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Genotypes Do Not Modify Lung Function In Response to Asthma Treatment NEW YORK -- November 19, 2009 -- Studies have suggested that patients with asthma who have a specific genotype might respond less well to certain treatments than those with a different genotype. However, a study published in this week’s edition of The Lancet shows that patients with either genotype respond to combination treatment with longacting beta2 agonists plus moderate-dose inhaled corticosteroids, and that this treatment should be continued for these patients. Michael E Wechsler, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with an inhaled corticosteroid. In the randomised controlled trial, adult patients with moderate asthma were enrolled in pairs of similar lung capacity and ethnic origin, according to whether they had the B16 amino-acid makeup arginine-arginine (Arg-Arg; n = 42) or B16 glycine-glycine ; n = 45) genotype. Individuals in a matched pair were assigned to receive inhaled longacting salmeterol 50 mcg twice a day or placebo given in a double-blind, crossover design for two 18-week periods. An inhaled corticosteroid (hydrofluoroalkane beclometasone 240 mcg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). The team found that PEF did not differ between treatment groups, with both recording very similar lung function. However, responsiveness to methacholine was also assessed and revealed that Arg-Arg patients did not benefit from addition of salmeterol with respect to this important marker of airway hyper-responsiveness, whereas Gly-Gly patients did. Another interesting finding was that African-Americans with the Arg-Arg genotype (20% of African Americans) did not improve with respect to lung function with the addition of salmeterol to the inhaled corticosteroid the way African-American Gly-Gly patients did. This may modify the risk benefit ratio of longacting beta agonists in this population. “These findings provide reassurance that, in the general population, patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype,” the authors wrote. “However, we need to further investigate the importance of the genotype-differentiated response in airway reactivity favouring Gly/Gly participants, as well as the finding that African-Americans with the the Arg/Arg genotype might not benefit from treatment with salmeterol.” In an accompanying comment, H. William Kelly, MD, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, said: “Studies of single-nucleotide polymorphisms are probably limited because response is mediated by numerous factors and interactions. Genome-wide association studies currently underway that can evaluate the interactions between phenotypes and several genetic polymorphisms and their combinations, as well as other response elements, are more likely to provide clinically significant findings.” SOURCE: The Lancet E-mail this page to a friend or colleague! To print, use this version