Genetics and the variability of treatment response in asthma

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Presentation transcript:

Genetics and the variability of treatment response in asthma Elliot Israel, MD, FAAAAI, FCCP Journal of Allergy and Clinical Immunology Volume 115, Issue 4, Pages S532-S538 (April 2005) DOI: 10.1016/j.jaci.2005.01.029 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Distribution of patients experiencing a particular change in FEV1. Green bars represent patients receiving montelukast, 10 mg once daily; pink bars represent patients receiving inhaled beclomethasone, 200 μg twice daily. Adapted with permission from Malmstrom et al. Annals of Internal Medicine 1999.1 Journal of Allergy and Clinical Immunology 2005 115, S532-S538DOI: (10.1016/j.jaci.2005.01.029) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Distribution of yearly change in hip bone density in relation to the average number of daily puffs of inhaled corticosteroid. The solid line represents the mean change. The dashed lines indicate the 95 percent confidence interval for the mean. Adapted with permission from Israel EBT, Fitzmaurice GM, Kotlov TV, LaHive K, LeBoff MS. N Engl J Med. 2001;345:941-7. Copyright © 2001 Massachusetts Medical Society. All rights reserved.3 Journal of Allergy and Clinical Immunology 2005 115, S532-S538DOI: (10.1016/j.jaci.2005.01.029) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Effect of genetic polymorphisms at position 16 of the β2-agonist on AM PEFR in patients using regular albuterol versus prn for 16 weeks followed by a 4 week run-out. Arg/Arg patients who received regularly scheduled beta-agonist treatment (Arg/Arg-Regular) experienced a 30.5 ± 12.1 L/min decline in AM peak expiratory flow relative to those who received as-needed treatment (Arg/Arg-PRN; P=0.012). Gly/Gly patients were not affected by regular treatment (Gly/Gly-Regular). Adapted with permission from Israel et al. American Journal of Respiratory and Critical Care Medicine 2000.9 Journal of Allergy and Clinical Immunology 2005 115, S532-S538DOI: (10.1016/j.jaci.2005.01.029) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Effect of regular albuterol (Albuterol) versus placebo albuterol (Placebo) on AM PEFR during the 16 week treatment period and 8 week washout within each genotype at the 16th position of the β2-agonist. A, Arg/Arg. B, Gly/Gly. Wild type, 5 binding motif repeat alleles; mutant, non-5 repeat alleles; heterozygote, 1 mutant+1 wild-type allele. Patients with the Arg/Arg genotype exhibited significantly improved PEFR in the placebo phase more than the albuterol phase (10 L/min; P=0.0209) In contrast, patients with the Gly/Gly genotype experienced greater improvement in their PEFR during the regular albuterol phase as compared to the placebo phase (14 L/min; P=0.0175). Reprinted with permission from Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomized, placebo-controlled cross-over trial. Lancet 2004;364:1505-12.11 Journal of Allergy and Clinical Immunology 2005 115, S532-S538DOI: (10.1016/j.jaci.2005.01.029) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Percent change in FEV1 from baseline for patients with mutations at the ALOX5 core promoter locus treated with the 5-lipoxygenase inhibitor ABT-761. Adapted with permission from Drazen et al. Copyright © 1999 Nature Genetics.15 Journal of Allergy and Clinical Immunology 2005 115, S532-S538DOI: (10.1016/j.jaci.2005.01.029) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions