Bronchodilator reversibility in patients with COPD revisited: short-term reproducibility

Steven Pascoe,1 Wei Wu,2 Chang-Qing Zhu,3 Dave Singh4 1GSK, Respiratory Medicines Development Center, 2PAREXEL International, Research Triangle Park, NC, USA; 3GSK, Clinical Statistics (Respiratory), Middlesex, UK; 4Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, University of Manchester, Manchester, UK Abstract: Categorization of patients with COPD as reversible or nonreversible to a bronchodilator may change over time. This post hoc analysis aimed to determine if an individual’s reversibility, when treated as a continuous variable, could predict his/her future response to two short-acting bronchodilators: albuterol and ipratropium. The analysis was completed using data from a 4-week, randomized, open-label, two-period crossover study (NCT01691482; GSK study DB2114956). Patients received albuterol (doses: UK =4×100 µg/puff; US =4×90 µg/puff) followed 1 hour later by ipratropium (4×20 µg/puff) or vice versa during treatment Period 1. The order of treatments was reversed during Period 2. Predefined efficacy end points included pre- and post-bronchodilator forced expiratory volume in 1 second. The correlation coefficient between bronchodilator response on Days 1 and 10 was investigated, as well as the correlation between treatment response on Day 1 and the mean treatment response on Days 5–10, for each individual patient. Bronchodilator response to albuterol on Day 1 was strongly correlated with that on Day 10 (r=0.64; n=53). The correlation coefficient of bronchodilator treatment response on Day 1 and Days 5–10 was 0.78 (P<0.001; n=53) and 0.76 (P<0.001; n=54) for albuterol and ipratropium, respectively. A single measurement of the initial bronchodilator response to albuterol or ipratropium was, therefore, highly correlated with the subsequent mean bronchodilator response over 5–10 days, demonstrating its potential usefulness for future treatment decisions. Keywords: bronchodilator responsiveness, FEV1, correlation, short-acting bronchodilators, spirometr