Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study.

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.

Oxygen uptake efficiency slope: A submaximal test evaluation tool that provides cardiopulmonary reserve data in individuals with Parkinson's disease.

BACKGROUND: Oxygen uptake efficiency slope (OUES) is a method for investigating cardiorespiratory fitness and is proposed as an alternative to overcome the limitations of traditional measures such as peak oxygen consumption (VO2peak) for patients who do not achieve a maximum response, such as in Parkinson's disease (PD). OBJECTIVE: To assess the performance of individuals with PD during the six-minute walk test (6MWT) using the OUES. METHODS: This is an observational cross-sectional study including 12 individuals with PD and 12 healthy controls. Participants performed the 6MWT along with an analysis of exhaled gas kinetics. The OUES was determined from the last 16 s of the walk test. Multiple linear regression analyses were computed to explore associations between the independent (OUES) and the dependent variables (VO2peak) controlled by group. RESULTS: The OUES was associated to VO2peak on the 6MWT (ß=0.24, p<0.01) in individuals with PD. The PD group had low performance on the 6MWT with a shorter distance walked (mean difference: -113.1 m; 95% CI: -203.2, -59.1) and worse cardiopulmonary condition with lower OUES values (mean difference: -0.52 [l/minO2]/[l/minVE]; 95% CI: -0.83, -0.21) found in this same group. CONCLUSIONS: Our results suggest that OUES is related to VO2peak during the 6MWT, and therefore it could be used as a submaximal test evaluation tool which provides cardiopulmonary reserve data in individuals with PD.

Impact of moderate-severe persistent allergic rhinitis on thoraco-abdominal kinematics and respiratory muscle function.

Objective: To assess thoraco-abdominal kinematics, respiratory muscle strength and electromyographic activity of the diaphragm (EAdi) in moderate-severe allergic rhinitis (AR) patients. Methods: A cross-sectional study involving 40 individuals (20 in the AR group) and 20 in the control group [CG]) was conducted. Ventilatory pattern and chest wall volume distribution (optoelectronic plethysmography), respiratory muscle strength (manovacuometry and sniff nasal inspiratory pressure [SNIP]), and EAdi were assessed in both groups. Results: The AR patients had impaired thoraco-abdominal kinematics (reduced total chest wall volume) (p = 0.004), lower values of total respiratory cycle time (p = 0.014) and expiratory time (p = 0.006). They also presented an increase of percentage contribution of the abdominal rib cage (p = 0.475) and respiratory rate (p = 0.019). A positive correlation among pulmonary rib cage tidal volume and MIP (r = 0.544; p < 0.001), SNIP (r = 0.615; p < 0.001), and MEP (r = 0.604; p < 0.001) was observed. After adjusting for age, BMI and gender through multivariate analysis, the individuals with AR presented lower values ​​of MIP (ß = -24.341; p < 0.001), MEP (ß = -0.277; p < 0.001), SNIP (ß = -34.687; p < 0.001) and RMS (ß = -0.041; p = 0.017). Conclusions: The individuals with moderate-severe persistent AR had worse respiratory muscle strength, diaphragm activation and chest wall volume distribution with a higher abdominal contribution to tidal volume than the control group. These findings reinforce the notion that the upper and lower airways work in an integrated and synergistic manner.

Impact of Gas Flow and Humidity on Trans-Nasal Aerosol Deposition via Nasal Cannula in Adults: A Randomized Cross-Over Study.

BACKGROUND: Trans-nasal pulmonary aerosol delivery using high flow nasal cannula (HFNC) devices is described with the administration of high gas flows exceeding patient inspiratory flow (HF) and with lower flows (LF). The aim of this pilot clinical trial was to compare deposition and distribution of radiolabeled aerosol via nasal cannula in healthy adults across three rates of gas flow delivered with active heated humidification, and to further identify the impact of aerosol administration without heated humidity. METHODS: Twenty-three (23) healthy adults (16F) were randomized to receive aerosol with active heated humidification or unheated oxygen at gas flows of 10 L/min (n = 8), 30 L/min (n = 7), or 50 L/min (n = 8). Diethylenetriaminepentaacetic acid labeled with 1 millicurie (37 MBq) of Technetium-99m (DTPA-Tc99m) was mixed with NaCl to a fill volume of 1 mL, and administered via mesh nebulizer placed at the inlet of the humidifier. Radioactivity counts were performed using a gamma camera and the regions of interest (ROIs) were delimited with counts from the lungs, upper airways, stomach, nebulizer, circuit, and expiratory filter. A mass balance was calculated and each compartment was expressed as a percentage of the total. RESULTS: Lung deposition (mean ± SD) with heated humidified gas was greater at 10 L/min than 30 L/min or 50 L/min (17.2 ± 6.8%, 5.71 ± 2.04%, and 3.46 ± 1.24%, respectively; p = 0.0001). Using unheated carrier gas, a lung dose of aerosol was similar to the active heated humidification condition at 10 L/min, but greater at 30 and 50 L/min (p = 0.011). Administered gas flow and lung deposition were negatively correlated (r = -0.880, p < 0.001). CONCLUSIONS: Both flow and active heated humidity inversely impact aerosol delivery through HFNC. Nevertheless, aerosol administration across the range of commonly used flows can provide measurable levels of lung deposition in healthy adult subjects (NCT02519465).

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.

Anatomically Based Analysis of Radioaerosol Distribution in Pulmonary Scintigraphy: A Feasibility Study in Asthmatics.

INTRODUCTION: Manual analysis of two-dimensional (2D) scintigraphy to evaluate aerosol deposition is usually subjective and has reduced sensitivity to quantify regional differences between central and distal airways. AIMS: (1) To present a method to analyze 2D scans based on three-dimensional (3D)-linked anatomically consistent regions of interest (ROIs); (2) to evaluate peripheral-to-central counts ratio (P/C2D) and penetration indices (PIs) for a set of 16 subjects with moderate-to-severe asthma; and (3) to compare the reproducibility of this method against one with manually traced ROIs. METHODS: Two-dimensional scans were analyzed using custom software that scaled onto 2D-projections' 3D anatomical features, obtained from population-averaged computed tomography (CT) chest scans. ROIs for a rectangular box (bROI) and an anatomically shaped ROI (aROI) were defined by computer and by manually tracing the standard rectangular box (manual ROI [mROI]). These ROIs were defined five nonconsecutive times for each scan and average value and variability of the P/C2D were estimated. Based on CT estimates of lung and airways, volumes lying under the bROI and aROI, a 2D penetration index (PI2D) and a 3D penetration index (PI3D), were defined as volume-normalized ratios of aerosol deposition in central and peripheral ROIs and in central and distal airways, respectively. RESULTS: P/C2D values and their variability, were influenced by the shape and method to define the ROIs: The P/C2D was systematically greater and more variable for mROI versus bROI (p < 0.005). The P/C2D for aROI was higher and its variability lower than those for the bROI (p < 0.001). The PI2D was in average the same for aROI and bROI, and is substantially (∼30 × ) greater than PI3D (p < 0.001). Both PI2D and PI3D, obtained with our analysis, compared well with literature values obtained with two scans (deposition and volume). CONCLUSION: Our results demonstrate that 2D scintigraphy can be analyzed using anatomically based ROIs from 3D CT data, allowing objective and enhanced reproducibility values describing the distribution pattern of radioaerosol deposition in the tracheobronchial tree.

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.

Evaluation of lung function and deposition of aerosolized bronchodilators carried by heliox associated with positive expiratory pressure in stable asthmatics: a randomized clinical trial.

While administration of medical aerosols with heliox and positive airway pressure are both used clinically to improve aerosol delivery, few studies have differentiated their separate roles in treatment of asthmatics. The aim of this randomized, double blinded study is to differentiate the effect of heliox and oxygen with and without positive expiratory pressure (PEP), on delivery of radiotagged inhaled bronchodilators on pulmonary function and deposition in asthmatics. 32 patients between 18 and 65 years of age diagnosed with stable moderate to severe asthma were randomly assigned into four groups: (1) Heliox + PEP (n = 6), (2) Oxygen + PEP (n = 6), (3) Heliox (n = 11) and (4) Oxygen without PEP (n = 9). Each group received 1 mg of fenoterol and 2 mg of ipratropium bromide combined with 25 mCi (955 Mbq) of Technetium-99m and 0.9% saline to a total dose volume of 3 mL placed in a Venticis II nebulizer attached to a closed, valved mask with PEP of 0 or 10 cm H2O. Both gas type and PEP level were blinded to the investigators. Images were acquired with a single-head scintillation camera with the longitudinal and transverse division of the right lung as regions of interest (ROIs). While all groups responded to bronchodilators, only group 1 showed increase in FEV1%predicted and IC compared to the other groups (p < 0.04). When evaluating the ROI in the vertical gradient we observed higher deposition in the middle and lower third in groups 1 (p = 0.02) and 2 (p = 0.01) compared to group 3. In the horizontal gradient, a higher deposition in the central region in groups 1 (p = 0.03) and 2 (p = 0.02) compared to group 3 and intermediate region of group 2 compared to group 3. We conclude that aerosol deposition was higher in groups with PEP independent of gas used, while bronchodilator response with Heliox + PEP improved FEV1 % and IC compared to administration with Oxygen, Oxygen with PEP and Heliox alone. Trial registration NCT01268462.

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.

Chest wall regional volume in heart failure patients during inspiratory loaded breathing.

Were evaluated individuals divided into two groups: we studied chronic heart failure (CHF) (19 patients with CHF plus cardiomegaly) and control (12 healthy volunteers) during performance of inspiratory loaded breathing (ILB). We evaluated: spirometry, functional capacity through the six-minute walk test (6MWT), and distribution of thoracoabdominal volumes via optoelectronic plethysmography (OEP), namely volume variations of pulmonary rib cage (Vrc,p), abdominal rib cage (Vrc,a), and abdomen (Vab). In each compartment, the percentage contributions of right and left sides were also calculated. During ILB, patients with heart failure were characterized by a significant reduction of the Vrc,a volume variations compared to the control group. Correlations were found between left %Vrc,a on the left side measured during ILB and left ventricular ejection fraction (r=0.468; p=0.049), and dyspnea after the 6MWT (r=-0.878; p<0.01).Then, patients with CHF and cardiomegaly are characterized by a reduced mobility in left part of the lower part of the rib cage, that contributes leading to increased perception of dyspnea during submaximal exercise.

Influence of change in lateral decubitus on pulmonary aerosol deposition.

BACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p≤0.05. RESULTS: Inhalation in the right lateral decubitus position presented higher counts (p≤0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p≤0.02) than in the posterior ROI of the right lung. CONCLUSIONS: The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy.

Influência da variação dos decúbitos laterais na deposição pulmonar de aerossol / Influence of change in lateral decubitus on pulmonary aerosol deposition

CONTEXTUALIZAÇÃO: O decúbito lateral apresenta as maiores mudanças em relação à ventilação pulmonar regional e é utilizado na rotina da fisioterapia respiratória. OBJETIVOS: Avaliar a influência do decúbito lateral na deposição pulmonar de radioaerossol durante a inalação em indivíduos jovens e relacionar os efeitos desse decúbito na rotina terapêutica. MÉTODOS: Em estudo randomizado em duas fases, foram incluídos oito homens voluntários saudáveis, com média de idade de 23,6±2,5 anos. Na primeira fase, inalou-se aerossol durante nove minutos no decúbito lateral sorteado e, após intervalo de cinco a sete dias, realizou-se a segunda fase. Para a cintilografia, inalou-se uma dose média de ácido dietilnotriaminopentacético marcado com tecnécio (DTPA - TC99m), com uma atividade radioativa em média de 25 milicuries (mCi). Ao final da inalação, as imagens foram adquiridas em câmaras de cintilação e analisadas por meio da divisão longitudinal e transversal dos pulmões em regiões de interesse (ROI). Para análise estatística, utilizou-se o teste t de Student pareado, considerando significativo p<0,05. RESULTADOS: A inalação em decúbito lateral direito apresentou, na ROI posterior do pulmão direito, um maior número de contagem (p<0,04) quando comparada à ROI posterior do pulmão esquerdo. No decúbito lateral esquerdo, observou-se um maior número de contagem no pulmão esquerdo (p<0,02) do que na ROI posterior do pulmão direito. CONCLUSÕES: A deposição das partículas de aerossol durante inalação apresentou um comportamento decúbito dependente nas duas fases do estudo, ratificando técnicas e recursos terapêuticos baseados na fisiologia da ventilação decúbito dependente e sugere a utilização do posicionamento corporal na rotina terapêutica.

BACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p<0.05. RESULTS: Inhalation in the right lateral decubitus position presented higher counts (p<0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p<0.02) than in the posterior ROI of the right lung. CONCLUSIONS: The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy.

Heliox and forward-leaning posture improve the efficacy of nebulized bronchodilator in acute asthma: a randomized trial.

BACKGROUND: Heliox and forward-leaning posture (torso inclined forward at 50-60° with the elbows resting on the thighs) are adjuncts in the administration of nebulized bronchodilator to patients with acute asthma. METHODS: We randomized 59 patients who presented to the emergency department in severe asthma crisis, into 4 treatment groups: nebulized bronchodilator + oxygen; nebulized bronchodilator + oxygen + forward-leaning posture; nebulized bronchodilator + heliox; and nebulized bronchodilator + heliox + forward-leaning posture. Before and after the bronchodilator treatments the subjects were seated with torso erect, breathing room air. Each subject received 2 doses, 20 min apart, of nebulized fenoterol (2.5 mg) plus ipratropium bromide (0.25 mg) in 3 mL of 0.9% saline, delivered with a semi-closed valved aerosol reservoir. The nebulizer was run with oxygen or 80:20 heliox. The post-treatment pulmonary function tests were performed 15 min after the second nebulization. The group's mean age was 35.1 ± 13.6 y, and there were 20 men and 39 women. RESULTS: The oxygen + forward-leaning-posture group had a greater FEV(1) improvement than the oxygen group (59% vs 38%, P = .02). The heliox + forward-leaning-posture group had a greater FEV(1) improvement than the oxygen group (103% vs 38%, P = .001) and the heliox group (103% vs 42%, P = .03). The heliox group had greater reduction in respiratory rate than the oxygen group (P = .03). The heliox + forward-leaning-posture group had significantly greater peak expiratory flow improvement than any of the other groups. CONCLUSIONS: Heliox plus forward-leaning posture during bronchodilator nebulization improves bronchodilator efficacy in patients with severe acute asthma. (ClinicalTrials.gov registration NCT00922350).