Asthma: Acute asthma flare-up in school-age children

Jones A^a, Leffler J^a, Mok D^a, Read J^a, Serralha M^a, Holt BJ^a, Bizzintino J^a,b, Khoo S-K^a,b, Rueter K^b, Laing I^a,b, Goldblatt J^b, LeSouef PN^b, Kusel M^a, Sly PD^c, Holt PG^a, Bosco A^a, Strickland DH^a.

^aDivision of Cell Biology, The Kids Research Institute Australia, The University of Western Australia, Subiaco, Australia,
^bSchool of Paediatrics and Child Health, The University of Western Australia, Princess Margaret Hospital, Subiaco, WA, Australia
^cQueensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia

Severe lower respiratory viral infections cause acute viral bronchiolitis in infancy and are a major risk factor for the pathogenesis of asthma later in life. The immune system of infants is in a transient state of functional immaturity relative to adults. Thus, findings in adults cannot be extrapolated to young children. Given that maturation of immunological function in early life can have a major impact on risk for infection and development of asthma related traits, detailed studies based on defined age groups will be essential. At present, our understanding of how antiviral responses change from infancy to older children is limited. Hence, a systematic study is required of the cellular and molecular mechanisms underlying acute viral respiratory illnesses from infants with bronchiolitis through to school age children with asthma. The aim of this study is to investigate the cellular and molecular immune responses in peripheral blood samples collected from children during an acute asthma flare-up. Peripheral blood mononuclear cells (PBMC) were collected during an acute asthma flare-up and following recovery. PBMC were phenotyped employing multiparametric flow cytometry (14-colours) and a subset was utilised for transcriptomic profiling. We have found that an asthma flare-up is associated with significant modulation of immune cell populations in peripheral blood.

Lay summary:
Asthma is a chronic disease of the airways affecting 2 million Australians. Viruses that infect the lungs can trigger asthma flare-ups severe enough to require hospitalisation in asthmatic children. Current treatments improve the symptoms of asthma but are unable to prevent the disease. The aim of this study is to identify differences in immune cells that are involved in the disease. This research will employ a combination of innovative technologies to compare cells in the blood from asthmatic children with healthy children. Ultimately, we hope to identify new treatment targets to prevent the development of asthma.

This project is funded by the National Health and Medical Research Council of Australia.