Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland

Abstract

Background: The prevalence of sporadic and familial idiopathic pulmonary fibrosis (IPF) cases in Finland was evaluated according to the revised recommendations of the American Thoracic Society. Methods: All Finnish pulmonary clinics (n=29) were included in the primary screening. Hospital data bases were used to identify patients with the diagnosis "alveolitis fibroticans idiopathica" (J84.1 in ICD-10 classification). The total number of patients with IPF was extrapolated based on the evaluation of random samples of case records in different centres. Families with more than one potentially affected member were identified from a questionnaire study and the diagnosis was verified from the medical records. Results: Using this approach, the nationwide prevalence of IPF in Finland was estimated to be 16-18/100 000. In 90% of the patients lung involvement was assessed by high resolution computed tomographic (HRCT) scanning and in 31% a surgical biopsy specimen was available, further confirming the diagnosis. Seventeen multiplex families with 2-5 affected family members were identified, giving a prevalence of 5.9/million for familial IPF in Finland. Both multiplex and sporadic families were clustered in Eastern Finland. This clustering reflects the demographic history of Finland in the 16th century and suggests that multiplex families may share a common ancestor in the last 20-25 generations. Conclusion: The familial form explained 3.3-3.7% of all Finnish cases of IPF diagnosed according to the revised international guidelines. Geographical clustering of multiplex families suggests a recent founder effect in patients with familial IPF.

Early Interstitial Lung Disease in Familial Pulmonary Fibrosis

“…Previous reports indicate that familial IPF is an autosomal dominant disease with variable penetrance (5,6). This mode of genetic transmission is also supported by our pedigrees, which demonstrate IPF in relatives from consecutive generations, approximately 50% of affected progeny descended from an affected individual, an approximately equal percentage of affected males and females, and evidence of male-tomale transmission (data not shown).…”

“…Despite significant progress in the understanding of mechanisms involved in lung fibrosis, the natural history of the disease is poorly understood, in part because the majority of patients present with advanced disease stages. In familial IPF, a rare condition accounting for less that 5% of total IPF cases, an early stage of asymptomatic lung disease has been previously reported by Marshall and coworkers (5), Hodgson and colleagues (6), and Bitterman and colleagues (7). The authors showed that changes in alveolar protein and cellular content could be detected in asymptomatic first-degree relatives of subjects affected with familial IPF, and changes in the alveolar microenvironment were present in the absence of detectable abnormalities in chest radiographs or pulmonary function tests (PFTs).…”

Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin

“…[3][4][5][6] Recent studies have revealed that some familial forms of pulmonary fibrosis are associated with mutations in the surfactant protein C gene (SFTPC). [7][8][9][10] Although much is known about the relationship between abnormalities in surfactant proteins, including surfactant protein C (SP-C), and the development of respiratory distress of the newborn, the mechanism by which alterations in SP-C lead to pulmonary fibrosis is unknown.…”

Familial Idiopathic Interstitial Pneumonia: Histopathology and Survival in 30 Patients

“…13 The most commonly described genetic predisposition in diffuse lung disease is for a familial form of IPF. [14][15][16][17] The occurrence of IPF in large family kindreds as well as in twins 18 adds further support for a yet-to-be identified genetic predisposition to chronic, particularly fibrosing, interstitial lung disease. Nevertheless, recent evidence suggests considerable pathologic diversity in F-IIP.…”