Spacer microbial contamination and asthma outcomes: case series.

OBJECTIVE: The primary method of drug delivery to treat asthma is through pressurized metered dose inhalers (pMDI). Asthma guidelines recommend that providers prescribe a spacer for all patients using pMDI. The objective of this study was to examine whether microbial contamination of spacer devices is associated with poor asthma outcomes. METHODS: This was a cross-sectional, single-center case series of seven pediatric patients with persistent asthma who had previously been prescribed a spacer. Spacers were swabbed with sterile cotton and samples assessed for bacterial/fungal growth. Parents completed a questionnaire including Asthma Control Test (ACT) and asthma control was assessed by an Allergist/Immunologist physician. RESULTS: Two (n = 2) children's parent-completed ACT score indicated poorly controlled asthma and three (n = 3) patients were noted to be poorly controlled by the physician. All but one caregiver reported cleaning the spacer with most reporting (n = 5) that they cleaned their child's spacer monthly and one (n = 1) reporting cleaning it every two weeks. One spacer had detected Candida albicans. There was not a statistically significant association between ACT score and microbial growth (p > 0.05). CONCLUSION: Most spacers in a pediatric sample were not contaminated, despite lack of consistent cleaning, as recommended by spacer manufacturers. Providers and pharmacists should discuss proper cleaning of spacers with caregivers of pediatric patients.

Inhaloterapia: recomendaciones para Argentina 2021 / Inhalotherapy: recommendations for Argentina 2021

Resumen En las últimas décadas ha habido un importante desarrollo de dispositivos inhalados (DI) que permiten aumentar la eficacia de las drogas y disminuir los eventos adversos. Su correcto uso es de fundamental importancia para el control de las enfermedades respiratorias obstructivas. En la Argentina no existen recomendaciones locales sobre el uso de los DI. Se revisó la base biofísica, indicación, ventajas y limitaciones, técnica de correcto uso, errores frecuentes, mantenimiento y limpieza de cada DI. El uso de nebulizaciones ha quedado restringido a la administración de drogas que no están disponibles en otros DI (ejemplo: tratamiento de fibrosis quística), o ante la falla de los otros DI. No deben ser usados durante la pandemia de SARS-CoV2. Los inhaladores de dosis medida (aerosol) deben ser indicados siempre con aerocámaras (AC), las que reducen la incidencia de eventos adversos y aumentan el depósito de la droga en el pulmón. Son los dispositivos de elección junto a los inhaladores de polvo seco. Los aerosoles se deben usar en pacientes que no generan flujos inspiratorios altos. Los inhaladores de polvo seco deben recomendarse en aquellos que pueden realizar flujos inspiratorios enérgicos. Se revisaron los diferentes DI en fibrosis quística y en pacientes con asistencia respiratoria mecánica. La elección del DI dependerá de varios factores: situación clínica, edad, experiencia previa, preferencia del paciente, disponibilidad de la droga y entrenamiento alcanzado con el correcto uso.

Abstract Last decades, a broad spectrum of inhaled devices (ID) had been developed to enhance efficacy and reduce adverse events. The correct use of IDs is a critical issue for controlling obstructive respiratory diseases. There is no recommendation on inhalation therapy in Argentina. This document aims to issue local recommendations about the prescription of IDs. Each device was reviewed regarding biophysical laws, indication, strength, limitations, correct technique of use, frequent mistakes, and device cleaning and maintenance. Nebulization should be restricted to drugs that are not available in other IDs (for example, for treatment of cystic fibrosis) or where other devices fail. Nebulization is not recommended during the SARS-CoV2 pandemic. A metered-dose inhaler must always be used with an aerochamber. Aerochambers reduce the incidence of adverse events and improve lung deposition. Metered-dose inhalers must be prescribed to patients who cannot generate a high inspiratory flow and dry powders to those who can generate an energetic inspiratory flow. We reviewed the use of different IDs in patients with cystic fibrosis and under mechanical ventilation. The individual choice of an ID will be based on several variables like clinical status, age, previous experience, patient preference, drug availability, and correct use of the device.

[Inhalotherapy: Recommendations for Argentina 2021]. / Inhaloterapia: Recomendaciones para Argentina 2021.

Last decades, a broad spectrum of inhaled devices (ID) had been developed to enhance efficacy and reduce adverse events. The correct use of IDs is a critical issue for controlling obstructive respiratory diseases. There is no recommendation on inhalation therapy in Argentina. This document aims to issue local recommendations about the prescription of IDs. Each device was reviewed regarding biophysical laws, indication, strength, limitations, correct technique of use, frequent mistakes, and device cleaning and maintenance. Nebulization should be restricted to drugs that are not available in other IDs (for example, for treatment of cystic fibrosis) or where other devices fail. Nebulization is not recommended during the SARS-CoV2 pandemic. A metered-dose inhaler must always be used with an aerochamber. Aerochambers reduce the incidence of adverse events and improve lung deposition. Metered-dose inhalers must be prescribed to patients who cannot generate a high inspiratory flow and dry powders to those who can generate an energetic inspiratory flow. We reviewed the use of different IDs in patients with cystic fibrosis and under mechanical ventilation. The individual choice of an ID will be based on several variables like clinical status, age, previous experience, patient preference, drug availability, and correct use of the device.

En las últimas décadas ha habido un importante desarrollo de dispositivos inhalados (DI) que permiten aumentar la eficacia de las drogas y disminuir los eventos adversos. Su correcto uso es de fundamental importancia para el control de las enfermedades respiratorias obstructivas. En la Argentina no existen recomendaciones locales sobre el uso de los DI. Se revisó la base biofísica, indicación, ventajas y limitaciones, técnica de correcto uso, errores frecuentes, mantenimiento y limpieza de cada DI. El uso de nebulizaciones ha quedado restringido a la administración de drogas que no están disponibles en otros DI (ejemplo: tratamiento de fibrosis quística), o ante la falla de los otros DI. No deben ser usados durante la pandemia de SARS-CoV2. Los inhaladores de dosis medida (aerosol) deben ser indicados siempre con aerocámaras (AC), las que reducen la incidencia de eventos adversos y aumentan el depósito de la droga en el pulmón. Son los dispositivos de elección junto a los inhaladores de polvo seco. Los aerosoles se deben usar en pacientes que no generan flujos inspiratorios altos. Los inhaladores de polvo seco deben recomendarse en aquellos que pueden realizar flujos inspiratorios enérgicos. Se revisaron los diferentes DI en fibrosis quística y en pacientes con asistencia respiratoria mecánica. La elección del DI dependerá de varios factores: situación clínica, edad, experiencia previa, preferencia del paciente, disponibilidad de la droga y entrenamiento alcanzado con el correcto uso.

In vitro and clinical characterization of the valved holding chamber AeroChamber Plus® Flow-Vu® for administrating tiotropium Respimat® in 1-5-year-old children with persistent asthmatic symptoms.

BACKGROUND: When characterizing inhalation products, a comprehensive assessment including in vitro, pharmacokinetic (PK), and clinical data is required. We conducted a characterization of tiotropium Respimat® when administered with AeroChamber Plus® Flow-Vu® anti-static valved holding chamber (test VHC) with face mask in 1-5-year-olds with persistent asthmatic symptoms. METHODS: In vitro tiotropium dose and particle size distribution delivered into a cascade impactor were evaluated under fixed paediatric and adult flow rates between actuation and samplings. The tiotropium mass likely to reach children's lungs was assessed by tidal breathing simulations and an ADAM-III Child Model. PK exposure to tiotropium in preschool children with persistent asthmatic symptoms (using test VHC) was compared with pooled data from nine Phase 2/3 trials in older children, adolescents, and adults with symptomatic persistent asthma not using test VHC. RESULTS: At fixed inspiratory flow rates, emitted mass and fine particle dose decreased under lower flow conditions; dose reduction was observed when Respimat® was administered by test VHC at paediatric flow rates. In <5-year-old children, such a dose reduction is appropriate. In terms of dose per kg/body weight, in vitro-delivered dosing in children was comparable with adults. Transmission and aerosol holding properties of Respimat® when administered with test VHC were fully sufficient for aerosol delivery to patients. At zero delay, particles <5 µm (most relevant fraction) exhibited a transfer efficacy of ≥60%. The half-time was>10 s, allowing multiple breaths. Standardized tidal inhalation resulted in an emitted mass from the test VHC of approximately one-third of labelled dose, independent of coordination and face mask use, indicating predictable tiotropium administration by test VHC with Respimat®. Tiotropium exposure in 1-5-year-old patients using the test VHC, when adjusted by height or body surface, was comparable with that in older age groups without VHCs; no overexposure was observed. Adverse events were less frequent with tiotropium (2.5 µg, n = 20 [55.6%]; 5 µg, n = 18 [58.1%]) than placebo (n = 25 [73.5%]). CONCLUSIONS: Our findings provide good initial evidence to suggest that tiotropium Respimat® may be administered with AeroChamber Plus® Flow-Vu® VHC in 1-5-year-old patients with persistent asthmatic symptoms. To confirm the clinical efficacy and safety in these patients, additional trials are required. CLINICAL TRIALS REGISTRY NUMBER: The trial was registered under NCT01634113 at http://www.clinicaltrials.gov.

A review of the in vitro and in vivo valved holding chamber (VHC) literature with a focus on the AeroChamber Plus Flow-Vu Anti-static VHC.

Valved holding chambers (VHCs) reduce the need for inhalation-actuation coordination with pressurized metered dose inhalers (pMDIs), reduce oropharyngeal drug deposition and may improve lung deposition and clinical outcomes compared to pMDIs used alone. While VHCs are thus widely advocated for use in vulnerable patient groups within clinical and regulatory guidelines, there is less consensus as to whether the performance differences between different VHCs have clinical implications. This review evaluates the VHC literature, in particular the data pertaining to large- versus small-volume chambers, aerosol performance with a VHC adjunct versus a pMDI alone, charge dissipative/conducting versus non-conducting VHCs, and facemasks, to ascertain whether potentially meaningful differences between VHCs exist. Inconsistencies in the literature are examined and explained, and relationships between in vitro and in vivo data are discussed. A particular focus of this review is the AeroChamber Plus® Flow-Vu® Anti-static VHC, the most recent iteration of the AeroChamber VHC family.

Are valved holding chambers (VHCs) interchangeable? An in vitro evaluation of VHC equivalence.

INTRODUCTION: The European Medicines Agency (EMA) requires that a specific valved holding chamber (VHC) is designated for use with a given pressurised metered dose inhaler (pMDI). No other regulatory authorities impose similar requirements, implying that VHCs are interchangeable. This in vitro study, employing EMA assessment criteria, assessed the equivalence of four anti-static VHCs (aVHCs) versus the non-conducting VHC most widely referenced in pMDI monographs, the AeroChamber Plus™ (AC+) VHC. MATERIAL & METHODS: The "reference" AC + VHC was prepared by soaking in detergent solution. The four test aVHCs (AeroChamber Plus™ Flow-Vu™ [AC + FV]; Compact Space Chamber Plus [CSC+]; InspiraChamber [IC]; OptiChamber Diamond™ [OCD]) were tested "out-of-packet". Twenty devices of each type were evaluated. A salbutamol pMDI was actuated into each VHC with a 2-s delay between actuation and Andersen Cascade Impactor (ACI) sampling. Drug deposition in four ACI particle size groups was assessed: Group 1, >5.8-10 µm; Group 2, >3.3-5.8 µm; Group 3, >1.1-3.3 µm; Group 4, ≤1.1 µm. Equivalence versus the reference VHC was demonstrated where the 90% confidence interval for the test/reference mass ratio was within 85-118%. RESULTS: The mass retained within the VHC was similar for the AC + VHC and AC + FV aVHC, but was approximately twice as great for the other aVHCs. Salbutamol deposition in all ACI groups with the AC + FV aVHC was equivalent to the reference AC + VHC. By contrast, deposition in ACI groups 1 to 3 with the CSC+, IC and OCD aVHCs was inequivalent to (approximately half that of) the reference VHC. Inter-device variability for each VHC type was greatest for the IC and least for the AC + VHC and AC + FV aVHC. CONCLUSIONS: The performance of VHCs that superficially resemble one another may differ markedly. Thus, as implied by EMA guidelines, VHCs should not automatically be considered to be interchangeable.

The in vitro and in vivo investigation of inhaled migraine therapies using a novel aerosol delivery system consisting of an air pressurized capsule device (APCD) in combination with a pMDI spacer for endotracheal dosing into beagle dogs.

CONTEXT: Aerosol delivery to animals in preclinical settings has historically been very challenging, requiring the use of techniques, such as intratracheal instillation and dry powder insufflation, that are somewhat invasive, inefficient and not representative of clinical inhalation. OBJECTIVE: The objective of this work is to develop a system to deliver dry powder to dogs in an efficient and effective manner for the study of new anti-migraine compounds in development. MATERIALS AND METHODS: The new device uses a metered aliquot of a dry gas to force dry powder drug from a pre-filled HPMC capsule into an AeroChamber® spacer for subsequent inhalation by the animal. RESULTS: The delivery of two invesigational migraine drugs via the new device was assessed in vitro using abbreviated Andersen cascade impaction and showed the device is capable of generating a reproducible delivered dose of up to ∼68% with more than 50% of the dose in the respirable range. In vivo studies have also been performed showing that this device effectively delivered the migraine drugs to spontaneously breathing dogs using a proprietary validated dog inhalation model. DISCUSSION: Results confirmed that the air pressurized capsule device (APCD) was effective in delivering the APIs to lungs of the animals. The in vivo data verified the advantages of inhaled delivery over oral delivery for this class of drugs and were used to establish the cardiopulmonary and respiratory side effect liability profile for these compounds. CONCLUSIONS: This work has demonstrated the utility of this device for quick and accurate screening of prospective drug candidates, representing a significant improvement in ease of use and reprodicibility over current delivery methods.

The effect of bronchodilators administered via aerochamber or a nebulizer on inspiratory lung function parameters.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) the clinical efficacy of bronchodilator therapy delivered via a nebulizer versus an aerochamber on FEV1 is controversial. No studies comparing changes in inspiratory pulmonary function parameters (ILPs) using these inhaler devices are currently available. This information might be of interest because due to dynamic bronchial compression, the relationship between the ILPs and dyspnea is more reliable than that between FEV1 and dyspnea. Therefore, our study aimed to investigate whether changes in ILPs after use of these inhaler devices were similar to the changes in FEV1 and correlate with VAS (Visual Analogue Scale). METHODS: Forty-one stable COPD patients participated in a crossover trial. Spirometry was performed before and after two puffs Combivent (200 mcg salbutamol and 20 mcg ipratropium per puff) using an aerochamber or 2 mL of Combivent (2.5 mg salbutamol and 250 mcg ipratropium per mL) using a nebulizer. Differences in lung function parameters and changes in VAS were measured. RESULTS: ILP values improved significantly from baseline after Combivent administration using both devices (p ≤ 0.004). With both devices, the mean percent changes were significantly greater for FEV(1) than the ILPs (p ≤ 0.003), except for IC (p = 0.19). The mean VAS score did not differ significantly between the devices (p = 0.33), but significant correlations were found between the VAS and forced inspiratory flow at 50% of the vital capacity (FIF(50)) and peak inspiratory flow (PIF) when a nebulizer was used. With an aerochamber, no significant correlations between lung function parameters and VAS were found. CONCLUSIONS: The present study demonstrates that ILPs improved significantly after using either device. Although significant correlations were found between the VAS and FIF(50) and PIF for the nebulizer, in stable COPD patients, the pMDI plus spacer is a better route of administration than a nebulizer.