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 FEV ≤ 50% Predicted.

BACKGROUND

Improved methods are needed to risk-stratify patients with cystic fibrosis (CF) and reduced FEV.

RESEARCH QUESTIONS

What are the predictors of death or lung transplantation (LTx) within 2 years among patients with CF whose FEV ≤ 50% predicted? Do these markers similarly predict outcomes among G551D patients taking ivacaftor since 2012?

STUDY DESIGN AND METHODS

Patients with CF, age ≥ 6 years with FEV ≤ 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.

RESULTS

FEV 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 FEV < 30% predicted. Among those taking ivacaftor in 2014, only FEV 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, FEV percent predicted, and cardiac index.

INTERPRETATION

Among individuals with CF and FEV ≤ 50% predicted, FEV percent predicted, oxygen therapy, and number of pulmonary exacerbations predicted 2-year death or LTx. Although limited by small sample size, only FEV remained predictive in patients receiving highly effective modulator therapy. Additional physiologic variables could improve prognostication in CF.