S.P. Newman

IMPAIRED CARDIOVASCULAR RESPONSIVENESS IN LIVER DISEASE

Cardiovascular responsiveness to reflex impaired in patients with cirrhosis compared with control subjects. Peripheral vascular responses to exogenous noradrenaline were also impaired in cirrhotic patients, but peripheral vascular responses to infused adrenaline and to angiotensin II were similar in both groups. Impaired cardiovascular reactivity in patients with chronic liver disease could predispose them to circulatory failure after haemorrhage or surgery and should be considered when prescribing drugs which affect autonomic activity.

Assessment of jet nebulisers for lung aerosol therapy.

The effect on nebuliser output of varying the flow rate of compressed air driving the device and the volume of respirator solution used was investigated in four brands of jet nebuliser. Raising the airflow rate from 4 to 6 1/min reduced the duration of nebulisation by approximately 40%, and a rise from 6 to 8 1/min reduced the duration by a further 15%. However, this change had only a slight effect on the proportion of the solution released. The volume of respirator solution placed in the nebuliser directly influenced the volume released as aerosol. After a 2 ml fill, less than 1 ml was released (50%). With a volume fill of 4 mg 60-80% was released, and with 6 ml 70-85% was released. Nebuliser output fell during nebulisation as the temperature of the solution dropped by 8-12 degrees C. A minimum 4 ml fill and an air-flow rate of 6 l/min are advocated to optimise nebuliser output.

REGIONAL LUNG CLEARANCE OF EXCESSIVE BRONCHIAL SECRETIONS DURING CHEST PHYSIOTHERAPY IN PATIENTS WITH STABLE CHRONIC AIRWAYS OBSTRUCTION

Clearance of excessive bronchial secretions labelled with inhaled radioactive polystyrene particles has been directly measured with a gamma-camera linked to a computer. Chest physiotherapy significantly increased clearance from central, intermediate, and peripheral lung regions and sputum yield. These findings confirm the value of this form of treatment, which has hitherto been in doubt, in removing excessive bronchial secretions from all lung regions and in aiding their expectoration.

The nasal distribution of metered does inhalers

The intranasal distribution of aerosol from a metered dose inhaler has been assessed using a radiotracer technique. Inhalers were prepared by adding 99Tcm-labelled Teflon particles (simulating the drug particles) to chlorofluorocarbon propellants, and scans of the head (and chest) taken with a gamma camera. Ten healthy subjects (age range 19-29 years) each performed two radioaerosol studies with the inhaler held in two different ways: either in a single position (vial pointing upwards) or in two positions (vial pointing upwards and then tilted by 30 degrees in the sagittal plane). The vast majority of the dose (82.5 +/- 2.8 (mean +/- SEM) per cent and 80.7 +/- 3.1 per cent respectively for one-position and two-position studies) was deposited on a single localized area in the anterior one-third of the nose, the initial distribution pattern being identical for each study. No significant radioaerosol was detected in the lungs. Only 18.0 +/- 4.7 per cent and 15.4 +/- 4.1 per cent of the dose had been removed by mucociliary action after 30 minutes, and it is probable that the remainder had not penetrated initially beyond the vestibule. Since the deposition pattern was highly localized and more than half the dose probably failed to reach the turbinates it is possible that the overall effect of nasal MDIs is suboptimal for the treatment of generalized nasal disorders.

The effects of changes in metered volume and propellant vapour pressure on the deposition of pressurized inhalation aerosols

The effects of changes in metered volume and propellant vapour pressure on the deposition of a pressurized inhalation aerosol have been studied in 10 patients with obstructive airway disease. Particles of Teflon (mass median aerodynamic diameter 3.2. μm), labelled with 99Tcm, were incorporated into canisters formulated with two different metered volume sizes (25 and 50 μ1) and with two different propellant vapour pressures (374 and 502 kPa). Increasing the metered volume had no effect on the quantity of aerosol deposited in the lungs, but produced a significantly (P < 0.05) more central pattern of deposition within the bronchial tree. An increase in vapour pressvre resulted in a significant (P < 0.05) increase in whole lung deposition and a significant (P < 0.05) reduction in extrathoracic deposition. It is concluded that changes in formulation alter the deposition pattern of metered dose aerosols, and might consequently bring about changes in clinical efficacy.

Inhaled aerosols: lung deposition and clinical applications

Although aerosol deposition in the lungs is often considered in the context of industrial hygiene, aerosols also play an important clinical role. Three principal mechanisms (inertial impaction, gravitational sedimentation and Brownian diffusion) account for the majority of aerosol deposition in the lungs. Deposition depends upon the mode of inhalation, the nature of the particles and physical characteristics of the subject inhaling the particles. Radioaerosols are widely employed in measurements of total and regional deposition, and topographical distribution may also be determined. Aerosols play an important role in the treatment of various forms of respiratory disease, with bronchodilators for the therapy of asthma being particularly important. On average only 10% of the therapeutic aerosol dose actually reaches the lungs. The rate of removal of insoluble radioaerosols deposited in the lungs may be used as an index of mucociliary transport. Aerosols are also used in a variety of other diagnostic and research procedures, particularly for ventilation scanning, alveolar clearance, measurement of alveolar permeability, and for measuring the size of pulmonary air space.

Calibration and measurement of the inhaled smoke volume in cigarette smoking

Sheahan et al. (Int. J. Appl. Radiat. Inst., vol.31, p.438, (1980)) described a radiotracer technique using 81Krm (Egamma =191 keV, T12/=13 s) for monitoring the volume of cigarette smoke inhaled by a smoker. A 81Krm generator (supplied by the MRC Cyclotron Unit, Hammersmith Hospital) was eluted with air which was then fed into a chamber of volume approximately 100 ml containing the cigarette. The subject held the chamber in his hand and smoked from it in the normal way. Work has been carried out to develop and refine this technique. A method of calibrating the inhaled smoke volume is described together with measurements of the accuracy of the technique.

Efficient nebulisation of powdered antibiotics

Abstract Antibiotic aerosols have a role to play in the treatment of certain respiratory tract infections, but relatively viscous antibiotic solutions may be difficult to nebulise efficiently. Solutions of ceftazidime and colistin, made up by adding 3 ml diluent to powder, have been nebulised in vitro by 4 combinations of jet nebuliser and compressor in order to determine the most efficient apparatus for use with each substance. Nebulisation time, droplet size and drug output were determined. Droplet mass median diameters varied according to the type of nebuliser and compressor, but were confined to the range 3.2–5.0 μm throughout the studies. For colistin, DeVilbiss and Turret were both efficient nebulisers, and the use of the more powerful Maxi compressor reduced nebulisation time. For ceftazidime, Turret nebuliser with Maxi compressor was the most efficient system, while the “dead” solution volume retained within the DeVilbiss nebuliser was unacceptably high. These results emphasize the need for careful choice of nebuliser and compressor for use with antibiotic aerosols.

An in vivo radiotracer method to allow for cigarette filter ventilation during smoking

A technique for monitoring the inhalation of cigarette smoke into the smokers lungs using the gas 81Krm (Egamma =191 keV, T12/=13 s) as a radiotracer was described by Sheahan et al. (Int. J. Appl. Radiat., Isot., vol.31, p.438-41, 1980). The krypton-air mixture was held in a chamber which surrounded the cigarette completely. However, a widespread method of reducing the tar and nicotine levels of British cigarettes is to dilute the smoke by incorporating ventilation holes into the corked paper surrounding the filter. The authors report a development of the cigarette chamber in which the ventilation holes are open to room air and only the volume of smoke drawn through the tobacco-filled part of the cigarette is radiolabelled. This volume may be subsequently inhaled completely or partially by a smoker and accurately measured (Woodman et al., ibid., vol.6, p.251, 1985).