Effect of Muc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: A common polymorphism in the MUC5B gene (rs35705950) is associated with susceptibility to idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP). We investigated predisposition of the MUC5B polymorphism to fibrotic interstitial pneumonias in Dutch Caucasian patient cohorts. Furthermore, we investigated the correlation between MUC5B genotype and survival in these cohorts. METHODS: Sporadic IPF (spIPF, n = 115), FIP (n = 55), idiopathic non-specific interstitial pneumonia (iNSIP, n = 43), connective tissue disease associated interstitial pneumonia (CTD_IP, n = 35) and a control cohort (n = 249) were genotyped for rs35705950. RESULTS: Rs35705950 minor allele frequency (MAF) in controls was 0.09. Case-control analysis showed significant allelic association with spIPF (MAF = 0.27; P = 5.0 × 10(-10)), FIP (MAF = 0.30; P = 2.7 × 10(-9)) and iNSIP (MAF = 0.22; P = 3.4 × 10(-4)). No association was observed in CTD_IP (MAF = 0.07). FIP subgroup analysis revealed an association between MUC5B and telomerase mutated FIP (P = 0.003), and between MUC5B and FIP with unknown genetic cause (P = 1.2 × 10(-8)). In spIPF carriership of MUC5B minor allele did not influence survival. In FIP MUC5B minor allele carriers had better survival (non-carriers 37 vs carriers 53 months, P = 0.01). In iNSIP survival analysis showed an opposite effect. Worse survival was found in iNSIP patients that carried the MUC5B minor allele (non-carriers 118 vs carriers 46 months, P = 0.027) CONCLUSION: This study showed that MUC5B minor allele predisposes to spIPF, FIP and iNSIP. In spIPF, survival is not influenced by MUC5B alleles. In FIP, MUC5B minor allele predicts better survival, pointing towards a subgroup of FIP patients with a milder, MUC5B-driven form of pulmonary fibrosis.

Ten-Year Survival in Patients with Idiopathic Pulmonary Fibrosis After Lung Transplantation.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. METHODS AND RESULTS: Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. CONCLUSIONS: This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.

[High mortality in patients with idiopathic pulmonary fibrosis on Dutch lung transplant waiting list]. / Hoge sterfte van patiënten met idiopathische pulmonale fibrose op Nederlandse longtransplantatiewachtlijst.

OBJECTIVE: To describe patients diagnosed with idiopathic pulmonary fibrosis (IPF) registered for lung transplantation and to evaluate the current referral guidelines for lung transplantation in the Netherlands. DESIGN: Retrospective study. METHOD: All patients diagnosed with interstitial lung disease and registered for lung transplantation from September 1989-June 2010 were included in this study. Patients who had been diagnosed with IPF according to the American Thoracic Society-European Respiratory Society criteria were included. Clinical data of these patients at the time of screening for lung transplantation and survival data were collected. RESULTS: In total, 289 patients with IPF were registered for lung transplantation. After a first waiting list. During the waiting period, 30 patients (33%) died, 7 were taken off the list due to newly developed comorbidity and excessive physical deterioration, 51 underwent transplantation and 2 were still on the waiting list at the time of study closure. At the time of screening, the mean FVC% predicted of these patients was 51% (SD: 19.0) and the mean diffusing capacity was 27% of predicted (SD: 9.3). CONCLUSION: One-third of the IPF patients on the waiting list died before donor lungs became available. The mean diffusing capacity of 27% of predicted at the time of screening was considerably lower than advised in the international guidelines for placement on the waiting list. This study, therefore, shows that the timing of screening IPF patients for lung transplantation can be improved in the Netherlands.