Recently nebulised antibiotics (gentamicin and carbenicillin) have been used successfully to treat respiratory tract infection in patients with cystic fibrosis. No information exists, however, on the choice of nebuliser or the ideal mode of operation with antibiotic solutions, which are often viscous. The aerosol output, droplet size, and nebulisation time were assessed for four common brands of jet nebuliser (Bird, DeVilbiss, Inspiron, and Upmist) used to nebulise 2 ml (80 mg) and 4 ml (160 mg) of gentamicin solution (Garamycin, Kirby-Warrick) at four compressed gas flow rates (6, 8, 10, and 12 l.min-'). There were considerable variations between the nebulisers, DeVilbiss and Upmist being most efficient in the release of respirable (< 5 um diameter) droplets. Droplet size and nebulisation time were inversely proportional to gas flow rate. Aerosol output and nebulisation time were increased by raising the volume fill from 2 to 4 ml, although nebulisation time could still be restricted to 12 minutes or less with DeVilbiss and Upmist at 12 l.min-'. The output of drug in droplets of below 5 um diameter ranged from 7.2 (SE 0.4) to 71.4 (4.3) mg, according to the type of nebuliser, flow rate, and volume fill. These studies suggest that for optimal drug delivery 4 ml gentamicin solution should be nebulised either at a fixed flow rate of 10-12 l.min-' or with a high flow compressor. Previous unsatisfactory clinical results with antibiotic aerosols may have been due in part to incorrect choice of nebuliser or inappropriate operating conditions, or both.Treatment of chest disorders by inhaled drugs has several potential advantages over use of the oral or intravenous route in that a smaller dose of drug can often be used, there is a low incidence of systemic side effects, and the drug generally begins to act rapidly.' Antibiotics were first given by inhalation in 1946,2 but for many years this form of treatment was considered to have no particular advantage in the treatment of respiratory tract infection.3 Recent studies, however, have shown an improvement in pulmonary function4 and a reduction in the frequency of hospital admission5 in selected patients with cystic fibrosis and Pseudomonas aeruginosa infection when treated regularly with nebulised antibiotics. Aerosol antibiotics offer the prospect of domiciliary treatment over relatively long periods,6 and their use is associated with higher sputum and Address for reprint requests: Dr SP Newman, Department of Thoracic Medicine, Royal Free Hospital, London NW3 2QG. Surprisingly little information exists on the output characteristics of nebulisers, and there is no information at all on the nebulisation of antibiotic solutions, which are more viscous than saline or water.The present study was carried out to assess the output, droplet size, and nebulisation time of four common brands of jet nebuliser used with a solution of gentamicin at four different compressed gas flow rates, as a basis for guidelines for the most efficient delivery of nebulised antibiotics....

Jet nebulisers are used commonly for aerosol therapy in patients with asthma and bronchitis, but the manufacturers' information regarding aerosol droplet size is often inadequate. In this study, mass median diameter, geometric standard deviation and the percentage of the aerosol mass contained within 'respirable' (less than 5 micron diameter) droplets have been measured for 11 brands of jet nebuliser with a solution of hypertonic (7%) saline at compressed gas flow rates between 6 and 121 min-1 using a laser light scattering device (Malvern Instruments 2600 HSD analyser). There was a considerable variation in droplet size between the nebuliser brands and among nebulisers of the same brand. Droplet size decreased with increasing compressed gas flow rate. These findings suggest that the quantity of drug available to the patient depends on the individual nebuliser used, and upon the pressure and flow of the compressed gas.

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, f, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, s The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.

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The effect of oxitropium bromide on lung mucociliary clearance, pulmonary function and viscoelastic properties of sputum was investigated in 10 asthmatics and 10 chronic bronchitics. A controlled, double-blind, crossover study was performed. Following a baseline (B) measurement the patients were, in a random order, allocated placebo (P) or oxitropium bromide (O; 0.1 mg/puff), administered from metered dose inhalers, which they used for 4 weeks at a dose of 2 puffs t.d.s. This test medication was used in conjunction with their normal medication. At the end of the treatment period the patients were assessed, the treatments were then crossed over and a final assessment made 4 weeks later. The administration of oxitropium bromide resulted in (1) small but statistically significant increases in pulmonary function ( < 10% vs. placebo); (2) increased penetrance of radioaerosol into the lungs (mean ± SEM alveolar deposition: 35 ± 3, 26 ± 3 and 24 ± 3 % for the O, P and B runs respectively; p < 0.025); (3) no significant change in particle clearance rate from the lungs despite their deeper penetration (mean ± SEM area under the tracheobronchial clearance curves between 0 and 6 h: 317 ± 26, 324 ± 25 and 287 ± 25 % · h for the O, P and B runs respectively; p > 0.1); (4) no alteration in sputum production, and (5) no significant changes in apparent viscosity (mean ± SEM: 640 ± 162, 446 ± 79 and 557 ± 115 mPa · s for the O, P and B runs, respectively; p > 0.1) and elasticity (mean ± SEM: 3,682 ± 1,383, 1,779 ± 353 and 2,061 ± 366 mPa for the O, P and B runs, respectively; p > 0.1) of sputum. When the two groups, i.e. the chronic bronchitics and asthmatics, were studied separately, no significant differences in any parameter measured (other than radioaerosol penetrance which was significantly enhanced on oxitropium bromide in chronic bronchitics) were noted between the three assessments