Clinical Characteristics of Cystic Fibrosis Patients Carrying Residual Function Mutations: Data from the European Cystic Fibrosis Patient Registry

Background: The clinical presentation of Cystic Fibrosis (CF) is variable. Mutations that exhibit residual function (RF) of the cystic fibrosis transmembrane conductance regulator (CFTR) are considered to have a milder disease, as compared to mutations with minimal CFTR function (MF).

Aim: To characterize the disease severity of RF patients, using the European CF Registry data.

Methods: A retrospective cohort study included data from the ECFSPR during 2008-2016. Demographic and clinical characteristics of RF and MF patients were compared. Lung function of patients who have longitudinal data for at least 3 consecutives years was compared between both groups. The death probability of both groups was compared.

Results: The MF group consisted of 37,958 patients while 6,636 patients were in the RF group. RF Patients were older than MF patients, were diagnosed at a later age, had lower sweat chloride and better FEV1. However, FEV1 declined with age while rates of chronic Pseudomonas Aeruginosa increased. A significant number of RF patients had FEV1 similar to MF patients. 4.5% of RF patients were treated with oxygen and 2.61% had lung transplants. 26.6% of RF patients were treated with pancreatic enzymes. These patients had a more severe clinical course. RF patients had shortened life spans, with mortality starting around 20 years.

Conclusion: RF Patients suffer from a life-shortening disease characterized by pulmonary function decline and a significant number of RF patients suffer from chronic respiratory infection. Augmenting CFTR function by CFTR modulators may improve survival and quality of life of patients carrying these mutations.