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Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough
Dominik Hartl1, Matthias Griese, Thomas Nicolai
1Children's Hospital of the Ludwig-Maximilians-University of Munich, Lindwurmstrasse 2a, D-80337 Munich, Germany.
Insights
Chemokines and their receptors, specifically CCR4+ CD4+ cells (TARC, MDC) and CXCR3+ CD8+ cells (ITAC), can differentiate asthmatic cough from chronic cough in children. This analysis aids in diagnosing childhood asthma.
Area of Science:
- Immunology
- Pediatric Pulmonology
- Biochemistry
Background:
- Differentiating asthmatic cough from other causes in children is challenging.
- Chemokines and their receptors play a role in T lymphocyte recruitment and differentiation.
Purpose of the Study:
- To investigate differences in T helper 1 (TH1)/T helper 2 (TH2) related chemokines and receptors in bronchoalveolar lavage fluid (BALF).
- To compare these markers in children with allergic asthma, chronic cough, and no airway disease.
Main Methods:
- Quantified TH1/TH2 chemokines and cytokines (e.g., IP-10, ITAC, Mig, IFN-gamma, TARC, MDC, IL-5, IL-4) in BALF using ELISA and multiplex arrays.
- Determined percentages of pulmonary lymphocytes expressing TH1 (CXCR3+, CCR5+) and TH2 (CCR4+, CCR3+) chemokine receptors via flow cytometry.
Main Results:
- Asthmatic children showed significantly increased pulmonary CCR4+ CD4+ cells and elevated TARC and MDC levels compared to other groups.
- In asthmatic children, CCR4+ CD4+ cells correlated with TARC, MDC, and serum IgE, and inversely with FEV1.
- Children with non-atopic chronic cough had significantly increased CXCR3+ CD8+ cells and ITAC levels.
Conclusions:
- Pulmonary CCR4+ CD4+ cells, CXCR3+ CD8+ cells, and their ligands (TARC, MDC, ITAC) effectively distinguish asthmatic children from those with non-atopic chronic cough.
- Analyzing these specific markers can aid in the diagnostic differentiation of childhood asthma from other causes of 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 alpha 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 FEV 1 . 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.
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