Demetri Pavia

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 (FEV1); 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 less than 0-01.

Factors influencing the size distribution of aerosols from jet nebulisers.

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 8 1 min-1 mass median diameters were halved (p less than 0.01) and there was an increase in the mass of aerosol within the optimum respirable range (less than 5 micron). To achieve this range the following individual flow rates were required: Turret 4 1 min-1, Acorn and Upmist 6 1 min-1, and Inspiron Mini-neb 8 1 min-1. A significant inverse relation (p less than 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 micron.

Effect of aerosol particle size on bronchodilatation with nebulised terbutaline in asthmatic subjects.

The bronchodilatation achieved by the beta 2 agonist terbutaline sulphate given as nebulised aerosol from different devices has been measured in seven patients with mild asthma (mean FEV1 76% predicted) over two hours after inhalation. The subjects were studied on four occasions. On three visits they received 2.5 mg terbutaline delivered from three different types of nebuliser, selected on the basis of the size distribution of the aerosols generated; and on a fourth (control) visit no aerosol was given. The size distributions of the aerosols expressed in terms of their mass median diameter (MMD) were: A: MMD 1.8 microns; B: 4.6 microns; C: 10.3 microns. The aerosols were given under controlled conditions of respiratory rate and tidal volume to minimise intertreatment variation. Bronchodilator response was assessed by changes in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and maximal flow after expiration of 50% and 75% FVC (Vmax50, Vmax25) from baseline (before aerosol) and control run values. For each pulmonary function index all three aerosols gave significantly better improvement over baseline than was seen in the control (p less than 0.05) and had an equipotent effect on FEV1, FVC, and PEF. Aerosol A (MMD 1.8 microns) produced significantly greater improvements in Vmax50 and Vmax25 than did B or C (p less than 0.05). These results suggest that for beta 2 agonists small aerosols (MMD less than 2 microns) might be advantageous in the treatment of asthma.

Particle penetration and clearance in the human lung. Results in healthy subjects and subjects with chronic bronchitis.

Five-micron diameter radioactive tracer particles have been employed to compare the depth of penetration into the lung during inhalation (by scanning) and the subsequent fast phase clearance (by whole lung counting) in eight healthy aged subjects and nine subjects with chronic bronchitis. All but one subject in each group were smokers. Under standard conditions of inhalation the uniform particles penetrated deeper into the healthy rather than into the bronchitic lung. In the scans in both groups the traverse counts at 1-inch intervals regressed from the hilum laterally to the periphery but the mean regression for the bronchitics (-10.13 ± 0.94 SE) significantly exceeded that for the healthy subjects (-5.26 ± 1.00 SE; P<.005). The particles were cleared from the bronchitic lungs faster than from the healthy lungs (mean retention at six hours 53% in bronchitics as compared with 70% in the healthy group).

Ipratropium bromide: mucociliary clearance rate and airway resistance in normal subjects

The effect of ipratropium bromide, a new anticholinergic drug, on the rate of clearance of secretions from the lung and on airways resistance was investigated in 12 healthy subjects in a double-blind cross-over trial with placebo and a control run without aerosol. Before taking the drug the subjects inhaled uniform 5 micrometer tracer particles of polystyrene in which 99mTc had been unleachably incorporated. The initial depth of deposition and the rate of clearance of the particles were obtained from serial gamma counts made externally to the chest over six hours. The difference between drug, placebo and control runs in the deposition patterns of the tracer particles and their subsequent rates of clearance were not significant. The drug treatment resulted in statistically significant falls in specific airway resistance at 1, 2, 3 and 6 hours (P less than 0.02). There was no objective or subjective evidence of side effects from the drug.

Aerosol inhalation and depth of deposition in the human lung. The effect of airway obstruction and tidal volume inhaled.

Ten patients with chronic bronchitis, whose FEV1.0 varied between 0.48 and 3.00 1, inhaled uniform 5-micronm particles tagged with technetium-99 in tidal volumes (VT) varying between 750 and 1830 ml. Their chests were scanned after inhalation to ascertain depth of deposition of the particles, and clearance from the lungs was monitored for 5 hr by serial whole-lung gamma counting. A significant inverse relationship (P less than .05) was found between depth of deposition after inhalation (D), measured horizontally across the lung as percentage per inch, and rate of clearance of the particles (5-hr retention [%] = 100- % cleared at 5 hr=69.12-3.02D). This confirmed previous findings. The depth of deposition depended directly on the FEV1.0 and VT (5-hr retention [%] = 0.026VT + 12.67FEV1.0-4.13); this resulted in a 14%-75% range for 5-hr retention. Regression slopes for VT and FEV1.0 were independently significant (P less than .05). The findings suggest that, as commonly administered at present, the therapeutic efficiency of most drugs given be aerosol will be reduced in proportion to the degree of airway obstruction as measured by the FEV1.0. The efficiency can be enhanced by increasing the depth of inspiration of the aerosol.

Long-term tobacco smoking and mucociliary clearance from the human lung in health and respiratory impairment.

The rate of mucociliary clearance was estimated from the removal of inhaled radioactive particles in 79 elderly subjects of whom 50 had healthy lungs and 29 had respiratory impairment that was obstructive in 13 and restrictive in 16. The 29 impaired subjects had on the average a faster clearance than the normal group, a difference that almost approached significance (5% level) at six hours after the inhalation of the aerosol. The obstructed subjects showed the fastest clearance with the restricted group intermediate between these and the normal group. No significant difference was found between the rates of clearance of smokers, nonsmokers, and exsmokers in either healthy or “diseased” groups.

Bromhexine and mucociliary clearance in chronic bronchitis

Abstract Lung mucociliary clearance was assessed in 9 patients with chronic bronchitis from the rate of removal of previously inhaled particles tagged with a radioisotope (99mTc) before and after the administration of bromhexine (Bisolvon) 16 mg three times daily. Serial whole-lung gamma counts showed on average a small but statistically significant faster clearance after the drug than in identical control runs ( P P

Response and acclimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette.

Ten symptomless smokers were switched from their usual cigarette to a low tar, low nicotine test cigarette for two weeks to investigate their immediate response and subsequent acclimatisation to the test cigarette. The tar (T) and nicotine (N) yields of the test cigarettes were T = 3.8 mg, N = 0.6 mg; the median yields of the usual cigarettes were T = 16.4 mg, N = 1.4 mg. The subjects were monitored over a six week period comprising a control period (usual cigarette), a test period (test cigarette), and a return period (usual cigarette), each lasting two weeks. The inhaled smoke volume (smoke from the burning tip of the cigarette which is subsequently inhaled) was measured with a non-invasive radiotracer technique. Puffing indices were recorded using an electronic smoking analyser and flowhead cigarette holder. Measurements were made at the beginning of the control period, at the beginning and end of the test period, and at the end of the return period. Subjects kept records of their cigarette consumption during each of the three periods. Apart from a small change in puff duration, cigarettes were smoked in the same way during the control and return periods. Mean and total puff volumes increased with the low tar, low nicotine cigarette but did not change from the beginning to the end of the test period. There was no significant change between the control, test, and return periods for mean inhaled smoke volume, total inhaled smoke volume, or cigarette consumption. It is concluded that when smokers are switched to a low tar, low nicotine cigarette the puff volume increases but there is no change in the inhaled smoke volume or daily consumption.