Elevated exhaled leukotriene B4 in the small airway compartment in children with asthma

Abstract Background Inflammatory processes in the asthmatic lung involve the large and small airway and alveolar sites. Leukotriene B 4 (LTB 4 ) is an important disease marker, but its role in inflammation of the small airways in asthma has not been established yet. Objective To distinguish between large and small airway or alveolar LTB 4 concentrations in children with asthma using the new technique of fractionated exhaled breath condensate sampling. Methods Sixty-eight children (9–17 years old, 33 children with asthma and 35 controls) underwent fractional exhaled nitric oxide (FeNO) measurements, lung function testing, and collection of fractionated exhaled breath condensate using a capnograph-based approach. The LTB 4 concentrations in the small airway or alveolar and large airway fractions were correlated to disease status, lung function impairment, and clinical parameters. Results Children with asthma had significantly higher LTB 4 concentrations in the small airway or alveolar fraction than controls (5.58 pg/mL; 95% interquartile range [IQR], 2.0–11.77 pg/mL; vs 2.0 pg/mL; 95% IQR, 2.0–6.2 pg/mL; P  = .003). No difference was found between the groups in the large airway fraction. Children with obstructive lung function impairment (forced expiratory volume in 1 second z score 4 concentrations compared with children without impairment (2.0 pg/mL; 95% IQR, 2.0–9.21 pg/mL; vs 18.32 pg/mL; 95% IQR, 3.7–23.02 pg/mL; P  = .04). Children with asthma but without pathologic obstructive lung function still had higher LTB 4 concentrations than controls (5.57 pg/mL; 95% IQR, 2.00–10.60 pg/mL; vs 2.00 pg/mL; 95% IQR, 2.00–6.20 pg/mL; P  = .01). Conclusion LTB 4 is detectable and elevated in the small airway or alveolar fraction of exhaled breath condensate in pediatric asthma. Because of the possibility of detecting elevated levels in patients without lung function impairment in controlled disease, it may be used as a noninvasive marker of small airways disease; however, future long-term studies are needed.