Optimizing Screening for Early Disease Detection in Familial Pulmonary Fibrosis (FLORIS): A Prospective Cohort Study Design

Abstract

Background: Familial pulmonary fibrosis (FPF) can be defined as pulmonary fibrosis in two or more first-degree family members. The first-degree family members of FPF patients are at high risk of developing FPF and are eligible for screening. Reproducible studies investigating risk factors for disease are much needed. Methods: Description of the screening study protocol for a single-center, prospective cohort study; the study will include 200 asymptomatic, first-degree family members of patients with FPF who will undergo three study visits in two years. The primary objective is determining the diagnostic value of parameters for detection of early FPF; the secondary objectives are determining the optimal timing of the screening interval and gaining insight into the natural history of early FPF. The presence of interstitial lung disease (ILD) changes on high-resolution computed tomography of the chest is indicative of preclinical ILD; the changes are determined at baseline. The comparison between the group with and without ILD changes is made for clinical parameters (pulmonary function, presence of digital clubbing, presence of Velcro-like crackles, blood count, liver- and kidney-function testing, patient-reported cough and dyspnea score) and exploratory parameters. Discussion: This study will be the first large-size, prospective, longitudinal cohort study for yearly screening of asymptomatic family members of FPF patients investigating the diagnostic value of parameters, including lung function, to detect early FPF. More effective screening strategies could advance early disease detection.

A new variant in theZCCHC8gene: diverse clinical phenotypes and expression in the lung

“…Two siblings also presented with the STS phenotypes IPF and bone marrow failure. Four paternal cousins had IPF, whereas HRCT of one female cousin, aged 68 years, displayed signs of emphysema and familial interstitial lung abnormalities (FILA) [ 17 ]. Furthermore, two paternal cousins died of acute myeloid leukaemia.…”

Diagnosis and Pharmacologic Management of Fibrotic Interstitial Lung Disease

“…Several studies have noted the presence of interstitial abnormalities on HRCT in asymptomatic relatives of pulmonary fibrosis patients, but the use of repeat HRCT as a screening mechanism in these individuals is probably not advisable based on radiation exposure and cost unless they are experiencing symptoms [ 37 , 38 ]. However, data regarding the use of alternate screening methods such as clinical evaluation and pulmonary function testing to reliably detect disease are limited and research is ongoing [ 39 ].…”