Effect of smoking status on the efficacy of the SMART regimen in high risk asthma - Reply.

Abstract

Thank you for your interest in our study. In response, the sample size was based on a total of 150 participants giving a power of 80% in a two-sided test with an α of 0.05 for detection of a high β agonist episode rate of 21.4%, an absolute risk reduction of about 15% and a relative risk of 0.6.1 To ensure generalizability of our findings to a ‘real world’ population with high risk asthma, there was no stratified selection of participants by smoking status.2 The key exclusion criteria of a diagnosis of chronic obstructive pulmonary disease or an onset of respiratory symptoms after the age of 40 years in current or ex-smokers with at least a 10-pack year smoking history were important to ensure our population comprised adults with asthma and not primarily chronic obstructive pulmonary disease. Bronchodilator responsiveness was not used to diagnose asthma due to the poor sensitivity and specificity of this measurement when used for this purpose3 and to ensure generalizability of the findings to a real-world population with asthma.4 Treatment with oral prednisone in the previous 4 weeks was an exclusion criterion. The rationale for this was to allow a period of stability prior to enrolment for participants with a recent severe asthma exacerbation. The main reason for withdrawal from the study was patient choice due to worsening asthma or other reasons (seven vs two and five vs three for Single combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) inhaled as both Maintenance And Reliever Therapy (SMART) vs Standard, respectively). All outcome measures contributed to the assessment of the safety profile of the randomized regimens, including but not limited to severe exacerbations, hospital admission or emergency department attendances, or systemic corticosteroid exposure (Tables 2 and 4), and high, marked and extreme β agonist use episodes, and high β agonist use episodes without subsequent medical review (Tables 3 and 5). 2 The findings do not imply that the SMART regimen overcomes the influence of smoking; rather, we conclude that due to the higher baseline risk of morbidity and at-risk behaviour in current and ex-smokers, the absolute reduction in risk with the SMART regimen compared with the standard regimen is greater than in non-smokers. Finally, recognizing that many smokers with asthma have features consistent with the asthma/chronic obstructive pulmonary disease overlap syndrome, we presume that our findings suggest that the favourable efficacy/safety profile of the SMART regimen, when compared with the standard maintenance ICS/LABA and short-acting β-agonist reliever therapy regimen, may also apply to those with asthma/chronic obstructive pulmonary disease overlap syndrome. R.B has been a member of the GlaxoSmithKline (NZ), AstraZeneca and Novartis advisory boards, consulted for Cytos Biotechnology and Pharmaxis, received research grants from AstraZeneca, Cephalon, Chiesi, Genentech, GlaxoSmithKline and Novartis, payment for lectures or support to attend meetings from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Nycomed and Otsuka Pharmaceuticals.