Prevention of adult asthma by early intervention during childhood: potential value of new generation immunomodulatory drugs
- TVW Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6872
- Professor P G Holt email:
Current treatment regimens for asthma are based principally upon active suppression of inflammatory processes within airway tissues of sufferers, and one of the major thrusts of research in this area is towards development of increasingly more selective and more potent anti-inflammatory drugs. The impetus for much of the recent activity in relation to drug development in this field stems from an increased understanding of the contribution of immunologically mediated mechanisms towards inflammation induced tissue damage in the asthmatic airway, and this has led to the identification of a new spectrum of drug targets associated specifically with T helper 2 (Th2) cell functions.
However, we argue below that this overall drug development/testing process may be conceptually flawed, not in relation to drug design per se, but at the key stage of selection of subjects for subsequent clinical studies. In brief, we suggest that the practice of testing new selective anti-inflammatory and/or immunomodulatory drugs exclusively in adult asthmatic subjects with established disease inadvertently selects for equivocal or, at worst, negative results in relation to efficacy because the disease process in these patients will frequently have progressed beyond a stage at which it is susceptible to such agents. If so, the potential value of newly developed therapeutic agents which may be efficacious at earlier stages of the disease, including those capable of blocking the progression from trivial allergy to persistent asthma, is unlikely to be recognised unless the testing process is redesigned specifically to address this important possibility.
Asthma as a multi-stage process: T cell sensitisation versus airways inflammation versus symptomatology
On the basis of studies from our group and others on the immunology and epidemiology of asthma in early life, we have developed a general working model for the relationship between respiratory allergy and persistent asthma which is summarised in fig1.1-3 This model envisages the development of asthma occurring in multiple stages …