Abstract
BackgroundCystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis.AimTo investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF.MethodsIn this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).ResultsSixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar.ConclusionAlthough there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to predict pulmonary exacerbations in children with CF with the chosen biomarkers and the method of EBC analysis. The biochemical measurements of EBC markers should be improved and other techniques should be considered.
Highlights
Cystic fibrosis (CF) is the most common life-shortening genetic disease in the Caucasian population, caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene [1]
There is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of exhaled breath condensate (EBC) acidity and the EBC inflammatory markers IL6, IL-8, tumor necrosis factor α (TNF-α) and migration inhibitory factor (MIF) is low
In an earlier cross-sectional study in 98 children with CF and healthy controls, we found that inflammatory markers in EBC were able to indicate presence, severity and stability of CF disease [12]
Summary
Cystic fibrosis (CF) is the most common life-shortening genetic disease in the Caucasian population, caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene [1]. Pulmonary exacerbations present clinically with a variety of symptoms such as increased cough, increased sputum production, increased dyspnea, decreased energy level and appetite, weight loss and decreases in lung function parameters [5]. These adverse events are treated with antibiotics when apparent, it is not yet possible to predict them. Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis
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