Objectives: While short-acting bronchodilators are commonly used in COPD treatment, comparative effectiveness data between modes of their delivery is limited. The study objective was to compare clinical and economic outcomes among COPD patients using short-acting bronchodilator nebulizers, inhalers or both.

Methods: A retrospective observational study was conducted using the HealthCore Integrated Research Database. Patients ≥40 years of age with COPD who had ≥1 medical and/or pharmacy claim between 2017-18 for levalbuterol, albuterol, ipratropium bromide or combination short-acting agents were identified (index date earliest claim). Patients were classified into the nebulizer, inhaler or mixed-use group (using both nebulizer and inhaler) based on a three-month exposure window and were continuously enrolled for 12 months pre-/3 months post-index. Inverse probability treatment weighted (IPTW) multivariable regressions were used to evaluate the COPD exacerbations, healthcare utilization and cost outcomes controlling for baseline imbalance.

Results: A total of 13,053 patients received only nebulizers, 79,541 patients received only inhalers and 17,421 received both (mixed-use). Baseline characteristics were well-balanced after IPTW. Compared to the nebulizer group, the inhaler group had fewer exacerbations (adjusted hazard ratio [aHR]=0.86; 95% confidence interval [CI]:0.83-0.89, p<0.001) while mixed use group had more (aHR=1.13;95% CI:1.09-1.18, p<0.001). Total and COPD-related healthcare utilization and cost was similar between the inhaler and nebulizer groups except COPD-related emergency department cost was lower in the inhaler group (adjusted per-patient-per-month (aPPPM) difference=-$36; p=0.03). The mixed-use group had higher healthcare utilization compared to the nebulizer group across all places of service and had $474 higher aPPPM medical and $64 higher aPPPM medication costs (all p<0.05).

Conclusions: Inhaler users experienced slightly fewer exacerbations compared to nebulizer users and had similar healthcare utilization and cost. Results suggest that short-acting bronchodilator delivery method does not play a large role on patient outcomes. The mixed-use group may represent a group with poorly controlled COPD.