Nebulized Therapies in COPD: Past, Present, and the Future

Abstract

Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating patients with chronic obstructive pulmonary disease (COPD). Inhalation devices consist of nebulizers and handheld inhalers, such as dry-powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Although pMDIs, DPIs and SMIs may be appropriate for most patients with COPD, certain patient populations may have challenges with these devices. Patients who have cognitive, neuromuscular, or ventilatory impairments (and receive limited assistance from caregivers), as well as those with suboptimal peak inspiratory flow may not derive the full benefit from handheld inhalers. A considerable number of patients are not capable of producing a peak inspiratory flow rate to overcome the internal resistance of DPIs. Furthermore, patients may have difficulty coordinating inhalation with device actuation, which is required for pMDIs and SMIs. However, inhalation devices such as spacers and valved holding chambers can be used with pMDIs to increase the efficiency of aerosol delivery. Nebulized treatment provides patients with COPD an alternative administration route that avoids the need for inspiratory flow, manual dexterity, or complex hand-breath coordination. The recent approval of two nebulized long-acting muscarinic antagonists has added to the extensive range of nebulized therapies in COPD. Furthermore, with the availability of quieter and more portable nebulizer devices, nebulization may be a useful treatment option in the management of certain patient populations with COPD. The aim of this narrative review was to highlight recent updates and the treatment landscape in nebulized therapy and COPD. We first discuss the pathophysiology of patients with COPD and inhalation device considerations. Second, we review the updates on recently approved and newly marketed nebulized treatments, nebulized treatments currently in development, and technological advances in nebulizer devices. Finally, we discuss the current applications of nebulized therapy in patients with COPD.

Keywords: COPD; inhaler; nebulizer.

Figure 1

The adult lung with dimensions and generations of the airways with predicted aerosol deposition. Notes: Reprinted from European Journal of Pharmaceutical Sciences, Vol 49/edition number 5, Nahar K, Gupta N, Gauvin R, et al., In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals, Pages No.805–818, Copyright (2013), with permission from Elsevier. Abbreviation: BSM, bronchial smooth muscle.

Figure 2

Examples of novel marketed nebulizers. Examples of the different types of commercially available nebulizers that incorporate newer aerosol generating technologies. PARI LC^® Sprint ( PARI, USA83); SideStream Plus^® (Philips, USA84); AeroEclipse^® II (Monaghan Medical Corporation, USA85); Micro Air^® NE-U22 ( Omron Healthcare, USA86); AKITA2^® APIXNEB (PARI Pharma GmbH, Germany87).