Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in children

Abstract

Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H(2)O(2)), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-gamma) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 +/- 0.3 pg/ml, 2.2 +/- 0.2 microM, 10.0 +/- 1.2 p.p.b. vs. 2.6 +/- 0.2 pg/ml, 1.4 +/- 0.1 microM, 15.4 +/- 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-gamma [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children.

Exhaled breath condensate: a comprehensive update

“…NO synthesis and release in the respiratory system have been indirectly assessed in EBC by quantifying levels of nitrate/nitrite, nitrotyrosine and S-nitrosothiols [ 83 , 143 ]. Nitrate and nitrite have been measured in EBC of patients with asthma [ 53 , 93 ], COPD [ 53 , 144 ], pulmonary fibrosis [ 145 ], bronchiectasis, cystic fibrosis [ 146 ], acute lung injury [ 147 ], primary ciliary dyskinesia [ 148 ] and community acquired pneumonia [ 149 ]. However, conflicting results exist between increased or unchanged nitrate/nitrite levels in some respiratory conditions [ 149 ].…”

Analysis of Inflammatory and Immune Response Biomarkers in Sputum and Exhaled Breath Condensate by a Multi-Parametric Biochip Array in Cystic Fibrosis

“…EBC has been acknowledged to be of limited value, due to the low levels of inflammatory biomarkers in CF (10)(11). We then used an ultrasensitive biochip array, with the result that some biomarkers were at the limit of detection.…”

“…Cytokine levels in sputum have been shown to be regulated by antibiotic therapy (6)(7)(8), but few data are available on the duration of the effect of antibiotic treatment and whether cytokines can be more sensitive biomarkers than spirometric parameters. Several research groups detected altered biomarkers of inflammation in EBC of CF patients, compared with controls (9)(10)(11). However, simultaneous data on multiple markers in CF EBC are limited.…”

Fractional Exhaled Nitric Oxide: Indications and Interpretation

“…FE NO is low in both children [40,63,146,147] and infants [134,148] with CF despite chronic airway inflammation, although FE NO levels similar to or higher than control subjects are also reported in children and infants with CF [93,139,149]. FE NO is negatively correlated with lung clearance index in CF [40] and FE NO is lower in patients with severe CF lung disease than in those with mild disease [147,150].…”