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Biomedical subjects

A Wanner

Publications and source records attributed to A Wanner.

At least 19 recordsLinked to original sources
PubMed1995

Hydrogen peroxide-scavenging properties of sheep airway mucus.

Reactive oxygen species released from luminal phagocytes in the airway can potentially injure the airway epithelium. Naturally occurring oxygen radical scavengers must therefore exist to protect the epithelium. This study was designed to determine whether the high-molecular-weight fraction of normal sheep tracheal mucus has hydrogen peroxide (H2O2)-scavenging activity. Lyophilized mucus from 10 sheep was reconstituted in phosphate-buffered saline (PBS) or Krebs-Henseleit buffer. H2O2 was added to these mucus samples to a final concentration of 15 microM, and the level of H2O2 remaining was measured over a 10 min period. From a zero-time level of 17 +/- 1.8 microM (mean +/- SD), the H2O2 concentration fell within 10 min to 8 +/- 1.7 microM in 0.05%; to 3.9 +/- 2.2 microM in 0.1%; to 2.6 +/- 2.4 microM in 0.2%; and to 1.2 +/- 1.5 microM in 0.4% mucus reconstituted in PBS. The results obtained in Krebs-Henseleit buffer were similar. The disappearance of H2O2 was not due to the transformation into hydroxyl radicals. Heat and acid denaturation and cleavage of carbohydrate-free peptides from glycoproteins by pronase E treatment abolished the scavenging potential. Fractionation of 0.4% mucus samples according to molecular weight by gel filtration revealed that only one fraction with proteins of M(r) > 110 kD contained the active scavenger. Polyacrylamide gel electrophoresis and lectin blotting with Ulex europaeus I (UEAI) showed that both the whole mucus and the actively scavenging gel filtration fraction contained a glycoprotein that comigrated with a 205 kD molecular weight marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Endothelin-1 promotes mitogenesis in airway smooth muscle cells.

Endothelin exists as three isoforms (ET-1, ET-2, and ET-3) and exhibits vasoconstricting, bronchoconstricting, and growth-promoting properties in vascular smooth muscle. In the airways, ET-1 immunoreactivity and mRNA have been detected and localized to the epithelium, smooth muscle, and endothelium in different species, including humans. It has been suggested that ET-1 may have a role in the airway smooth muscle hyperplasia and hypertrophy seen in patients with bronchial asthma. We studied ovine airway smooth muscle cells (SMC) in vitro and showed saturable binding of [125I]ET-1 with a dissociation constant (Kd) of 0.4 nM and high affinity binding sites (Bmax) for ET-1 (104 fmol/10(6) cells). This binding was functional as ET-1 promoted mitogenesis of these muscle cells as measured by increased cell number in the absence of serum. Twenty-four hours after exposing the cells to graded doses of ET-1 from 1 pM to 1 microM, cell number increased significantly over control in a dose-dependent manner. ET-1 also enhanced the transient expression of c-fos mRNA by 2.5-fold over control, with maximal expression occurring at 30 min. These observations provide evidence that: (1) airway SMC possess high affinity binding sites for ET-1, and (2) ET-1 is mitogenic for airway SMC as determined by increased cell number and amplification of c-fos mRNA expression. ET-1 may have a fundamental role in influencing the growth of smooth muscle in the airways.

Animals↗
PubMed1993

Protein kinase C-dependent phosphorylation of a ciliary membrane protein and inhibition of ciliary beating.

The present study examined whether protein kinase C phosphorylated a ciliary protein and whether this phosphorylation event was temporally correlated with a decrease in ciliary beat frequency. Activation of protein kinase C decreased ciliary beat frequency of sheep tracheal epithelium, an effect fully blockable by pretreatment of the tissue pieces with H-7, a protein kinase inhibitor. Using cilia removed from these epithelial surfaces and incubated in solutions containing stimulators of protein kinase C along with [gamma-32P]ATP or [gamma-35S]ATP, a single protein target of ciliary protein kinase C activity was identified. The protein is a polypeptide of molecular mass 37 kDa (p37) as estimated by SDS-polyacrylamide gel electrophoresis. Protein kinase C dependency of p37 phosphorylation was proven by showing that Calphostin C, a specific protein kinase C inhibitor, blocked label incorporation into p37 completely, and by demonstrating that purified protein kinase C phosphorylated p37. Inhibitors of cAMP-dependent kinase and calcium/calmodulin-dependent kinase did not change the phosphorylation of p37 in the presence of protein kinase C activators. p37 was recovered in a Triton X-100-extractable fraction of this ciliary preparation, suggesting that p37 is membrane associated. This hypothesis was further supported by the fact that p37 was present in a pellet representing reconstituted membranes. Thin-layer electrophoresis revealed that p37 was phosphorylated on serine and tyrosine residues, suggesting that the activation of protein kinase C also stimulated tyrosine kinase activity. p37 did not precipitate with annexin I or II antibodies. These results show that sheep tracheal cilia contain protein kinase C activity and that activated protein kinase C phosphorylates a membrane-associated ovine ciliary target, an effect temporally related to a protein kinase C-mediated decrease in ciliary beat frequency.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Microvascular and macrovascular endothelial cells produce different constrictor substances.

The media from cultured microvascular and macrovascular endothelial cells (conditioned media, CM) were collected and tested for constrictor activity in sheep coronary artery rings and tracheal smooth muscle strips in vitro (isometric force), expressed as percentage of contraction produced by 80 mM KCl. Both microvascular (micro) and macrovascular (macro) CM caused a sustained slow-onset contraction (P less than 0.05) of the coronary artery rings by 71 +/- 10% (micro; n = 7) and 67 +/- 8% (macro; n = 6) and tracheal smooth muscle strips by 33 +/- 14% (micro; n = 6) and 34 +/- 6% (macro; n = 11); the calcium antagonist gallopamil (10(-7) M) attenuated these effects by 25-55%. Unconditioned medium and medium conditioned by cultured tracheal smooth muscle cells had no constrictor activity on coronary artery rings or tracheal smooth muscle strips. Synthetic endothelin (ET-1) also produced contraction of coronary artery rings and tracheal smooth muscle strips. The mean levels of ET-1 measured by radioimmunoassay were 1,200 pg/ml in the macro CM and 33 pg/ml in the micro CM. Depleting macro CM of ET-1 by affinity columns constructed with protein A agarose and anti-ET-1 antibody removed the contractile activity for coronary artery rings and tracheal smooth muscle strips. Thus ET-1 did not appear to be the contractile substance in the micro CM. Preliminary characterization of the contractile substance in micro CM revealed that it was heat stable, had a molecular weight of less than 10,000, was inactivated by trypsin, and retained its activity after two cycles of freeze-thawing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Systemic pilocarpine increases deposition of and decreases responsiveness to inhaled carbachol in sheep.

The purpose of this study was to determine whether excessive airway secretions could serve as a barrier function against inhaled particulate matter. To increase airway secretions, six conscious sheep were treated with pilocarpine (0.8 mg/kg i.v.). Pilocarpine increased pulmonary resistance (RL) and total aerosol deposition within five breaths (AD5) as determined by the rebreathing of an inert monodisperse aerosol. When RL had returned to baseline, AD5 remained elevated [21 +/- 2% (SE), P < 0.05] and tracheal secretions were increased (237 +/- 77%, P < 0.05) above the values before pilocarpine administration. A carbachol aerosol dose-response curve was carried out at this time and compared with a control carbachol dose-response curve by calculating the dose of carbachol required to increase RL by 400% (PD400). Mean PD400 was increased postpilocarpine by 53 +/- 18 (P < 0.05) and 85 +/- 25% (P < 0.05) when normalized for increased aerosol deposition. Thus, pilocarpine decreased airway responsiveness to inhaled carbachol despite increasing aerosol deposition. The pilocarpine-induced airway hyporesponsiveness to inhaled carbachol is consistent with the hypothesis that excessive secretions have a protective role in the airways.

Administration, Inhalation↗
PubMed1992

Impairment of airway mucociliary transport by Pseudomonas aeruginosa products. Role of oxygen radicals.

We previously showed that the supernatant of a Pseudomonas aeruginosa (PA) culture and its constituents pyocyanin and 1-hydroxyphenazine inhibit ciliary activity of dispersed tracheal epithelial cells in vitro via the generation of oxygen radicals by phagocytes. In the present study, we wished to determine if tracheal mucus velocity (TMV) is also impaired by PA supernatant and if oxygen radicals have a mediating role. In conscious sheep, TMV (measured with a radiographic method) was determined before and serially following aerosol challenge with the cell-free supernatant of a PA culture or unconditioned culture medium (control). TMV decreased from a mean (+/- SEM) baseline of 6.7 +/- 1.1 mm/min (n = 6) by 29, 35, and 25% at 0.5, 3, and 24 h after challenge, respectively (p < 0.05), and returned to baseline 1 wk later (-6%, p = NS). Control medium had no effect on TMV (maximum decrease by 15% at 0.5 h). Aerosolized catalase blunted the effect of PA supernatant on TMV. To determine if the impairment of TMV involved ciliary inhibition, tissues were mounted in a chamber and ciliary beat frequency (CBF) and surface liquid velocity (SLV) were measured with a microscopic method. PA supernatant decreased both CBF (maximum mean decrease 12%; n = 5, p < 0.05) and SLV (maximum mean decrease 78%; n = 5, p < 0.05) in a dose-dependent fashion, with a correlation between the two parameters; these effects were blocked by catalase.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia.

To study the effect of the inflammatory mediator hydrogen peroxide (H2O2) on airway ciliary activity, we measured ciliary beat frequency (CBF) in cultured tracheal explants from sheep. Addition of H2O2 (10(-8) to 10(-4) M) produced a concentration-dependent mean (+/- SEM) decrease in CBF between 11.1 +/- 0.4% (P less than 0.01) and 100 +/- 0% (P less than 0.001); at each concentration, the maximal effect was reached by 20 to 25 min. Between 10(-8) and 10(-6) M H2O2, the decrease in CBF was reversible, lactate dehydrogenase (LDH) release was not significantly increased, and major morphologic lesions were not seen. At higher concentrations of H2O2, incomplete recovery of CBF (10(-5) M) or irreversible ciliostasis (10(-4) M) developed, and a significant increase in LDH and morphologic lesions were present. Catalase (2,000 U/ml) and H-7 (10(-5) M), a protein kinase inhibitor, abolished cilioinhibition produced by H2O2 at 10(-6) M and lower concentrations but not at 10(-5) M and higher concentrations. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, caused a dose-dependent (10(-11) to 10(-5) M), reversible decrease in CBF; this effect was abolished by H-7. We suggest that at nonlethal concentrations, H2O2 inhibits the beat frequency of airway epithelial cilia reversibly, through the activation of second messengers, including protein kinase C. This mechanism might contribute to the previously demonstrated impairment of mucociliary clearance in airway inflammation.

Animals↗
PubMed1991

Effect of histamine on tracheal mucosal perfusion, water content and airway smooth muscle in sheep.

We examined the response of tracheal mucosal blood flow normalized for systemic arterial pressure (Qtrn), water content (VH20) and luminal dead space (Vtr) to nebulized histamine in intact, lightly anesthetized sheep. Nebulized histamine produced rapid increases in mean Qtrn (+84%) and VH2O (+85%), and a decrease in mean Vtr (-17%) (P less than 0.05) within 5 min post completion of challenge. Mean Vtr rapidly returned to baseline, while mean Qtrn and VH2O remained elevated for 60 and 90 min after challenge, respectively. Pretreatment with chlorpheniramine (H1-antagonist) blocked the changes in Vtr and VH2O, and attenuated the increase in Qtrn. Metiamide (H2-antagonist) pretreatment abolished the increase in Qtrn and blunted the increase in VH2O, but had no effect on the decrease in VTR. 2-methylhistamine (H1-agonist) decreased mean Qtrn and Vtr (P less than 0.05) and dimaprit (H2-agonist) increased mean Qtrn (P less than 0.05) without changing Vtr. Neither 2-methylhistamine nor dimaprit significantly altered VH2O. Atropine blocked histamine induced decreases in Vtr and slightly attenuated the increases in Qtrn and VH2O. Thus, histamine increased airway smooth muscle tone and mucosal water content principally via H1 receptors, and mucosal perfusion via H2 receptors. The airway smooth muscle contraction involved muscarinic pathways.

Animals↗
PubMed1991

Effects of P. aeruginosa-derived bacterial products on tracheal ciliary function: role of O2 radicals.

The purpose of this investigation was to evaluate the effects of bacterial products derived from Pseudomonas aeruginosa on the function of airway cilia and to assess the role of phagocytes and oxygen radicals in the observed responses. Ciliary beat frequency (CBF) was measured in a perfusion chamber with a microscopic technique using tracheal epithelial cells obtained from normal sheep by brush biopsy (70% epithelial cells, 18% macrophages, 11% neutrophils). Baseline CBF ranged between 678 and 1,126 min-1. After 20 min of perfusion with the cell free supernatant of P. aeruginosa culture (mucoid strain), a concentration-dependent depression of CBF was observed with a 58% inhibition at a 1:1 dilution (P less than 0.05). The P. aeruginosa-derived products pyocyanin and 1-hydroxyphenazine also decreased CBF in a dose-related fashion. The cilion-inhibitory effects of the supernatant and bacterial products were markedly attenuated after centrifugation of the brush preparation (80% epithelial cells, 16.5% macrophages, 3.5% neutrophils). Glucose/glucose oxidase also caused a rapid, concentration-dependent cilioinhibition or ciliostasis. Catalase blocked or attenuated the ciliary effects of the supernatant, bacterial products and glucose/glucose oxidase. Thus bacterial products released from P. aeruginosa impaired ciliary activity by a pathway which involved neutrophils and was mediated by toxic oxygen radicals.

Animals↗
PubMed1991

Independent control of mucosal and total airway blood flow during hypoxemia.

In the larger airways, the blood circulation forms a subepithelial (mucosal) and outer (peribronchial) microvascular network. This raises the possibility that blood flow in these two networks is regulated independently. We used hypoxemia as a stimulus to induce changes in tracheal mucosal blood flow normalized for systemic arterial pressure (Qtr n) measured with an inert soluble gas technique and total bronchial blood flow (Qbr) and normalized Qbr (Qbrn) measured with an electromagnetic flow probe in anesthetized sheep. Fifteen minutes of hypoxemia [PO2 40 +/- 7 (SD) Torr] decreased mean Qtr n from 1.1 +/- 0.4 to 0.8 +/- 0.4 ml.min-1.mmHg-1.10(2) (-27%; P less than 0.05; n = 7) and increased mean Qbr n from 12.1 +/- 3.2 to 17.1 +/- 5.4 ml.min-1.mmHg-1.10(2) (+41%; P less than 0.05; n = 6). The rise in Qbr correlated with cardiac output (r = 0.68; P less than 0.05). Phentolamine pretreatment (0.1 mg/kg iv) blunted the hypoxemia-related decrease of mean Qtr n (-8%; P = NS). Tyramine (2.5 mg) applied locally to the trachea decreased mean Qtr n significantly after 30 and 45 min by 31 and 19%, respectively (P less than 0.05). 6-Hydroxydopamine (0.2 mg 4 times for 1 h locally applied) prevented the hypoxemia-induced as well as local tyramine-induced decrease in mean Qtr n (0 and 0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Morphometry of the subepithelial circulation in sheep airways. Effect of vascular congestion.

In order to quantitate the subepithelial microvascular volume and its relation to the airway lumen, we conducted a morphometric analysis of the vascular compartment in the wall of the trachea (within a 55-microns depth from the epithelial basement membrane) and of 1.0 and 0.5-mm bronchioles of sheep. The lungs were fixed by bronchial and pulmonary artery perfusion with glutaraldehyde under three experimental conditions: (1) bronchial artery pressure, 100 mm Hg pulmonary artery pressure, 20 mm Hg (control); (2) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pulmonary hypertension, PH); (3) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pharmacologic vasodilation with sodium nitroprusside, PH + V). Venous pressures were atmospheric. Under control conditions, the microvascular volume fraction comprised 12, 16, and 15% of the subepithelial tissue in the trachea and 1-mm and 0.5-mm bronchioles, respectively. PH increased the microvascular volume fraction in the bronchioles (p less than 0.05), but it had no effect on the microvasculature in the trachea. PH + V approximately doubled the microvascular volume fraction in the trachea and the bronchioles. PH increased the mean wall thickness, and PH and PH + V decreased the airway cross-sectional area in the 1-mm bronchioles. These observations demonstrate that the microvasculature constitutes a considerable volume fraction of the subepithelial airway tissue and that vascular congestion can narrow the bronchiolar lumen.

Animals↗
PubMed1991

Airway blood flow modifies allergic airway smooth muscle contraction.

We tested the hypothesis that airway perfusion modifies the contractile response of airway smooth muscle to allergen challenge by influencing the clearance of locally released spasmogens. In six intact, lightly sedated, sheep allergic to Ascaris suum, we measured tracheal mucosal blood flow (Qtr) with a soluble gas uptake method and tracheal dead space (Vtr), an index of airway smooth muscle tone, by helium dilution before and serially after local aerosol challenge with A. suum extract or ragweed extract (control). The former challenge was repeated during continuous intravenous infusion of either vasopressin or nitroglycerin, which by themselves had no effect on Vtr and decreased and increased Qtr, respectively. Ragweed had no effect on Qtr and Vtr, whereas A. suum increased mean (+/- SE) Qtr by 111 +/- 31% (p less than 0.05) and decreased mean Vtr by 15 +/- 2% (p less than 0.05) immediately after challenge, with Qtr returning to baseline by 40 min and Vtr by 80 min. Vasopressin infusion prevented the A. suum-induced increase in Qtr and prolonged the decrease in mean Vtr (p less than 0.05). During nitroglycerin infusion, A. suum failed to alter Qtr or Vtr. Vasopressin and nitroglycerin had no effect on the contractile responses of tracheal smooth muscle to A. suum in vitro. These results indicate that the effects of vasopressin and nitroglycerin on antigen-induced airway smooth muscle contraction in vivo were due to alterations in airway blood flow rather than to alterations in the release of or airway smooth muscle responsiveness to chemical mediators.

Acetylcholine↗
PubMed1991

Lipid mediators contribute to oxygen-radical-induced airway responses in sheep.

The purpose of this study was to determine if the bronchoconstriction and airway hyperresponsiveness (AHR) resulting from aerosolized xanthine (x; 0.1%)-xanthine oxidase (xo; 4.1 U) and the subsequent production of oxygen radicals is mediated by the secondary generation of lipid mediators. In seven conscious sheep, specific lung resistance (SRL) was measured before and after x-xo challenge; approximately 30 min later when SRL had returned to baseline, airway responsiveness to carbachol was determined from dose-response curves by calculating the cumulative provocating dose of carbachol in breath units (BU, defined as one breath of a 1% wt/vol carbachol solution) that increased SRL 400% over baseline (PD400). Inhaled x-xo caused in immediate increase in SRL of 162 +/- 36% (mean +/- SE; p less than 0.05) over baseline and decreased PD400 from a baseline value of 32.5 +/- 5.0 to 16.6 +/- 1.7 BU (p less than 0.05). Pretreatment with the H2O2 scavenger, catalase (CAT,; 38 mg aerosol), methylprednisolone succinate (MS; 1 mg/kg given intravenously), the cyclooxygenase inhibitor, indomethacin (IND; 2 mg/kg given intravenously), and the PAF antagonist, WEB-2086 (3 mg/kg given intravenously) all attenuated the x-xo-induced increase in SRL (p less than 0.05); the leukotriene D4 antagonist, MK-571 (5 mg by aerosol) had no effect. All agents inhibited the x-xo-induced decrease in PD400: mean BUs were 27 after CAT, 32 after WEB-2086, 34 after IND, 31 after MS, and 25 after MK-571 (all p less than 0.05 versus x-xo alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mucociliary interaction in vitro: effects of physiological and inflammatory stimuli.

Mucociliary transport in the airways is governed by the interaction between ciliary activity and the depth and rheological properties of the liquids (mucus) covering the epithelial surface. A change in one of these parameters may not predict the direction and magnitude of a concomitant change in mucociliary transport. We therefore determined the effects of physiological (neurotransmitters) and pathological (inflammatory mediators) stimuli on ciliary beat frequency (CBF), surface liquid velocity (SLV), surface liquid depth (SLD), and viscoelasticity of mucus in pieces of sheep trachea (n = 5 for each treatment) mounted in a chamber such that the submucosal side was bathed with Krebs-Henseleit perfusate (KH) and the luminal side was exposed to conditioned air. SLV, SLD, and CBF were measured with a microscope provided with an electronic micrometer and strobe light. Apparent viscosity and shear elastic modulus were measured with a microcapillary method using mucus collected at the downstream end of the preparation. Control CBF, SLV, and SLD were 11.6 +/- 0.4 (SE) Hz, 91 +/- 8 micron/s, and 33 +/- 5 microns, respectively, at base line and did not change during KH perfusion for 100 min. Perfusion with both acetylcholine and epinephrine (10(-5) to 10(-3) M) produced concentration-dependent increases in mean CBF (maximum increases at 10(-3) M of 16 and 9%, P less than 0.05), whereas only acetylcholine increased mean SLV (+56% at 10(-3) M, P less than 0.05). Perfusion with platelet-activating factor (10(-7) to 10(-5) M) decreased both mean CBF and SLV in a dose-dependent fashion (-6 and -63% at 10(-5) M, P less than 0.05), whereas antigen perfusion (1:60 dilution) increased mean CBF (+10%, P less than 0.05) but decreased SLV (-47%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Effect of ozone on the postnatal development of lamb mucociliary apparatus.

We determined whether exposure to O3 early in the postnatal period impairs the normal development of the mucociliary apparatus in lambs and whether such changes lead to prolonged abnormalities in mucociliary function. Lambs were exposed to air (controls) or to 1 ppm O3 for 4 h/day for 5 days during the 1st wk of life. Tracheal mucus velocity (TMV), a marker of lung mucociliary clearance, was measured in vivo at birth (0 wk) and up to 24 wk later, and tracheal secretory function was measured (in vitro) and the morphology of the tracheal mucosa was determined at 0 and 2 wk in both groups. In the control group, TMV increased 94% from 0 to 2 wk (P less than 0.05), continued to increase until reaching a plateau at 8 wk, and then remained constant from 8 to 24 wk. In contrast, O3-exposed lambs showed a 24% decrease in TMV from 0 to 2 wk (P less than 0.05 vs. control), and throughout the remaining time TMV remained below (P less than 0.05) that observed in control lambs. O3 exposure partially prevented the age-dependent decrease in basal secretion of tracheal macromolecules normally observed between 0 and 2 wk. These changes in secretory function were associated with a significant increase in tissue conductance (37%, P less than 0.05 vs. 0 wk), predominantly the result of active chloride secretion. The functional changes induced by O3 were associated with a retardation of the normal morphological development of the tracheal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Persistence of enhanced aerosol deposition in the lung after recovery from carbachol-induced airway obstruction.

Time course recovery from induced airway obstruction by carbachol infusion (CI; 0.2 microgram.kg-1.min-1 for 40 min), carbachol aerosol (CA; 10 breaths of 2% solution), and histamine aerosol (HA; 25-50 breaths of 5% solution) challenge was investigated in conscious sheep (n = 6 each). Total lung aerosol deposition and airway caliber as assessed by pulmonary airflow resistance (RL) were measured every 20-30 min up to 4 h after the challenges. Aerosol deposition was measured by monitoring aerosol concentration continuously with a laser aerosol photometer while the sheep rebreathed 1.0-micron-diam inert oil droplets delivered by a 0.25-liter bag-in-box system driven by a respiratory pump at a breathing frequency of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as percentage of the initial aerosol concentration was determined and used as an aerosol deposition index. Percent changes in AD5 from baseline were compared with corresponding changes in RL. Both RL and AD5 increased after Cl, CA, and HA: 192-477% for RL and 23-44% for AD5 (P less than 0.05). Mean RL return to baseline values 1 h after CI and HA and 2 h after CA. Mean AD5 returned to baseline at 1 h post-HA. In contrast, mean AD5 remained elevated for 2-4 h after CI and CA (P less than 0.05), and the increased AD5 could not be reversed by a bronchodilator aerosol. The persistence of enhanced aerosol deposition long after the return of RL to baseline suggests that complete recovery of airway conditions after CI and CA takes much longer than predicted by RL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗