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

Article metrics

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. 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).

  2. 2

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

  3. 3

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

  4. 4

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

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 11

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

  12. 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).

  13. 13

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

  14. 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).

  15. 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).

  16. 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).

  17. 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).

  18. 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).

  19. 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).

  20. 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).

  21. 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).

  22. 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).

  23. 23

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

  24. 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).

  25. 25

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

  26. 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. 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).

  28. 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).

  29. 29

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

  30. 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).

  31. 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).

Download references

Author information

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Further reading