Hygroscopic behavior of nebulized aerosols: not as important as we thought?
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Aerosols↗
Biomedical subjects
G C Smaldone
Publications and source records attributed to G C Smaldone.
Aerosolized antibiotics in mechanically ventilated patients: delivery and response.
OBJECTIVES: To determine whether aerosolized antibiotics can be delivered efficiently to the lower respiratory tract in mechanically ventilated patients and to define possible clinical responses to these agents. DESIGN: Prospective serial study with cases as their own control. SETTING: A 10-bed respiratory care unit for patients with chronic respiratory failure in a tertiary university hospital. PATIENTS: Ventilator dependent patients who are otherwise medically stable. All subjects had a tracheostomy in place, were colonized with gram-negative organisms, and produced purulent secretions which could be sampled daily. INTERVENTIONS: Six patients received nine courses of nebulized therapy, which consisted of treatments every 8 hrs of gentamicin (80 mg) or amikacin (400 mg) for 14 to 21 days. MEASUREMENTS AND MAIN RESULTS: Doses to the lung were measured using radiolabeled aerosols and antibiotic concentrations in sputum. The response was assessed by a) changes in the volume of respiratory secretions; b) effect on bacterial cultures; and c) changes in the inflammatory cells and mediators of inflammation of the respiratory secretions (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha], soluble intercellular adhesion molecule-1 [sICAM-1], and human leukocyte elastase). On average, patients inhaled 35.4 +/- 5.08% (SD) of the initial drug placed in the nebulizer (neb-charge). Of this neb-charge, 9.50 +/- 2.78% was found on the respirator tubing and tracheostomy tube and 21.9 +/- 7.15% was actually deposited in the lungs. The remainder of the neb-charge was sequestered in the nebulizer or exhaled. Trough sputum concentrations averaged 4.3 +/- 3.2 microg/mL/mg neb-charge (range 234 to 520 microg/mL) and increased to 16.6 +/- 8.1 microg/mL/mg neb-charge (range 1005 to 5839 microg/mL) immediately after therapy (p = .011). Serum concentrations were undetectable in most determinations except for a single patient who was in renal failure (8.7 microg/mL amikacin). Treatment caused a significant reduction in the volume of secretions (p = .002). Weekly cultures revealed eradication of Pseudomonas species, Serratia marcescens, and Enterobacter aerogenes in most of the trials. Before antibiotic treatment, concentrations of IL-1beta were higher than those reported in acute respiratory distress syndrome. Throughout the duration of the study, IL-1beta correlated significantly with the absolute number of macrophages, neutrophils, and lymphocytes, respectively (r2 = .55, p = .002; r2 = .50, p < .0004, r2 = .36, p = .005). TNF-alpha concentrations correlated with lymphocytes and neutrophils, respectively (r2 =.27, p = .013, r2 = .21, p = .033). sICAM-1 concentrations increased two-fold (p < .001) during treatment and then returned to baseline. The volume of secretions was related to neutrophil and IL-1beta concentrations, respectively (r2 = .25, p = .008, r2= .35, p = .006). CONCLUSIONS: Nebulizer delivery of aerosolized aminoglycosides is efficient and predictable. In our clinical model, aerosolized antibiotics can make a significant impact on respiratory secretions. Their efficacy in treatment of critically ill patients remains to be determined.
Adult↗
Airway dynamics, oesophageal pressure and cough.
This study hypothesizes that: peak supramaximal airflow during cough reflects expiratory muscle effort, and that expiratory muscle function during cough might be assessed from the airflow signal alone. We monitored airflow and oesophageal pressure (Poes) in normal subjects during cough generated under two conditions: 1) voluntarily from functional residual capacity (FRC); and 2) involuntarily after inhalation of citric acid (CA). Maximal expiratory cough flow was quantified as the quotient of maximal flow during a given cough divided by maximal flow at the matched volume of thoracic gas (Vtg) as identified on the maximal expiratory flow-volume curve. We found: flow ratios correlated poorly with Poes; the variance of flow ratios associated with a series of voluntary coughs was poorly explained by Poes. During CA inhalation, when the Vtg compressed during cough could not be controlled, correlation of Poes with flow ratio remained poor. We conclude that to study the motor limb of the cough reflex, measurements of both airflow and oesophageal pressure are required.
Administration, Inhalation↗
Respirable mass: vague and indefinable in disease.
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Administration, Inhalation↗
Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients.
Lung transplant recipients who have persistent acute cellular rejection are at increased risk for the development of chronic rejection, the leading cause of reduced long-term survival. This study evaluated the use of aerosolized cyclosporine as rescue therapy for unremitting acute rejection. Between June 1993 and March 1996, 18 patients with rejection that failed to resolve after therapy with pulse steroids and antilymphocyte globulin were enrolled in the study. Aerosolized cyclosporine A (300 mg) treatment was initiated for 10 consecutive days followed by a maintenance regimen of 3 days per week. Efficacy was assessed by graft histologic and pulmonary function testing. With the use of linear regression, results in these patients were compared with those in 23 control patients, matched for histologic acute rejection, who had continued to receive conventional rescue therapy. Two patients were unable to tolerate the treatments and were withdrawn from the study. Significant improvement in histologic rejection occurred in 14 of the remaining 16 patients after a mean of 37 days of aerosolized cyclosporine therapy. Measures of forced vital capacity and forced expiratory volume in 1 second (change in percent predicted/100 days plus or minus the standard error) increased over time in the treated patients whereas the condition of control patients declined despite repeated attempts at conventional rescue (forced vital capacity, aerosolized cyclosporine group, 4.6 +/- 2.9 vs control group -8.1 +/- 1.9, p = 0.001; forced expiratory volume in 1 second, aerosolized cyclosporine group, 2.1 +/- 4.4 vs control group -9.8 +/- 2.6, p = 0.043). Renal and hepatic toxicity during cyclosporine therapy was not observed. The incidence of acute histologic rejection (> or = A2) decreased from 2.49 +/- 0.68 episodes/100 days before aerosolized cyclosporine therapy to 0.72 +/- 0.3 episodes/100 days (p < 0.05). In summary, aerosolized cyclosporine is a safe and effective therapy for acute rejection that has failed to improve with conventional treatment.
Acute Disease↗
Dose-related reversal of acute lung rejection by aerosolized cyclosporine.
This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.
Acute Disease↗
RhDNase I aerosol deposition and related factors in cystic fibrosis.
To identify factors influencing lung dose of aerosolized recombinant human deoxyribonuclease (rhDNase I), we used gamma camera and filter techniques to measure deposition in 15 clinically stable patients with cystic fibrosis (CF) (five males and 10 females, age 6-31 yr, mean 16.9) who were on chronic daily therapy. Total and regional deposition were correlated with breathing pattern, pulmonary function, demographic factors, and disease severity. In addition, the effects of each patient's measured lung dose on pulmonary function was estimated by stopping the drug and observing changes in spirometry over a 2-wk follow-up period. After discontinuance of the drug, all patients reported worsening of dyspnea and difficulty producing sputum. There was a significant decrease in FEV1 (% predicted, mean +/- SE, 86.9% +/- 5.57 to 77.8% +/- 5.73, p < 0.005), but all patients completed the study. In some patients, as much as 48% of the deposited aerosol was found in the pharynx (range 0.0 to 0.30 mg, mean 0.089 mg +/- 0.029), and pharyngeal deposition correlated negatively with tidal volume (r = -0.696, p < 0.006) and age (r = -0.743, p < 0.005). For the lungs, deposition ranged between 0.16 mg and 0.78 mg of the 2.5 mg nebulizer dose (mean 0.47 +/- 0.04 mg) and correlated negatively with FEV1 (% predicted, r = -0.611, p = 0.0152). However, the spirometric decrements following cessation of therapy did not correlate with the lung dose of the drug. Analysis of regional deposition within the lungs indicated a wide range of distribution between central and peripheral zones. In conclusion, the deposition pattern of rhDNase I aerosols in patients with CF is largely influenced by respiratory physiology, which itself depends upon age and severity of lung disease. As the patients grow there is a decrease in upper airway deposition and more particles are presented to the lungs where those patients with more airways disease have enhanced pulmonary deposition. Upper airway deposition of rhDNase I is significant, especially in younger patients, and may be related to laryngeal side effects.
Adolescent↗
Aerosol delivery during continuous nebulization.
BACKGROUND AND OBJECTIVES: Continuous administration of aerosolized beta 2-agonists has been suggested as an effective treatment for severe reversible airways disease. To facilitate continuous therapy and avoid a feed system for small-volume nebulizers (SVNs), a large-volume medication nebulizer (Vortran HEART) was developed. The goal of this study was to determine actual drug delivery of the HEART and conventional SVNs for both adult and pediatric breathing patterns. DESIGN: Output studies were conducted on comparable samples of CIS-US AeroTech II and Hospitak PowerMist SVNs and Vortran HEART large-volume continuous nebulizers. To duplicate clinical aerosol delivery via an aerosol mask, drug particles were inhaled through the mouth of a model of a human face for two test breathing patterns (adult = tidal volume (Vt) of 500 mL, 20 breaths/min, duty cycle of 40%; pediatric = VT of 100 mL, 35 breaths/min, duty cycle of 40%), generated by a ventilator. Radiolabeled particles of saline solution, confirmed to behave identically to albuterol, were collected on absolute filters at the mouth of the face to measure the actual mass of albuterol particles delivered to the airway opening. RESULTS: The AeroTech II and PowerMist SVNs delivered 5.14 and 3.74 mg/h, respectively, for the adult breathing pattern and 2.97 and 2.48 mg/h, respectively, for the pediatric breathing pattern. Drug delivery rates of the HEART were a function of drug concentration and ranged from 0.87 to 3.48 mg/h for the adult breathing pattern. For the pediatric breathing pattern, drug delivery rate was a function of drug concentration and inspired minute ventilation and ranged from 0.41 to 1.83 mg/h. CONCLUSION: Our data demonstrate that drug delivery to the patient, expressed as inhaled mass over time, is similar for continuous nebulization (HEART system) and intermittently filled SVNs. In addition, for all nebulizers, the influence of the pediatric breathing pattern needs to be considered. Continuous nebulization permits the redistribution of health-care personnel and may reduce the costs of therapy.
Adrenergic beta-Agonists↗
Measuring nebulizer output. Aerosol production vs gravimetric analysis.
STUDY OBJECTIVES: The function of jet nebulizers has been measured traditionally by gravimetric methods, i.e., by weighing nebulizers before and after nebulization. Newer techniques measure aerosol output directly by analyzing aerosolized drug or tracer, i.e., radioactive 99mTc. Because of evaporation, the equivalence of these methods is uncertain. The aim of this study was to determine if the gravimetric method is an accurate measure of aerosol production under different conditions of aerosol generation (i.e., nebulizer type, flow rate, pressure, volume fill, and concentration of solution used to nebulize a drug). METHODS: In the first phase of the study, we measured the aerosol output of nine commercially available jet nebulizers (AvaNeb; Up-Draft-Hudson RCI; Cirrus-Intersurgical Inc; DeVilbiss 646-DeVilbiss; Powermist-Hospitak, Inc; Respirgard II-Marquest Medical Products; Seamless-Seamless/Dart Respiratory; Salter; Salter Labs; Airlife-Baxter Health Care) run under commonly used conditions (2.5 mL volume fill, 2.0 mL normal saline solvent, 0.5 mL albuterol, flow of 6 L/min, and pressures averaging 15.0 +/- 2.3 [mean +/- SD] pounds per square inch [on the] gauge [psig] provided by a DeVilbiss PulmoAide compressor) with simultaneously measured gravimetrics and filtered radioactivity. Each nebulizer was run to dryness with data acquired every 2 min. The change in the weight of the nebulizer and radioactivity captured on the filter were expressed as percentages of the total in the nebulizer solution. In the second phase of the study, the experiments were repeated using the same nebulizers with a volume fill of 5 mL (diluted to half normal saline solution plus albuterol), flow of 10 L/min, and pressures of 35.6 +/- 8.8 psig. RESULTS: The cumulative (sum of all 2-min runs) weight loss for each individual nebulizer ranged from 25.00 to 64.55% and cumulative aerosol captured varied from 12.63 to 38.76%. While different, the weight loss and aerosol captured were closely correlated (y = -0.62 + 0.62x; r = 0.961, p < 0.0001). Changing volume fill and concentration of solvent did not affect this correlation (p = 0.921 and 0.373, respectively). However, changing flow from 6 L/min to 10 L/min significantly (p = 0.02) affected the relationship (y = -3.80 + 0.83x; r = 0.969, p < 0.001). CONCLUSIONS: When compared with direct methods such as filtering generated particles, the gravimetric method of assessing nebulizer function overestimates aerosol output by 1.8 +/- 0.18 times, presumably because of the loss of solvent during nebulization. However, the relationship between methods is predictable and appears unaffected by changing the type of nebulizer, volume fill, and concentration of solvent. Changes in nebulizer flow and pressure significantly affected the correlation. Gravimetric methods can be used as simple and convenient screening techniques for comparing jet nebulizers under a wide range of experimental conditions.
Adrenergic beta-Agonists↗
Factors in measurement of dose by gamma scintigraphy.
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Administration, Inhalation↗
Aerosolized cyclosporine in lung recipients with refractory chronic rejection.
This study evaluated aerosolized cyclosporine as rescue therapy for lung transplant recipients with unremitting chronic rejection. Nine patients with histologic active obliterative bronchiolitis and progressively worsening airway obstruction refractory to conventional immune suppression received aerosolized cyclosporine. Improvement in rejection histology was seen in seven of nine patients. We compared the changes in the FVC and FEV1 over time using linear regression analysis in these seven histologic responders and nine historical control patients. During the pretreatment period for both the experimental and control groups, the FVC and FEV1 declined at comparable rates. After aerosolized cyclosporine there was stabilization of pulmonary function, whereas in the controls there was continued decline. Cyclosporine blood levels were less than 50 ng/ml 24 h after an aerosolized dose of 300 mg in five patients receiving oral tacrolimus. Nephrotoxicity, hepatotoxicity, and a greater than expected rate of infection was not observed. This study suggests that aerosolized cyclosporine is safe and may be effective therapy for refractory chronic rejection in lung transplant recipients.
Adult↗
Aerosolized drug delivery in the 90s.
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Administration, Inhalation↗
Utility of technetium-99m-DTPA in determining regional ventilation.
UNLABELLED: The goal of this study was to determine the usefulness of radiolabeled aerosols in the assessment of regional ventilation in tracheotomized patients maintained on mechanical ventilation. METHODS: Three commercially available radioaerosol nebulizer kits were studied on the bench to determine nebulizer efficiency and particle distribution of 99mTc-DTPA aerosols. We studied ventilated tracheotomized human subjects with a gamma camera and simultaneously measured regional ventilation with 81mKr gas and 99mTc-DTPA aerosol. Images were compared by analysis of radioactivity distributions in computer-generated regions of interest. RESULTS: The UltraVent nebulizing system produced the smallest particles with a mass median aerodynamic diameter of 0.9 micron compared to the AeroTech I and Venti-Scan II systems, which both produced aerosols of 1.3 microns. Despite relatively small particle sizes, 99mTc-DTPA deposition images with the UltraVent nebulizer did not accurately represent regional ventilation as measured by 81mKr equilibrium. Visual inspection of images revealed significant amounts of particle deposition in the region of the trachea which was diminished but not eliminated following replacement of the tracheotomy tube inner cannula. Based on regional analysis, correlation between radioactivity distributions of both isotopes was poor (r = 0.262, p = 0.162) with segmental analysis suggesting that the upper and middle lung regions were significantly affected by residual tracheal activity. CONCLUSION: The lungs of patients maintained on mechanical ventilation can be imaged after the inhalation of 99mTc-DTPA from commercially available delivery kits, but the correlation between aerosol deposition and regional ventilation is poor. Better definition of ventilated lung segments is obtained when using a gas such as 81mKr because tracheal activity with the radiolabeled gas is minimized.
Adult↗
Technique for measurement of oropharyngeal clearance in the elderly.
In elderly patients, gram negative bacterial colonization often preceeds nosocomial pneumonia. As we propose that a critical factor influencing this change from normal to gram negative predominance is an alteration in oral clearance, we designed this study to validate a technique for measurement of oropharyngeal clearance in a large number of nursing home residents. We modified a protocol of La Force et al who utilized an atomizer to radiolabel oropharyngeal secretions. We determined the output per spray of a DeVILBISS model 152 atomizer and found that 3 sprays of 5 mCi of 99mTc-HSA in 4 ml saline delivered 263 microCi in 0.21 ml. To measure clearance, we designed a portable, collimated ratemeter. It has a lead lined tapered aluminium frame 15 cm high, originating from a 7.5 cm rectangular base which is fitted to the scintillator. On the bench we demonstrated that this collimator, used to confine detection to the face, did not alter sensitivity and linearity of the ratemeter in our specific experimental conditions. When the ratemeter was collimated and its window off, its sensitivity was 5 times greater than the gamma camera with no loss of linearity. However, distance had a significant effect on the ratemeter's sensitivity whereas it had little effect on the gamma camera. Finally, in thirteen patients we assessed the ratemeter's accuracy in measurement of oropharyngeal clearance by comparing curves obtained simultaneously from the ratemeter and gamma camera. While each curve had its own characteristics, both devices provided remarkably similar data and there were no significant differences (r = 0.967, p < 0.0001). We conclude that oropharyngeal clearance can be conveniently and accurately studied in elderly patients at the bedside with a collimated ratemeter. The high sensitivity provides a measure of clearance with low levels of radioactivity exposure, allowing repeated studies over time.
Aged↗
Delivery and distribution of aerosolized cyclosporine in lung allograft recipients.
The aim of the present study was to identify factors determining the delivery to and distribution of aerosolized cyclosporine A (CSA) in the lungs of patients with severe pulmonary allograft rejection. Five such patients inhaled a previously characterized radioaerosol consisting of 4 to 6 cc of CSA (50 mg/ml) in ethanol mixed with technetium-99m (99mTc) bound to human serum albumin, generated by an AeroTech II nebulizer. The total dose of CSA depositing in the lungs was determined with a previously described inspiratory/expiratory mass-balance filter technique. Regional distribution of drug within the lungs was measured using a gamma camera. In addition, the following physiologic parameters were measured: regional volume and ventilation using xenon-133 (133Xe) equilibrium and 133Xe washout, respectively, and regional perfusion using intravenous 99mTc macroaggregates. The relationships between these parameters and regional drug deposition were assessed using linear regression analysis. The lung dose ranged from 20 to 53 mg (0.097 to 0.175 mg CSA deposited per milligram placed in nebulizer). In recipients of single-lung allografts, preferential drug deposition occurred either in the allograft (two patients) or in the native lung (one patient). Marked nonuniformities in regional distribution were also apparent in two double-lung allograft recipients. There was a weak but statistically significant correlation between regional drug deposition and regional ventilation, as measured by 133Xe washout (r = -0.542, p = 0.014), suggesting that although regional ventilation is important, it is not the only factor determining regional deposition in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency.
Using an in vitro model, we compared efficiencies of jet nebulizers and metered-dose inhalers (MDI) with actuator devices to deliver albuterol in various conditions of mechanical ventilation. Factors tested included influence of humidification, MDI actuator device (Aerovent spacer or Marquest 172275 MDI adaptor), and synchronization of MDI to the respiratory cycle. With the nebulizer (AeroTech II) filled with 2.5 mg albuterol sulfate in 3 ml water and run until dry, inhaled mass was 42 +/- 2.6% and mass median aerodynamic diameter (MMAD) was 1.3 microns on a nonhumidified circuit. With the MDI+ Aerovent, the inhaled mass percentage per 90 microgm puff was 15.4 +/- 0.2% with humidification and 25.1 +/- 3.7% without humidification, actuations being synchronized with the beginning of inspiration and separated by a 1-min pause. Failure to synchronize actuations with inspiration or to pause 1 min resulted in significant reductions in inhaled mass (by 35 and 72%, respectively). The Marquest adaptor was less efficient, with an inhaled mass of 7.2 +/- 0.7% under optimal conditions. Metered-dose inhaler actuation during expiration resulted in relatively large particles (MMAD = 2.0 microns). All other MDI actuations led to essentially biphasic distributions, with particles greater than 1 micron following a distribution similar to the nebulizer and the overall MMAD estimated to be 0.22 microns. The AeroTech II delivered a cumulative 1,000 micrograms of drug (2,500 x 0.40) over 40 min. To achieve that amount, the MDI connected to the Aerovent and used in its most efficient sequence would require 45 timed puffs (90 micrograms per puff, 25.1% mean inhaled mass) and take 45 min of an experienced therapist's time.(ABSTRACT TRUNCATED AT 250 WORDS)
Aerosols↗
Deposition of amphotericin B aerosols in pulmonary aspergilloma.
The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
Tracheal aspirates in long-term mechanically ventilated patients. A human model of gram-negative infection and airway inflammation.
It is well known that patients requiring long-term mechanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative organisms. However, useful parameters to objectively describe the airway inflammation associated with airway instrumentation and colonization have not been well define. In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique population for studying airway inflammation and infection. To quantitate production of respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h period. Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%). With these techniques, patients were then studied serially over a 4- to 7-week period. Total cell count, inflammatory cell differential, and two indices of airway inflammation, human neutrophil elastase (HLE) and soluble-intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored. The mean total cell count was 42.2 x 10(6) cells per gram of secretions when patients were clinically stable and not receiving antibiotics. The average differential was neutrophils 69.9%, macrophages 26.9%, and lymphocytes 2.8%. Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was 83 ng/mL. Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of secretions was measured (p < 0.018). The total cell count and percent neutrophils decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%, respectively. While these changes were not statistically significant, the absolute number of airway neutrophils over the 6 h decreased sevenfold (p < 0.014). Similarly sICAM-1 burden (micrograms per 6-h period) also decreased significantly (p < 0.034). These patients provide a unique human model for future studies specifically designed to assess the effect of novel modalities of anti-inflammatory and antimicrobial agents on respiratory secretions.
Adult↗