Ariel Berlinski

Albuterol delivery by 4 different nebulizers placed in 4 different positions in a pediatric ventilator in vitro model.

BACKGROUND: The type of aerosol generator and the position in the ventilator circuit are crucial to determine aerosol delivery during mechanical ventilation. We compared lung deposition of albuterol aerosols generated by 4 different nebulizers placed in-line in 4 different positions in a pediatric ventilator model. METHODS: Two brands of continuously operated jet nebulizer (6 L/min, oxygen), an ultrasonic, and a vibrating mesh were compared when placed at the ventilator, the humidifier, the Y-piece, and 30 cm before the Y-piece. The jet, ultrasonic, and vibrating mesh nebulizers were operated for 5, 15, and 15 min, respectively. The tested solutions contained 2.5 mg, 5.0 mg, and 7.5 mg of albuterol sulfate. The ventilator settings were: pressure-regulated volume control mode, tidal volume 200 mL, breathing frequency 20 breaths/min, PEEP 5 cm H2O, FIO2 0.4, inspiratory time 0.75 s, bias flow 2 L/min, and heater 37°C. The circuit was connected in series to a 5.5 mm cuffed endotracheal tube, a deposition filter, and a lung model. Albuterol was measured by spectrophotometry. RESULTS: Intra-device comparison: the jet and vibrating mesh nebulizers performed best at either the ventilator or humidifier, and worst at the Y-piece. The ultrasonic nebulizer performed best at the humidifier and worst at the Y-piece. Inter-device comparison: the vibrating mesh nebulizer outperformed both jet nebulizers at all tested positions, and the ultrasonic nebulizer when placed at either the ventilator or the humidifier. Lung deposition increased for the jet and ultrasonic nebulizers, but not for vibrating mesh nebulizer, when increasing the loading volume while maintaining the nominal dose. CONCLUSIONS: The vibrating mesh nebulizer was the most efficient device. The nebulizers were more efficient when placed at either the ventilator or the humidifier, and less efficient when placed at either the Y-piece or 30 cm from the Y-piece. These conclusions are valid for the tested conditions. Data regarding optimization of operating conditions should not be extrapolated among nebulizers of different operating principles.

Breathing resistance and ultrafine particle deposition in nasal-laryngeal airways of a newborn, an infant, a child, and an adult.

As a human grows from birth to adulthood, both airway anatomy and breathing conditions vary, altering the deposition rate and pattern of inhaled aerosols. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children. This study numerically evaluated the age-related effects on the airflow and aerosol dynamics in image-based nose–throat models of a 10-day-old newborn, a 7-month-old infant, a 5-year-old child, and a 53-year-old adult. Differences in airway physiology, breathing resistance, and aerosol filtering efficiency among the four models were quantified and compared. A high-fidelity fluid-particle transport model was employed to simulate the multi-regime airflows and particle transport within the nasal–laryngeal airways. Ultrafine particles were evaluated under breathing conditions ranging from sedentary to heavy activities. Results of this study indicate that the nasal–laryngeal airways at different ages, albeit differ significantly in morphology and dimension, do not significantly affect the total deposition fractions or maximum local deposition enhancement for ultrafine aerosols. Further, the deposition partitioning in the sub-regions of interest is different among the four models. Results of this study corroborate the use of the in vivo-based diffusion parameter (D0.5Q−0.28) over the replica-based parameter in correlating nasal–laryngeal depositions of ultrafine aerosols. Improved correlations have been developed for the four age groups by implementing this in vivo-based diffusion parameter as well as the Cunningham correction factor.

Nebulized Albuterol Delivery in a Model of Spontaneously Breathing Children With Tracheostomy

BACKGROUND: Nebulized therapy is commonly used in spontaneously breathing tracheostomized patients, despite a lack of recommended devices and techniques. I compared albuterol dose delivered to a model of spontaneously breathing children with tracheostomy, using different nebulizers, tracheostomy tube sizes, inhalation techniques, and breathing patterns. METHODS: A tracheostomy model was connected in series to a breathing simulator, with a filter interposed. I simulated the breathing patterns of a 16-month-old child and 12-year-old child, and tested tracheostomy tubes with internal diameters of 3.5 mm and 5.5 mm. Albuterol nebulizer solution (2.5 mg/3 mL) was used. A breath-enhanced nebulizer (Pari LC Plus), a breath-actuated nebulizer (AeroEclipse), and a nebulizer that continuously delivers aerosol (Up-Draft II Opti-Neb) were operated for 5 min at 6 L/min with wall air. The Up-Draft II was tested with T-piece and mask interfaces, with an extension tube, and with and without assisted breathing (every breath and every other breath). The amount of albuterol delivered was analyzed via spectrophotometry. Particle size distribution was measured with a cascade impactor. RESULTS: The Pari LC Plus was more efficient than the Up-Draft II or AeroEclipse. Assisted breathing with the Up-Draft II with extension increased albuterol delivery with every other breath (second best device/configuration), being superior to every breath technique. Adding an extension tube increased delivered albuterol. T-piece was more efficient than mask. Breathing patterns with larger tidal volume increased albuterol delivery. Tracheostomy size had less impact on drug delivery. Mass median aerodynamic diameter decreased by 48–74% when passing through the tracheostomy tubes, and 0.8% of the nominal dose was deposited in the tracheostomy tube. CONCLUSIONS: Albuterol delivery in a model of spontaneously breathing children with tracheostomy is influenced by type of device and configuration, use of assisted breathing, breathing pattern, and tracheostomy tube size. Mass median aerodynamic diameter significantly decreases during passage through a tracheostomy tube.

Effect of face mask dead volume, respiratory rate, and tidal volume on inhaled albuterol delivery†

Pediatric patients often require metered‐dose inhaler (MDI) with holding chamber (HC) to overcome lack of coordination when receiving inhaled therapy. In infants and young children unable to use a mouthpiece, it is necessary to use a mask interface. We compared the effect of varying mask static dead volume (SDV), respiratory rate (RR), and tidal volume (VT) on albuterol captured at the mouth opening (ACMO) in an in vitro model.

Survey of Aerosol Delivery Techniques to Spontaneously Breathing Tracheostomized Children

BACKGROUND: Therapeutic inhaled aerosols are often delivered to spontaneously breathing tracheostomized children. Although aerosol delivery can be affected by several factors, no recommendations for device/drug formulation choice are available. We hypothesized that practice modalities will vary among different institutions. METHODS: The respiratory care departments in institutions in the United States that train pediatric pulmonologists were surveyed regarding their practices of delivering aerosols to spontaneously breathing tracheostomized children. Characteristics of the institution; use of metered-dose inhalers (MDIs), nebulizers, and dry powder inhalers; use of a resuscitation bag to aid aerosol delivery (assisted); types of medication used; and factors affecting choice of delivery method were recorded. RESULTS: Of the invited institutions, 81% (38/47) participated, with 68% of them being freestanding childrens hospitals. MDIs were used by 92% of the institutions surveyed, with similar use of unassisted (32%, with 83% of them using spacers), assisted (34%, with 100% of them using non-valved spacers), and both techniques (34%). Nebulizers were used by 97% of the institutions surveyed, with all using unassisted and 32% also using assisted technique. Tracheostomy aerosol mask was the most commonly used interface (89%). Assisted technique for either MDI or nebulizer was used by 68% of the institutions surveyed, with similar use of flow-inflating bag, self-inflating bag, and both devices. Types of inhaled medications utilized by surveyed institutions included aerosolized antibiotics (82%), corticosteroids (100%), short-acting β agonists (100%), combination therapy (32%), and mucolytics (84%). Dry powders were not used. Patient cooperation was the most frequent and single most important factor influencing the choice of delivery method. CONCLUSIONS: A wide variation in practice of delivering aerosols to spontaneously breathing tracheostomized children was noted. In-vivo and in-vitro studies are needed to support clinical recommendations.

Albuterol delivery via metered dose inhaler in a spontaneously breathing pediatric tracheostomy model

Little data are available regarding efficiency of drug delivery devices and techniques despite their widespread use in spontaneously breathing tracheostomized patients. We compared patient dose achieved with different devices, inhalation techniques, tracheostomy tube sizes and breathing patterns using a spontaneously breathing tracheostomized pediatric model.

In Vitro Evaluation of Aerosols Delivered via the Nasal Route.

BACKGROUND: Infants and young children are obligate nose breathers; therefore, a transnasal route seems the logical delivery method of inhaled aerosols. The efficiency of aerosol delivery depends on several factors, such as interface, type of nebulizer, and patient age and breathing pattern. We hypothesized that the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head model and breathing pattern of an older child would result in a higher lung dose. We also hypothesized that the use of an anatomically correct model would more accurately reflect lung dose than models that do not include airways. METHODS: A model comprising a breathing simulator and an anatomically correct model of a 7-month-old infant and a 5-y-old child with an interposed collection filter (lung dose) were used. Breathing patterns of a newborn, infant, and child were used with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol mass was determined via spectrophotometer (276 nm). RESULTS: Lung dose varied between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh nebulizer. The front-loaded mask was the most efficient interface. We also found that higher tidal volumes were associated with higher lung doses and that the use of a larger airway model resulted in a lower lung dose. Finally, the model showed a good correlation with in vivo data and rendered lung doses severalfold lower than previous data obtained with oral models. CONCLUSIONS: Careful pairing of the aerosol generator and interface is very important during transnasal aerosol delivery.

Predictors and Outcome of Low Initial Forced Expiratory Volume in 1 Second Measurement in Children with Cystic Fibrosis

OBJECTIVE To identify the characteristics of children with cystic fibrosis with low initial forced expiratory volume in 1 second (FEV1) % predicted and to investigate their outcome. STUDY DESIGN Patients were categorized into low or high initial FEV1 groups using cluster analysis. Comparisons of the demographic and clinical data were performed between the 2 groups. RESULTS From 122 children, 21 clustered into the low and 101 into the high FEV1 group. The mean FEV1 was 69% ± 12% predicted for the low and 95% ± 12% predicted for the high FEV1 group (P < .001). The low FEV1 group had lower body mass index percentiles (P = .003), were hospitalized more frequently (P = .001), and had been on dornase alfa longer (P = .006). Low FEV1 group had more patients with positive cultures for Pseudomonas aeruginosa (P = .002) and Stenotrophomonas maltophilia (P < .001) and had more total number of cultures positive for mucoid P. aeruginosa (P = .009) and methicillin resistant Staphylococcus aureus + P. aeruginosa (P = .005). The low FEV1 group continued to have low FEV1 measurements, their FEV1 declined slower, required more hospitalizations per year (P = .01), and had more cultures for mucoid (P = .003) and nonmucoid P. aeruginosa (P = .02) ± methicillin resistant S. aureus (P = .002) in comparison with the high FEV1 group. Poor adherence was associated with lower initial FEV1 values in females, and early, rapid decline of FEV1 in males. CONCLUSIONS Some children with cystic fibrosis may present with poor lung function early in life and continue to have subnormal lung function associated with reduced body mass index, more frequent hospitalization, and higher rates of infection. Such children may benefit from careful evaluation and close follow-up.

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

BACKGROUND: The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasal-laryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasal-laryngeal model of a 53-year-old adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a high-fidelity fluid-particle transport model, and were validated against the measurements made with the 3-dimensional models fabricated from the same airway computed tomography images. RESULTS: Significant differences in nasal morphology were observed among the 5 subjects, in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first 5 years of life. The nasal airway volume ratios of the 10-day, 7-month, 3-year, and 5-year-old subjects were 6.4%, 18.8%, 24.2%, and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in air flow, pressure drop, deposition fraction, and particle accumulation. The computational fluid dynamics predicted pressure drops and deposition fractions were in close agreement with in vitro measurements. CONCLUSIONS: Age effects are significant in both breathing resistance and micrometer particle deposition. The image/computational-fluid-dynamics coupled method provides an efficient and effective approach in understanding patient-specific air flows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis.

Optimization of a Procedure Used to Measure Aerosol Characteristics of Nebulized Solutions Using a Cooled Next Generation Impactor

BACKGROUND Cooling the Next Generation Impactor (NGI) is recommended to minimize evaporation due to heat transfer from impactor to aerosols when evaluating nebulized solutions. This methodology increases testing time for serial testing procedures. We hypothesize that after an initial prolonged cooling time, experiments could be repeated after shorter recooling times without sacrificing accuracy. METHODS Three units of continuous output (HUDSON) and breath enhanced (PARI LC Plus) nebulizers were operated (6 L/min) with albuterol solution (2.5 mg/3 mL) into a cooled (4°C) NGI (internal and external filters) calibrated at 15 L/min. Mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), % particles <5 μm (P%<5), and % particles 1-3 μm (P%1-3) were compared with three different protocols. Initial cooling of the NGI (90 min for all protocols) was followed by two measurements with recooling intervals of either 90 and 90 (protocol A), 60 and 60 (protocol B), or 30 and 30 min (protocol C). Albuterol was diluted and measured by spectrophotometry (276 nm). RESULTS MMAD, GSD, P%<5, and P%1-3 for first measurements of all protocols (n = 9) were: 3.47 ± 0.21 μm, 2.31 ± 0.07, 67.3 ± 2.6%, and 40 ± 2.3% (PARI) and 4.56 ± 0.35 μm, 2.16 ± 0.08, 54 ± 3.7%, and 22.4 ± 2.8% (HUDSON). No differences were found between cooling protocols (p > 0.05). Percentage of variation from first measurement ranged from: -3.9 to +2.1% (PARI) and -4.1 to +2.9% (HUDSON) for MMAD; -5.6 to +2.6% (PARI) and -4.9 to +1.9% (HUDSON) for GSD; 0 to +4.6% (PARI) and -3.7% to +5.7% (HUDSON) for P%<5; and -2.4 to +5.2% (PARI) and -1.8 to +4.9% (HUDSON) for P%1-3. CONCLUSIONS Aerosol characteristics of nebulized solutions determined by NGI are not affected by performing two repeat measurements after recooling the impactor for either 30 or 60 min after an initial 90-min time.