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Biomedical subjects

C S Garrard

Publications and source records attributed to C S Garrard.

At least 37 records · Page 2Linked to original sources
PubMed1989

Lung mucociliary transport in asymptomatic asthma: effects of inhaled histamine.

Bronchial mucociliary clearance (CB) and tracheal mucus velocity (TMV) were measured during the course of repeated inhalations of histamine in six subjects with asthma who had no symptoms in a double-blind, crossover study with a radioaerosol technique. Subjects inhaled a technetium 99m-labeled ferric oxide aerosol with an aerodynamic diameter of approximately 8 microns. CB was recorded for 2.5 hours with a gamma camera, and TMV measured with a multidetector probe situated over the extrathoracic trachea. Histamine was administered repeatedly in concentrations previously shown to produce a 20% fall in forced expired volume in 1 second and at intervals allowing 90% recovery of pulmonary function. Histamine produced a 28% increase in CB (p less than 0.001, analysis of variance) and an 87% increase in TMV (p less than 0.001, analysis of variance) above control values, which was not significantly different from that previously observed in normal subjects receiving significantly higher concentrations of histamine. We conclude that histamine stimulates the mucus transport mechanism in subjects with asthma and that there is a relative hypersensitivity to histamine when these subjects are compared with normal subjects.

Administration, Inhalation↗
PubMed1988

The effect of inhaled histamine on human tracheal mucus velocity and bronchial mucociliary clearance.

The effect of inhaled histamine on human tracheal mucus velocity (TMV) and bronchial mucociliary clearance (CB) was investigated in six healthy subjects using radioaerosol techniques in a randomized double-blind crossover study. Subjects inhaled repeated doses of either phosphate-buffered saline (PBS) or histamine, immediately after the inhalation of a radioaerosol and during the subsequent 2.5-h clearance measurements. Histamine was administered in concentrations previously demonstrated to induce a 20% fall in FEV1 at intervals permitting 90% recovery (mean recovery time = 25 min). Both TMV and CB were significantly increased by inhaled histamine (p less than 0.001). Average TMV throughout the 2.5-h studies increased from 4.9 +/- 1.3 to 8.4 +/- 1.6 mm/min. The increase in TMV above control values became apparent from 5 to 20 min after the first histamine administration. The percentage of aerosol clearance in 60 min increased 33%. The enhancement of CB became statistically significant at 21 min and persisted throughout the 2.5-h measurements (p less than 0.05). The increase in CB could not be attributed to differences in aerosol deposition because measurements of aerosol penetration were not significantly different between PBS and histamine studies. These data indicate that the bronchoconstriction caused by histamine is accompanied by an increase in tracheal and bronchial mucus transport. Release of histamine, as part of an inflammatory response, may alter mucociliary clearance in humans.

Administration, Inhalation↗
PubMed1987

Sources of error and variability in the determination of anaerobic threshold in healthy humans.

The derivation of anaerobic threshold (AT) from the ventilatory responses to incremental exercise is associated with several sources of variability including true biological variability and the error attributable to the observer interpretation of data. To define and quantitate the sources of variability in AT determination we exercised 6 healthy volunteers 6 times and submitted plots of ventilation (Ve), CO2 production (VCO2), respiratory exchange ratio (R) and the ventilatory equivalent for oxygen (Ve/VO2) in random order to 4 independent observers. Within-subject variability in AT ranged from 7 to 55% depending on the subject, ventilatory parameter and observer with an overall mean coefficient of variability of 24%. Significant day-to-day variability was demonstrated in 4 of the 6 subjects using AT values derived from at least one of the ventilatory parameters (Anova, p less than 0.05-p less than 0.001). Mean values for AT obtained with the Ve and VCO2 plots (1.91 and 1.69 liter/min VO2) were significantly lower than those obtained from R and Ve/VO2 plots (2.28 and 2.6 liters/min VO2; p less than 0.001, Anova). Anova showed significant differences in AT values derived by one of the observers compared to the other three (p less than 0.001). A significant observer/ventilation parameter interaction was also found (p less than 0.001) due to one observer consistently estimating higher values of AT from the R plots. The observer error in deriving AT from each exercise test using the Ve plots = 24%, for VCO2 = 19% for R = 29% and for Ve/VO2 = 15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The reproducibility of the respiratory responses to maximum exercise.

In order to investigate the reproducibility of maximum progressive exercise we studied 6 healthy volunteers twice a day for 3 nonconsecutive days. The average within-subject coefficients of variation for the maximal ventilatory and heart rate (HR) responses ranged from 3.8% for HR to 12% for minute ventilation (Ve) and anaerobic threshold. Three-way analysis of variance revealed no significant variations in exercise parameters for the group as a whole except for the carbon dioxide output (VCO2) and respiratory exchange ratio (R) which was significantly greater in the afternoon (p less than 0.05). This was attributed to dietary effects of carbohydrate loading upon VCO2 and was associated in 1 subject with a significant increase in Ve (p less than 0.01). In another subject, morning values of Ve were consistently and significantly (p less than 0.05) greater than the afternoon values which could only be attributed to increased effort as indicated by an increased oxygen uptake. Tests of resting pulmonary mechanics (FEV1, FVC, FRC, RAW) measured before each exercise procedure showed no significant diurnal or day-to-day variations. Results indicate that while the maximal responses to progressive exercise are generally reproducible and the first exercise procedure can usually be considered representative, diurnal variations in R, VCO2 and Ve may occur which can be best avoided on repeated testing by exercising subjects at a standardized time of day.

Adult↗
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↗
PubMed1985

Modifications of lung clearance mechanisms by acute influenza A infection.

Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity (4.9 +/- 1.9 mm/min) by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

Adult↗
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

Pattern of carbon dioxide stimulated breathing in patients with chronic airway obstruction.

The pattern of stimulated breathing during carbon dioxide inhalation was studied in a group of 21 patients with severe irreversible airways obstruction (mean FEV1 = 0.9 litre, mean FEV1/FVC% = 50%). Carbon dioxide rebreathing experiments were performed, the ventilatory response being defined in terms of total ventilation (V) and CO2 sensitivity (S). Breathing pattern was defined by the changes in tidal volume (delta VT) and respiratory frequency (delta f) and the maximum VT achieved (VTmax). Contrary to some previous studied no significant relationship could be demonstrated between the severity of airway obstruction (FEV1/FVC%, Raw) and the ventilatory response to rebreathing (V, S, delta VT, delta f, VTmax). However, measurements of dynamic lung volume (FEV1, FVC, IC) were found to be significantly correlated with the breathing pattern variables (delta VT, delta f, VTmax). Resting PaO2 and PaCO2 were significantly correlated with delta VT but not delta f. Results indicate that the degree of airway obstruction does not dictate the ventilatory or breathing pattern response to carbon dioxide induced hyperpnoea. In contrast it is the restriction of dynamic lung volume, by limiting the VT response, that appears to determine the ventilatory and breathing pattern response in patients with severe airway obstruction.

Airway Obstruction↗
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

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↗
PubMed1979

The pattern of breathing in patients with chronic airflow obstruction.

1. The pattern of breathing in 12 patients with severe irreversible airflow obstruction has been studied during ventilatory stimulation by rebreathing CO2. Mean maximum tidal volume response was only 1.23 +/- 0.30 litres (mean +/- SD); this represented 65% of mean measured vital capacity and 82% of mean measured inspiratory capacity. During the course of rebreathing mean total breath duration was reduced from 3.48 +/- 0.93 to 2.44 +/- 0.48 s. 2. End-expiratory thoracic gas volume (FRC) was elevated at rest in all subjects and increased significantly by a further 0.50 +/- 1.90 litres during ventilatory stimulation in 10 of the 12 subjects. The maximum increase in FRC was proportional to the degree of airflow obstruction afforded by the airways in each subject. 3. It is suggested that the increase in FRC during ventilatory stimulation is responsible for the diminished tidal volume response and is an important determinant of breathing pattern and symptomatology in patients with airflow obstruction.

Adult↗
PubMed1978

The pattern of stimulated breathing in man during non-elastic expiratory loading.

1. The pattern of breathing expressed as the relationship between tidal volume and the components of breath interval was studied in normal subjects during CO2 rebreathing, both under unloaded conditions and following the introduction of a non-elastic expiratory resistance. 2. Under unloaded conditions end-expiratory thoracic gas volume (FRC) measured plethysmographically did not alter during the course of the rebreathing experiment. Maximum tidal volume attained (VT, max.) was equal to or just less than the inspiratory capacity of the subject measured at rest. Expiratory reserve volume was not encroached upon even at the highest levels of ventilation. 3. Under loaded conditions the pattern of breathing was altered. VT, max. was diminished in all subjects and FRC showed a progressive rise during rebreathing which was proportional to the resistive load afforded by the artificial resistance. There were no consistent differences in the components of breath duration either at rest or on maximal ventilatory stimulation between the loaded and unloaded states. 4. It is suggested that the pattern of breathing adopted under conditions of expiratory non-elastic loading is influenced more by the secondary effects of breathing at an elevated lung volume, than by the effect of the non-elastic load per se.

Adult↗