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 (NCT 02519465).

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 ± 3.38% and 12.05 ± 2.96%, respectively) than JN (12.51 ± 6.31% and 3.14 ± 1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ± 1.3% versus 46.44 ± 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.

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.

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 ؉ forwardleaning-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. CON-CLUSIONS: Heliox plus forward-leaning posture during bronchodilator nebulization improves bronchodilator efficacy in patients with severe acute asthma. (ClinicalTrials.gov registration NCT00922350).

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.

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.

Background: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory

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/C 2D ) 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/C 2D were estimated. Based on CT estimates of lung and airways, volumes lying under the bROI and aROI, a 2D penetration index (PI 2D ) and a 3D penetration index (PI 3D ), were defined as volume-normalized ratios of aerosol deposition in central and peripheral ROIs and in central and distal airways, respectively. Results: P/C 2D values and their variability, were influenced by the shape and method to define the ROIs: The P/C 2D was systematically greater and more variable for mROI versus bROI ( p < 0.005). The P/C 2D for aROI was higher and its variability lower than those for the bROI ( p < 0.001). The PI 2D was in average the same for aROI and bROI, and is substantially (*30 • ) greater than PI 3D ( p < 0.001). Both PI 2D and PI 3D , 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.