Published online: September 19, 2017
Children with severe asthma utilize disproportionate amounts of healthcare resources compared with other asthmatic children. Many of these high-risk patients do not respond to therapies that control allergic inflammation and continue to experience symptoms despite the use of inhaled corticosteroids. A role for a specific type of immune cell called Th2 cells, has long been recognized in the development and maintenance of asthma in allergic patients. Such cells promote the production of allergic antibodies, and characteristic profiles of inflammation in the lower airways. However, little is known about the immune cells and mediators involved in severe asthma in children.
In an Original Research Article published in The Journal of Allergy and Clinical Immunology (JACI), Wisniewski and colleagues aimed to construct a comprehensive picture of the immune landscape in the lower airways of children with treatment-refractory severe asthma. The study analyzed a variety of immune cells and secreted proteins in fluid obtained from the lower airways of 52 children with severe asthma between 6 months and 17 years of age. Most children (73%) were allergic, and multiple allergies to cat, dust mite, tree and grass pollens, fungi, and foods were common, especially among children over 6 years of age. In addition, 92% of the children had evidence of current or past exposure to respiratory bacteria or viruses, based on any past pneumonia or standard clinical tests.
Although Th2 cells were present in the lower airways, they were vastly outnumbered by a distinct type of T cell called Th1 cells. Those Th1 cells identified were adorned with proteins that play a key role in fighting infections caused by respiratory pathogens. In addition to the findings in T cells, analysis of 25 secreted factors identified higher levels of an anti-viral protein called IL-28A, as well as other anti-microbial proteins, in asthmatics who were allergic to dust mite and inhaled fungi (Aspergillus fumigatus and Alternaria alternata). The presence of a dominant Th1 signature linked to specific allergies from an early age provides a new paradigm for severe asthma. The authors suggest that more work is needed to assess whether therapies that regulate Th1 cells, might benefit those children with severe asthma whose disease does not respond to guideline-based management.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.