Puéchal X, Fajac I, Bienvenu T, Desmazes-Dufeu N, Hubert D, Kaplan J C, Menkès C J, Dusser D J
Services de Rhumatologie, Groupe Hospitalier Cochin, Université René Descartes, Paris, France.
Eur Respir J. 1999 Jun;13(6):1281-7. doi: 10.1183/09031936.99.13612889.
This study investigated the clinical characteristics and the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients with symptomatic diffuse bronchiectasis (DB) associated with rheumatoid arthritis (RA). Twenty-six patients with both RA and DB (group RA+DB) and control groups of 29 consecutive patients with RA but no bronchiectasis (group RA) and 29 patients with symptomatic DB of unknown origin (group DB) were prospectively studied. Among the patients of the RA+DB group, four (15.4%) were heterozygous for the CFTR gene deltaF508 mutation, whereas no deltaF508 mutation was found in patients of the RA and the DB groups (both, p<0.05). This frequency of deltaF508 mutation was also higher than the expected frequency (2.8%) in the general European population (p<0.04). Sweat chloride values and nasal potential differences were normal in three out of four patients carrying the deltaF508 mutation. In the RA+DB group, those with deltaF508 mutation had more frequent chronic sinusitis (p<0.05), a trend toward a more severe pulmonary involvement, and a lower value of nasal potential differences (p<0.01) whereas their rheumatic features had no particularity. In the RA+DB group, patients with adult-onset bronchiectasis (including two with deltaF508 mutation) had a greater reduction in total lung capacity (p<0.05) and lower nasal potential differences (p<0.005) than those with childhood-onset bronchiectasis. This study suggests a possible deleterious effect of the cystic fibrosis transmembrane conductance regulator mutated protein in the airways which may predispose to the development and severity of bronchiectasis in patients suffering from rheumatoid arthritis.
本研究调查了伴有类风湿关节炎（RA）的有症状弥漫性支气管扩张（DB）患者的临床特征以及囊性纤维化跨膜传导调节因子（CFTR）基因的可能参与情况。前瞻性研究了26例患有RA和DB的患者（RA+DB组）以及29例连续的患有RA但无支气管扩张的患者对照组（RA组）和29例有症状的不明原因DB患者（DB组）。在RA+DB组患者中，4例（15.4%）CFTR基因deltaF508突变呈杂合状态，而在RA组和DB组患者中均未发现deltaF508突变（两者p<0.05）。这种deltaF508突变频率也高于欧洲普通人群的预期频率（2.8%）（p<0.04）。携带deltaF508突变的4例患者中有3例汗液氯化物值和鼻电位差正常。在RA+DB组中，携带deltaF508突变的患者慢性鼻窦炎更常见（p<0.05），有肺部受累更严重的趋势，且鼻电位差值更低（p<0.01），而其风湿性特征无特殊性。在RA+DB组中，成年期发病的支气管扩张患者（包括2例携带deltaF508突变的患者）比儿童期发病的支气管扩张患者肺总量下降更大（p<0.05），鼻电位差值更低（p<0.005）。本研究提示囊性纤维化跨膜传导调节因子突变蛋白在气道中可能具有有害作用，这可能使类风湿关节炎患者易发生支气管扩张并加重其严重程度。
