increase in frequency of cough (88%) and a change in its character (67%) were the most common symptoms associated with an exacerbation. Fever (28%), increase in sputum volume (42%) and purulence (35%) were also common features. Chest pain, dyspnea, hemoptysis and tachypnea were rare. 56% had a worsening in their chest auscultatory findings during an exacerbation. Spirometry was not significantly different between stable and exacerbation state. 35% of exacerbations failed to respond to oral antibiotic therapy and required hospital admission. Prophylactic antibiotic therapy was the only significant predictor of failure of oral therapy with adjusted odds ratio of 6.77 (95% CI 2.06–19.90; p = 0.003).

Conclusions

Important clinical features of non-CF exacerbation in bronchiectasis were changes in cough frequency or character, and worsening chest signs; which resolved on therapies. However there is a high failure rate of oral antibiotic therapy and use of prophylactic antibiotic therapy increases this risk.     

Inhaled mannitol in the treatment of non-cystic fibrosis bronchiectasis in adults

Bronchiectasis is a chronic disorder characterized by impaired mucociliary clearance and a relentless cycle of infection, inflammation and bronchial wall injury, which has a debilitating impact on the patient's quality of life and results in increased morbidity and mortality. It is a disease for which there are no currently registered therapeutic products, limited epidemiological data and no validated endpoints that have been accepted by the majority of regulatory authorities. This article reviews the evidence base for the efficacy of inhaled dry powder mannitol in patients with non-cystic fibrosis (CF) bronchiectasis. The few published papers on this topic concluded that mannitol, when inhaled as a dry powder, is a promising treatment for bronchiectasis. It is designed to hydrate the lungs and restore normal mucociliary clearance mechanisms in the lungs. Based on the available evidence, mannitol inhalation is well tolerated and improves the quality of life of patients with non-CF bronchiectasis. There is a need for well designed and adequately powered multicentre trials to establish the potential usefulness of mannitol as a treatment for non-CF bronchiectasis.     

Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

BackgroundInhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations.MethodsWe performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154.ResultsTwelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70–5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81–18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28–1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82–0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV₁, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35–3.27) at the end of therapy, with a number needed to treat of 6.ConclusionsIA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.     

The role of viral infections in pulmonary exacerbations of patients with non-cystic fibrosis bronchiectasis: A systematic review

BackgroundBronchiectasis is a cause of increased morbidity of the respiratory system. Exacerbations among patients with non-CF (cystic fibrosis) bronchiectasis result in reduced pulmonary function and poor quality of life. While the role of bacteria in triggering exacerbations in patients with non- CF bronchiectasis has been well studied, little is known about viral infections in these patients. We aimed to review the evidence on the role of respiratory viruses in the exacerbations of non-CF bronchiectasis.MethodsRelevant literature was searched on the MEDLINE/PubMed database. Seven studies satisfied the criteria and were included in this review.ResultsAccording to the included articles, respiratory viruses are often identified in exacerbations of patients with non-CF bronchiectasis with the most frequent being human rhinovirus and influenza viruses. When a virus is isolated during an exacerbation patients have more symptoms from the upper respiratory tract. One study showed that detection of Epstein- Barr virus among patients with non-CF bronchiectasis is correlated with faster reduction of pulmonary function and progression of the disease.ConclusionViruses seem to have a role in the exacerbation of patients with non-CF bronchiectasis. However, the exact nature and importance of this role remain elusive. Viruses are also isolated during the stable period of the disease. Further well-designed studies are necessary to clarify this complex issue.     

Bronchiectasis in severe asthma and asthmatic components in bronchiectasis

Asthma and bronchiectasis are different diseases; however, differentiating them can be difficult because they share several symptomatic and physiological similarities. Approximately 20% of patients with bronchiectasis have eosinophilic inflammation, 34% show wheezing, and 7–46% have comorbid asthma, although comorbidity with severe asthma may be limited as shown in 3.3% of cases of bronchiectasis. Meanwhile, 25–68% of patients with severe asthma have comorbid bronchiectasis, and at least two phenotypes are present in the accompanying bronchiectasis: eosinophilic bronchiectasis and chronic infectious bronchiolitis/bronchiectasis. Recent studies show that type-2-targeted biologics are effective for eosinophilic bronchiectasis and theoretically effective for some of the remaining cases when used before oral corticosteroids. Further studies are needed to identify treatment strategies for severe asthma with comorbid bronchiectasis and vice versa.     

Advantages and drawbacks of long-term macrolide use in the treatment of non-cystic fibrosis bronchiectasis

Non-cystic fibrosis (non-CF) bronchiectasis is a respiratory disease characterized by persistent airway inflammation and dilation of bronchial wall driven by various causes. Patients with bronchiectasis suffer from excessive sputum production, recurrent exacerbations, and progressive airway destruction. Major therapy for bronchiectasis is focused on breaking the “vicious cycle” of mucus stasis, infection, inflammation, and airway destruction. Growing evidences have been shown that macrolides possess immunoregulatory and anti-inflammatory functions beyond their antimicrobial effects. Macrolide antibiotics have been effectively used in the treatment of diffuse panbronchiolitis, CF and bronchiolitis obliterans syndrome. Currently a number of clinical trials were performed to assess macrolide treatment in the management of non-CF bronchiectasis. The purpose of this paper is to review the efficacy and potential risks of these recent studies on the use of macrolides in non-CF bronchiectasis.     

河北省正定农村居民肺心病死亡及动态分析

目的 研究农村居民慢性肺心病死亡率的动态变化趋势。方法 分析河北省正定农村居民24年死亡监测资料。结果 24年死亡率呈下降趋势,总死亡率下降了22.5％(标化死亡率下降了44.5％);男性下降了20.2％(43.1％),女性下降了25.2％(49.1％)。每年冬季为死亡最高期,特别1月下旬。肺心病死亡年龄曲线高峰后移5岁。结论 健康保健,医疗与卫生工作的改善及戒烟、环境污染控制,均可能是慢性肺心病死亡率下降的原因。     

High risks of all-cause and cardiovascular deaths in apparently healthy middle-aged people with preserved glomerular filtration rate and albuminuria: A prospective cohort study

Background

The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated.

Methods

A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45–119 ml/min/1.73 m²) were enrolled and divided into six groups (group 1, eGFR: 90–119 without albuminuria; group 2, eGFR: 90–119 with albuminuria; group 3, eGFR: 60–89 without albuminuria (reference); group 4, eGFR: 60–89 with albuminuria; group 5, eGFR: 45–59 without albuminuria; group 6, eGFR: 45–59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin–creatinine ratio ≥ 30 mg/g). Outcomes included all-cause death (ACD), cardiovascular death (CVD) and neoplasm-related death (NPD). Multivariable-adjusted mortality rate ratios (RR) and their 95% confidence intervals (CIs) in the groups were estimated by Poisson's regression analysis.

Results

The highest risk of ACD (RR (95% CIs): 3.95 (2.08–7.52)), CVD (7.15 (2.25–22.7)) and NPB (3.25 (1.26–8.38)) was observed in group 2. Subjects in group 2 were relatively young and had the highest levels of body mass index, blood pressure and HbA_1c and the highest prevalence of diabetes and metabolic syndrome.

Conclusion

Coexistence of preserved eGFR and albuminuria increases risks for ACD, CVD and NPD. Relatively young metabolic persons having both preserved eGFR and albuminuria should be considered as a very high-risk population.