Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough

Background: Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T(H)1 and T(H)2 cells. Objective: We sought to determine whether levels of T(H)1/T(H)2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease. Methods: The T(H)1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell a chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T(H)2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3(+) and CCR5(+) (T(H)1) and CCR4(+) and CCR3(+) (T(H)2) chemokine receptors were determined in BALF by flow cytometry. Results: Pulmonary CCR4(+)CD4(+) cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4+CD4+ cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV1. In contrast, CXCR3(+)CD8(+) cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3(+)CD8(+) cells correlated with levels of ITAC and IFN-gamma. Conclusion: Pulmonary CCR4(+)CD4(+) and CXCR3(+)CD8(+) cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.