Background: Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications. Methods: 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA. Results: In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95 % CI 0.31, 1.00], p = 0.05). Conclusions: Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma. Trial registration: ClinicalTrials.gov NCT00608764 , first received 1/28/2008.
Bibliographical noteFunding Information:
The authors (RB, MKH, RPB, MTD, JMW, EAR, CPH) assert that they have no conflicts of interest to disclose directly pertaining to the content of this study. Robert Busch, and Elizabeth Regan declare that they have no conflicts of interest. Russell Bowler has served on the Advisory Board to Boehringer-Ingelheim. MeiLan Han has served as a consultant for Regenerson, Glaxo-Smith-Kline, and Boehringer-Ingelheim. Mark Dransfield has served as a consultant for Glaxo-Smith-Kline, Boehringer-Ingelheim, and Ikaria. J Michael Wells and Mark Dransfield both declare that their institution has received research grant support from the American Heart Association, National Heart Lung and Blood Institute, Glaxo-Smith-Kline, and Forest and has received contracted support for enrollment in clinical trials from Aeris, AstraZeneca, Boehringer-Ingelheim, Boston Scientific, Centocor, Glaxo-Smith-Kline, Forest, Otsuka, Pearl, Pfizer, PneumRx, and Pulmonx. Craig Hersh has received lecture fees from Novartis and consulting fees from CSL Behring.
This study was supported by NIH grants T32 HL007427, R01HL094635, R01NR013377, P01HL105339, R01HL089897 and R01HL089856. The COPDGene Study is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion.
© 2016 Busch et al.
- Adrenergic beta-agonists
- COPD exacerbation
- Chronic obstructive pulmonary disease
- Inhaled corticosteroid
- Inhaled medications
- Long-acting beta-agonist
- Prospective cohort study