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Biomedical subjects

W M Foster

Publications and source records attributed to W M Foster.

At least 37 records · Page 2Linked to original sources
PubMed1992

Aerosolized atropine sulfate: influence of inhalation pattern on effective blockade of vagal airway tone.

The influence of aerosolized atropine sulfate on airway tone was evaluated in nine healthy adult subjects using three modes of inhalation and a dosimeter to deliver equal doses of aerosol. For six of the subjects additional studies with radioaerosols and scintillation scans were accomplished to qualify lung distributions of deposited aerosol. The three breathing patterns, identified as Tidal, IC, and VC, had average inspiratory volumes of 0.66 +/- 0.1, 2.10 +/- 0.4, and 4.31 +/- 0.9 (SD) L and were initiated from the rest position of the lung for the first two patterns, and residual volume for the third pattern. Total nebulization time and concentration inhaled were identical for each pattern at an atropine dose of 0.025 mg/kg body weight. Average inspiratory flow rates had means of 0.40 +/- 0.1, 0.64 +/- 0.2, and 0.82 +/- 0.2 (SD) L/s for the respective inhalations. Functional indices of FEV1, MMF, and Vmax50 and anticholinergic side effects were assessed for a 4-h period after aerosol administration. Functional improvement and duration of effect were maximal with the IC pattern. Within the first hour, absolute increases in FEV1 averaged 240 ml above baseline (6.2% increase). Increases for MMF and Vmax50 were on average greater than 23% above baseline (airflow benefit exceeded baseline by 0.91 +/- 0.4 L/s for MMF and 1.14 +/- 0.4 L/s for Vmax50). Except for xerostomia, which was present after all patterns, systemic side effects (tachycardia, blurred vision, and urinary retention) occurred only with VC pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Aerosolized lidocaine reduces dose of topical anesthetic for bronchoscopy.

Conventional aerosol techniques were used to determine if inhalation of lidocaine can supplement topical anesthesia applied during bronchoscopy. Aerosols of either saline or lidocaine (50 mg at either 2 or 4% concentrations) were generated by jet nebulizer and administered with or without intermittent positive-pressure breathing. Patients (n = 38) after aerosol inhalation were administered 2% lidocaine (atomized and instilled) for suppression of the gag reflex, control of cough, and airway anesthesia. For five of the patients, prior to bronchoscopy, additional studies with radioaerosols and scintillation scans were accomplished with the same aerosol methodology to demonstrate lung distribution of deposited aerosol. For five patients who received 2% lidocaine aerosol prior to bronchoscopy, the subsequent topical dose of anesthetic required for the procedure was 186 +/- 34 (SEM) mg lidocaine. Nine patients in a control group received saline aerosol and required significantly more anesthetic, i.e., 308 +/- 26 mg; procedures were completed on average within 50 min. The largest difference was in the amount delivered to the upper airway (naris, pharynx, epiglottis, and larynx), i.e., 144 +/- 26 mg for saline control versus 48 +/- 16 mg for lidocaine aerosol protocol. Airways distal to the cords required less anesthesia also, on average, 77 mg for the saline control versus 46 mg for the lidocaine aerosol protocol (p < 0.05). Topical anesthetic dosage data were replicated in 12 additional patients studied by a different bronchoscopist. No additional benefit was afforded by premedication with 4% lidocaine aerosol rather than the 2% aerosol (n = 12). We conclude that aerosol modalities can supplement topical anesthesia during bronchoscopy, primarily by reducing the dose required to anesthetize the upper airway.

Administration, Inhalation↗
PubMed1991

T3 preserves respiratory function in sepsis.

Sepsis produces profound hypothyroidism. This hypothyroid state is associated with altered lung metabolism and structural integrity. We studied the respiratory function of rats during sepsis-induced hypothyroidism with or without T3 treatment. Forty-four male Holtzman rats underwent cecal ligation and puncture (CLP). Treatment was administered at six hours after surgery consisting of intraperitoneal injection of T3 (15 micrograms/kg, n = 19) or saline (n = 25). At 20 hours (Group A) or 30 hours (Group B) following CLP, respiratory drive was assessed by serial occlusion pressure technique (P0.1). The rats were killed and static elastance determined by serial air inflation to 10 cc. The lungs were excised for weight determination. The P0.1 values were significantly greater in T3-treated animals over controls in Group A (9.3 +/- 0.7 vs. 6.6 +/- 2.2, p less than 0.05 by t test); elastance was significantly improved by T3 treatment in Group B (p less than 0.05 by two-way ANOVA). Lung weight, pH, pO2, pCO2, respiratory rate (RR), and mortality were not significantly different between groups. Control animals were hypothyroid by 20 hours after CLP (T3 less than 12.5 ng/dL) whereas T3-treated animals were euthyroid (T3 = 145 +/- 43 ng/dL). Pulmonary dysfunction frequently accompanies sepsis; the euthyroid state appears protective. We found a significantly improved respiratory drive in septic animals with T3 treatment. Lung elastance was similarly improved in late sepsis with T3 treatment. The data suggest that T3 treatment preserves respiratory function in septic rats as evidenced by respiratory drive and compliance.

Airway Resistance↗
PubMed1991

Influence of inhaled atropine on lung mucociliary function in humans.

The influence of aerosolized atropine sulfate on lung airway mucus clearance was investigated in healthy human subjects who were nonsmokers. Mucus transport was measured with radiolabeled insoluble particles inhaled by mouth and deposited onto mucosal surfaces; subsequent retention of radiolabel was quantitated over a 4- to 5-h period by a noninvasive, posteriorly aligned, gamma camera. Placebo and atropine clearance tests were matched in a given subject for initial and for final (24-h postinhalation) deposition pattern of labeled aerosol at the onset and conclusion, respectively, of tracheobronchial particle clearance. In seven subjects mucociliary function was delayed after inhalation of 0.025 mg/kg body weight atropine sulfate as compared with placebo (0.9% NaCl). On the basis of the area under the activity versus time curves, retention times during atropine exceeded placebo times by more than 30% (p less than 0.01). At 90 min postatropine inhalation, the Vmax50 exceeded baseline values by 21% (p less than 0.01). Urine retention was present in one subject and xerostomia was present in all subjects after atropine. These data suggest that a single dose of atropine sulfate delivered topically to the airway surfaces delays the continuous flow of airway mucus in healthy subjects and that basal autonomic tone is an inherent factor for optimal secretion and/or removal of tracheobronchial secretions.

Administration, Inhalation↗
PubMed1990

Large and small airway responses to bronchoconstrictors in the guinea pig and ferret.

In the isolated, perfused lung lobe of the ferret we evaluated the bronchoconstrictor response of its airways to methacholine and histamine, pharmacologic agents associated with the asthmatic state. The bronchus of excised lobes was cannulated and needle scarifications were made on the pleural surface to allow perfusate to exit. Lung airways were perfused at constant flow with equilibrated 95% O2/5% CO2, warmed Krebs-Ringers solution. Perfusion pressure was measured as a gauge of airway resistance. A concentration-dependent smooth muscle contraction of the ferret lung lobes was observed to methacholine and histamine. The ED50's of methacholine and histamine were 6.41 x 10(-6) M +/- 1.38 x 10(-6) (SEM) and 6.41 x 10(-6) M +/- 1.38 x 10(-6) (SEM) and 2.39 x 10(-6) M +/- 0.53 x 10(-6) (SEM), respectively. The maximum level of bronchoconstriction developed in the ferret (2.42 mmHg/ml/min +/- 0.28 SEM (resistance units] in response to methacholine, was six times greater than that found for histamine (0.42 mmHg/ml/min +/- 0.05 SEM). Responses to both agonists were less pronounced in the ferret lung preparation than those in a similar lung preparation of guinea pig. Compliance changes in both animals were also evaluated. The ferret did not demonstrate a compliance change in response to histamine as was seen for methacholine, suggesting that resistance changes precede compliance changes, or that the ferret airways are particularly resistant to histamine. Despite a lesser contractile response, the ferret has the advantage of a relatively large lung and long trachea that allow study in several preparations obtained from a single animal. It should prove a useful animal model for study of pulmonary pharmacology.

Airway Resistance↗
PubMed1990

Determining deposition sites of inhaled lung particles and their effect on clearance.

An essential component of lung defense is clearance of particulates and infectious vectors from the mucus membrane of the tracheobronchial tree and the alveolar regions of the lung. To partition clearance between these areas we determined the bronchial branching pattern, the anatomical sites of particle deposition, and subsequent clearance in the same animal. Using a 2.85-microns particle tagged with 57Co for inhalation and deposition in the sheep lung, we followed clearance via a series of computer-stored gamma-scintillation lung images. The same sheep was reinhaled, and the particle distributions for both inhalations were compared. After the animals were killed, the bronchial branching pattern and length of the bronchial tree were documented. The number of particles depositing in all bronchi down to 1 mm diam was determined by scintillation counting, and the number in respiratory bronchioles and alveoli was microscopically counted. We conclude that particles deposited in bronchi greater than or equal to 1 mm diam clear in 2-4 h postdeposition. Bronchi distal to 1-mm-diam bronchi and alveoli clear evenly over 72 h, and the number of particles equal to the tracheobronchial deposition cleared after 45 h.

Animals↗
PubMed1990

Supramicron-sized particle clearance from alveoli: route and kinetics.

Particles inhaled and deposited in the alveoli of the lung, i.e., distal to the tracheobronchial mucociliary escalator, may theoretically be cleared by several routes, including solubilization, lymphatic drainage, and the mucociliary pathway. We studied the clearance routes and kinetics of an inert insoluble carbonized polystyrene particle of supramicron size (2.85 micron count median diameter) tagged with 57Co (half-life 270 days) in the adult unanesthetized sheep. The rate of particle clearance, assessed by gamma scintillation camera of the whole lung, showed a three-exponential function, comprising a rapid initial phase in the first 44 h of clearance for tracheobronchial deposition followed by a slower phase of mostly alveolar clearance in the next 30 days and a final phase of very slow relatively pure alveolar clearance. A balance study of particle route during clearance and autopsy of regional thoracic lymph nodes, blood, liver, and spleen demonstrated that this supramicron-sized particle cleared from alveoli predominantly via the mucociliary escalator of the tracheobronchial tree. Whole-lung lavage studies showed particle and macrophage recovery rates suggesting a sequestered state for alveolar-deposited particles, which may partly account for their slow clearance rates. The failure to find interstitial penetration by alveolar-deposited particles indicates that the macrophages engulfing these particles, at low particle burdens, travel normally in only one direction, i.e., from interstitium to alveolus and then to the mucociliary escalator.

Animals↗
PubMed1990

Cough-enhanced mucus clearance in the normal lung.

We studied the effectiveness of cough for clearing mucus in 12 nonsmoking subjects with normal lung function. On 2 separate study days, each subject breathed 6-microns Mass Median Aerodynamic Diameter 99mTc-labeled iron oxide particles under controlled breathing conditions while they were seated in front of a gamma camera. Retention (R) of lung activity was measured over the initial 2 h and again at 24 h after particle inhalation. On the control day the subject sat quietly in front of the camera, while on the cough day each subject performed 60 controlled coughs during the 1st h of retention measurements. By paired analysis, retentions at both 1 and 2 h (R1 and R2, respectively) for the cough measurements were significantly less than control (mean control R1 = 85% vs. mean cough R1 = 72%, P less than 0.002; mean control R2 = 75% vs. mean cough R2 = 65%, P less than 0.02). Retention at 24 h (R24) was not significantly different between cough and control measurements (mean cough R24 = 35% and mean control R24 = 32%). Thus coughing increased the rate at which the radiolabeled particles were cleared from the bronchial airways in these individuals. Follow-up experiments with subjects performing rapid inhalations rather than cough showed similar enhanced particle clearance to that seen with cough. These results suggest that the observed enhancement of mucus clearance by cough (and rapid inhalation) in the normal lung may be due to a stimulation of the mucociliary apparatus rather than via a two-phase gas-liquid flow mechanism.

Adult↗
PubMed1989

Calculating concentration of inhaled radiolabeled particles from external gamma counting: external counting efficiency and attenuation coefficient of thorax.

We determined the overall external counting efficiency of radiolabeled particles deposited in the sheep lung. This efficiency permits the noninvasive calculation of the number of particles and microcuries (microCi) from gamma-scintillation lung images of the live sheep. Additionally, we have calculated the attenuation of gamma radiation (120 keV) by the posterior chest wall and the gamma-scintillation camera collection efficiency of radiation emitted from the lung. Four methods were employed in our experiments: (1) by light microscopic counting of discrete carbonized polystyrene particles with a count median diameter (CMD) of 2.85 microns and tagged with cobalt-57 (57Co), we delineated a linear relationship between the number of particles and the emitted counts per minute (cpm) detected by well scintillation counting; (2) from this conversion relationship we determined the number of particles inhaled and deposited in the lungs by scintillation counting fragments of dissected lung at autopsy; (3) we defined a linear association between the number of particles or microcuries contained in the lung and the emitted radiation as cpm detected by a gamma scintillation camera in the live sheep prior to autopsy (external counting efficiency); and (4) we compared the emitted radiation from the lungs of the live sheep to that of whole excised lungs in order to calculate the attenuation coefficient (ac) of the chest wall. The mean external counting efficiency was 4.00 X 10(4) particles/cpm (5.1 X 10(-3) microCi/cpm), the camera collection efficiency was 1 cpm/10(4) disintegrations per minute (dpm), and the ac had a mean of 0.178/cm. The external counting efficiency remained relatively constant over a range of particles and microcuries, permitting a more general use of this ratio to estimate number of particles or microcuries depositing after inhalation in a large mammalian lung if a similarly collimated gamma camera system is used.

Animals↗
PubMed1987

Ozone exposure alters tracheobronchial mucociliary function in humans.

Mucociliary function is a primary defense mechanism of the tracheobronchial airways, and yet the response of this system to an inhalational hazard, such as ozone, is undefined in humans. Utilizing noninvasive techniques to measure deposition and retention of insoluble radiolabeled particles on airway mucous membranes, we studied the effect on mucus transport of 0.2 and 0.4 ppm ozone compared with filtered air (FA) in seven healthy males. During 2-h chamber exposures, subjects alternated between periods of rest and light exercise with hourly spirometric measurement of lung function. Mechanical and mucociliary function responses to ozone by lung airways appeared concentration dependent. Reduction in particle retention was significant (P less than 0.005) (i.e., transport of lung mucus was increased during exposure to 0.4 ppm ozone and was coincident with impaired lung function; e.g., forced vital capacity and midmaximal flow rate fell by 12 and 16%, respectively, and forced expiratory volume at 1 s by 5%, of preexposure values). Regional analysis indicated that mucus flow from distal airways into central bronchi was significantly increased (P less than 0.025) by 0.2 ppm ozone. This peripheral effect, however, was buffered by only a marginal influence of 0.2 ppm ozone on larger bronchi, such that the resultant mucus transport for all airways of the lung in aggregate differed only slightly from FA exposures. These data may reflect differences in regional diffusion of ozone along the respiratory tract, rather than tissue sensitivity. In conclusion, mucociliary function of humans is acutely stimulated by ozone and may result from fluid additions to the mucus layer from mucosal and submucosal secretory cells and/or alteration of epithelial permeability.

Adult↗
PubMed1986

Airway mucus membrane: effects of beta-adrenergic and anticholinergic stimulation.

Mucus hypersecretion and non-continuous clearance of tracheobronchial mucus contribute to airflow obstruction in several pulmonary disease entities. Bronchospasm, which is frequently associated with bronchial asthma, can present simultaneously with mucus transport abnormalities. Therapy designed to dilate airways may produce secondary effects, which are deleterious to effective transport of lung mucus. Sympathomimetic agents, such as beta-adrenergic agonists, reduce the tone of bronchial smooth muscle and enhance the flow of mucus within lung airways. Parasympatholytic agents also improve airflow in the lungs, but their effects at the mucus membrane of the airways may not be beneficial. Atropine, an anticholinergic agent, apparently has dose-dependent effects on human mucociliary function and, administered orally, can reduce large airway mucus transport. However, newer anticholinergic agents, such as ipratropium bromide, are effective bronchodilators and do not exhibit unfavorable effects on lung mucus transport in either subjects with normal mucus secretion or those with hypersecretory disease entities, such as bronchitis. In mildly symptomatic asthmatic patients, aerosolized ipratropium decreased airway obstruction without consistent positive or negative influence on lung mucociliary function.

Adrenergic beta-Agonists↗
PubMed1985

Disassociation in the mucociliary function of central and peripheral airways of asymptomatic smokers.

Mucociliary function of peripheral airways in asymptomatic smokers may be impaired and contribute to the abnormal airway changes described in these subjects. Techniques using the inhalation and deposition of radioactive particles followed by gamma camera imaging were applied to healthy subjects discordant for smoking habit to determine if mucus transport of peripheral and central airways was altered by smoking. Smokers (n = 8) averaged 26 +/- 2 yr (mean +/- SEM) and less than 7.5 pack-years of smoking, with pulmonary function within normal limits; when compared with the nonsmokers (n = 8) of similar age, their expiratory volumes were similar, i.e., FEV1 as a percent of predicted averaged 94.5 +/- 4% (mean +/- SEM) in the smokers and 98.8 +/- 4% in the nonsmokers. Using 24-h particle retention and planar distribution of particles in the chest as indexes of peripheral and central deposition, the 2 groups had similar deposition patterns. Mucus clearance of particles deposited onto tracheobronchial airways was quantitated as the interval between initial deposition and the time required to attain 75, 50, and 25% retention levels. Six of the 8 smokers had 75% retention times comparable to those of the nonsmokers, but the 50 and 25% retention times differed significantly between the 2 groups (p less than 0.025). Smokers cleared lung mucus at slower rates, i.e., the intervals to attain 25 and 50% retention levels were 60 to 90% greater than the mean values observed for nonsmokers. Velocity of mucus streaming within stem bronchi was comparable for the 2 groups; beta 2-adrenergic stimulation increased mucus transport in the smokers to the baseline control rates of the nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1981

Respiratory drugs influence lung mucociliary clearance in central and peripheral ciliated airways.

Radiolabelling of mucus and gamma-camera imaging techniques were utilized to differentiate mucociliary function in large central and small peripheral bronchi of man. Lung mucus clearance was analyzed for the entire right lung field and a peripheral region, which was representative of mucus clearance from airways distal to lobar bronchi. On control days, healthy subjects breathed monodisperse particles, average size 4.19 micrometers, and achieved central patterns of deposition with mouth breathing at rest. Matched deposition patterns were achieved on treatment days when isoetharine or isoproterenol influence on mucus clearance was measured and compared to control. Whole and peripheral lung clearances were increased by beta-adrenergic aerosol: isoetharine/control clearance ratios for whole and peripheral lung average 1.47 and 1.50, respectively; similar results were found for isoproterenol with ratios of 1.47 and 1.23, respectively. These data indicated that in healthy subjects the peripheral bronchi have the longest turn-over times for replacement of their mucous linings, and that these airways, like the larger airways of the trachea and main bronchi, can be stimulated by beta-adrenergic agents to increase their base-line flow of mucus.

Adrenergic beta-Agonists↗