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G C Smaldone

Publications and source records attributed to G C Smaldone.

70 records · Page 4Linked to original sources
PubMed1987

Human variation in the peripheral air-space deposition of inhaled particles.

Intersubject variability in both peripheral air-space dimensions and breathing pattern [tidal volume (VT) and respiratory frequency (f)] may play a role in determining intersubject variation in the fractional deposition of inhaled particles that primarily deposit in the lung periphery (i.e., distal to conducting airways). In healthy subjects breathing spontaneously at rest, we measured the deposition fraction (DF) of a 2.6-microns monodisperse aerosol by Tyndallometry while simultaneous measurement of VT and f were made. Under these conditions particle deposition occurs primarily in the peripheral air spaces of the lung. As an index of peripheral air-space size, we used measurements of aerosol recovery (RC) as a function of breath-hold time (t) (Gebhart et al. J. Appl. Physiol. 51: 465-476, 1981). In each subject, we measured RC (aerosol expired/aerosol inspired) of a 1.0-micron monodisperse aerosol as a function of breath-hold time for inspiratory capacity breaths of aerosol. The half time (t1/2) (the breath-hold time to reach 50% RC with no breath hold) is proportional to a mean diameter (D) of air spaces filled with aerosol. In the 10 subjects studied, we found a variable DF, range 0.04-0.44 [0.25 +/- 0.12 (SD)]. DF correlated most closely with 1/f, or the period of breathing (r = 0.96, P less than 0.01). There was no significant correlation between DF and t1/2 as an index of peripheral air-space size. In fact there was little deviation in t1/2 in these normal subjects [coefficient of variation (CV) = 0.12].(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1987

Quantitative deposition of aerosolized gentamicin in cystic fibrosis.

In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF. Particle size, distribution, and output from a commercially available nebulizer were measured. Thirteen patients with CF inhaled aerosol (MMAD = 1.1 micron) containing gentamicin (160 mg in nebulizer) and 99mTc-labeled human serum albumin. Patients' sputum and serum were analyzed for gentamicin levels by immunoenzymatic assay (Emit; Syva Corp., Palo Alto, CA). Using a gamma camera and suitable filters, central versus peripheral deposition (C/P ratio) and whole lung deposition were measured and related to sputum gentamicin levels. Gentamicin deposit averaged 12.3 mg +/- 5.9 (SD) or 7.69% of the original amount placed in the nebulizer. Peak sputum levels averaged 376.6 micrograms/ml +/- 275, whereas serum levels were undetectable in all patients. When peak sputum levels were normalized for the amount deposited, a close correlation with C/P ratio was obtained (r = 0.88, p less than 0.05). Furthermore, an inverse relationship was found between the C/P ratio and the %FEV1 (r = 0.76, p less than 0.05). Finally, a bell-shaped relationship between deposited dose and minute ventilation was seen in the patients (r = 0.88, p less than 0.05), i.e., an optimal minute ventilation was shown. These relationships may be important when designing future clinical studies.

Aerosols↗
PubMed1985

Evaluation of quantitative aerosol techniques for use in bronchoprovocation studies.

To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall. For this calibration, the phantom is a simulated lung containing a known amount of radioactivity. Radioactive counts emitted from the phantom are assumed to be attenuated in the same manner as the intact human lung. The present article describes a technique to determine directly the amount of inhaled aerosol deposited in the lung and simultaneously to calibrate the gamma camera for each individual subject. We used right angle light scattering and a gamma camera to measure individual values of the deposition fraction (DF) of inhaled aerosol deposited in the lung and the coefficient of attenuation (AC) of gamma rays in normal and obstructed lungs of human subjects. Radiolabeled monodisperse aerosols 1 and 2 microns in diameter were used. Knowledge of the activity of the inhaled aerosol (microcurie per liter), the volume inhaled, and the measured DF determined each subject's AC (counts per minute per microcurie). DF varied by an order of magnitude in normal (0.04 to 0.48) and obstructed (0.16 to 0.75) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Quantitative assays of pharmacologic aerosols used in studying asthma.

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols. The lack of specific radioimmune or radioenzyme assays coupled with the cross-reaction of organic contaminants with conventional chemical reagents for measuring methacholine required the development of separative techniques to isolate the methacholine from the organic aerosol contaminants. With aqueous extraction and column separation we have been able to completely isolate the methacholine from these contaminants. This allows the application of standard spectrophotometric assays for methacholine to quantitate the methacholine in the resulting solution. These separative techniques will permit the use of these aerosols in quantitative studies of airway reactivity.

Aerosols↗
PubMed1985

Location of flow-limiting segments via airway catheters near residual volume in humans.

Previous studies have demonstrated sites of flow limitation in the central airways of dogs and humans. At low lung volumes, however, during a forced expiration, it is not clear whether flow-limiting segments (FLS) move into the lung periphery. Using intrabronchial lateral pressure catheters, we located FLS in human subjects at all lung volumes between functional residual capacity (FRC) and residual volume (RV). Three individuals with severe intracranial hemorrhage maintained on ventilators were studied. Partial maximal flow-volume curves were generated from 1 liter above FRC to RV by lowering downstream pressure and using the interrupter technique. Sites of FLS were defined as the most downstream points where lateral pressure did not change with driving pressure. FLS were found in all subjects in the central airways. In one subject, FLS moved from segmental bronchi to the first subsegmental bronchus as RV was approached but not beyond. In the other two subjects, FLS remained fixed in location at all measured lung volumes. At constant volume, multiple FLS were located, all in parallel, e.g., fixed in left upper, left lower, and right middle lobar bronchi. In conclusion, sites of flow limitation remain in the central airways as lung volume approaches RV. FLS may move peripherally within the central airways but not beyond proximal subsegmental bronchi.

Aged↗
PubMed1985

Enhancement of particle deposition by flow-limiting segments in humans.

Severe chronic obstructive pulmonary disease is associated with central deposition of inhaled aerosols. This pattern may be due to functional narrowing of the large airways during expiration at flow-limiting segments (FLS). Using a gamma camera and 2.5-micron particles, we compared the pattern of aerosol deposition following quiet breathing with that after a controlled forced expiration (cough) when FLS are known to form in central airways. Lung size measurement by 133Xe allowed construction of regions of interest over the central airways and lung periphery. Deposition in these regions was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. In addition, using right-angle light scattering, the fraction of inhaled particles deposited with each breath (DF) was determined. During control studies, airflow and tidal volume were continuously monitored to insure that tidal loops were well below the maximum expiratory flow-volume (MEFV) curve. To create dynamic compression, cough was used to generate a partial MEFV curve, while inspiratory flow, tidal volume, and functional residual capacity were maintained close to quiet breathing. With cough, C/P ratios increased markedly from 1.04 +/- 0.18 to 2.21 +/- 0.61 (P less than 0.01, n = 6). DF for the lung and airways did not significantly change (0.43 +/- 0.11 to 0.45 +/- 0.09, P = NS). The greater enhancement of regional deposition in the central airways with deposition unchanged over the whole lung demonstrates that, during cough, peripheral deposition is actually reduced when compared with quiet breathing. We conclude that dynamic compression at FLS can be an important factor in the central deposition of inhaled particles.

Humans↗
PubMed1985

Flow limitation, cough, and patterns of aerosol deposition in humans.

We studied deposition of radioactive monodisperse 1.5-micron aerosol in humans following inhalation during quiet breathing. Two groups were studied: normal, defined by tidal loops below the maximum expiratory flow-volume (MEFV) envelope [forced expiratory volume at 1 s at percent of forced vital capacity (FEV1%) 62-78]; and flow-limited, with tidal loops superimposed on MEFV relationship (FEV1% 21-57) and flow-limiting segments (FLS) known to exist in central airways. During simultaneous imaging with a gamma camera, fraction of inhaled aerosol deposited in the lung (DF) was determined by right-angle light scattering. With regions of interest defined by an equilibrium image of 133Xe, regional deposition was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. Deposition was uniform throughout the lung in normal subjects [C/P 1.02 +/- 0.07 (SD), n = 6]. In flow-limited group, central deposition predominated (C/P 1.98 +/- 0.64, n = 6, P less than 0.05). Tidal volume and inspiratory flow, forces thought to influence deposition during inspiration, were not different between groups. Spontaneous cough occurred in five flow-limited subjects during aerosol inhalation, with further increase in central deposition when compared with quiet breathing (C/P 1.85 +/- 0.60 to 2.69 +/- 0.600, P less than 0.01). During cough, tidal volume (ml) was reduced significantly (576 +/- 151 to 364 +/- 117, P less than 0.01) with no change in inspiratory flow (l/s) (1.37 +/- 0.23 to 1.38 +/- 0.40, P = NS). DF, however, was unaffected by cough (0.34 +/- 0.13 to 0.61 +/- 0.12, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1985

Effect of exercise on deposition and subsequent retention of inhaled particles.

To investigate the effect of exercise and its associated increase in ventilation on the deposition and subsequent retention of inhaled particles, we measured the fractional and regional lung deposition of a radioactively tagged (99mTc) monodisperse aerosol (2.6 microns mass median aerodynamic diam) in normal human subjects at rest and while exercising on a bicycle ergometer. Breath-by-breath deposition fraction (DF) was measured throughout the aerosol exposures by Tyndallometry. Following each exposure gamma camera analysis was used to 1) determine the regional distribution of deposited particles and 2) monitor lung retention for 2.5 h and again at 24 h. We found that DF was unchanged between ventilation at rest (6-10 l/min) and exercise (32-46 l/min). Even though mouth deposition was enhanced with exercise, it was not large enough to produce a significant difference in the deposition fraction of the lung (DFL) between resting and exercise exposures. The central-to-peripheral distribution of deposited aerosol was larger for the exercise vs. resting exposure, reflecting a shift of particle deposition to more central bronchial airways. Apical-to-basal distribution was not different for the two exposures. Retention at 2.5 h and 24 h (R24) was reduced following the exercise vs. the resting exposure, consistent with greater bronchial deposition during exercise. The product of DFL and R24 gave a measure of fractional burden at 24 h (B24), i.e., the fraction of inhaled aerosol residing in the lungs 24 h after exposure. B24 was not significantly different between rest and exercise exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Voluntary induced alterations in regional ventilation in normal humans.

We tested the hypothesis that voluntary changes of thoraco-abdominal shape can influence regional ventilation via altering regional pleural pressure swings (Ppl). Regional ventilation was measured simultaneously with regional Ppl during tidal volume breathing maneuvers in five normal subjects while they were performing one of three thoracoabdominal patterns of breathing: normal, preferential intercostal (IC), or preferential diaphragmatic (DIA). In every subject, the lower lung region's 133Xe washout rate was faster than the upper region's, regardless of the pattern of thoracoabdominal breathing adopted. Although IC breathing tended to make regional ventilation more homogeneous, DIA breathing tended to augment regional ventilation inhomogenities. On the average, the Ppl values were greatest in the lower lung region, regardless of the thoracoabdominal pattern adopted; however, IC breathing reduced and DIA breathing increased regional Ppl inhomogenities. When the ratios of the Ppl (lower/upper) were plotted vs. the ratios of the regional 133Xe washout decay constants (lower/upper), a significant positive correlation was found. These data suggest that a causal relation between regional tidal Ppl and regional ventilation exist, thus supporting the concept that thoracoabdominal shape changes can influence regional ventilation.

Adult↗
PubMed1983

Production of pharmacologic monodisperse aerosols.

Monodisperse aerosols containing a range of chemical material, including pharmacologically active substances, were produced by using a modified Sinclair-LaMer condensation generator. Instead of the usual hot-wire technique, an ultrasonic nebulizer was used to suspend nuclei in the gas phase as an aqueous polydisperse aerosol. This technique allowed the generation of monodisperse oil (sebacate) aerosols containing nuclei of sodium chloride, histamine, methacholine, antigen, iron oxide, methylene blue, uranine, radioactive technetium pertechnetate, and technetium-labeled human serum albumin. Quantitative agonist activity was demonstrated for each active nucleus. Particle sizes ranged from 0.65 to 3 microns, with a geometric standard deviation of 1.1-1.2. This system can produce a stable, monodisperse, biologically active radiolabeled aerosol for a period of several hours.

Aerosols↗
PubMed1983

Role of alveolar recruitment in lung inflation: influence on pressure-volume hysteresis.

The behavior of terminal lung units (alveoli) with changes in lung volume is controversial. For example, different investigators using similar techniques have suggested that alveoli expand homogeneously or, conversely, get smaller with increases in lung volume. We studied this problem by filling excised dog lobes with monodisperse aerosol and observing deposition at zero airflow. Under these conditions, the deposition of particles is inversely proportional to a mean alveolar linear dimension (ALD). With this technique, changes in ALD were assessed as the lung ventilated along its pressure-volume (PV) curve. PV curves were generated using a rapid cycling technique that minimized trapping and allowed reversible regulation of inflation-deflation hysteresis. Irreversible changes in PV hysteresis were assessed by rinsing the lung with Tween. With significant PV hysteresis, the ALD progressively decreased with inflation to total lung capacity (TLC). With deflation from TLC, the ALD was unchanged until low volumes were reached, when it decreased markedly. When PV hysteresis was minimized (reversibly or irreversibly), inflation and deflation ALD were superimposed. These data are consistent with progressive alveolar recruitment with inflation to TLC and derecruitment with deflation. The correlation between alveolar dimensions and PV hysteresis suggests that shifts in the PV curve can be accounted for by changes in the population of units. The number open at any given point is determined by the dynamic history of inflation.

Aerosols↗
PubMed1981

Response of collateral channels to histamine: lack of vagal effect.

A new technique using a monodispersed aerosol of histamine delivered to sublobar bronchi through a flexible fiber-optic bronchoscope was used to study the role of the vagus nerve and the effect of anesthesia in the response of collateral channels to exogenous histamine. Studies were performed in paralyzed dogs anesthetized with pentobarbital sodium or alpha-chloralose. Challenges with histamine aerosol were delivered to separate bronchi in each animal before and after bilateral cervical vagotomy. Resistance through collateral channels increased in a reproducible manner following histamine challenge. Vagotomy resulted in no significant change in base-line resistance through collateral channels. The response of collateral channels to exogenous histamine aerosol was not significantly affected by vagotomy or the type of anesthesia used. We conclude that vagal reflexes do not play a significant role in the response of collateral channels to exogenous histamine.

Airway Resistance↗
PubMed1976

Delineation of flow-limiting segment and predicted airway resistance by movable catheter.

Using intrabronchial lateral pressure catheters, we determined the precise location and movement of the flow-limiting segment (FLS) in excised dog and human lungs; under maximal flow conditions, profiles of resistance and transmural pressure from the "mouth" to segmental bronchi were also obtained. In the same lungs, using the interrupter technique, IVFP curves were constructed; with these curves and lung compliance, the relationship between Vmax and Pel was studied using the analysis of Pride et al. The FLS consisted of well-demarcated short lengths (2-3 cm) of the trachea at large lung volumes which moved to lobar or semental bronchi at small volumes (10-20% TLC). These relationships, coupled with observations of the movement of the equal pressure point (EPP), support the idea that in the excised lung the location of the FLS is determined by both the location of the EPP and the compliance of the downstream airway wall; thus FLS MAY NOT FOLLOW UPSTREAM MOVEMENTS OF EPP until EPP reaches a more compliant segment of the bronchial tree (lobar and proximal segmental bronchi). Upstream resistance (Rs) and transmural pressure of collapse (Ptm') calculated indirectly from the slope and intercept of the Vmax vs. Pel relationship accurately predicted values of resistance and transmural pressure measured directly in the same lungs at a point just upstream to FLS.

Airway Resistance↗
PubMedDate not supplied

Relationship between tracheobronchial particle clearance rates and sites of initial deposition in man.

Mucociliary clearance was compared in three groups of normal subjects; each group inhaled a different type of aerosol (sebecate, iron oxide, and aqueous) labelled with 99Tc, to determine the relationship between deposition pattern and the subsequent total lung clearance. Standardization for deposition was accomplished by measuring a central to peripheral ratio (C/P) of deposited radioactivity in the thorax. Lung particle retention at 30, 60, 90, 120 min, and 24 h was measured, and compared at each time period to the C/P ratio. A linear relationship between the retention of aerosol at each time period and the C/P ratio was seen among all aerosols, e.g., aerosol with high C/P ratios had less retention of aerosol at a given time period than aerosols with more diffuse deposition patterns and lower C/P ratios. Furthermore, the relationship was similar to that of the more traditional measurement of regional deposition, the 24-h percentage retention. Lung particle retention was compared among aerosols, using analysis of covariance to standardize for C/P ratio. The intersubject variability was similar among all three aerosol groups. Thus, mucociliary clearance can be standardized in healthy subjects by using an initial deposition index, the C/P ratio, with similar accuracy to the 24-h percentage retention, as an index of aerosol deposition. The use of the C/P ratio, however, has distinct advantages over the 24-h retention, in that studies can be conveniently shortened, used with short lived isotopes, and be adapted to techniques investigating lung permeability instead of tracheobronchial clearance. An unexpected finding was the more rapid clearance of sebecate particles, compared with iron oxide or aqueous particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗