Rationale: Diffuse cystic lung diseases (DCLDs) represent a heterogeneous group of distinct pathophysiological entities that share a common phenotype of multiple thin-walled pulmonary cysts. Identifying DCLDs can result in earlier treatment, identification of malignancy, and family screening. A national referral centre for DCLDs was established in Ireland in 2019. The aim of this study was to describe the characteristics and clinical presentation of DCLDs.

Methods: Data on all DCLD cases from 2019-2022 was collated. This included patient demographics, genetics, history of pneumothorax, biopsy results, pulmonary function tests and therapies. Lymphangioleiomyomatosis (LAM), Birt-Hogg-Dube syndrome (BHD), Lymphocytic Interstitial Pneumonia (LIP) and Pulmonary Langerhans Cell Histiocytosis (PLCH) comprised most patients. Groups were compared by ANOVA. 

Results: 109 patients with DCLD were included. The median age was 58 years old. 79% of patients were female and LAM was most common diagnosis (43%). 35% of patients had a history of pneumothorax with a significantly higher rate in BHD compared to other DCLDs (p=0.013) Significant variation existed across groups with lower baseline FEV1pp in PLCH and LAM compared to BHD and LIP (p=0.024). PLCH was associated with a lower DLCO at diagnosis (p=0.049). 31 patients underwent lung biopsy, indicating that improved diagnostic approaches negates the need for this in most patients.

Conclusions: Our data indicates that despite their rarity, DCLDs share common features, yet differ in presentation and clinical course. With increased risk of malignancy and possible progressive disease, it is increasingly important to screen for these conditions.