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Biomedical subjects

D B Yeates

Publications and source records attributed to D B Yeates.

At least 55 records · Page 3Linked to original sources
PubMed1985

Aerosol penetration and mucociliary transport in the healthy human lung. Effect of low serum theophylline levels.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.

Adult↗
PubMed1984

A phoswich multidetector probe for measuring tracheal mucus velocity.

A simple, reliable, compact and sensitive detection system was required to measure the position as a function of time of local concentrations of tracers tagged with 99Tcm as they are transported up the trachea by mucociliary activity. A multidetector probe to meet these requirements was designed and constructed: it consists of three pairs of NaI(Tl)/CsI(Na) phoswich sandwiches arranged in line so that measurements of response in six positions can be made. Each crystal was 8 mm thick, 1.5 mm deep and formed an arc of 90 degrees with an internal radius of 7 cm. Spatial resolution and background reduction were achieved by pulse height and pulse shape analysis and the use of tungsten parallel-plate collimators. At the face of the collimators the system had a spatial resolution of 9 mm FWHM and a sensitivity of 3.78 X 10(-2) CPS Bq-1 (1400 CPS microCi-1). Background radiation response was typically 1 CPS per crystal. Determinations of tracheal mucus velocity have been made in man. This multidetector probe could be adapted to other velocity measurements over an extended range and for the measurement of activity profiles when high sensitivity is desired.

Gamma Rays↗
PubMed1984

Unsedated animal models of pulmonary mucociliary transport.

Measurements of the rate of mucociliary transport in the airways of the lower respiratory tract have been shown to be influenced by the techniques and protocols used. To avoid the effects associated with invasive techniques and anesthesia in animal models used to study the effect of maturation, drugs, disease, and inhaled pollutants on mucociliary transport we have developed unsedated dog and baboon models of mucociliary transport using radioaerosol techniques. As far as they have been tested these animal models of mucociliary transport react to drugs such as isoproterenol and atropine in the same manner as in man.

Aerosols↗
PubMed1983

A mathematical model of particle retention in the air-spaces of human lungs.

Knowledge of the total and regional lung retention of particles inhaled continuously by man over long periods can be useful in understanding the potential role of inhaled particles in the pathogenesis of lung diseases. Owing to practical and ethical considerations, however, little or no experimental information exists. A mathematical model of particle retention simulating environmental and occupational exposures has therefore been developed that takes into account particle deposition, tracheobronchial clearance, and two phases of alveolar clearance in the Weibel A anatomical lung model. The derived equations of retention kinetics predict retention of particles as a function of exposure time. For a continuous exposure (simulating environmental conditions) to 4 microns particles, the model predicts that retained particles approach an equilibrium between deposited and cleared particles with the 95% level being reached in 293 days. For an intermittent exposure (simulating occupational conditions) equilibrium is approached in five years. The whole lung burden of particles is predicted to be 9% of the total mass that entered the lung after a one-year environmental exposure and 1.5% after a 25-year occupational exposure. The equilibrium surface concentration and integrated dose of particles per airway generation predict enhanced risk to the pathogenic effects of inhaled particles in the large airways and respiratory bronchioles.

Air Pollution↗
PubMed1981

Coordination of mucociliary transport in human trachea and intrapulmonary airways.

A wide range of both mucus velocities in the trachea and rates of bronchial mucociliary clearance have been measured in humans. To investigate the coordination of mucociliary transport in the intrapulmonary and extrapulmonary airways, simultaneous measurements of tracheal mucus velocity and lung clearance were made in 22 healthy nonsmoking adults. Each subject inhaled several breaths of an iron oxide aerosol tagged with 99mTc. Measurements of retained activity in the right lung were made for 2.25 h with a pair of 5 x 2 in. NaI (T1) detectors. Tracheal mucociliary transport rates (TMTR) were measured with a probe containing six vertically aligned rectangular NaI (T1) detectors. The mean TMTR was 5.1 +/- 2.9 mm/min. The mean time for the first bolus to be detected on the multidetector probe (large airway transit time, LATT) was 52 +/- 24 min. At this time the percent cleared (Bi) was 24 +/- 15% and the rate of clearance (Bi) was 0.64 +/- 0.35%/min. The mean percent cleared within a 2-h interval (B120) was 51 +/- 22%. The TMTR was closely correlated with Bi and Bi with B120. The TMTR was also correlated to B120, but not closely correlated with LATT. It is suggesting that coordination of mucus transport throughout the airways of the lung represents the nonchallenged state and is responsible for the maintenance of normal bronchial toilet.

Adult↗
PubMed1981

The characterization of radioaerosol deposition in the healthy lung by histogram distribution analysis.

Thirteen healthy nonsmoking volunteers inhaled an 8.1 micrometers (MMAD) radioaerosol on two occasions. Aerosol deposition pattern within the right lung, as recorded by a gamma camera, was expressed as the 3rd and 4th moments of the distribution histogram (skew and kurtosis) of radioactivity during the first ten minutes after aerosol inhalation. Deposition pattern was also expressed as the percentage of deposited activity retained within the lung at 24 hr (24 hr % retention) and found to be significantly correlated with measures of skew (P less than 0.001). Tests of pulmonary function (FEV1, FVC, and MMFR) were significantly correlated with skew. Correlations were also demonstrated for these pulmonary function tests with 24 hr % retention but at lower levels of significance. Results indicate that changes in measures of forced expiratory airflow in healthy human volunteers influence deposition pattern and that the skew of the distribution of inhaled radioactivity may provide an acceptable index of deposition pattern.

Adult↗
PubMed1981

Effects of drugs on mucociliary transport in the trachea and bronchial airways.

Pharmacologically active agents may change transport rates regionally within the airways of the lung, as well as affect the overall magnitude of the clearance of inhaled deposited radioaerosols. To investigate these possibilities the response of ethanol on pulmonary retention was determined and the responses of both the trachea and bronchial airways were measured after either oral administration of metaproterenol or inhalation of sulfuric acid mist. In the healthy nonchallenged lung, the velocity of mucociliary transport in the trachea was related to the percentage of activity cleared from the lung in two hours. Indices representing different portions of the pulmonary retention curve were also correlated. Changes in this interdependence of mucociliary transport within airways were produced by all agents. Metaproterenol increased tracheal mucus velocity but not lung clearance. Alcohol changed pulmonary retention in both magnitude and direction depending on the individual, resulting in an increase in variability of pulmonary mucociliary clearance between persons. Thus, to evaluate the effects of drugs or pollutants on the lower respiratory tract, measurements of mucociliary transport should be made in both the trachea and the bronchial airways.

Aerosols↗
PubMed1981

Theoretic analysis of sites of aerosol deposition in the human lung.

A new model of aerosol deposition in the human lungs has been developed. It incorporates the deposition probability equations of Landahl and Findeisen in the Horsfield Asymmetric Model 1 of the lung. The deposition model takes into account the regional distribution of ventilation by incorporating principles of ventilatory mechanics into the determination of flow distribution in the lung. Calculations are performed for a 4 micrometers aerosol inhaled with a breathing pattern consisting of a 1,000 ml tidal volume and an average inspiratory flow of 500 ml/sec. A ventilation gradient from base to apex of 1.10 is assigned. The results show that deposition by impaction dominates in the large airways, while deposition by sedimentation dominates in the small airways and alveoli. Calculations of surface concentrations of particles deposited in the airways reveal that the segmental and subsegmental bronchi receive the highest concentrations. The gradient of particles deposited per unit lung volume from base to apex equals 1.13 which is very close to the ventilation gradient. The new model is the first attempt to assess the distribution of deposited particles in an asymmetric model of the lung, using a realistic distribution of ventilation.

Aerosols↗
PubMed1980

Deposition, retention, and clearance of inhaled particles.

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.

Aerosols↗
PubMed1978

A mathematical description of the airways of the human lungs.

To study the physiological implications of the morphological structure of the conducting airways of the human lungs algorithms are derived for Model I of Horsfield et al. (1971). These algorithms produce descriptions of every pathway from the trachea to the respiratory bronchioles in terms of the combined airway orders. The distributions of surface area and circumference with airway order for this model are given. Also illustrated is the frequency distribution of pathway lengths in the lungs. Computations involving fluid flow in the airways are illustrated by developing a model for mucociliary clearance.

Computers↗
PubMed1976

Mucociliary transport in trachea of patients with cystic fibrosis.

Mucociliary tracheal transport rates were measured in 20 patients with cystic fibrosis, in whom these rates ranged from 0 to 12.8 mm/min. The patients were divided into 3 roughly equal groups on the basis of their transport rates. (1) Those in whom no abnormality in mucociliary transport was detected in the trachea; (2) those in whom normal transport rates were measured but in whom abnormalities such as cessation, or reversal of bolus movement were observed; (3) those in whom no normal transport rates were observed. In the first group the rates were similar to those observed in a population of healthy adults. These normal rates were observed in some patients who had a productive cough. The mean mucociliary tracheal transport rate increased with increasing maximum midexpiratory flow. Those patients with a low Shwachman score and poor arterial oxygen tension tended to fall into groups 2 and 3. In the ciliary dyskinesia assay in rabbit trachea the serum from the patients with the higher transport rates tended to initiate more rapid discharge of material from the epithelium and ciliary dyskinesia.

Adolescent↗
PubMed1975

Mucociliary tracheal transport rates in man.

A new method for measuring mucociliary tracheal transport rates (MTTR's) is described. An aqueous aerosol containing albumin microspheres labeled with 99mTc was inhaled in such a manner that it was deposited in local concentrations in the large airways. These boli of microspheres were transported up the trachea and their MTTR's measured using a gamma camera. MTTR's were measured in 42 healthy nonsmoking adults (32 men and 10 women, mean age 28 yr). The mean MTTR's appeared to be log normally distributed with a geometric mean of 3.6 mm/min and a coefficient of variation of 75%. The MTTR's of men and women were similar. Each individual's short-term coefficient of variation was 25%. Twenty-two repeat studies 1 wk to 15 mo apart showed the variation within individuals was less than between individuals. The parasympatholytic drug, atropine (0.6 mg iv) decreased MTTR's for at least 3 h. Inhalation of the sympathomimetic drug, Th1165a increased MTTR's. Chronic and acute smoking did not appreciably change the MTTR'S.

Adrenergic beta-Agonists↗