Quantification of Proteus syndrome-associated lung disease

Background Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to progressive respiratory symptoms and require surgical intervention. This retrospective study seeks to quantify the radiographic features of Proteus syndrome-associated lung disease using computed tomography (CT) of the chest. The first method derives a Cystic Lung Score (CLS) by using a computer-aided diagnostic tool to quantify the fraction of cystic involvement of the lung. The second method yields a Clinician Visual Score (CVS), an observer reported scale of severity based on multiple radiographic features. The aim of this study was to determine if these measurements are associated with clinical symptoms, pulmonary function test (PFT) measurements, and if they may be used to assess progression of pulmonary disease. Results One hundred and thirteen imaging studies from 44 individuals with Proteus syndrome were included. Dyspnea and oxygen use were each associated with higher CLS ( p = 0.001 and < 0.001, respectively) and higher CVS ( p < 0.001 and < 0.001). Decreases in percent predicted FVC, FEV 1 , and DLCO each correlated with increased CLS and CVS. The annual increase of CLS in children, 5.6, was significantly greater than in adults, 1.6. ( p = 0.03). The annual increase in CVS in children, 0.4, was similar to adults, 0.2 ( p = 0.36). Conclusions Proteus syndrome-associated lung disease is progressive. The rate of cystic progression is increased in children. Increased scores in CLS and CVS were associated with clinical symptoms and decreased pulmonary function. Both methods were able to detect change over time and were associated with clinically meaningful outcomes which may enable their use in interventional studies.