Studies on the immunological mechanisms underlying progression versus resolution of asthma between adolescence and adulthood

Mok D^a, Hollams EM^a, Bosco A^a, Strickland D^a, de Klerk N^a, Sly PD^b, Holt PG^a.
Division of Cell Biology^a and Centre for Biostatistics^b, The Kids Research Institute Australia, University of Western Australia, Perth, Australia
^bQueensland Children’s Medical Research Institute, Brisbane, Australia.

It is now recognized that late onset and persistent (early onset) asthma in young adults represent different forms of the disease that are likely to be driven by different mechanisms, and are therefore likely to need different treatment. However details of the underlying mechanisms driving progression of asthma in this age range, or the spontaneous remission which frequently occurs, are sparse. We are studying these in the Western Australian Pregnancy (Raine) Cohort, using clinical material collected  in the 22 year respiratory follow-up of ~1000 participants, complementing a similar follow-up that took place at age 14 years. In addition to collecting clinical data relating to asthma, both follow-ups created an archive of cryobanked viable immune cell samples (peripheral blood mononuclear cells) that were collected from subjects at the time of clinical assessment, at both 14 and 23 years. We are continuing studies at both ages to identify immunological markers associated with remitting asthma, persistent asthma, and late-onset asthma. Data collection will continue until late 2017, including systems level transcriptomic analyses on aeroallergen specific Th-memory responses to aeroallergens associated with atopic asthma risk, and analysis of IgE-dependent basophil activation.

Plain language summary: During the teen years asthma spontaneously resolves in approx. 50% of affected subjects, who are replaced by another group of “late onset” asthmatics that often show immune response profiles that are subtley different to typical teenage asthmatics. The current level of understanding of what inflammatory mechanisms drive asthma in the persistent versus late onset young adult asthmatics is frustrating the development of newer and more effective asthma therapies for this age group.  This project seeks new information on these disease mechanisms, to  help propel development of new and better anti-asthma drugs.

Funder: National Health and Medical Research Council of Australia.