Interchanging Reusable and Disposable Nebulizers Used with Home-Based Compressors May Result in Inconsistent Dosing: A Laboratory Investigation with Device Combinations Supplied to the US Healthcare Environment.

INTRODUCTION: Reusable nebulizer-compressor combinations deliver inhaled medications for patients with chronic lung diseases. On hospital discharge, the patient may take home the disposable nebulizer that was packaged and combine it with their home compressor. Though this practice may reduce waste, it can increase variability in medication delivery. Our study compared several reusable and disposable nebulizers packaged with compressor kits used in the US. We included a common disposable hospital nebulizer that may not be supplied with popular home kits but may be brought home after a hospitalization or emergency department visit. We focused on fine droplet mass < 4.7 µm aerodynamic diameter (FDM<4.7 µm), associated with medication delivery to the airways of the lungs. METHODS: We evaluated the following nebulizer-compressor combinations (n = 5 replicates): 1. OMBRA® Table Top Compressor with MC 300® reusable and Airlife™ MistyMax™ 10® disposable nebulizer, 2. Sami-the-Seal® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 3. VIOS® compressor with LC Sprint® reusable, and VixOne® and Airlife™ MistyMax™ disposable nebulizers, 4. Innospire® Elegance® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 5. Willis-the-Whale® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 6. Pari PRONEB® Max compressor with LC Sprint® reusable and Airlife™ MistyMax 10™ disposable nebulizer. We placed a 3-ml albuterol solution (0.833 mg/ml) in each nebulizer. A bacterial/viral filter was attached to the nebulizer mouthpiece to capture emitted medication, with the filter exit coupled to a simulator of a tidal breathing adult (rate = 10 cycles/min; Vt = 600 ml; I/E ratio = 1:2). The filter was replaced at 1-min intervals until onset of sputter. Droplet size distributions (n = 5 replicates/system) were determined in parallel by laser diffractometry. RESULTS: Cumulative FDM<4.7 µm varied from 381 ± 33 µg for the best performing combination (Proneb/LC-Sprint) to 150 ± 21 µg for the system with the lowest output (VIOS®/MistyMax 10™). CONCLUSIONS: Substituting one nebulizer for another can result in large differences in medication delivery to the lungs.

Non-Pharmaceutical Techniques for Obstructive Airway Clearance Focusing on the Role of Oscillating Positive Expiratory Pressure (OPEP): A Narrative Review.

Mucus secretion in the lungs is a natural process that protects the airways from inhaled insoluble particle accumulation by capture and removal via the mucociliary escalator. Diseases such as cystic fibrosis (CF) and associated bronchiectasis, as well as chronic obstructive pulmonary disease (COPD), result in mucus layer thickening, associated with high viscosity in CF, which can eventually lead to complete airway obstruction. These processes severely impair the delivery of inhaled medications to obstructed regions of the lungs, resulting in poorly controlled disease with associated increased morbidity and mortality. This narrative review article focuses on the use of non-pharmacological airway clearance therapies (ACTs) that promote mechanical movement from the obstructed airway. Particular attention is given to the evolving application of oscillating positive expiratory pressure (OPEP) therapy via a variety of devices. Advice is provided as to the features that appear to be the most effective at mucus mobilization.

Cost-effectiveness of the Aerobika* oscillating positive expiratory pressure device in the management of COPD exacerbations.

INTRODUCTION: COPD places a huge clinical and economic burden on the US health care system, with acute exacerbations representing a key driver of direct medical costs. Current treatments, although effective in reducing symptoms and limiting exacerbations, do not adequately target the underlying disease processes that drive exacerbation development. The Aerobika* oscillating positive expiratory pressure (OPEP) device has been shown in a real-world effectiveness study to lower the frequency of moderate-to-severe exacerbations during a 30-day post-exacerbation period. This study sought to determine the impact on exacerbations and costs and to determine the cost-effectiveness of the Aerobika* device. METHODS: Data from published literature and national fee schedules were used to model the cost-effectiveness of the Aerobika* device in patients who had experienced an exacerbation in the previous month, or a post-exacerbation care population. Exacerbation trends and the impact of the Aerobika* device on reducing exacerbation frequency were modeled using a one-year Markov model with monthly cycles and three health states: (i) no exacerbation, (ii) exacerbation, and (iii) death. Scenario analysis and one-way sensitivity analysis (OWSA) were also performed. RESULTS: When the effect of Aerobika* device was assumed to last 30 days, use of the device resulted in cost-savings ($553 per patient) and improved outcomes (ie, six fewer exacerbations per 100 patients per year) compared to no OPEP/positive expiratory pressure therapy. When the effect of the Aerobika* device was assumed to extend beyond the conservative 30-day time frame, the Aerobika* device remained the dominant strategy (21 fewer exacerbations per 100 patients per year; cost savings of $1,952 per patient). Consistency in findings after performing OWSAs indicates the robustness of results. CONCLUSION: The Aerobika* device is a cost-effective treatment option that provides clinical benefit and results in direct medical cost savings in a post-exacerbation care COPD population.

Development and Evaluation of a Family of Human Face and Upper Airway Models for the Laboratory Testing of Orally Inhaled Products.

Many orally inhaled products are supplied with a facemask instead of a mouthpiece, enabling aerosolized medication to be transferred from the inhaler to the lungs when the user lacks the capability to use a mouthpiece. Until recently, laboratory evaluation of an orally inhaled product-facemask was frequently undertaken by removing the facemask, treating the facemask adapter as being equivalent to a mouthpiece. Measurements of delivered drug mass were therefore subject to bias arising from the absence of dead volume, had the facemask been present. We have described the development of the Aerosol Delivery to an Anatomic Model (ADAM) infant, small child, and adult faces and upper airways, and their subsequent evaluation. Each model possesses physical features of appropriate size, and the soft tissues are also simulated. Rudimentary underlying bony structure is also present, because its purpose is only to provide support, enabling the mechanical response of the facial soft tissues when a facemask is applied to be realized. A realistic upper airway (nasopharynx for the infant model, naso- and oropharynx for the child and oropharynx for the adult models) is also incorporated, so that each model can be used to determine the mass of inhaled medication likely to penetrate as far as the lungs where therapy is intended to be applied. Measurements of the mass of pressurized metered-dose inhaler-delivered salbutamol at a filter distal to the upper airway of each model, simulating age-appropriate tidal breathing, were remarkably consistent, almost all being in the range 0.3 to 1.0 µg/kg across the model age ranges, when expressed as a fraction of body weight.

A Retrospective Study of the Effectiveness of the AeroChamber Plus® Flow-Vu® Antistatic Valved Holding Chamber for Asthma Control.

INTRODUCTION: Electrostatic charge in valved holding chambers (VHCs) may lead to inconsistent metered-dose inhaler (MDI) asthma drug delivery. We compared the AeroChamber Plus® Flow Vu® Antistatic Valved Holding Chamber (AC+FV AVHC) with non-antistatic control VHCs in terms of asthma exacerbations, resource use, and cost in an asthma population. METHODS: Patients included in an adjudicated claims database with AC+FV AVHC or non-antistatic VHC (control VHC) use between 1/2010 and 8/2015 (index) who were treated with an inhaled corticosteroid (ICS) or a combination of an ICS and a long-acting ß2 agonist MDI within 60 days before or after the index date, were diagnosed with asthma, and had ≥12 months of pre- and ≥30 days of post-index health plan enrollment were included. Cohorts were matched 1:1 using propensity scores. We compared incidence rates (IR) of exacerbation, time to first exacerbation using Kaplan-Meier survival analysis, occurrence of exacerbations, and healthcare resource use and costs using generalized linear models. RESULTS: 9325 patients in each cohort were identified. The IR of exacerbations per 100 person-days (95% CI) was significantly higher in the control VHC cohort than the AC+FV AVHC cohort [0.161 (0.150-0.172) vs. 0.137 (0.128-0.147)]. A higher proportion of exacerbation-free patients was observed in the AC+FV AVHC cohort. Among the 4293 patients in each cohort with ≥12 months of follow-up, AC+FV AVHC patients were found to be 10-12% less likely than control VHC patients to experience an exacerbation throughout the study period. A lower proportion of the AC+FV AVHC patients had an ED visit compared to the control VHC patients (10.8% vs. 12.4%). Exacerbation-related costs for the AC+FV AVHC cohort were 23%, 25%, 20%, and 12% lower than those for the control VHC cohort at 1, 6, 9, and 12 months, respectively. CONCLUSIONS: The AC+FV AVHC was associated with lower exacerbation rates, delayed time to first exacerbation, and lower exacerbation-related costs when compared to control non-antistatic VHCs.

Developing ways to evaluate in the laboratory how inhalation devices will be used by patients and care-givers: the need for clinically appropriate testing.

The design of methods in the pharmaceutical compendia for the laboratory-based evaluation of orally inhaled product (OIP) performance is intentionally aimed for simplicity and robustness in order to achieve the high degree of accuracy and precision required for the assurance of product quality in a regulated environment. Consequently, performance of the inhaler when used or even misused by the patient or care-giver has often not been assessed. Indeed, patient-use-based methodology has been developed in a somewhat piecemeal basis when a need has been perceived by the developing organization. There is, therefore, a lack of in-use test standardization across OIP platforms, and often important details have remained undisclosed beyond the sponsoring organization. The advent of international standards, such as ISO 20072:2009, that focus specifically on the OIP development process, together with the need to make these drug delivery devices more patient-friendly as an aid to improving compliance, is necessitating that clinically appropriate test procedures be standardized at the OIP class level. It is also important that their capabilities and limitations are well understood by stakeholders involved in the process. This article outlines how this process might take place, drawing on current examples in which significant advances in methodology have been achieved. Ideally, it is hoped that such procedures, once appropriately validated, might eventually become incorporated into the pharmacopeial literature as a resource for future inhaler developers, regulatory agencies, and clinicians seeking to understand how these devices will perform in use to augment ongoing product quality testing which is adequately served by existing methods.