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.     

微生物感染及定植在非囊性纤维化支气管扩张症中的研究进展

呼吸道微生物感染及定植被认为是非囊性纤维化支气管扩张症发病的主要原因.以往认为非囊性纤维化支气管扩张症患者的呼吸道感染大多局限于极少数典型病原体,如铜绿假单胞菌、流感嗜血杆菌;然而,近年来已经有越来越多的研究认识到新兴潜在病原体所造成的感染.肺微生物组学研究的兴起,为探讨不同核心菌群及其交互作用,及其对该疾病加重及免疫功能的影响,提供了更广阔的研究前景.     

雾化吸入抗菌药物在成人非囊性支气管扩张治疗方面的研究进展

支气管扩张是一种高发病率和高病死率的慢性肺部疾病,以咳嗽、咳脓性痰、反复感染和气道损伤为特征。非囊性纤维化支气管扩张症是支气管扩张的一种,我国常见。目前,非囊性纤维化支气管扩张症治疗方式仅限于理疗以清除痰液和抗生素以治疗急性感染。本文旨在探讨雾化吸入抗菌药物在成人非囊性支气管扩张治疗方面的研究进展。     

The relationship between insulin, IGF-I and weight gain in cystic fibrosis

OBJECTIVE: In cystic fibrosis, reduced body mass is related to low levels of IGF-I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction. PATIENTS AND DESIGN: We measured serum levels of insulin, IGF-I, IGFBP-I, IGFBP-3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99-17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory. RESULTS: The mean height standard deviation score (SDS (SD)) was -0.54 (0.97) and the body mass index SDS -0.24 (1.09). Both body mass index SDS (r = -0.40, P = 0.0003) and IGF-I SDS (r = - 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF-I and IGFBP-3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP-I were inversely related to those of IGF-I and insulin (r = - 0.43, P = 0. 0004, r = - 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP-I (r = - 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF-I (P = 0. 04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP-I (P = 0.01). CONCLUSIONS: We conclude that progressive insulin deficiency may result in reduced IGF-I levels and IGF-bioactivity and may determine weight gain and statural growth in cystic fibrosis.     

The relationship between genotype and exercise tolerance in children with cystic fibrosis

The relationship between fitness and genotype in children with cystic fibrosis (CF) and at least one copy of the DeltaF508 mutation was examined. Genotype was classified according to the second CF mutation. Fitness was measured by peak aerobic capacity (using a modified Bruce protocol during treadmill exercise) and anaerobic power (using the Wingate test on a cycle ergometer). The class of cystic fibrosis transmembrane regulator proteins (CFTR) mutation was statistically related with aerobic capacity, peak anaerobic power, body mass index, lung function (forced expiratory volume in one second), and disease severity as measured by the Shwachman score. Patients with mutations causing defective CFTR production (Class I) or processing (Class II) had a significantly lower peak aerobic capacity (28.6 +/- 4.2 ml/kg/min and 31.7 +/- 5.4 ml/kg/min, respectively) than those with a mutation conferring defective regulation of CFTR (Class III) (43.9 +/- 6.4 ml/kg/min). The peak anaerobic power in subjects with mutations inducing decreased CFTR conduction (Class IV) or CFTR mRNA (Class V), were significantly higher (11.4 +/- 1.7 and 11.6 +/- 1.5 watts/kg, respectively) than children with Class I (9.7 +/- 1.4 watts/kg), Class II (9.8 +/- 1.4 watts/kg), or Class III (10.5 +/- 1.8 watts/kg) mutations. There were no statistically significant differences in the lung function of patients with the different mutations. These results indicate a relationship between CF genotype and some measures of fitness, the mechanisms of which remain to be determined.     

Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis.

An unusual case of endobronchial polyposis associated with extensive bronchiectasis in the context of cystic fibrosis (CF) has been described. A 15-yr-old female patient with CF underwent partial pneumonectomy for extensive bronchiectasis and frequent infective pulmonary exacerbations. Cylindrical bronchiectasis with associated purulent bronchitis and bronchiolitis, together with inflammatory polyposis, was noted in the resected lung. To the best of the authors' knowledge, this is the first report of multiple endobronchial polyposis and may represent a rare complication of bronchiectasis in a patient with cystic fibrosis. On-going infection and the cellular composition of the polyps are discussed in relation to their possible aetiological relevance and relationship to upper respiratory tract polyps.     

Early bronchiectasis in cystic fibrosis detected by surveillance CT

There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life‐shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited‐slice high‐resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.     

Duodenal pH in cystic fibrosis and its relationship to fat malabsorption

To investigate the relationship between duodenal pH levels and supplemental pancreatic enzyme function in cystic fibrosis, 18 children with this condition had pH recordings performed from the second and fourth part of the duodenum. Compared to age-matched controls, patients with cystic fibrosis had significantly longer periods below a pH of 4.0 in the postprandial period and significantly less time above pH 5.8. These values correspond to the pH levels at which lipase is irreversibly destroyed (pH 4.0) and enteric coating of enzyme supplements dissolves (pH 5.8). A significant relationship was found between the pH recordings from the fourth part of the duodenum and the degree of residual fat malabsorption while taking enteric-coated enzyme supplements. Four patients with an excessively acidic duodenum and residual fat malabsorption despite high-dose enzyme supplementation were treated with misoprostol (Searle), a known acid-reducing agent. There were significant improvements in both duodenal pH values and fat absorption. We conclude that there is a wide range of duodenal pH values found in patients with cystic fibrosis and that the efficiency with which enzyme supplements work is closely related to these pH levels. Administration of misoprostol to those patients with excessively acidic duodenal pH levels as well as residual malabsorption appears to be of benefit in improving both the excessively acidic pH levels and the fat malabsorption.Dr. Robinson is a trainee research fellow of the Royal Children's Hospital Research foundation in the Professorial Department of Thoracic Medicine, Royal Children's Hospital. Reprints will not be available.     

The relationship between sleep disturbance and pulmonary function in stable pediatric cystic fibrosis patients

BACKGROUND: Cystic fibrosis (CF) is the most common inherited disease affecting northern European populations. It is characterized by a progressive clinical course that causes diurnal and nocturnal pulmonary and gastrointestinal symptoms. OBJECTIVES: To determine whether clinically stable pediatric patients with CF have lower sleep efficiency than healthy control subjects, and to examine the relationship between sleep efficiency and pulmonary function. METHODS: Forty-four CF patients and 40 control subjects completed 5 days of actigraphy recordings. Additionally, sleep questionnaires were independently completed by all study participants and their parents. Pulmonary function testing was performed in all patients with CF. Multiple regression analysis was used to measure the independent correlation between sleep variables and pulmonary function. RESULTS: CF patients had significantly lower sleep efficiency than control subjects. The FEV1 of these patients correlated positively with sleep duration and efficiency, and negatively with the number and duration of nocturnal awakenings, age, and body mass index (BMI). The independent effect of FEV1 on sleep was first examined. Age and FEV1 were the only variables that predicted sleep duration (R2 = 0.3; p = 0.0007), while FEV1 was the only variable predicting sleep efficiency (R2 = 0.28; p = 0.0002). When the independent effect of sleep on FEV1 was analyzed, sleep efficiency, BMI percentile, and gender predicted FEV1 (R2 = 0.46; p < or = 0.0001). The frequency of nocturnal cough reported by patients and their parents was an independent predictor of FEV1. CONCLUSIONS: Pediatric patients with CF and stable pulmonary function have lower sleep efficiency and more frequent nocturnal awakenings than do healthy control subjects. After adjustment for demographic characteristics, there was an independent and significant correlation between sleep parameters and FEV1, when either sleep variables or FEV1 were used as dependent variables. These findings suggest a bidirectional relationship between sleep disturbance and CF lung disease.