Good Things in Small Packages: an Innovative Delivery Approach for Inhaled Insulin.

PURPOSE: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 µm particle size distribution. METHODS: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea. Human factors use testing was designed to determine the ability to perform inspiratory manuevers with LED guidance within target flow limits. In vivo testing with healthy normal subjects of radiolabeled aerosol compared 2 breathing patterns for lung deposition efficiency, distribution, and subject preference. RESULTS: CFD demonstrated that flows ≤5 L/min and ≥15 L/min reduced the delivery efficiencg. Prototypes tested with inspiratory flow of 10 L/min provided up to 70% of dose delivered distal to the model throat with aerosols of 3 to 6 µm. Users guided by LED were able to inhale for 8-24 s with 5 s breath hold. Lung dose >70% with peripheral to central ratios >2.0 were achieved, with subject preference for the longer inspiratory time with breath hold. CONCLUSION: The device design phase integration led to a novel design and inspiratory pattern with greater levels of peripheral deposition than previously reported with commercial inhalers. The rationale and process of the application of these methods are described with implications for use in future device development.

A mesh nebulizer is more effective than jet nebulizer to nebulize bronchodilators during non-invasive ventilation of subjects with COPD: A randomized controlled trial with radiolabeled aerosols.

BACKGROUND: Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described. AIM: To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV. METHODS: A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total. RESULTS: Both inhaled and lung doses were greater with VMN (22.78 ±â€¯3.38% and 12.05 ±â€¯2.96%, respectively) than JN (12.51 ±â€¯6.31% and 3.14 ±â€¯1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ±â€¯1.3% versus 46.44 ±â€¯5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN. CONCLUSIONS: VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV.

Respiratory muscles stretching acutely increases expansion in hemiparetic chest wall.

Individuals post-stroke may present restrictive ventilatory pattern generated from changes in the functionality of respiratory system due to muscle spasticity and contractures. Objective was to assess the acute effects after respiratory muscle stretching on the ventilatory pattern and volume distribution of the chest wall in stroke subjects. Ten volunteers with right hemiparesis after stroke and a mean age of 60 ±â€¯5.7 years were randomised into the following interventions: respiratory muscle stretching and at rest (control). The ventilatory pattern and chest wall volume distribution were evaluated through optoelectronic plethysmography before and immediately after each intervention. Respiratory muscle stretching promoted a significant acute increase of 120 mL in tidal volume, with an increase in minute ventilation, mean inspiratory flow and mean expiratory flow compared with the control group. Pulmonary ribcage increased 50 mL after stretching, with 30 mL of contribution to the right pulmonary rib cage (hemiparetic side) in comparison to the control group. Respiratory muscle stretching in patients with right hemiparesis post-stroke demonstrated that acute effects improve the expansion of the respiratory system during tidal breathing. CLINICAL TRIAL REGISTRATION: NCT02416349 (URL: https://clinicaltrials.gov/ct2/show/ NCT02416349).

Respiratory mechanics of neurological patients undergoing mechanical ventilation under water heated humidifier and a heat exchanger filter model. / Mecânica respiratória de pacientes neurocríticos sob ventilação mecânica submetidos à umidificação aquosa aquecida e a um modelo de filtro trocador de calor.

OBJECTIVES: In mechanically ventilated patients, humidifier devices are used to heat and moisturize the inspired gas. Heating and humidifying inspired gas may prevent complications associated with the respiratory mucosa dryness such as mucus plugging and endotracheal tube occlusion. Two devices have been commonly used to this, either heated humidifier or the heat moisture exchange filter. This study aimed to compare the effects of the heated humidifier and a model of heat moisture exchange filter on respiratory mechanics in mechanically ventilated neurological patients. METHODS: This was a randomized crossover trial, involving 31 neurological patients under mechanical ventilation randomly assigned to the humidification devices. Expired tidal volume, peak inspiratory flow, peak expiratory flow, static compliance, dynamic compliance and respiratory system resistance were evaluated. Statistical analysis used the Kolmogorov-Smirnov test and Student's t test for paired samples, in which P values < 0.05 were considered significant. RESULTS: The heat moisture exchanger filter decreased expired tidal volume, peak inspiratory flow, peak expiratory flow (p < 0.001) and dynamic compliance (p = 0.002), and increased respiratory system resistance (p < 0.001). CONCLUSION: In the studied population, the use of a heat moisture exchange filter model leaded to several changes on respiratory mechanics parameters.

Mecânica respiratória de pacientes neurocríticos sob ventilação mecânica submetidos à umidificação aquosa aquecida e a um modelo de filtro trocador de calor / Respiratory mechanics of neurological patients undergoing mechanical ventilation under water heated humidifier and a heat exchanger filter model

OBJETIVOS: Em pacientes sob ventilação mecânica, dispositivos de umidificação são utilizados para aquecer e umidificar o gás inspirado. O aquecimento e umidificação do gás inspirado podem prevenir complicações associadas ao ressecamento da mucosa respiratória, como a formação de tampão mucoso e oclusão do tubo endotraqueal. Com esse objetivo, dois dispositivos têm sido comumente utilizados: os umidificadores aquosos aquecidos e os filtros trocadores de calor e umidade. O objetivo deste estudo foi comparar o efeito da utilização do umidificador aquoso aquecido e de um modelo de filtro trocador de calor e umidade sobre a mecânica respiratória de pacientes neurocríticos sob ventilação mecânica. MÉTODOS: Trata-se de um ensaio clínico, cruzado e randomizado, onde 31 pacientes neurocríticos sob ventilação mecânica foram submetidos de forma aleatória às duas formas de umidificação. Foram avaliados o volume corrente expirado, pico de fluxo inspiratório, pico de fluxo expiratório, complacência estática, complacência dinâmica e resistência do sistema respiratório. Para análise estatística dos resultados obtidos foram utilizados os testes de Kolmogorov-Smirnov e t-Student para amostras pareadas, considerando-se a significância estatística quando observado um valor de p < 0,05. RESULTADOS: A utilização de um modelo de filtro trocador de calor e umidade promoveu a redução do volume corrente expirado, pico de fluxo inspiratório, pico de fluxo expiratório (p < 0,001) e complacência dinâmica (p = 0,002), além do aumento da resistência do sistema respiratório (p < 0,0001). CONCLUSÃO: Na população estudada, a utilização de um modelo de filtro trocador de calor e umidade promoveu a modificação de diversos parâmetros da mecânica respiratória.

OBJECTIVES: In mechanically ventilated patients, humidifier devices are used to heat and moisturize the inspired gas. Heating and humidifying inspired gas may prevent complications associated with the respiratory mucosa dryness such as mucus plugging and endotracheal tube occlusion. Two devices have been commonly used to this, either heated humidifier or the heat moisture exchange filter. This study aimed to compare the effects of the heated humidifier and a model of heat moisture exchange filter on respiratory mechanics in mechanically ventilated neurological patients. METHODS: This was a randomized crossover trial, involving 31 neurological patients under mechanical ventilation randomly assigned to the humidification devices. Expired tidal volume, peak inspiratory flow, peak expiratory flow, static compliance, dynamic compliance and respiratory system resistance were evaluated. Statistical analysis used the Kolmogorov-Smirnov test and Student's t test for paired samples, in which P values < 0.05 were considered significant. RESULTS: The heat moisture exchanger filter decreased expired tidal volume, peak inspiratory flow, peak expiratory flow (p < 0.001) and dynamic compliance (p = 0.002), and increased respiratory system resistance (p < 0.001). CONCLUSION: In the studied population, the use of a heat moisture exchange filter model leaded to several changes on respiratory mechanics parameters.