D. Pavia

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.

Simple instructions for using pressurized aerosol bronchodilators

Although the manufacturers of pressurized aerosol bonchodilators issue instructions for using the inhalers, little or no experimental verification exists. Bronchodilatation has been measured after controlled inhalations of 500 μg terbutaline sulphate given in a systematic series of investigations to 8 patients with reversible airways obstruction at 2 different inhalation flow rates (25 1/min and 80 1/min), 3 different lung volumes (20%, 50% and 80% vital capacity) and followed by 2 different breath-holding pauses (4 and 10 seconds). The results indicate that patients may release the aerosol at any time during the course of a slow deep inhalation which should be followed by 10 seconds of breath-holding. This will ensure an optimal bronchodilator response.

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 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.

Effect of oral N-acetylcysteine on mucus clearance.

Oral N-acetylcysteine has been advocated as a mucolytic agent for use in chronic bronchitis. We have investigated the effects of regular use of this drug at a dose of 200 mg thrice daily for 4 weeks in nine patients with chronic bronchitis on lung function, lung mucociliary clearance and sputum viscosity in a controlled, double-blind, crossover study. No significant differences were found in lung function, mucociliary clearance curves or sputum viscosity following treatment with N-acetylcysteine compared to control or placebo measurements.

Quantitative comparison of 99Tcm-aerosol and 81Krm ventilation images

Quantitative indices are described for assessing the distribution of ventilation imaging agents (radioaerosols, in particular) within the lung. They have been applied to images obtained with 99Tcm aerosol particles (0.5-2.0 micrometer diameter) and with 81Krm gas in 12 patients with a wide range of lung function. In patients with normal lung function aerosol distribution was similar to that of 81Krm. In patients with airways obstruction, the aerosol tended to penetrate less well than 81Krm to the lung periphery and to show a less homogeneous distribution there. Quantitative analysis confirms that the aerosol technique is an effective substitute for 81Krm in patients with normal lung function. When lung function is impaired aerosol images may still be valuable particularly in confirming a diagnosis of pulmonary embolism though they must be interpreted with caution in attempting to exclude that diagnosis. We conclude that small particle radioactive aerosols provide a readily available ventilation technique for clinical ventilation-perfusion imaging.

The effect of unproductive coughing/FET on regional mucus movement in the human lungs

The study was designed to ascertain the movement of mucus from proximal and peripheral regions within the human lungs during cough and the forced expiration technique (FET). Mucus movement was measured using a radioaerosol technique. Seven patients (mean +/- SEM age: 63 +/- 3 years) with airways obstruction (% predicted FEV1: 44 +/- 4) participated in the study. Each patient underwent three assessments in a randomized manner: control/cough/FET. Peak expiratory flow rate (PEFR) was measured at the mouth during cough and FET. None of the patients produced sputum during the assessment periods. Both cough and FET compared with control increased, on average, mucus clearance from all regions; statistical significance was achieved only for central lung regions with cough (P less than 0.05). There was no significant correlation between PEFR during cough/FET and regional lung clearance.

Effect of terbutaline administered from metered dose inhaler (2 mg) and subcutaneously (0.25 mg) on tracheobronchial clearance in mild asthma

Tracheobronchial mucus clearance was measured in nine mild asthmatics, using an objective radioaerosol technique, on 3 separate days at intervals of 1 week. Immediately after radioaerosol inhalation, drug or placebo was administered via subcutaneous injection (SC) plus metered dose inhaler (MDI)--2 puffs. Three randomized treatments were used: saline placebo SC plus 2 mg terbutaline by MDI (1 mg per puff); 0.25 mg terbutaline SC plus placebo (propellants and surfactant only) by MDI; and double placebo. Changes in lung mucociliary clearance showed an inverse relationship to baseline clearance of both proximal and distal ciliated airways following inhaled terbutaline, whereas terbutaline SC related inversely only to baseline clearance of the distal ciliated airways. This may reflect the surface concentrations of drug, established by each route.

Effect of oral antibiotics on lung mucociliary clearance during exacerbation of chronic obstructive pulmonary disease

It has been well established that lung mucociliary clearance is depressed in patients with chronic obstructive pulmonary disease. This study examines whether oral antibiotics have a detectable effect on this clearance mechanism during exacerbation in patients with such disease. Twelve patients with a mean +/- SE age of 63 +/- 2 years participated in a randomized, double-blind, parallel group study to assess the effect of 1 week of treatment with amoxycillin (500 mg t.d.s.) or ciprofloxacin (500 mg b.d.) on lung mucociliary clearance during exacerbation. Lung mucociliary clearance rates were measured by a non-invasive radioaerosol technique. Both drugs on average resulted in small, non-significant, enhancement of mucociliary clearance. Following treatment, the numbers of coughs were reduced in both groups and significantly (P < 0.05) after treatment with ciprofloxacin. Sputum production was also significantly reduced (P < 0.01) in both groups. The magnitude of improvement in lung mucociliary clearance was relatively modest following 1 week of treatment with either antibiotic. Since the number of coughs was significantly less after ciprofloxacin treatment the measured enhancement of lung mucociliary transport is probably, however, an underestimate.