Currently COPD is defined by an FEV1/FVC<0.7. However, mounting evidence suggests that this spirometric definition of COPD may be insufficient. Indeed, many current and former smokers with a normal FEV1/FVC (>0.7), termed GOLD 0 by the GOLD committee and SG 0 by the COPD Foundation, manifest symptoms of COPD, disability due to those symptoms and clinically significant exacerbations. When carefully studied, this group has evidence of occult airflow obstruction consistent with airway disease not detected by simple spirometry suggesting that many GOLD 0 smokers with symptoms have chronic obstructive lung disease consistent with COPD, but do not fit into current management guidelines. Because this population is large, the health burden posed by these people with undiagnosed chronic lung disease is significant and whether they would benefit from therapy is entirely unknown. Yet a significant percentage of these patients are already being treated in the community with bronchodilators without guidance or evidence. The trial proposed here will test the following overarching hypothesis: symptomatic current and former smokers with spirometric values in the GOLD 0 range (FEV1/FVC>0.7) will derive benefit from inhaled bronchodilator therapy, even though they are currently excluded from the current GOLD and COPD Foundation guideline recommendations. The clinical trial that stems from this hypothesis will have far reaching impact regardless of the outcome. If treated subjects experience symptomatic benefit, then we would provide evidence to alter current treatment guidelines. If treatment provides no benefit in this group, this would provide important guidance for community physicians.
Our specific aims will be achieved in a double blind, randomized controlled parallel group 12 week trial of bronchodilator therapy versus placebo in 570 subjects who have symptoms (defined as CAT=10) despite normal spirometry (FEV1/FVC>0.7). Specifically, we propose the following aims: (1) Determine whether current and former smokers with symptoms (GOLD 0), will benefit from therapy with indacaterol 75 mcg qd, a long-acting beta agonist (LABA), as compared to placebo with improvements as measured by the proportion experiencing improvement in SGRQ = 4 points and other patient reported outcomes; (2) Determine whether this group will benefit from therapy with indacaterol as compared to placebo with improvements in physiology (lung function, 6 minute walk test); (3) Identify predictors of response based on post-hoc analyses of other physiological measurements. Our over-riding goal is to determine the value of bronchodilator therapy for symptom and physiologic improvement in mild COPD. As these data have never been collected and physicians currently have no evidence on which to base treatment decisions, the outcome of this simple, pragmatic study could have significant impact on both our understanding of this disease and our ability to appropriately treat patients with early COPD.
COPD is a highly prevalent disorder associated with significant symptoms, exercise limitation and 'flare-ups' of the disease. Our ability to help patients with mild COPD is hampered by lack of data as COPD treatments have not been rigorously evaluated in this patient population. This study proposes to determine whether bronchodilator therapy results in symptomatic improvement in smokers with mild COPD thereby providing physicians much needed evidence upon which to base treatment decisions.
