No abstract

Several factors may affect the delivery of a nebulized aerosol to the lung through an endotracheal tube during mechanical ventilation. To study these factors in vitro, a model representing ventilation of an adult patient was constructed by linking a Servo 900C ventilator to a standard humidified circuit and an endotracheal (ET) tube positioned within a pipe representing the trachea. This was connected via a filter to a lung simulator. Nebulizers filled with 99mTc human serum albumin were positioned in the circuit, and the delivery of nebulized aerosol through the ET tube into the filter was measured using a gamma camera. With the use of an inspiratory phase-activated System 22 Acorn jet nebulizer, typical adult ventilator settings, and a 3-ml nebulizer solution volume, 5.4% of the nebulizer dose reached beyond the end of the ET tube. This was increased by increasing the inspiratory time, reducing the respiratory rate or respiratory minute volume, and by repositioning the nebulizer on the inspiratory limb of the Y-piece and was reduced by slowing the driving gas flow to the nebulizer. Under the same conditions, delivery was 3.1 and 4.4% using the Samsonic and Fisoneb ultrasonic nebulizers, respectively. Increasing the fill volume and the addition of an aerosol storage chamber increased delivery with all three nebulizers. These experiments suggest some simple ways of improving aerosol delivery during mechanical ventilation, including increasing the volume of nebulizer fill, repositioning the nebulizer in the ventilator circuit, adding an aerosol storage chamber, and adjusting ventilator settings to maximize delivery.

Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted.

Background There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. Methods Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (Q""Tc HSA (50 ,ug); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. Results Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2*2 (0.8)% with 1*5% and 0 7% depositing in the right and left lungs respectively; 0.90%o of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). Conclusions Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients. (Thorax 1993;48:154-159)

Background -Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition ofa spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo. Methods -Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labeliled human serum albumin (9Tc-HSA (50 tg); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple Tpiece or a 600 ml spacer. Results -The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2-2 (0-7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18-2 min v 18-3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46-2% v 47-1% respectively). Conclusions -The combination ofa spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation. (Thorax 1995;50:50-53)

The regulation of the Saccharomyces cerevisiae GAL genes in response to galactose as a source of carbon has served as a paradigm for eukaryotic transcriptional control over the last 50 years. Three proteins-a transcriptional activator (Gal4p), an inhibitor (Gal80p), and a ligand sensor (Gal3p)-control the switch between inert and active gene expression. The molecular mechanism by which the recognition of galactose within the cell is converted into a transcriptional response has been the subject of considerable debate. In this study, using a novel and powerful method of localizing active transcription factors within the nuclei of cells, we show that a short-lived complex between Gal4p, Gal80p, and Gal3p occurs soon after the addition of galactose to cells to activate GAL gene expression. Gal3p is subsequently replaced in this complex by Gal1p, and a Gal4p-Gal80p-Gal1p complex is responsible for the continued expression of the GAL genes. The transient role of the ligand sensor indicates that current models for the induction and continued expression of the yeast GAL genes need to be reevaluated.

Objective pulmonary function (PF) evaluation is essential for the diagnosis, monitoring, and management of many pediatric respiratory diseases as seen in the emergency room, intensive care, and outpatient settings. In this paper, the development and testing of a new noninvasive PF instrument, pneuRIP TM , which utilizes respiratory inductance plethysmography (RIP) are discussed. The pneuRIP TM hardware includes a small circuit board that connects to the RIP bands and measures and wirelessly transmits the band inductance data to any designated wirelessly connected tablet. The software provides indices of respiratory work presented instantaneously in a user-friendly graphical user interface on the tablet. The system was tested with ten normal children and compared with an existing system, Respitrace (Sensormedics, Yorba Linda, CA), under normal and loaded breathing conditions. Under normal breathing, the percentage differences between the two systems were 2.9% for labored breathing index (LBI), 31.8% for phase angle (U), 4.8% for percentage rib cage (RC%), and 26.7% for respiratory rate (BPM). Under loaded breathing, the percentage differences between the two systems were 1.6% for LBI, 4.1% for U, 8.5% for RC%, and 52.7% for BPM. For LBI, U, and RC%, the two systems were in general agreement. For BPM the pneuRIP TM is shown to be more accurate than the respitrace when compared to manually counting the breaths: 13.2% versus 36.4% accuracy for normal breathing and 16.9% versus 60.7% accuracy for breathing under load, respectively.

1. This study was performed to determine the variability of two different scintigraphic methods of measuring pulmonary aerosol deposition, and to examine nebulizer particle size and drug output as potential sources of this variability. 2. A radioaerosol was produced from a 3 ml solution of 99mTc-labelled colloidal human serum albumin (0.05 mg, 37 MBq) using a standard jet nebulizer and air compressor. This was inhaled on three separate occasions by nine healthy male subjects. One one of these occasions, a further inhalation was performed to assess immediate repeatability using increased 99mTc activity (92 MBq). 3. Intrapulmonary aerosol deposition was measured with a gamma-camera and was corrected for tissue attenuation and geometric distribution by using two different methods. 4. Estimated mean pulmonary deposition was 4.3% of the nebulizer dose using a lung phantom correction method, and 6.1% using a tissue attenuation method. For these two methods respectively variability between subjects (coefficient of variation) was 54 and 47%. For both methods, within-subject variability (coefficient of variation) was 37% between occasions and 23% within occasions. 5. The particle-size output of several nebulizers was highly reproducible (coefficient of variation less than 4%), but the nebulizer mass and radionuclide output of two nebulizers was more variable (coefficient of variation 5-19%), and appeared to be an important contributor to the variability in pulmonary aerosol deposition. 6. The data presented here for pulmonary deposition, used with appropriate power statistics formulae, can be used to estimate the sample sizes required for comparative studies of lung aerosol deposition.