Can Guideline-defined Asthma Control Be Achieved?

Abstract

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.

Fluticasone propionate/formoterol: A fixed-combination therapy with flexible dosage

“…The results of numerous randomized and controlled clinical studies have demonstrated the efficacy of using ICS/LABA (an inhaled corticosteroid combined with a long-acting inhaled β 2 -agonist) in a single inhaler for the treatment of asthma of patients not controlled by low doses of inhaled steroids [21][22][23][24][25][26]. Moreover, it has been shown that the combination of these drugs considerably improved the management of asthma symptoms, including mild and severe exacerbations, as compared with the administration of ICS as monotherapy [27,28].…”

Pharmacogenetics of the β2-Adrenergic Receptor Gene

“…These SNPs cause coding changes of the amino acid (AA) product at each codon or amino acid position relative to the start codon. Denoted as AA 1 codon AA 2 (AA 1 and AA 2 referring to the amino acid products of the two differing alleles) these SNPs include Gly 16 Arg, Gln 27 Glu, Val 34 …”

“…Two ADRβ2 polymorphisms, Gly 16 Arg and Gln 27 Glu, have both been shown to influence the downregulation of the β2-adrenergic receptor in Chinese hamster fibroblasts and human airway smooth muscle cells. 36,37 In Chinese hamster fibroblasts, substitution of the amino acid combination or haplotype Arg 16 27 ) results in resistance to isoproterenol-induced downregulaton of the receptor. 36 In human airway smooth muscle cells the findings were similar: receptors with the Gly 16 genotype underwent enhanced agonist-promoted downregulaton while the Gln 27 genotype showed attenuation of agonist-promoted desensitization with isoproterenol.…”

“…In vitro studies suggest that two ADRβ2 polymorphisms, Gly 16 Arg and Gln 27 Glu, play a significant role in receptor down-regulation and desensitization and, in theory, may predict susceptibility to asthma phenotypes and the adverse effects of SABA therapy. These polymorphisms have served as the fundamental basis of interpreting in vivo, candidate gene analyses of ADRβ2.…”

“…In addition a large number of clinical trials have shown that the addition of a LABA to an inhaled corticosteroid reduces exacerbations and improves asthma control. [22][23][24][25][26][27] . This background information on the potential adverse effects of beta agonist therapy is important because it emphasizes the heterogeneity in therapeutic responses to beta agonist therapy and the importance of understanding pharmacogenetic responses with beta agonist therapy in asthma.…”