Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.

In this randomised double-blind study, patients >or=40 years old with COPD, a smoking history of >or=10 pack-years, a pre-bronchodilator FEV(1) of

Although the use of pressurised aerosol inhalers is widespread, little is known about the actual deposition of the aerosol in the respiratory tract, since this has previously been difficult to measure. We have incorporated Teflon particles (mean various conditions and for assessment of theracentages of the dose deposited on the conducting airways and in the alveoli are unknown. In this paper we present the first direct measurement of the deposition of pressurised inhalation aerosols, using an objective in vivo radioactive technique. MethodsIn order to study the deposition of pressurised aerosols, we have incorporated Teflon particles (density 2'1 gm cm-3), generated by the spinning disc technique,7 into metered-dose inhalers. A fine suspension of fluorocarbon resin (Teflon 120, Dupont) in a mixture of 40% ethanol and 99mtech-netium (Tc) was delivered to the centre of the rapidly rotating disc. The particles generated (mean diameter 2 ,tm, standard deviation 0 4 ,tm) were allowed to settle onto the base of a large airtight tank inside which the generator was situated. After collection, the 99mTc was firmly sealed within the particles by heating at 2400C for five minutes.The pressurised canisters and valves used in this study were those available commercially for the delivery of terbutaline sulphate (Bricanyl, Astra Pharmaceuticals). Eight mg of the Teflon particles were placed inside an open canister, and 2 ml of 52 on 9 May 2018 by guest. Protected by copyright.

ABSTRACr The size distribution of saline and bronchodilator (terbutaline) aerosol droplets generated from four widely used jet nebulisers (Acorn, Upmist, Turret, and Inspiron Mini-neb) has been measured with a Malvern 2200 Laser Particle Sizer. The mass median diameter of aerosol droplets generated by each nebuliser was strongly influenced by the driving flow rate of compressed air. By increasing the flow rate from 4 to 81 min-' mass median diameters were halved (p < 0-01) and there was an increase in the mass of aerosol within the optimum respirable range (<5 ,m). To achieve this range the following individual flow rates were required: Turret 4 1 min-', Acorn and Upmist 6 1 min-t, and Inspiron Mini-neb 8 1 min-t. A significant inverse relation (p < 0.001) was found between mass median diameter and the geometric standard deviation, indicating that the aerosols were smaller but more heterodisperse at high flow rates. Changes in drug concentration had little effect on aerosol size. In 72% of the nebulisations followed to dryness there was no significant change in mass median diameter during the course of nebulisation and in the remainder it was less than 1-3 Am.

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. Effect of lung function and mode of inhalation on penetration of aerosol into the human lung. The method using radioactive tracer particles has been applied to study the effect of the mode of inhalation of aerosols on the depth of deposition in the lungs of 50 patients with airways obstruction. The findings show that the penetration of particles is directly related to: (1) volume inspired per breath (VI); (2) forced expiratory volume in one second (FEVY); and inversely related to (3) flow rate during inhalation (V). In mathematical terms, alveolar deposition (%)= 40 3 (VI)+ 10-98 (FEV1)-0 75 (V)+40 4; for this regression F=4-41 and P<001.Topical administration of drugs into the bronchial tree by inhalation of aerosol often has advantages over the oral and parenteral routes, particularly in patients with reversible airways obstruction. The dose is relatively small (Lal et al., 1972) and response may be more rapid (Plit et al., 1972). The main benefit of this route, however, is that high levels of the drug are concentrated at the site of action in the lung, giving the desired therapeutic action while minimising undesired systemic side effects.The efficacy of topical therapy depends on the proportion of the inhaled drug which is deposited in the lung (Blackwell et al., 1974) and, for certain drugs, that proportion that is retained in the more peripheral parts (Godfrey et al., 1974). Some of the factors which determine penetrance of aerosol have long been known to particle physicists (Hatch and Gross, 1964 MethodThe tracer technique used here to assess depth of deposition and clearance of inhaled particles in humans has been fully reported by . Polystyrene particles (5±0 7 um) were generated by a spinning disc (May, 1949) and inhaled via the mouth of the patients seated upright. The particles were tagged unleachably (Few et al., 1970) with the gamma-emitting radionuclide teehnetium-99m (99mTc). The volume inspired in a single breath (Vi), 0 1 1, 0 30, 0 50, 0'75 or 0-88 litre, was randomly allocated to each patient and determined by an automatic valve. After inspiration there was an obligatory 3-second breath-holding pause before exhalation. The average flow rate during inhalation was measured by a pneumotachograph. The mean, range, and standard deviation (SD) of the flow rate during inhalation (V) for the 44 patients for whom measurements were available were 25'4 (13 3-50 4; SD±7 9) 1/min. Immediately after inhalation the patients washed out their mouths and then swallowed some water to remove radioaerosol from the oropharynx and oesophagus.Immediately afterwards and six hours later gamma radiation from the patients' lungs was counted by 194

Background -In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance. This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique (FET) in patients with airways obstruction. Methods -Nineteen patients (11 men and eight women) of mean (SE) age, % predicted FEV1, and daily sputum wet weight of 64 (2) years, 52 (6)%, and 37 5 (7 9) g respectively participated in the study. Only four of these studies examined the effectiveness of cough in clearing lung secretions on a regional basis from the lungs.8 1014 The other studies considered effectiveness only for mucus clearance from the lungs as a whole. The regional clearance studies have given conflicting evidence as to the effectiveness of cough in peripheral regions of the lungs.The forced expiratory technique (FET) or "huffing" was introduced by physiotherapists as an alternative to coughing for the removal of excess lung secretions.'5 Its introduction was based on the claim that it reduces transpulmonary pressure compared with cough, thereby resulting in less airway compression and closure.'6 Its effect on mucus clearance from the lungs as a whole using radioaerosols has been studied in patients with hypersecretion."We now report a study on the effect of cough and FET on regional mucus clearance in a group of patients with airways disease and varying amounts of daily sputum production. This study also examined the possible association between cough/FET and the maximum expiratory flow attained during these manoeuvres, the viscoelasticity of the expectorated secretions, and a measure of hypersecretion in these patients. Methods PATIENTSNineteen patients (1 1 men, eight women) with a mean (SE) age of 64 (2) years participated in the study. Twelve patients (six women) had chronic obstructive pulmonary disease (COPD) and seven (two women) had bronchiectasis. Fifteen patients were on inhaled bronchodilators of whom eight were also taking oral bronchodilator therapy, and 12 were maintained with inhaled corticosteroid therapy (one of them was also taking oral corticosteroids).

The relative value of chest physiotherapy (including cough) and cough alone for the removal of excessive tracheobronchial secretions has been assessed in six patients with stable chronic obstructive lung disease. After labelling with inhaled radioactive tracer particles, clearance of secretions from selected central and peripheral lung regions was followed with a gamma camera linked to a computer. Cough alone and chest physiotherapy (including cough) were equally effective in the enhancement of central lung clearance. Physiotherapy but not cough alone accelerated peripheral lung clearance (p < 0 05). Sputum yield was greater during physiotherapy than during cough (p < 0-05). These findings confirm the value of chest physiotherapy and high-light the limitation of cough in patients with excessive tracheobronchial secretion and impaired mucociliary clearance.Since the description of simple manoeuvres in 1915,1 chest physiotherapy has become established in the treatment of chronic lung conditions associated with excessive tracheobronchial secretions. Objective evidence for its value, however, is both lacking and controversial.2 3 Using the radioaerosol tracer technique,4 we were able to establish the efficacy of the various combined manoeuvres of the chest physiotherapist with cough in aiding the removal of excessive secretions from central, intermediate and peripheral lung regions. Oldenburg et al,5 however, using similar techniques subsequently produced data suggesting that cough alone was as effective as chest physiotherapy combined with cough. We have therefore examined critically the relative roles of cough alone and chest physiotherapy with cough in enhancing regional lung clearance. MethodsSix patients (three men and three women) with stable chronic airway obstruction and regular daily expectoration took part in the study. Written informed consent from the patients and approval of the local ethics committee were obtained. Three patients had chronic obstructive bronchitis and three bronchiectasis. Three were non-smokers, two exsmokers, and one a current smoker. Their physical characteristics and ventilatory function are summarised in table 1.The labelling of tracheobronchial secretions by an aerosol containing uniform 5 ,um polystyrene particles firmly tagged with 99mTc (half-life 6 h) has been fully described previously.6 After the controlled inhalation of radioaerosol, the clearance of particles deposited throughout the tracheobronchial tree was monitored by external gamma counting using a Nuclear Enterprises Mark III gamma camera. Counts were collected from the anterior chest over five-minute periods at halfhourly intervals from 30 to 150 minutes after