MedWire News: Severe asthma in children is characterized by distinct molecular patterns of airway inflammation, which may account for ongoing symptoms despite corticosteroid treatment, say US researchers.
Writing in the Journal of Allergy and Clinical Immunology, Anne Fitzpatrick (Emory University School of Medicine, Atlanta, Georgia) and colleagues explain that severe childhood asthma is a heterogeneous disorder, but affected children share many similar clinical features, including gas trapping, bronchial hyper-responsiveness, and aeroallergen sensitization, and poor response to treatment.
However, they add that that the molecular and cellular patterns of inflammation that distinguish severe from moderate asthma in children are not known.
To investigate, the team analyzed levels of 23 cytokines and chemokines in bronchoalveolar lavage (BAL) fluid and alveolar macrophage (AM) samples collected from 53 children, aged 5–17 years, with severe (n=31) or moderate (n=22) asthma, and 30 healthy adult controls.
Univariate analysis of BAL fluid revealed that levels of interleukin (IL)-6 and IL-13 were elevated in asthma patients compared with controls, but levels of the 23 cytokines and chemokines did not differentiate between children with moderate and severe asthma in univariate analysis.
However, when linear discriminant analysis of BAL fluid was performed, the model of 23 cytokines and chemokines resulted in good separation of the three groups, with correct identification of 100% of controls, 86% of the children with moderate asthma, and 91% of children with severe asthma.
Stepwise analysis of BAL fluid that excluded the healthy controls revealed that RANTES (CCL5) was the strongest differentiating factor between patients with moderate and severe asthma.
When the 11 cytokines and chemokines detected in AM lysate were included in the model, linear discriminant analysis resulted in correct identification of 93% of controls, 83% of children with moderate asthma, and 100% of children with severe asthma.
In AM lysate, IL-6 was the strongest discriminator between all of the groups.
Fitzpatrick and team conclude: “By using the supervised method of linear discriminant analysis, we provide the first preliminary evidence of the molecular phenotype of severe asthma in children.”
They add: “Improved classification of children with severe asthma may assist with the development of targeted therapeutics for this group of children who are difficult to treat.”
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