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.

Impact of Oscillating Positive Expiratory Pressure Device Use on Post-Discharge Hospitalizations: A Retrospective Cohort Study Comparing Patients with COPD or Chronic Bronchitis Using the Aerobika® and Acapella® Devices.

Purpose: Managing and preventing disease exacerbations are key goals of COPD care. Oscillating positive expiratory pressure (OPEP) devices have been shown to improve clinical outcomes when added to COPD standard of care. This retrospective database study compared real-world resource use and disease exacerbation among patients with COPD or chronic bronchitis prescribed either of two commonly used OPEP devices. Patients and methods: Patients using the Aerobika® (Trudell Medical International, London, ON, Canada) or Acapella® (Smiths Medical, Wampsville, New York, USA) OPEP device for COPD or chronic bronchitis were identified from hospital claims linked to medical and prescription claims between September 2013 and April 2018; the index date was the first hospital visit with an OPEP device. Severe disease exacerbation, defined as an inpatient visit with a COPD or chronic bronchitis diagnosis, and all-cause healthcare resource utilization over 30 days and 12 months post-discharge were compared in propensity score (PS)-matched Aerobika device and Acapella device users. Results: In total, 619 Aerobika device and 1857 Acapella device users remained after PS matching. After discharge from the index visit, Aerobika device users were less likely to have ≥1 severe exacerbation within 30 days (12.0% vs 17.4%, p=0.01) and/or 12 months (39.6% vs 45.3%, p=0.01) and had fewer 12-month severe exacerbations (mean, 0.7 vs 0.9 per patient per year, p=0.01), with significantly longer time to first severe exacerbation than Acapella users (log-rank p=0.01). Aerobika device users were also less likely to have ≥1 all-cause inpatient visit within 30 days (13.9% vs 20.3%, p<0.001) and 12 months (44.9% vs 51.8%, p=0.003) than Acapella users. Conclusion: Patients receiving the Aerobika OPEP device, compared to the Acapella device, had lower rates of subsequent severe disease exacerbation and all-cause inpatient admission. This suggests that Aerobika OPEP device may be a beneficial add-on to usual care and that OPEP devices may vary in clinical effectiveness.

A Real-World Evidence Study Assessing the Impact of Adding the Aerobika Oscillating Positive Expiratory Pressure Device to Standard of Care Upon Healthcare Resource Utilization and Costs in Post-Operative Patients.

INTRODUCTION: The aim of this real-world study was to measure the benefit of the Aerobika oscillating positive expiratory pressure (OPEP) device when added to standard of care (defined as incentive spirometry [IS]) for post-operative patients. METHODS: Adults aged ≥ 18 years who were hospitalized for cardiac, thoracic or upper abdominal surgery between 1 September 2013 and 30 April 2017 were identified from IQVIA's Hospital Charge Detail Master (CDM) database; the index date was the date of the first hospitalization for surgery. The control cohort (IS) included patients who had ≥ 1 CDM record within 12 months prior to the index date and ≥ 1 record after discharge, evidence of IS use during index hospitalization and no evidence of use of a PEP or OPEP device at any time during the study period. The Aerobika OPEP cohort was selected in a similar manner, except that patients were required to have evidence of Aerobika OPEP use during the index hospitalization. Aerobika OPEP patients were 1:1 matched to IS patients using propensity score (PS) matching. Hospital readmissions and costs were measured at 30 days post-discharge from the index hospitalization. RESULTS: After PS matching, 144 patients were included in each cohort. At 30 days post-discharge, compared to the control (IS) cohort there were significantly fewer patients in the Aerobika OPEP cohort with ≥ 1 all-cause re-hospitalizations (13.9 vs. 22.9%; p = 0.042). The patients in the Aerobika OPEP cohort also had a shorter mean length of stay (± standard deviation) (1.25 ± 4.04 vs. 2.60 ± 8.24 days; p = 0.047) and lower total unadjusted mean all-cause cost per patient ($3670 ± $13,894 vs. $13,775 ± $84,238; p = 0.057). Adjusted analyses suggested that hospitalization costs were 80% lower for the Aerobika OPEP cohort versus the IS cohort (p = 0.001). CONCLUSION: Our results suggest that the addition of the Aerobika OPEP device to standard of care (IS) is beneficial in the post-operative setting. FUNDING: Trudell Medical International.

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.

A novel, versatile valved holding chamber for delivering inhaled medications to neonates and small children: laboratory simulation of delivery options.

BACKGROUND: Delivery of bronchodilator to infants and small children from a pressurized metered-dose inhaler with valved holding chamber (pMDI-VHC) is limited by airway narrowness, short respiratory cycle time, and small tidal volume (V(T)). There is a need for a versatile, efficient VHC, given the variety of treatment modalities. METHODS: We tested the AeroChamber Mini VHC (the internal geometry of which is optimized for aerosol delivery, and which accepts a pMDI canister that has a dose counter) in experiments to determine differences in the delivery of hydrofluoroalkane-propelled albuterol (90 microg/actuation) during: mechanical ventilation via endotracheal tube (ETT); manual resuscitation via ETT; and spontaneous breathing via face mask. We tested 5 units of the AeroChamber Mini VHC per test. We simulated the tidal breathing of a premature neonate (V(T) 6 mL), a term neonate (V(T) 20 mL), and a child approximately 2 years old (V(T) 60 mL). We collected the aerosol on an electret filter and quantitatively assayed for albuterol. RESULTS: The total emitted mass of albuterol per actuation that exited the VHC was marginally greater during spontaneous breathing (12.1 +/- 1.8 microg) than during manual resuscitation (10.0 +/- 1.1 microg) (P = .046). Albuterol delivery via mechanical ventilation, though comparable with the premature-neonate model (3.3 +/- 1.2 microg), the term-neonate model (3.8 +/- 2.1 microg), and the 2-y-old-child model (4.2 +/- 2.3 microg) (P = .63), was significantly lower than in the spontaneous-breathing and manual-resuscitation models (P < .001). In the neonatal models the total emitted mass was similar with the spontaneous-breathing model (6.0 +/- 1.0 microg with the premature-neonate model, 10.5 +/- 0.7 microg with the term-neonate model) and the manual-resuscitation model (5.5 +/- 0.3 microg premature-neonate model, 10.7 +/- 0.9 microg term-neonate model) (P > or = .46 via one-way analysis of variance). CONCLUSION: The reduced delivery of albuterol during mechanical ventilation (compared to during spontaneous breathing and manual resuscitation via ETT) was probably associated with the saturated atmosphere in the breathing circuit (37 degrees C, relative humidity > 99%), compared to the ambient air (22 +/- 1 degrees C, 44 +/- 7% relative humidity). The AeroChamber Mini VHC may provide a versatile alternative to VHCs that are designed exclusively for one aerosol treatment modality.

Electrostatics and inhaled medications: influence on delivery via pressurized metered-dose inhalers and add-on devices.

The movement of inhaler-generated aerosols is significantly influenced by electrostatic charge on the particles and on adjacent surfaces. Particle charging arises in the aerosol formation process. Since almost all inhalers contain nonconducting components, these surfaces can also acquire charge during manufacture and use. Spacers and valved holding chambers used with pressurized metered-dose inhalers to treat obstructive lung diseases are particularly prone to this behavior, which increases variability in the amount of medication available for inhalation, and this is exacerbated by low ambient humidity. This may result in inconsistent medication delivery. Conditioning the device by washing it with a conductive surfactant (detergent) or using devices made of charge-dissipative/conducting materials can mitigate electrostatic charge. This review discusses sources of electrostatic charge, the processes that influence aerosol behavior, methods to mitigate electrostatic charge, and potential clinical implications.

The importance of nonelectrostatic materials in holding chambers for delivery of hydrofluoroalkane albuterol.

INTRODUCTION: Electrostatic attraction of aerosolized particles to the inner walls of an aerosol holding chamber (HC) made from a nonconducting material can reduce medication delivery, particularly if there is a delay between actuation and inhalation. OBJECTIVE: Compare total emitted mass and fine-particle mass (mass of particles < 4.7 microm) of hydrofluoroalkane-propelled albuterol from similar-sized HCs manufactured from conductive material (Vortex), charge-dissipative material (AeroChamber Max), and nonconductive material (OptiChamber Advantage, ProChamber, Breathrite, PocketChamber, and ACE), with and without wash/rinse pretreatment of the HC interior with ionic detergent, and with 2-s and 5-s delays between actuation and inhalation. METHODS: All the HCs were evaluated (1) directly from their packaging (with no wash/rinse pretreatment) and (2) after washing with ionic detergent and rinsing and drip-drying. We used an apparatus that interfaced between the HC mouthpiece and the induction port of an 8-stage Andersen cascade impactor to simulate a poorly coordinated patient, with delays of 2 s and 5 s between actuation and inhalation/sampling, at 28.3 L/min. RESULTS: With the 2-s delay, the delivered fine-particle mass per actuation, before and after (respectively) wash/rinse pretreatment was: AeroChamber Max: 23.8 +/- 4.8 microg, 21.5 +/- 3.2 microg; Vortex: 16.2 +/- 1.7 microg, 15.5 +/- 2.0 microg; OptiChamber Advantage: 2.6 +/- 1.2 microg, 6.7 +/- 2.3 microg; ProChamber: 1.6 +/- 0.4 microg, 5.1 +/- 2.5 microg; Breathrite: 2.0 +/- 0.9 microg, 3.2 +/- 1.8 microg; PocketChamber: 3.4 +/- 1.6 microg, 1.7 +/- 1.6 microg; ACE: 4.5 +/- 0.9 microg, 5.4 +/- 2.9 microg. Similar trends, but greater reduction in aerosol delivery, were observed with the 5-s delay. Significantly greater fine-particle mass was delivered from HCs made from conducting or charge-dissipative materials than from those made from nonconductive polymers, even after wash/rinse pretreatment (p < 0.01). The fine-particle mass was also significantly greater from the AeroChamber Max than from the Vortex, irrespective of wash/rinse pretreatment or delay interval (p < 0.01). CONCLUSION: HCs made from electrically conductive materials emit significantly greater fine-particle mass, with either a 2-s or 5-s delay, than do HCs made from nonconducting materials, even with wash/rinse pretreatment.

Levalbuterol aerosol delivery with a nonelectrostatic versus a nonconducting valved holding chamber.

BACKGROUND: Hydrofluoroalkane-propelled levalbuterol (Xopenex) aerosol is a recently approved formulation for delivery via metered-dose inhaler for the treatment or prevention of bronchospasm in adults, adolescents, and children > or = 4 years of age who have reversible obstructive airway disease. Valved holding chambers (VHCs) made from conventional polymers are susceptible to accumulation of electrostatic charge, which can be minimized by prewashing with ionic detergent, but it may be desirable to be able to use the product straight from the package, without pretreatment, especially during an exacerbation. METHODS: We studied the performance of the AeroChamber Plus and AeroChamber Max VHCs in delivering hydrofluoroalkane-propelled levalbuterol. Both VHCs were prewashed, rinsed, and drip-dried before testing. The AeroChamber Max is manufactured from charge-dissipative material and was therefore also evaluated without prewashing. Aerosol samples were collected at 28.3 L/min with an Andersen 8-stage cascade impactor, per the procedure specified in Chapter 601 of the United States Pharmacopeia. RESULTS: The mean +/- SD fine-particle mass (mass of aerosol particles < 4.7 microm aerodynamic diameter) values were 33.5 +/- 1.4 microg and 36.3 +/- 1.1 microg with the AeroChamber Max, without and with wash/rinse pretreatment, respectively, and 28.5 +/- 2.4 microg with the prewashed AeroChamber Plus. CONCLUSIONS: We think the small differences we observed are unlikely to be of clinical importance, given the inter-patient variability seen with inhaled drug delivery. The performance of the AeroChamber Max was substantially comparable whether or not it was prewashed.