Familial pulmonary fibrosis: a UK consensus framework for the investigation and management of patients and their relatives

Abstract

There is a growing recognition that genetic predisposition contributes to the development of fibrotic interstitial lung disease. Adult onset monogenic disease is most commonly due to dysfunctional telomere maintenance, with a small proportion caused by surfactant biology disorders. These conditions can be associated with additional intra- and extra-pulmonary features which themselves may require surveillance or treatment, making it important to make a genetic diagnosis. The recent introduction in England of a genetic testing panel accessible to respiratory physicians means that genetic information for these individuals is increasingly available but there is currently little standardisation of the subsequent management of patients and their relatives, which can be complex. This consensus considers the causes and clinical features of familial pulmonary fibrosis and provides a suggested framework for genetic investigation and clinical management of both patients and their relatives. We suggest an initial workup that may help identify those with monogenic disease, with focus on key points in the history and examination that may identify features of a telomere or surfactant biology disorder. We highlight that clinical and radiological presentations are diverse, and discuss the importance of making a genetic diagnosis to inform multidisciplinary management and facilitate screening of close family members. We also discuss the many outstanding uncertainties and challenges, including the investigation and management of non-monogenic familial pulmonary fibrosis and the management of asymptomatic family members who have inherited a potentially disease-causing genetic variant. We suggest a pathway for the workup and management of patients with familial pulmonary fibrosis, aiming to standardise clinical care for patients and their relatives and provide a framework for the development of a national database to facilitate disease phenotyping and clinical research to improve the evidence base for clinical practice.