Risk factors for lung disease progression in children with cystic fibrosis; a longitudinal cohort study

Abstract

Introduction: In cystic fibrosis (CF), progression of lung disease is predisposed by various factors. Early identification of risk factors for disease progression is of importance to closer monitor and intervene in this life-limiting disease. Aim: To study risk factors for lung disease progression in a large cohort of children with CF. Methods: Longitudinal data from 2009 to 2014 of all children with CF (≥5 years of age) registered in the Dutch CF Registry were studied. Lung disease progression was defined as decline in FEV 1 %pred and pulmonary exacerbation (PEx) rate. Risk factors measured at baseline included: sex, age, best FEV 1 %pred, best FVC%pred, genotype, BMI z-score, pancreatic insufficiency, medication use (proton pump inhibitors [PPI], prophylactic antibiotics, and inhaled corticosteroids), CF related diabetes, allergic bronchopulmonary aspergillosis, and colonisation with Pseudomonas aeruginosa . Results: Data of 545 children with CF were studied. PPI use was significantly related to both an accelerated annual decline in FEV 1 %pred (p=0.017) and PEx (p=0.006). Moreover, the risk of future PEx was increased in patients with a lower FEV 1 %pred (p=0.007), use of prophylactic antibiotics (p=0.006), Pseudomonas colonization (p=0.032), and exacerbations in the past (p=0.002). Other studied factors were not significantly related to lung disease progression. Conclusion: We were able to reveal several risk factors for lung disease progression in a large cohort of Dutch children with CF followed during six years. Particularly the potential risk of PPI use needs attention and further study. The precise mechanism underlying this risk is unclear.