Progressive Pulmonary Lesion due to Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction: A Case Study From Japan.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride ion channel, and occurs frequently in the Caucasian population but rarely in Asia. Elevated sweat chloride using the sweat test is a gold standard for CF diagnosis, but it is not readily available in Japan. A 22-year-old man, who had past histories characteristic of CF, such as recurrent pneumonia, sinusitis, and pneumothorax, was referred to our hospital due to bronchiectasis and bronchial asthma. Examination revealed severely impaired lung dysfunction and abnormal chloride ion concentration in the sweat test corresponding to intermediate values, indicative of CFTR dysfunction. Analysis of his CFTR gene failed to detect any CF-causing variants, but showed the haplotype known to express a smaller amount of intact CFTR protein and associated with several pulmonary diseases. A diagnosis was made of bronchiectasis caused by CFTR dysfunction, and he was treated with inhalation solution of dornase alfa, hypertonic saline solution, and tobramycin at the age of 25; however, his lung deteriorated, and he died at the age of 32. As a result of retrospective reviewing of the lung images and functions from childhood, we found that pneumonia in childhood developed to cystic bronchiectasis in adulthood, and obstructive ventilator dysfunction already existed at the age of 13, progressing to the devastating decline of lung function as he grew. Pulmonary disease due to CFTR dysfunction in Japan has a poor prognosis because of challenges to access to the sweat test and a lack of recognition for CF.