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

## TL;DR

A Japanese man with cystic fibrosis-like symptoms and CFTR dysfunction had progressive lung disease and poor outcomes due to limited diagnostic access and awareness.

## Contribution

Highlights the challenges of diagnosing and managing CFTR-related pulmonary disease in Japan due to limited sweat test access and low recognition.

## Key findings

- Pulmonary dysfunction due to CFTR haplotype was diagnosed despite absence of known CF-causing gene variants.
- Progressive lung deterioration began in childhood and worsened into adulthood despite treatment.
- CFTR-related pulmonary disease in Japan has poor prognosis due to diagnostic and awareness limitations.

## Abstract

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.