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 H 2 O, 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.)

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 ␤-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 FEV 1 , 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)

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.

NCT02416349 (URL: https://clinicaltrials.gov/ct2/show/ NCT02416349).