Stable pulmonary function in Birt-Hogg-Dubé syndrome: a four-year longitudinal study

Background Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder caused by mutations in the folliculin (FLCN) gene, characterized by cutaneous fibrofolliculomas, renal tumours, and pulmonary cysts. These cysts increase the risk of spontaneous pneumothorax (PTX) and may impact lung function. However, the long-term pulmonary impact of BHD remains poorly understood. This cohort study aimed to evaluate pulmonary function in BHD patients over four years. Method A descriptive double-centre cohort study of retrospective data conducted across three Danish regions, assessing clinical and thoracic imaging characteristics and pulmonary function test (PFT) parameters in patients with BHD. Results Data from 373 BHD patients were analysed. The mean age at diagnosis was 47.3 years (±15.9), and 52.8% were women. Pulmonary cysts were present in 85% of patients, and 37.5% had at least one PTX (median of two per patient). Baseline PFT parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC), residual volume (RV), and diffusion capacity for carbon monoxide (DLCO), were within or above normal ranges. A subgroup of 140 patients contributed longitudinal follow-up data during the four-year observation period. After adjusting for age, gender, smoking, pleurodesis, and baseline values, statistically significant, minor physiologic declines in FEV1, FVC, and DLCO were observed. Conclusion Although BHD patients had normal baseline lung function, small but statistically significant declines in FEV1, FVC, and DLCO occurred over four years. However, the clinical relevance of these changes appeared limited, as all mean values remained within normal ranges.