Kraemer Richard, Deloséa Natascha, Ballinari Pietro, Gallati Sabina, Crameri Reto
Division of Human Genetics, Department of Paediatrics, University of Bern, Inselspital, CH-3010 Bern, Switzerland.
Am J Respir Crit Care Med. 2006 Dec 1;174(11):1211-20. doi: 10.1164/rccm.200603-423OC. Epub 2006 Sep 7.
The relationship between sensitization to Aspergillus fumigatus and progression of pulmonary function is not yet established in cystic fibrosis (CF).
We aimed to evaluate onset of A. fumigatus sensitization and development of allergic bronchopulmonary aspergillosis (ABPA), as well as to determine the physiologic factors of lung function influencing these mechanisms in CF.
Serial annual lung function tests performed in 122 children with CF (62 males; 60 females; age: 6-18 yr) provided data pertaining to FRC measured by plethysmography, lung clearance index, volume of trapped gas, effective specific airway resistance, and forced expiratory indices (FEV1, FEF at 50% VC). Specific IgE to recombinant A. fumigatus allergens, rAspf1 and rAspf3, served as marker for sensitization, and to rAspf4 and rAspf6 as indications for a serologic ABPA, were clinically diagnosed (Nelson criteria). By linear mixed-effect model analysis, five patient groups, (1) not sensitized and free from Pseudomonas aeruginosa, (2) intermittently P. aeruginosa colonized, (3) chronically P. aeruginosa infected, (4) sensitized, and (5) with ABPA, were retrospectively evaluated.
A. fumigatus sensitization was best reflected by increased rAspf1+3-specific IgE levels, whereas, in most patients, sensitization was preceded by P. aeruginosa infection. Patients with ABPA demonstrated the most severe progression in all lung function parameters, and FEF at 50% VC, volume of trapped gas, and effective specific airway resistance were the best predictors (p < 0.0001). However, regarding distinction between sensitization to A. fumigatus and development of ABPA in the course of CF, chronic P. aeruginosa infection has to be taken into account.
Airway narrowing, gas trapping, and small airway disease are the major targets for functional derangement in ABPA.
在囊性纤维化（CF）中，对烟曲霉的致敏作用与肺功能进展之间的关系尚未明确。
我们旨在评估烟曲霉致敏的起始情况及变应性支气管肺曲霉病（ABPA）的发生发展，并确定影响CF中这些机制的肺功能生理因素。
对122例CF儿童（62例男性；60例女性；年龄：6 - 18岁）进行连续年度肺功能测试，提供了与通过体积描记法测量的功能残气量、肺清除指数、潴留气体量、有效比气道阻力以及用力呼气指标（FEV1、50%肺活量时的FEF）相关的数据。针对重组烟曲霉变应原rAspf1和rAspf3的特异性IgE作为致敏的标志物，针对rAspf4和rAspf6的特异性IgE作为血清学ABPA的指标，采用临床诊断（尼尔森标准）。通过线性混合效应模型分析，对五个患者组进行回顾性评估，这五个组分别为：（1）未致敏且无铜绿假单胞菌定植，（2）间歇性铜绿假单胞菌定植，（3）慢性铜绿假单胞菌感染，（4）致敏，（5）患有ABPA。
rAspf1 + 3特异性IgE水平升高最能反映烟曲霉致敏情况，而在大多数患者中，致敏发生在铜绿假单胞菌感染之前。患有ABPA的患者在所有肺功能参数方面进展最为严重，50%肺活量时的FEF、潴留气体量和有效比气道阻力是最佳预测指标（p < 0.0001）。然而，在CF病程中区分烟曲霉致敏和ABPA的发生时，必须考虑慢性铜绿假单胞菌感染。
气道狭窄、气体潴留和小气道疾病是ABPA功能紊乱的主要靶点。
