每日一题_2023.02.07

A 45-year-old white woman presents to her physician complaining of several months of worsening shortness of breath. Previously she was told she had asthma because she was hav- ing intermittent episodes of wheezing combined with a productive cough and difficulty catching her breath. She used to run two miles every morning but can no longer walk more than 10 city blocks without stopping. She has never smoked. On physical examination she is using her accessory muscles to assist with res- piration. Pulmonary examination is notable for an increased decreased FEV1/FVC ratio, decreased air movement with each breath, and increased resonance upon percussion. X-ray of the chest is shown in the image. Which of the following is the most likely underlying cause for this patient’s disease?

一名45岁白人女性到医师处就诊，主诉数月来呼吸急促加重。之前她被告知患有哮喘，因为她有间歇性喘息，伴有咳痰和呼吸困难。她以前每天早上都要跑两英里，但现在已经不能连续走10个街区了。她从未吸烟。体格检查时，她正在使用辅助肌来辅助呼吸。值得注意的肺部检查表现为FEV1/FVC下降比值增加，每次呼吸时空气移动减少，叩击时共振增加。胸部x线检查如图所示。下列哪项是该患者疾病最有可能的根本原因?

(A)  A genetic mutation resulting in deficient levels of a protease 导致蛋白酶水平缺乏的基因突变

(B)  A genetic mutation resulting in deficient levels of a protease inhibitor 导致蛋白酶抑制剂水平缺乏的基因突变

(C)  A mutation in the p53 gene p53基因的突变

(D)  A mutation of the CFTR gene, which en- codes a regulated chloride channel 编码调节氯离子通道的CFTR基因突变

(E)  Airway inflammation, airflow obstruction, and bronchial hyperresponsiveness 气道炎症、气流阻塞和支气管高反应性

答案解析：

该患者患a1-抗胰蛋白酶缺乏症，这是一种以丝氨酸蛋白酶抑制剂a1-抗胰蛋白酶缺乏症为特征的遗传病。这种蛋白在正常情况下具有抑制肺内中性粒细胞弹性蛋白酶的功能。当缺乏时，弹性蛋白酶的活性过多，破坏肺泡壁中的弹性蛋白和胶原蛋白，进展为肺气肿。大多数a1-抗胰蛋白酶缺乏症患者为Z等位基因纯合子。临床上，a1-抗胰蛋白酶缺乏症可累及肺、肝，较少累及皮肤。在肺部，最常见的表现是早发的全腺泡性肺气肿，在肺基底部比肺尖部更明显。最常见的症状是缓慢加重的呼吸困难，尽管患者最初可能主诉咳嗽、咳痰或喘息。与此例一样，早期以喘息和咳痰为主诉就诊的患者可能被告知患哮喘。尽管治疗哮喘最初可能改善症状，但不能减缓疾病的进展。她的胸部x光片显示出这种疾病的典型特征;过度充气的肺，扁平的膈肌，以及由于肺纹理减少而透亮的肺(由于覆盖在上面的乳腺组织，在这个分辨率下很难看到，但我们预计肺纹理在基底部将特别缺乏)。a1-抗胰蛋白酶缺乏也可引起肝硬化和皮肤脂膜炎。

正确答案：B