Treatment and demographic factors affecting time to next pulmonary exacerbation in cystic fibrosis

Abstract

Background: Pulmonary exacerbations (PEx) are important CF clinical events.

Methods: We studied time to next PEx following intravenous (IV) antibiotic PEx treatment among Cleveland Ohio CF center patients occurring between January 2010 and September 2014. Patient demographics, clinical presentations, and treatments were modeled by Cox proportional hazards regression to identify covariates associated with time to next PEx.

Results: 193 patients were treated for PEx; 155 had a subsequent IV-treated PEx. Six covariates were associated with future PEx hazard: number of PEx in the prior year (hazard ratio 25.1 for ≥3 and 4.4 for 1-2 prior-year PEx versus none; P<.0001), IV treatment duration in weeks (1.2; P=.0004), percent hospital treatment (1.1; P=.0018), and chronic inhaled aminoglycosides (2.5; P<.0001), leukotriene modifiers (1.8; P=.0031), and high dose ibuprofen (0.52; P=.0006).

Conclusions: Time to next PEx was profoundly associated with prior-year PEx, suggestive of high-risk PEx phenotypes that warrant recognition and further study.

Keywords: Cystic fibrosis; Pulmonary exacerbation phenotype.

Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1. Disposition of Covariates for Cox Proportional Hazards Regression

A total of 65 covariates (gray shaded area) were analyzed by univariate Cox proportional hazards regression and sorted by P value. Among 25 covariates with P<.10 box were discarded for reasons shown and retained modeling>

Figure 2. Kaplan-Meier Survival Plots of Time to Next PEx by Prior-Year PEx

Survival curves are shown for time from the end of PEx treatment to either censor (vertical dashes) or next PEx care episode stratified by the number of PEx care episodes experienced in the prior calendar year (in text at the end of each curve). Numbers of patients remaining at risk for PEx in each group are shown below the figure.

Figure 3. Forest Plot of Final Cox Proportional Hazards Regression Model

Four categorical variables and two continuous variables remaining from the original 20 retained covariates (Figure 1) after backwards selection with a requirement of covariate P <.01. point estimates and associated p-values for covariates are shown.>

Figure 4. Covariate distributions by Prior-year PEx subgroup

Percentages of all patients (vertical dashes), and Prior-year PEx patient subgroups (circles) in which categorical covariates included in Cox proportional hazards regression (Figure 1) were positive.