Development and Internal Validation of a Prognostic Model of the Probability of Death or Lung Transplantation Within 2 Years for Patients With Cystic Fibrosis and FEV₁ ≤ 50% Predicted.

Abstract

Improved methods are needed to risk-stratify patients with cystic fibrosis (CF) and reduced FEV₁. What are the predictors of death or lung transplantation (LTx) within 2 years among patients with CF whose FEV₁ ≤ 50% predicted? Do these markers similarly predict outcomes among G551D patients taking ivacaftor since 2012? Patients with CF, age ≥ 6 years with FEV₁ ≤ 50% predicted as of December 31, 2014, were identified in a data set that merged Cystic Fibrosis Foundation and United Network for Organ Sharing (UNOS) registries. The least absolute shrinkage and selection operator (LASSO) method was applied to a randomly selected training set to select important prognostic variables. Accuracy and association of the model with death or LTx with 2 years (2-year death or LTx) were validated via logistic regression on an independent test set. Sensitivity analyses explored predictors for patients with UNOS data. FEV₁ percent predicted (OR, 1.51 for 5% decrease; 95% CI, 1.27-1.81), number of pulmonary exacerbations treated with IV antibiotics (OR, 1.35; 95% CI, 1.11-1.65), and continuous or nocturnal oxygen (OR, 3.71; 95% CI, 1.81-7.59) were significantly associated with 2-year death or LTx. Our model predicted outcomes with greater sensitivity (ratio of sensitivity, 1.26; 95% CI, 1.02-1.54), ratio of positive predictive value (1.25; 95% CI, 1.05-1.51), and ratio of negative predictive value (1.04; 95% CI, 1.01-1.07) than FEV₁ < 30% predicted. Among those taking ivacaftor in 2014, only FEV₁ remained associated with 2-year death or LTx. For patients with UNOS data, LASSO identified additional covariates of interest, including noninvasive ventilation use, low hemoglobin, pulmonary arterial systolic pressure, supplemental oxygen, mechanical ventilation, FEV₁ percent predicted, and cardiac index. Among individuals with CF and FEV₁ ≤ 50% predicted, FEV₁ percent predicted, oxygen therapy, and number of pulmonary exacerbations predicted 2-year death or LTx. Although limited by small sample size, only FEV₁ remained predictive in patients receiving highly effective modulator therapy. Additional physiologic variables could improve prognostication in CF.