Biomedical subjects

W D Bennett

Publications and source records attributed to W D Bennett.

At least 19 recordsLinked to original sources

PubMed2001

Induced sputum derives from the central airways: confirmation using a radiolabeled aerosol bolus delivery technique.

Indirect evidence suggests that induced sputum derives from the surfaces of the bronchial airways. To confirm this experimentally, we employed a radiolabeled aerosol bolus delivery technique that preferentially deposits aerosol in the central airways in humans. We hypothesized that there would be significantly more radioactivity recovered in an induced sputum sample, and greater airways clearance of radiolabeled particles, immediately after a central versus peripheral airways deposition. Ten healthy volunteers underwent radiolabeled aerosol deposition ((99m)Tc sulfur colloid particles) to the central and peripheral airways on separate occasions followed immediately by induced sputum or no sputum (control), while seated in front of a gamma camera. Radioactivity was measured in the selected sputum sample, processed cell pellet, and supernatant fraction. Significantly more radioactivity was present in all portions of the sputum sample after central versus peripheral airways deposition (i.e., selected sample: 15,607 counts +/- 2,985 versus 943 counts +/- 298, p = 0.001). Clearance from the whole lung was significantly greater 40 min after central versus peripheral airways deposition (48 +/- 3% versus 5 +/- 1%, p = 0.0001). Compared with control, induced sputum greatly enhanced clearance after central deposition (48 +/- 3% versus 11 +/- 6%, p = 0.0001), but not after peripheral deposition (5 +/- 1% versus 3 +/- 0.8%). These results provide direct evidence that induced sputum derives from the central airways with little or no contribution from the peripheral airways.

Administration, Inhalation↗

PubMed2001

Effect of aerosolized uridine 5'-triphosphate on mucociliary clearance in mild chronic bronchitis.

Previous studies show that uridine 5'-triphosphate (UTP), a P2Y(2) receptor agonist, is effective at acutely enhancing mucociliary clearance in healthy, nonsmoking adults. UTP solution for inhalation is being developed by Inspire Pharmaceuticals under the compound number INS316. In a double-blind, randomized, crossover, placebo-controlled study we tested the single-dose effect of UTP in chronic smokers with mild chronic bronchitis (n = 15) by measuring the clearance of (99m)Tc-Fe(2)O(3) particles (4.0 microm mass median aerodynamic diameter [MMAD]) after inhalation of nebulized placebo (0.9% saline) and two doses of UTP (20 and 100 mg in the nebulizer). On each study day, gamma camera scanning was performed over a 2-h period. After an initial deposition scan, subjects inhaled placebo or UTP during the first 20 min of scanning. Analysis of whole lung clearance showed that the retention-time curves for each day were biphasic and that the earliest break point in the average curves occurred at 50 min. Mean particle clearance rate (Clr in %/min) through 50 min for placebo treatment was Clr = 0.65 +/- 0.27 whereas treatment with UTP showed Clr significantly increased to 0.95 +/- 0.48 and 0.93 +/- 0.44 for the 20-mg and 100-mg dose respectively, p < 0.005 for both as compared with placebo. These data show that mucociliary clearance associated with mild chronic bronchitis is acutely improved with minimal doses of aerosolized UTP, presumably because of its stimulation of ciliary beating and hydration of airway secretions.

Administration, Inhalation↗

PubMed2001

Effects of inhaled iron oxide particles on alveolar epithelial permeability in normal subjects.

Pulmonary inflammation secondary to oxidant generation catalyzed by transition metals associated with inhaled particles is one factor postulated to underlie the acute health effects of particulate air pollution. We postulated that inhaled iron oxide particles with associated amounts of soluble iron should induce mild pulmonary inflammation and lead to altered alveolar epithelial integrity and altered gas exchange. To test this hypothesis we examined the effects of inhaled iron oxide particles on alveolar epithelial permeability. Sixteen healthy subjects inhaled aerosols of iron oxide particles (1.5 microm mass median aerodynamic diameter) having either high or low water-soluble iron content [3.26 +/- 0.25 (SE) and 0.14 +/- 0.04 microg soluble iron/mg of particles, respectively] for 30 min at an average mass concentration of 12.7 mg/m(3). Alveolar epithelial permeability was assessed by measuring the pulmonary clearance of an inhaled radiolabeled tracer molecule ((99m)Tc-DTPA, diethylene triamine pentaacetic acid) using a gamma camera at 1/2 h and 24 h post particle exposure. Carbon monoxide lung diffusing capacity (DL(CO)) and spirometry were also performed before and after breathing the iron oxide. As a control, on a separate day, the procedures were duplicated except that the subject breathed particle-free air. For those subjects breathing aerosols with high soluble iron, we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (97.4 +/- 15.4 vs. 116.1 +/- 15.5 min, respectively) or 24 h postinhalation (105.1 +/- 13.8 vs. 106.9 +/- 12.9 min, respectively). Likewise, for those subjects breathing aerosols with low soluble iron content we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (108.6 +/- 31.9 vs. 95.6 +/- 10.8 min, respectively) or 24 h postinhalation (130.0 +/- 18.0 vs. 105.8 +/- 13.7 min, respectively). We found no significant differences in DL(CO) between particle exposures and air exposures. Minor differences in spirometric measurements were noted but were not statistically significant. We conclude that inhalation of iron oxide particles did not cause an appreciable alteration of alveolar epithelial permeability, lung diffusing capacity, or pulmonary function in healthy subjects under the studied conditions.

Administration, Inhalation↗

PubMed2001

Regional deposition of coarse particles and ventilation distribution in healthy subjects and patients with cystic fibrosis.

The efficacy of inhaled pharmaceuticals depends, in part, on their site of respiratory deposition. Markedly nonuniform ventilation distribution may occur in persons with obstructive airways diseases and may affect particle deposition. We studied the relationship between regional deposition (RDep) and regional ventilation (RVent) in a group of 12 cystic fibrosis (CF) patients with mild to moderate airway obstruction (63 +/- 8% predicted FEV1) and 11 healthy nonsmoking volunteers (104 +/- 13% predicted FEV1) using planar scintigraphic methods. RDep was assessed from initial deposition and 24-h retention images for monodisperse technetium-99m-labeled iron oxide particles (5-microm MMAD). Regional volumes and RVent were assessed from xenon-133 equilibrium and washout, respectively. Six regions of interest per lung were established by dividing each lung into thirds by height and approximately half by width. The two lower regions of the left lung were not analyzed due to activity in the stomach. Remaining regions were categorized as central (two interior-most regions) and peripheral (eight exterior regions). RDep and RVent were computed for the eight peripheral regions. Tracheobronchial (TB) deposition was estimated for each of the peripheral regions as the difference between initial activity and decay-corrected 24-h retention or parenchymal deposition. RDep was computed as the fraction of material within a region normalized to regional volume. RVent for each region was determined by normalizing the xenon washout rate for that region by the total washout rate for the eight peripheral regions. Significant linear associations were found between RDep and RVent in both the healthy subjects and CF patients. In healthy subjects, RDep in the TB airways was positively associated with RVent (p = 0.03). In CF patients, RDep in the TB airways was negatively associated with RVent (p = 0.04) and RDep in the parenchyma was positively associated with RVent (p < 0.001). The initial pattern of RDep in the lung was not significantly associated with RVent in either group. These data suggest that significant coarse particle deposition may occur in the TB airways of poorly ventilated lung regions in CF patients, whereas, particle deposition in the TB airways of the healthy subjects follows ventilation.

Administration, Inhalation↗

PubMed1999

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume.

The regional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the lung volume at which the boluses are delivered. To evaluate the effect of end-inspiratory lung volume on aerosol bolus delivery, we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5-microm mass median aerodynamic diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at lung volumes of 50, 70, and 85% of total lung capacity (TLC) end inhalation. By gamma camera analysis, we found significantly greater deposition in the left (L) vs. right (R) lungs at the 70 and 85% TLC end inhalation; ratio of deposition in L to R lung, normalized to L-to-R ratio of lung volume (mean L/R), was 1.60 +/- 0.45 (SD) and 1. 96 +/- 0.72, respectively (P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 +/- 0.37, not significantly different from 1.0. These data suggest that the L and R lungs may be expanding nonuniformly at higher lung volumes. On the other hand, subsequent retention of deposited particles at 2 and 24 h postdeposition was independent of L/R at the various lung volumes. Thus asymmetric bolus ventilation for these very shallow boluses does not lead to significant increases in peripheral alveolar deposition. These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗

PubMed1999

In vivo characterization of the transitional bronchioles by aerosol-derived airway morphometry.

Effective airway dimensions (EADs) were determined in vivo by aerosol-derived airway morphometry as a function of volumetric lung depth (VLD) to identify and characterize, noninvasively, the caliber of the transitional bronchiole region of the human lung and to compare the EADs by age, gender, and disease. By logarithmically plotting EAD vs. VLD, two distinct regions of the lung emerged that were identified by characteristic line slopes. The intersection of proximal and distal segments was defined as VLD(trans) and associated EAD(trans). In our normal subjects (n = 20), VLD(trans) [345 +/- 83 (SD) ml] correlated significantly with anatomic dead space (224 +/- 34 ml) and end of phase II of single-breath nitrogen washout (360 +/- 53 ml). The corresponding EAD(trans) was 0.42 +/- 0. 07 mm, in agreement with other ex vivo measurements of the transitional bronchioles. VLD(trans) was smaller (216 +/- 64 ml) and EAD(trans) was larger (0.83 +/- 0.04 mm) in our patients with chronic obstructive pulmonary disease (n = 13). VLD(trans) increased with age for children (age 8-18 yr; P = 0.006, n = 26) and with total lung capacity for age 8-81 yr (P < 0.001, n = 61). This study extends the usefulness of aerosol-derived airway morphometry to in vivo measurements of the transitional bronchioles.

Adolescent↗

PubMed1999

Effect of aerosolized uridine-5'-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.

Administration, Inhalation↗

PubMed1999

Cellular and biochemical response of the human lung after intrapulmonary instillation of ferric oxide particles.

Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 microm-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. Our findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles. These findings may have relevance to the acute health effects associated with increased levels of ambient particulate air pollutants.

Adult↗

PubMed1999

Combinatorial libraries by portioning and mixing.

Combinatorial chemistry--due to its radically new synthetic methods--can be considered a forerunner of chemistry in the next century. One of the most important methods is the portioning-mixing (split-mix) synthesis which embodies the combinatorial principle. It is easily realized. Both manual and automatic devices have been described. Some features that contribute to its popularity include: it produces all possible structural combinations of the monomers, it has outstanding productivity, it leads to the formation of individual compounds in nearly equimolar quantities (affected by statistics and incomplete reactions), and it can be applied to all classes of organic compounds. Since an enormously large number of compounds can be produced in principle in a relatively short time, some practical considerations are discussed that can be useful in library design. Encoding organic libraries by peptide or nucleotide sequences or with binary tags are also described together with methods for tagging macroscopic support units with electronic chips, two dimensional bar codes or colored resin and capsule caps. Among the deconvolution strategies, the iteration method, positional scanning, omission libraries, the Selectide and the Pharmacopeia methods are mentioned. A collection of libraries prepared by portioning-mixing is also included in graphical format.

Organic Chemicals↗

PubMed1998

Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space.

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual's airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 micron mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04-0.43, coefficient of variation = 0.54) and increased with decreasing ADS (r = -0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 +/- 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 +/- 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 +/- 0. 44 and 1.82 +/- 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗

PubMed1998

Effect of ventilation distribution on aerosol bolus dispersion and recovery.

It has been speculated that convective ventilatory inhomogeneities are an important factor influencing aerosol bolus behavior in the compromised lung. Multiple-breath 133Xe washout (MBWXe) is a commonly accepted test of ventilation distribution. By comparing aerosol bolus parameters to MBWXe in 9 healthy subjects and 14 cystic fibrosis patients with mild-to-moderate airway obstruction, we have attempted to discern the effect of altered ventilation distribution on aerosol bolus dispersion and recovery. Aerosol boluses (150-ml width) were delivered to the volumetric penetrations of 250 and 500 ml. Similar tidal volumes (approximately 1.25 liters) and flow rates (0.4 l/s) were used for aerosol bolus and MBWXe maneuvers. Associations between bolus parameters and ventilation distribution were only observed in the cystic fibrosis patients. We conclude that aerosol bolus dispersion and recovery are both influenced by convective ventilatory inhomogeneities induced by airway obstruction in these patients.

Adolescent↗

PubMed1998

Retention and intracellular distribution of instilled iron oxide particles in human alveolar macrophages.

Bronchoalveolar lavage (BAL) was used to sample retention of particles within the alveolar macrophage (AM) compartment at various times from 1 to 91 d following intrapulmonary instillation of 2. 6-microm-diameter iron oxide (Fe2O3) particles in human subjects. Particles were cleared from the lavagable AM compartment in a biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term clearance half-time of 110 d, comparable to retention kinetics determined by more traditional methods. The intracellular distribution of particles within lavaged AMs was similar in bronchial and alveolar BAL fractions. AMs with high intracellular particle burdens disappeared from the lavagable phagocytic AM population disproportionately more rapidly (shorter clearance half-time) than did AMs with lower particle burdens, consistent with the occurrence of a particle redistribution phenomenon as previously described in similar studies in rats. The rates of AM disappearance from the various particle burden categories was generally slightly slower in bronchial fractions than in alveolar fractions. The instillation of particles induced a transient acute inflammatory response at 24 h postinstillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages in BAL fluids. This response was subclinical and was resolved within 4 d PI.

Administration, Inhalation↗

PubMed1996

Variability of fine particle deposition in healthy adults: effect of age and gender.

Recent epidemiologic studies suggest increased mortality among the elderly in association with particulate air pollution. We investigated the variability in fractional deposition (DF) of inhaled particles (2 microns mass median aerodynamic diameter [MMAD]) in 62 subjects with normal lung function, aged 18 to 80 yr. Each subject inhaled 2-microns monodisperse carnauba wax particles while following a breathing pattern previously determined by respiratory inductance plethysmography in that subject (i.e., particles inhaled) was determined by laser aerosol photometry and pneumotachometry at the mouth. DF (mean DF = 0.29 +/- 0.06 (ages 18 to 40 yr), 0.29 +/- 0.07 (ages 41 to 60 yr), and 0.26 +/- 0.06 (age over 60 yr) was independent of age. There was a tendency toward greater DF in female than in male subjects; DF = 0.30 +/- 0.07 (females) and 0.27 +/- 0.06 (males) (p = 0.06); however, because the males had 45% higher minute ventilations than the females, the deposition rate (Drate), or particles depositing per unit of time, was 30% greater in males than in females (p = 0.004). Multiple regression analysis showed that among all subjects, the variability in DF was best predicted by variability in the breathing period (T) associated with the pattern used to breathe the particles, and by the subject's specific airway resistance (sRAW). These results may prove useful in determining age- and gender-relative risks that may be associated with the inhalation of pollutant particles in ambient air.

Adolescent↗

PubMed1996

Effect of uridine 5'-triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis.

Cystic fibrosis (CF) is characterized by abnormal airway epithelial electrolyte transport leading to viscous airway secretions that are difficult to clear. By enhancing Cl- secretion onto and blocking Na+ absorption from the airway surface, treatment with aerosolized uridine 5'-triphosphate (UTP) plus amiloride may improve the rheology of airway secretions and enhance mucociliary clearance in patients with CF. After performing safety studies of aerosolized UTP/amiloride in adult patients with CF, we investigated the effects of inhaled vehicle and UTP/amiloride on mucociliary clearance of [99mTc] iron oxide particles from the airways of adult patients with CF (n = 14). We found no clinically significant adverse effects from inhalation of therapeutic doses of UTP/amiloride. Mean baseline peripheral clearance rates during the first 40 min of clearance measurements were significantly less in patients with CF than in normal subjects (mean +/- SE: 0.30 +/- 0.05 versus 0.54 +/- 0.07%/min, respectively; p = 0.01). Aerosolized UTP and amiloride in combination improved mucociliary clearance from the peripheral airways of the CF lungs to near normal values (0.51 +/- 0.09%/min; p = 0.04) during this period. These data support the concept for the use of UTP in combination with amiloride as therapy to improve clearance of secretions from the lungs of patients with CF.

Adult↗

PubMed1996

Acute safety and effects on mucociliary clearance of aerosolized uridine 5'-triphosphate +/- amiloride in normal human adults.

Impaired mucociliary clearance contributes to the pathophysiology of several airways diseases including cystic fibrosis, asthma, and chronic bronchitis. Extracellular triphosphate nucleotides (adenosine 5'-triphosphate [ATP], uridine 5'-triphosphate [UTP]) activate several components of the mucociliary escalator, suggesting they may have potential as therapeutic agents for airways diseases. We conducted initial (Phase I) studies of acute safety and efficacy of aerosolized UTP alone and in combination with aerosolized amiloride, the sodium channel blocker, in normal human volunteers. Safety was assessed by measurement of pulmonary function. Neither UTP alone nor in combination with amiloride caused any clinically significant adverse effects on airway mechanics, (subdivisions of) lung volumes, or gas exchange. Acute efficacy of UTP and amiloride alone and in combination, was assessed by measuring changes in the clearance of inhaled radiolabeled particles. A 2.5-fold increase in mucociliary clearance was seen in response to UTP alone and in combination with amiloride. We conclude that aerosolized UTP +/- amiloride clearly enhances mucociliary clearance without acute adverse effects in normal adults, and may have therapeutic potential to enhance airways clearance in diseases characterized by retained airways secretions.

Adult↗

PubMed1995

Measuring alveolar dimensions at total lung capacity by aerosol-derived airway morphometry.

A technique based on particle sedimentation, aerosol-derived airway morphometry (ADAM), was modified to investigate the morphometry of human lung airspaces at full inflation in 54 subjects with normal lung function, ages 18 to 69 years. The technique compares the recovered concentrations of monodisperse aerosol particles after gravitational settling during breath holds to determine effective airspace diameters (EADs) as a function of volumetric lung depth. The method is simple and non-invasive, requiring only several inhalations of aerosol to total lung capacity, breath holds at end inhalation and exhalation to residual volume (RV). The method is sensitive enough to detect differences in the smallest observed airspaces (EADmin) due to normal aging of healthy lungs when older subjects are compared to younger subjects. The average EADmin was larger (p = 0.009) for the oldest adults (293 +/- 54 um, s.d., 50-70 years, n = 13) at the deepest volumetric lung depth (near 40% of TLC into the lung) when compared to the youngest adults (250 +/- 38 um, s.d., 18-40 years, n = 22). The two groups had similar EADs at a depth of 5% of TLC. No gender difference in EADmin was found when comparing all males and females. No correlation was found between EADs and TLC implying number of alveolar airspaces rather than airspace size determines lung volume. The effects of changing the aerosol inhalation volume to TLC ratio was also investigated. Compared to the dichotomous Weibel morphometric model, the average EADs of 22 18-40 year old subjects were found to be equivalent near 1% TLC and 40% TLC, but were larger in size than the model between those extremes with a maximum difference occurring at approximately 3% TLC. This method appears to be extremely sensitive to in vivo changes in airspace dimensions and may prove useful in determining changes in these dimensions associated with normal lung development and early disease states.

Adolescent↗

PubMed1995

Dispersion of aerosol boluses in the human lung: dependence on lung volume, bolus volume, and gender.

The dispersion of aerosol boluses in the human lungs has been studied in health and disease, usually as a means of investigating convective mixing. However, there are limited data on the roles of critical factors, such as the volume of inhaled boluses, lung inflation, and gender on dispersion. To examine these factors, we measured the difference in volume variance between exhaled and inhaled boluses (sigma 2V) of a 0.5-micron aerosol in 11 healthy male and 12 healthy female subjects as a function of tidal volume (VT = 1,000 and 1,500 ml in females and 1,000 and 2,000 ml in males), bolus penetration volume (Vi at 250-ml increments over each VT), and bolus volume (target VBol = 75, 150, and 300 ml). Analysis of variance showed marginally significant gender effects (P = 0.073) on sigma 2V, with sigma 2V greater in males than in females. There was also a significant effect of VBol on sigma 2V (P < 0.001). A Vi-dependent mean volume shift between inhaled and exhaled boluses (delta V) was observed at all Vi except 500 ml. The observation of gender and VBol effects and the existence of a nonzero delta V suggest that convective mixing mechanisms other than longitudinal dispersion alone occur in the healthy lung. The lack of VT dependence suggests a minimal role of lung inflation above functional residual capacity on dispersion. The dependence of sigma 2V on Vi2 up to 1,750 ml and minimal VBol effects demonstrates that convective mixing processes continue far into the gas exchange regions of the lung and support a significant role for axial streaming.

Adolescent↗

PubMed1995

Retention of insoluble particles after local intrabronchial deposition in dogs.

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24-48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.

Animals↗