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Drug development strategies for asthma: in search of a new paradigm

Nature Immunology volume 5, pages 695–698 (2004)Cite this article

The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach.

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Figure 1: Blocking the progression of intermittent infant wheezing to persistent asthma: protection of airway tissues during critical growth and differentiation in early childhood.

References

  1. Weiss, K.B. & Sullivan, S.D. The health economics of asthma and rhinitis. 1. Assessing the economic impact. J. Allergy Clin. Immunol. 107, 3–8 (2001).

    Article  CAS  Google Scholar 

  2. Paramesh, H. Epidemiology of asthma in India. Indian J. Peds. 69, 309–312 (2002).

    Article  CAS  Google Scholar 

  3. Holgate, S. The inflammation-repair cycle in asthma: the pivotal role of the airway epithelium. Clin. Exp. Allergy 28 S5, 97–103 (1998).

    Article  Google Scholar 

  4. Martinez, F.D. Viral infections and the development of asthma. Am. J. Respir. Crit. Care Med. 151, 1644–1647 (1995).

    Article  CAS  Google Scholar 

  5. Oddy, W.H. et al. Association between breast feeding and asthma in 6 year old children: findings from a prospective birth cohort study. Br. Med. J. 319, 815–819 (1999).

    Article  CAS  Google Scholar 

  6. Stein, R.T. et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354, 541–545 (1999).

    Article  CAS  Google Scholar 

  7. Custovic, A., Simpson, B.M., Simpson, A., Kissen, P. & Woodcock, A. Effect of environmental manipulation in pregnancy and early life on respiratory systems and atopy during first year of life: a randomised trial. Lancet 358, 188–193 (2001).

    Article  CAS  Google Scholar 

  8. Peat, J.K. et al. Serum IgE levels, atopy and asthma in young adults: results from a longitudinal cohort study. Allergy 51, 804–810 (1996).

    Article  CAS  Google Scholar 

  9. Sherrill, D., Stein, R., Kurzius-Spencer, M. & Martinez, F. Early senstization to allergens and development of respiratory symptoms. Clin. Exp. Allergy 29, 905–911 (1999).

    Article  CAS  Google Scholar 

  10. Holt, P.G. & Sly, P.D. Interactions between respiratory tract infections and atopy in the aetiology of asthma. Eur. Respir. J. 19, 538–545 (2002).

    Article  CAS  Google Scholar 

  11. Hislop, A.A. & Pandya, H.C. Structural development. in Childhood Asthma and Other Wheezing Disorders (ed. Silverman, M.) 37–56 (Arnold, London, 2002).

    Google Scholar 

  12. Hibbert, M.E., Hudson, I.L., Lanigan, A., Landau, L.I. & Phelan, P.D. Tracking of lung function in healthy children and adolescents. Pediatr. Pulmonol. 8, 172–177 (1990).

    Article  CAS  Google Scholar 

  13. Hall, C.B. Respiratory syncytial virus and parainfluenza virus. N. Engl. J. Med. 344, 1917–1928 (2001).

    Article  CAS  Google Scholar 

  14. Braun-Fahrlander, C. et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl. J. Med. 347, 869–877 (2002).

    Article  Google Scholar 

  15. Holt, P.G. et al. Genetic 'risk' for atopy is associated with delayed postnatal maturation of T-cell competence. Clin. Exp. Allergy 22, 1093–1099 (1992).

    Article  CAS  Google Scholar 

  16. Baldini, M. et al. A polymorphism in the 5′-flanking region of the CD14 gene is associated with circulating soluble CD14 levels with total serum IgE. Am. J. Resp. Cell Mol. Biol. 20, 976–983 (1999).

    Article  CAS  Google Scholar 

  17. Lauener, R.P. et al. Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 360, 465–466 (2002).

    Article  CAS  Google Scholar 

  18. Culley, F.J., Pollott, J. & Openshaw, P.J. Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J. Exp. Med. 196, 1381–1386 (2002).

    Article  CAS  Google Scholar 

  19. Johnston, S.L. et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am. J. Respir. Crit. Care Med. 154, 654–660 (1996).

    Article  CAS  Google Scholar 

  20. Ernst, P., Ghezzo, H. & Becklake, M.R. Risk factors for bronchial hyperresponsiveness in late childhood and early adolescence. Eur. Respir. J. 20, 635–639 (2002).

    Article  CAS  Google Scholar 

  21. Kjellman, B. & Gustafsson, P.M. Asthma severity, allergy and lung function during middle life in subjects with asthma in childhood. Respir. Med. 96, 716–724 (2002).

    Article  CAS  Google Scholar 

  22. Moller, C. et al. Pollen immunotherapy reduces the development of asthma in children with season rhinoconjunctivitis (the PAT-study). J. Allergy Clin. Immunol. 109, 251–256 (2002).

    Article  Google Scholar 

  23. Holt, P.G. A potential vaccine strategy for asthma and allied atopic diseases in early childhood. Lancet 344, 456–458 (1994).

    Article  CAS  Google Scholar 

  24. Björkstén, B., Sepp, E., Julge, K., Voor, T. & Mikelsaar, M. Allergy development and the intestinal microflora during the first two years of life. J. Allergy Clin. Immunol. 108, 516–520 (2001).

    Article  Google Scholar 

  25. Patino, C.M. & Martinez, F.D. Interactions between genes and environment in the development of asthma. Allergy 56, 279–286 (2001).

    Article  CAS  Google Scholar 

  26. The Childhood Asthma Management Program (CAMP) Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N. Engl. J. Med. 343, 1054–1063 (2000).

  27. Nelson, D.J., McMenamin, C., McWilliam, A.S., Brenan, M. & Holt, P.G. Development of the airway intraepithelial dendritic cell network in the rat from class II MHC (Ia) negative precursors: differential regulation of Ia expression at different levels of the respiratory tract. J. Exp. Med. 179, 203–212 (1994).

    Article  CAS  Google Scholar 

  28. Holt, P.G. & Sly, P.D. Prevention of adult asthma by early intervention during childhood: potential value of new generation immunomodulatory drugs. Thorax 55, 700–703 (2000).

    Article  CAS  Google Scholar 

  29. Holt, P.G. & Sly, P.D. Allergic respiratory disease: strategic targets for primary prevention during childhood. Thorax 52, 1–4 (1997).

    Article  CAS  Google Scholar 

  30. Martinez, F.D. Toward asthma prevention –- does all that really matters happen before we learn to read. N. Engl. J. Med. 349, 1473–1475 (2003).

    Article  CAS  Google Scholar 

  31. Giacoia, G.P. Incentive to study drugs in children and other governmental initiatives: Will patients with asthma benefit? J. Allergy Clin. Immunol. 106, S118–S124 (2000).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Telethon Institute for Child Health Research, and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia

    Patrick G Holt & Peter D Sly

  2. Arizona Respiratory Center, University of Arizona, Tucson, Arizona, USA

    Fernando D Martinez

  3. Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Scott T Weiss

  4. Centre for Allergy Research and Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Bengt Björkstén

  5. Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany

    Erika von Mutius

  6. University Hospital Charite-Virchow, Berlin, Germany

    Ulrich Wahn

Authors
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  7. Ulrich Wahn
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Holt, P., Sly, P., Martinez, F. et al. Drug development strategies for asthma: in search of a new paradigm. Nat Immunol 5, 695–698 (2004). https://doi.org/10.1038/ni0704-695

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