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).

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.

Radioaerosol Pulmonary Deposition Using Mesh and Jet Nebulizers During Noninvasive Ventilation in Healthy Subjects.

BACKGROUND: In vivo deposition studies of aerosol administration during noninvasive ventilation (NIV) are scarce in the literature. The aim of this study was to compare radioaerosol pulmonary index and radioaerosol mass balance in the different compartments (pulmonary and extrapulmonary) of radio-tagged aerosol administered using vibrating mesh nebulizers and conventional jet nebulizers during NIV. METHODS: This was a crossover clinical trial involving 10 healthy subjects (mean age of 33.7 ± 10.0 y) randomly assigned to both treatment arms of this study: group 1 (NIV + vibrating mesh nebulizer, n = 10) and group 2 (NIV + jet nebulizer, n = 10). All subjects inhaled 3 mL of technetium-99m diethylenetriaminepentaacetic acid (25 mCi) and 0.9% saline solution via vibrating mesh and jet nebulizers during NIV through a face mask secured with straps while receiving positive inspiratory and expiratory pressures of 12 and 5 cm H2O, respectively. Scintigraphy was performed to count radioaerosol particles deposited in the regions of interest to determine radioaerosol mass balance from the lungs, upper airways, stomach, nebulizer, ventilator circuit, inspiratory and expiratory filters, and mask as a percentage. RESULTS: Vibrating mesh nebulizers deposited 972,013 ± 214,459 counts versus jet nebulizer with 386,025 ± 130,363 counts (P = .005). In a determination of mass balance, vibrating mesh nebulizers showed a higher deposition of inhaled radioaerosol compared with jet nebulizers (23.1 ± 5.8% vs 6.1 ± 2.5%, P = .005) and a higher proportion of radioaerosol deposited into the lungs (5.5 ± 0.9% versus 1.5 ± 0.6%, respectively, P = .005). The residual drug volume was lower with vibrating mesh nebulizers (5.1 ± 1.5%) compared with jet nebulizers (41.3 ± 4.2%, P = .005). CONCLUSIONS: During NIV in healthy subjects, vibrating mesh nebulizers delivered > 2-fold more radiolabeled drug into the respiratory tract compared with conventional jet nebulizers. Additional studies are recommended in subjects with asthma, COPD, bronchiectasis, and cystic fibrosis to better understand differences in both aerosol delivery and response. (ClinicalTrials.gov registration NCT01889524.).

Scintigraphic assessment of radio-aerosol pulmonary deposition with the acapella positive expiratory pressure device and various nebulizer configurations.

BACKGROUND: The Acapella device produces high-frequency oscillations and positive expiratory pressure to promote bronchial secretion clearance. Its performance during aerosol delivery has not been described. We evaluated the effect of nebulizer and Acapella configuration on pulmonary deposition of radio-tagged aerosol in healthy subjects. METHODS: Ten healthy male subjects (mean age 24.4 ± 2.2 y) participated in a crossover study that compared pulmonary delivery of 4 mL of technetium-99m-labeled diethylene triamine penta-acetic acid (25 mCi) and 0.9% saline solution via jet nebulizer. We tested 3 configurations: nebulizer attached to the distal end of the Acapella; nebulizer placed between the mouthpiece and the Acapella; and nebulizer alone (control). With scintigraphy we measured radio-aerosol deposition in 6 lung regions: upper, middle, lower, central, intermediate, and peripheral. RESULTS: Deposition was similar between the right and left lungs, with no significant differences between device configurations. Lung deposition was less with the nebulizer attached to the Acapella than with nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs) or without the Acapella (P = .003 and P = .001 for the right and left lungs, respectively). There was no significant difference between the setup without Acapella and the setup with the nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs). On the vertical axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (upper region P < .001, middle region P = .001, lower region P = .003), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (upper and middle region both P = .001, lower region P = .002), with up to a 3-fold difference in the middle and lower regions. On the central-peripheral axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (central region P < .001, peripheral region P < .001), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (central and peripheral regions both P = .002), with differences of 3-4-fold between the central and peripheral regions. CONCLUSIONS: Placing the nebulizer distal to the Acapella, as recommended by the manufacturer, decreased intrapulmonary deposition, compared to placing the nebulizer between the Acapella and the patient airway, or delivering aerosol without the Acapella in the circuit. (ClinicalTrials.gov NCT01102166).

Noninvasive ventilation coupled with nebulization during asthma crises: a randomized controlled trial.

BACKGROUND: Despite the clinical improvements attributed to noninvasive ventilation (NIV) during asthma crises, and the well established effects of nebulization, there are few studies on the effects of these interventions together. We hypothesized that nebulization coupled to NIV should raise radio-aerosol pulmonary deposition in asthmatics. The aims of this study were to assess the effects of coupling ß-agonist nebulization and NIV during asthma exacerbations on radio-aerosol pulmonary deposition, using scintigraphy and cardiopulmonary parameters, to correlate pulmonary function with radio-aerosol deposition index, radio-aerosol penetration index, and pulmonary clearance. METHODS: In this controlled trial, 21 adults with moderate to severe asthma attack were randomized to a control group (n = 11) or experimental group (NIV + nebulizer group, n = 10). All subjects inhaled bronchodilators for 9 minutes, and after particles were counted with a gamma camera to analyze regions of interest and pulmonary clearance at 0, 15, 30, 45, and 60 min. RESULTS: Breathing frequency (P = < .001) and minute ventilation (P = .01) were reduced, and tidal volume was increased (P = .01) in the NIV + nebulizer group, compared with the control group. The NIV + nebulizer group had improvement from baseline values, compared to the control group in the following parameters: FEV(1) 46.7 ± 0.5% of predicted vs 29.8 ± 8.9% of predicted, P = .02), FVC (41.2 ± 1.5% of predicted vs 23.2 ± 7.1% of predicted, P = .02), peak expiratory flow (67.3 ± 38.3% of predicted vs 26.9 ± 12.1% of predicted, P = .01), and inspiratory capacity (54.9 ± 28.8% of predicted vs 31.2 ± 9.1% of predicted, P = .01). No differences were observed between groups regarding radio-aerosol deposition index or pulmonary clearance. Negative correlations were found between FEV1, forced expiratory flow during the middle half of the FVC maneuver (FEF(25-75%)), inspiratory capacity, and radio-aerosol penetration index. CONCLUSIONS: Coupling nebulization and NIV during asthma exacerbation did not improve radio-aerosol pulmonary deposition, but we observed clinical improvement of pulmonary function in these subjects. (ClinicalTrials.gov registration NCT01012050).

Trocador de calor e umidade: proteção contra infecções pulmonares? Estudo piloto / Heat and moisture exchanger: protection against lung infections? Pilot study

O objetivo deste trabalho foi realizar um estudo bacteriológico comparativo entre os sistemas de umidificação aquoso aquecido (UAA) e filtro trocador de calor e umidade (FTCU) quanto à colonização bacteriana e a incidência de infecção respiratória em pacientes submetidos à ventilação mecânica (VM). Trata-se de uma pesquisa prospectiva, controlada e randomizada, na qual 15 pacientes internados na Unidade de Terapia Intensiva (UTI) foram distribuídos em dois grupos. O primeiro fez uso de UAA (n=7) e o outro de FTCU (n=8). Foram coletadas amostras da secreção traqueal, condensado do circuito e FTCU na admissão do paciente, no quarto e oitavo dias, e realizada análise bacteriológica dos mesmos. Quanto às características antropométricas, não observou-se diferenças entre os grupos estudados. A prevalência de pneumonia associada à ventilação (PAV) foi de 57,1% no UAA e 62,5% no FTCU. Ao realizar a análise bacteriológica quantitativa entre eles, não foram observadas variações, sugerindo não haver diferença na prevenção de PAV entre os sistemas de umidificação; porém a presença das mesmas bactérias na secreção traqueal e no condensado e ausência destas na membrana do FTCU podem indicar que a principal fonte de contaminação é o próprio paciente.

The aim of this study was to conduct a bacteriological research comparing the aqueous heated humidification systems (HH) and filter heat and moisture exchanger (FHME) and to bacterial colonization and the incidence of respiratory infection in patients undergoing mechanical ventilation. It is a prospective, controlled trial, in that 15 intensive care unit (ICU) patients were divided into two groups. The first made use of HH (n=7) and the other, FHME (n=8). We collected samples of tracheal secretions, and condensate circuit FHME at admission in the fourth and eighth day and bacteriological analysis of the same place. Regarding the anthropometric characteristics, no differences were observed between the groups. The prevalence of ventilator associated pneumonia (VAP) was 57.1% in the HH and 62.5% in FHME. When performing quantitative bacteriological analysis between the group and HH and FHME, differences were not observed, suggesting no variation in the prevention of VAP between the humidification systems, but the presence of these bacteria in the tracheal and condensate and in the absence of these membrane FHME may indicate that the main source of contamination is the patient himself.

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.

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.

Associação da pressão positiva expiratória ao final da expiração ao nebulizador ultrassônico: efeito na deposição de aerossol no pulmão / Association of positive end expiratory pressure to ultrassonic nebulizer: effect on aerosol deposition into lungs

Este estudo visou comparar deposição de aerossol no pulmão mediante o uso de nebulizador ultra-sônico (US), sem e com utilização de válvula de pressão positiva expiratória final (PEEP), comparando ainda duas pressões da válvula, de 5 cmH2O e de 10cmH2O. Para analisar a deposição de aerossol, foram delimitadas regiões de interesse...

This study aimed comparing aerosol deposition into lungs using an ultrasonic (US) nebulizer, with and without using a positive end expiratory pressure (PEEP) valve, also comparing two valve pressures, 5 cmH2O and 10cmH2O. Twelve young healthy volunteers were submitted to Tc99m radioaerosol inhalation generated by nebulizer in three stages:

Nebulization associated with bi-level noninvasive ventilation: analysis of pulmonary radioaerosol deposition.

UNLABELLED: Nebulization associated with noninvasive ventilation is used in emergency services and intensive care units. PURPOSES: To compare pulmonary radioaerosol deposition during jet nebulization associated to noninvasive ventilation versus spontaneous breathing nebulization; to measure the rate of lung depuration and the correlation between lung deposition, inspiratory flow and tidal volume (V(t)) using scintigraphy. SUBJECTS: Thirteen healthy volunteers (with normal spirometry), mean age (23.3+/-1.49) years, body mass index 21.2+/-2.3 kg/m(2). METHODS: Nebulization was performed in spontaneous breathing and associated with bi-level noninvasive ventilation (inspiratory pressure=12 cm H(2)O, expiratory pressure=5 cm H(2)O). The radioaerosol used in the nebulization was technetium (Tc99m) with diethylene triamine penta acetic acid, generated over a period of 9 min in a jet nebulizer. Analysis was performed through scintigraphy. Statistical analysis was performed by analysis of variance (for repeated measures), Bonferroni method, Student's t-test and Person's correlation. RESULTS: There was a decrease in radioaerosol lung deposition with nebulization associated to noninvasive ventilation (mean counts in spontaneous breathing 200,510+11,012 and mean counts in noninvasive ventilation 106,093+2811 (P<0.001). During spontaneous breathing nebulization there was a significant correlation between V(t) and radioaerosol deposition (r=0.565, P<0.05), also between inspiratory flow and radioaerosol deposition in the lungs (r=0.141, P<0.05). However, there was no correlation between V(t) and pulmonary deposition of radioaerosol in bi-level noninvasive ventilation nebulization (r=0.082). CONCLUSION: During nebulization with noninvasive ventilation in healthy volunteers, there was an increase in V(t) associated to a higher inspiratory flow rate, without resulting in a significant increase in pulmonary radioaerosol deposition.

Which pulmonary volume should be used in physiotherapy to obtain higher maximal inspiratory pressure in COPD patients?

BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) present pulmonary hyperinflation as the main cause of mechanical disadvantages in respiratory muscles. Measurement of the force generated by those muscles is converted into pressure changes. The aim of the present study was to evaluate the maximal inspiratory pressure (MIP) from the residual volume (RV) and from the functional residual capacity (FRC), in patients with COPD, and to determine which pulmonary volume should be used in physiotherapy so as to obtain higher MIP results. METHOD: An investigation of 18 male patients with stable COPD. Patients were examined using a manual vacuometer to measure the MIP of 20 daily manoeuvres. Ten measurements were taken from the RV and 10 from the FRC, taken alternately with an interval of 1 minute between each measurement, for five consecutive days. RESULTS: Increases in MIP were obtained from the RV measurements (mean +/- SE) from 59.7 (+/- 5.2) to 66.6 (+/- 5.3) cm H2O (F(4,64) = 3.34; p < 0.015) and from the FRC measurements, from 55.4 (+/- 4.9) to 64.4 (+/- 4,8) cm H2O (F(4,64) = 6.72; p < 0.001). Post hoc analysis showed an increase, over consecutive days, in both RV and FRC. For FRC, an increase was revealed on the second and third days, a fall was found on the fourth day and a new increase was found on the last day. MIP reached different levels, between RV and FRC, on the first (t = 2.888; p = 0.010) and fourth (t = 2.165; p = 0.045) days. CONCLUSION: In the present study, MIP reached higher levels at FRC during the five days of evaluation, and a learning effect occurred in the patients. Motor units from the respiratory muscles may have been recruited in order to perform the manoeuvres during the days of evaluation. The study suggests that there is good evidence for the use of the FRC as a parameter to find the major MIP value.