Characterization of aerosol output from various nebulizer/compressor combinations.

OBJECTIVES: Different commercially available nebulizers and compressors are available. However, the optimal combination for drug delivery is unknown. METHODS: Flow rates of five different compressors (n = 3/compressor) tested alone and in combination with five different commercial nebulizers (n = 9 of each brand of nebulizer) were evaluated. Thereafter, the performances of the different nebulizers were evaluated using 2.5 mg albuterol solution (0.5 mL) added to 2.5 mL saline at flow rates of 2, 3, 4, and 5 L/minute using a laser particle analyzer. Volume median diameter and percentage of particles in the respirable range (1-5 microm) were calculated from this data. Time for nebulization (in seconds) and residual volume (in milliliters) were also recorded. RESULTS: The mean flow rates for the compressors evaluated without a nebulizer attached ranged from 6.6 L/minute (LifeCare Freedom-neb; LifeCare International, Lafayette, CO) to 12.2 L/minute (DeVilbiss Pulmo-Aide; DeVilbiss Health Care, Somerset, PA). Flow rates for the nebulizer/compressor combinations ranged from 2.08 L/minute (Pari LC Jet Proneb; Pari Respiratory Equipment, Richmond, VA) to 5.42 L/minute (Puritan Bennett Raindrop; Puritan Bennett, Lenexa, KS/Omron Compare; Omron, Health Care,Vernon Hills, IL). Using the repeated measure ANOVA model, the interaction between flow rate and device was significant (P < 0.001) for both percentage of particles in the respirable range and log volume median diameter. It was observed that the percentage of particles in the respirable range for the Pari LC Jet did not increase across flow rates in contrast to the other 4 nebulizers. All comparisons to the Pari LC Jet at 2 L/minute were significant. CONCLUSIONS: Marked variability exists in the flow rates among different commercially available compressors used for home nebulization of inhaled pulmonary medications. Different nebulizer/compressor combinations have markedly different performance characteristics which could result in different efficacy and safety profiles of the medications being administered via these devices. We recommend that this type of information be used as a starting point for selecting different nebulizer/compressor combinations. Further clinical evaluation is warranted.     

Comparison of histamine bronchial challenges with the Wright nebulizer and the dosimeter

In twenty adult asthmatics studied in a stable state, histamine bronchial challenges were carried out at one-week intervals with the Wright nebulizer and with the dosimeter-DeVilbiss apparatus. Dose-response curves were analysed for sensitivity, defined as the minimal histamine dose causing a 20% fall in FEV₁ (PC₂₀), and for reactivity, defined as the slope of the dose-response curve once the reaction starts to occur. A significant relationship (r=0·80) was found for the sensitivity obtained with the two nebulizers. PC₂₀ was indeed reproducible within a two folds concentration of histamine in sixteen of the twenty patients. A significant difference (P < 0·01) was found in the reactivity to the two different apparatus, reactivity being greater with the Wright nebulizer in twelve out of fifteen patients so tested. Sensitivity and reactivity showed a borderline relationship (r=0·47) with the Wright nebulizer but not with the dosimeter. A significant correlation (P < 0·05) was found to exist between the initial FEV₁ (in % of the predicted value) and the observed sensitivity and reactivity as assessed with the Wright nebulizer, but not as assessed with the dosimeter. We conclude that histamine bronchial challenges with the Wright nebulizer and with the dosimeter yield reproducible results if the threshold of a 20% fall in FEV₁ is taken as positive. However, the two methods produce different results in terms of reactivity.     

Standardization of inhalation provocation tests: Influence of nebulizer output,particle size,and method of inhalation

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 μm aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 μm AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV₁) by 20% (PC₂₀). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC₂₀. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.     

Sputum induction: effect of nebulizer output and inhalation time on cell counts and fluid-phase measures

BACKGROUND: A knowledge of the factors that can affect induced sputum results is essential in order to standardize the procedure. OBJECTIVE: We investigated the influence of nebulizer output on sputum cell counts and fluid phase measurements at increasing times of sputum induction. METHODS: Eighteen adults with stable asthma inhaled an aerosol of 3% hypertonic saline to induce sputum after 7, 14 and 21 min on 2 days separated by 48 h. On one day, in random order, the ultrasonic nebulizer used had a relatively low output of 0.87 mL/min (particle size 5.58 microm mass median aerodynamic diameter, MMAD) and, on the other, a higher output of 1.90 mL/min (particle size 4.14 microm MMAD). The sputum was selected from each expectorate and examined blind to the induction procedures. RESULTS: With both nebulizers, the 14- and 21-min samples were lower in weight, neutrophils, eosinophils, eosinophil cationic protein (ECP) and interleukin (IL)-8 and higher in macrophages. The higher output nebulizer induced sputum with higher cell viability and lower ECP and IL-8. CONCLUSION: The results identify that the volume of hypertonic saline inhaled in sputum induction influences the fluid-phase measurements. The duration of induction does alter the cell counts and suggests that the later expectorated sputum samples originate from more peripheral airways. The results draw attention to the need to standardize the volume and time of nebulization to accurately interpret and compare results.     

The effect of inspiratory flow rate regulation on nebulizer output and on human airway response to methacholine aerosol

Increased inspiratory flow rate has been demonstrated to decrease pulmonary deposition of inhaled aerosols. To study the effect of inspiratory flow rate regulation on the physiologic response to an active substance administered by aerosol, we compared the effect of high unregulated flow rate (66 to 212 L/min) with regulated low flow rate (20 to 35 L/min) on nebulizer output and on the pulmonary response to methacholine in patients with asthma. Four No. 646 DeVilbiss nebulizers were used in sequence with a nebulization dosimeter to deliver tenfold incremental concentrations of methacholine aerosol (mass median aerodynamic diameter = 1.52 micron; geometric standard deviation = 1.96) ranging from 0.025 to 25 mg/ml. When flow was unregulated, nebulizer output was not greater than when flow was regulated, but coefficients of variation of output were significantly greater (p less than 0.01). The PD20 on the two unregulated days was significantly different (p = 0.01), whereas the PD20 on the two flow regulated days was not significantly different (p greater than 0.05). We conclude that regulation of inspiratory flow rate at rates within the range of tidal breathing significantly decreases variability in nebulizer output and variation of pulmonary responses to methacholine challenge.     

A standard method of intermittent inhaled therapy via a jet nebulizer

Current methods of inhaled therapy using gas-propelled nebulizers lack standardization. The frequent use of nebulized therapy in a continuous flow may be the major reason for the inconsistency of the actual fraction of nebulized drug delivered to the patient. In an effort to achieve consistency in the amount of drug delivered to the patient, we evaluated an intermittent system of nebulized therapy, using a fingertip controlled nebulizer, in 18 adolescent asthmatics. This mode of delivery was found to be highly efficient, providing a nebulized fraction of more than 70% of the initial volumes used (0.75 to 2.6 mL). Initial volumes of 0.9 mL and above were equally efficacious, indicating no further benefit of using higher volumes. Nebulized fractions were found to be highly consistent from one patient to another (+/- 1 SD of 14.1%). We conclude that control of the actual dose delivered to the patient can be best achieved through an intermittent mode of delivery.     

Systematic variations in polymer gel dosimeter calibration due to container influence and deviations from water equivalence

There are a number of gel dosimeter calibration methods in contemporary usage. The present study is a detailed Monte Carlo investigation into the accuracy of several calibration techniques. Results show that for most arrangements the dose to gel accurately reflects the dose to water, with the most accurate method involving the use of a large diameter flask of gel into which multiple small fields of varying dose are directed. The least accurate method was found to be that of a long test tube in a water phantom, coaxial with the beam. The large flask method is also the most straightforward and least likely to introduce errors during the set-up, though, to its detriment, the volume of gel required is much more than other methods.     

Measurements of Gamma-Knife helmet output factors using a radiophotoluminescent glass rod dosimeter and a diode detector

A radiophotoluminescent (RPL) glass rod dosimeter (GRD) and a small active volume p-type silicon diode detector are used for the measurement of the output factors from Gamma-Knife fields. The GRD system consists of small rod-shaped glass chip detectors and an automatic readout device. The output factors measured with the GRD from the 14, 8 and 4 mm helmets relative to the 18 mm helmet are 0.981, 0.942 and 0.877, respectively. Similarly, the corresponding output factors measured with the p-type silicon diode detector are 0.980, 0.949 and 0.867, respectively. The output factors are corrected for the end effect for each helmet. The output factors obtained from both detectors are in good agreement with the values in a recent publication and the values recommended by Elekta, the manufacturer. The directional dependence of these detectors is also measured. For the Gamma-Knife angle ranging from 6 to 36 degrees in the y-z plane of the stereotactic space, the measured angular dependence of the GRD is approximately 1.0% at a 4 MV x-ray beam. The response of the silicon diode detector indicates approximately 3-4% directional dependence for the same angular range for a 6 MV x-ray beam. The Gamma-Knife helmet output factors measured with the silicon diode detector are corrected for angular dependence.     

Importance of sampling method in DNA analysis of lung cancer.

Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out.     

Continuous aerosol therapy system using a modified Collison nebulizer.

A Collison nebulizer was incorporated into an exposure system for administering antiviral compounds as continuous aerosols to mice infected with influenza virus. The nebulizer was modified to control aerosol output by varying the liquid feed rate. A multiple regression equation was developed from data obtained with uranine dye to define the aerosol concentration of the dye in the system as a function of the concentration of the dye in the spray fluid and the rate at which it was aerosolized. The rate of change of the concentration of the test solution due to evaporative losses was also ascertained for a 1-ml/min feed rate over a 23.5-h period of operation. Procedures are outlined for using these relationships to determine the concentration of a given drug that will result in a given dose. Performance data for the drug ribavirin are presented.