Search PubMed⌕ Search

Biomedical subjects

G K Adams

Publications and source records attributed to G K Adams.

At least 37 records · Page 2Linked to original sources
PubMed1986

The effect of bronchial obstruction on central airway deposition of a saline aerosol in patients with asthma.

We studied the effect of bronchial obstruction on central airway deposition of a 0.9% saline aerosol (MMAD = 1.12 micron; sigma g = 2.04) labeled with 99mTc sulfur colloid. Radioaerosol was inhaled on 2 occasions by 8 patients with asthma. The degree of bronchial obstruction at the time of radioaerosol inhalation was measured by the FEV1. Mucociliary clearance of the radioaerosol was used as an index of regional aerosol distribution, because clearance from the densely ciliated central airways occurs more rapidly than from the peripheral, nonciliated regions of the lung. Using the Weibel lung model and an average mucociliary clearance rate of 1 mm/min, we determined that clearance of the radioaerosol from lung generations 1 to 5 (central airways) would be complete within approximately 90 min. Central airway deposition was therefore quantified as radioaerosol clearance in 97 min using a gamma camera. On Days 1 and 2, clearance ranged from 0 to 45% and from 0 to 17%, respectively; FEV1 as a percent of predicted FEV1 ranged from 36 to 88 on Day 1, and on Day 2 from 54 to 92. Radioaerosol clearance was inversely correlated with the baseline FEV1, with r = -0.7673 (linear regression analysis; p less than 0.05). These data suggest that the magnitude of bronchial obstruction is a determinant of aerosol distribution within the lung of patients with asthma and that increased bronchial obstruction enhances central airway deposition of inhaled particles.

Aerosols↗
PubMed1985

The effect of inspiratory flow rate regulation on nebulizer output and on human airway response to methacholine aerosol.

Increased inspiratory flow rate has been demonstrated to decrease pulmonary deposition of inhaled aerosols. To study the effect of inspiratory flow rate regulation on the physiologic response to an active substance administered by aerosol, we compared the effect of high unregulated flow rate (66 to 212 L/min) with regulated low flow rate (20 to 35 L/min) on nebulizer output and on the pulmonary response to methacholine in patients with asthma. Four No. 646 DeVilbiss nebulizers were used in sequence with a nebulization dosimeter to deliver tenfold incremental concentrations of methacholine aerosol (mass median aerodynamic diameter = 1.52 micron; geometric standard deviation = 1.96) ranging from 0.025 to 25 mg/ml. When flow was unregulated, nebulizer output was not greater than when flow was regulated, but coefficients of variation of output were significantly greater (p less than 0.01). The PD20 on the two unregulated days was significantly different (p = 0.01), whereas the PD20 on the two flow regulated days was not significantly different (p greater than 0.05). We conclude that regulation of inspiratory flow rate at rates within the range of tidal breathing significantly decreases variability in nebulizer output and variation of pulmonary responses to methacholine challenge.

Aerosols↗
PubMed1985

Effect of repeated antigen exposure on antigen-and mediator-induced bronchospasm in sheep.

We studied the effects of repeated exposures of antigen on airway reactivity to mediators of anaphylaxis and immediate response to the antigen. Seven antigen-sensitive sheep were exposed to aerosols of Ascaris suum antigen 5 times biweekly; a control group of seven sheep underwent the same exposure regimen with saline vehicle. Sheep were assigned to experimental (Ascaris) or control groups so the distribution of animals with regard to bronchial reactivity to mediators was about the same. Airway reactivity was assessed by determining the effects of aerosolized histamine (10-1,000 micrograms), prostaglandin F2 alpha (PGF2 alpha, 10-300 micrograms), and a stable analogue of thromboxane A2 (U-46619, 1-100 micrograms) on lung resistance (RL) and dynamic lung compliance (Cdyn). Before treatment, experimental and control groups showed similar changes in RL and Cdyn, with analogue greater than histamine greater than PGF2 alpha. At the highest dose of each agonist, mean increases in RL were 50, 123, and 29%, respectively, and mean decreases in Cdyn were 21, 45, and 12%. During the first 15-min exposures to antigen aerosol, mean RL had increased by 125% and Cdyn decreased by 38% of base-line values; hyperinflation following the exposures reduced the changes to 56 and 31%, respectively. Changes in RL and Cdyn during the final antigen exposures and following postexposure hyperinflation were reduced significantly (P less than 0.05) compared with the initial exposures. Baseline RL and Cdyn before and after the exposures to antigen or saline were not significantly different. Airway reactivity to histamine, PGF2 alpha, or analogue was not significantly altered in these atropinized animals over the range of doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1985

Increased in vitro airway responsiveness in sheep following repeated exposure to antigen in vivo.

We have studied the effect of repeated in vivo antigen exposure on in vitro airway responsiveness in sensitized sheep. Fourteen sheep underwent five biweekly exposures to aerosolized Ascaris suum antigen or saline. Following this exposure regimen, the animals were killed and tracheal smooth muscle and lung parenchymal strips were prepared for in vitro studies of isometric contraction in response to histamine, methacholine, prostaglandin F2 alpha, and a thromboxane A2 analogue. No alteration in tracheal smooth muscle responsiveness was observed between saline- and antigen-exposed tissue. In contrast, by use of lung parenchymal strips as an index of peripheral airway responsiveness, significant increases in responsiveness to histamine and a thromboxane A2 analogue (10(-6) and 10(-5) M) were observed in antigen-exposed tissue compared with saline controls. These results demonstrate that repeated antigen exposure in vivo selectively increase the responsiveness of peripheral lung smooth muscle to certain chemical mediators of anaphylaxis.

Animals↗
PubMed1985

Indomethacin enhances response of human bronchus to antigen.

We studied the effect of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid metabolism, on antigen-induced contraction of passively sensitized human bronchus in vitro. Incubation with indomethacin (3 microM) prior to antigen challenge produced significant enhancement of both the early (histamine-dependent) and late (SRS-A-dependent) phases of the contraction. Indomethacin potentiated anaphylactic histamine release from the bronchial tissue by approximately twofold but had no significant effect on basal tone or responsiveness to exogenous histamine. These data suggest that inhibition of the cyclooxygenase pathway results in potentiation of antigen-induced constriction of human bronchus principally through enhanced release of anaphylactic mediators from airway mast cells.

Anaphylaxis↗
PubMed1983

Comparative studies of human basophils and mast cells.

Atopic disease in humans results primarily from the activity of tissue mast cells and circulating basophils. These two very similar cell types have recently been purified to near homogeneity and studies have begun to identify the biochemical mechanisms of mediator release, to explore the effects of pharmacologic manipulation of the response, and to determine unambiguously which mediators are derived from mast cells and basophils. This report will review studies examining various parameters of histamine release, the role of cyclic AMP in histamine release, and the production of arachidonic acid metabolites and their pharmacologic modulation.

Animals↗
PubMed1983

Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells.

Purified human lung mast cells released histamine, leukotrienes, prostaglandin (PG) D2, thromboxane B2 (TxB2), and PGF2 alpha in response to anti-IgE stimulation. Incubation of the cells for 24 h with 10(-6) M dexamethasone, a treatment that inhibits mediator release from human basophils, had no effect on the release of these mediators from mast cells. Dexamethasone treatment of human lung fragments led to little or no inhibition of anti-IgE-induced release of the mast cell-derived mediator, histamine, but produced a significant inhibition of the release of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. As was the case with purified mast cells, the steroid did not inhibit the release of PGD2 or TxB2 from human lung fragments. Comparison of the quantities of PGD2 and TxB2 produced by purified cells and human lung fragments reveals that the mast cells produce quantities of these metabolites sufficient to account for the entire amount produced by challenged lung fragments. Dexamethasone inhibited spontaneous release from lung fragments of all cyclooxygenase products measured. These results suggest that the human lung parenchymal mast cell phospholipase is not inhibited by dexamethasone, whereas other phospholipase(s) in the lung are inhibited by the steroid. These results may be useful in explaining the resistance of acute allergic reactions, including anaphylaxis, to steroids, despite the potent antiinflammatory activity of steroids on subacute and chronic inflammation, such as in bronchial asthma, which may be initiated by IgE-dependent mechanisms.

Autacoids↗
PubMed1982

Generation of leukotrienes by purified human lung mast cells.

Although mediator release from mast cells and basophils plays a central role in the pathogenesis of human allergic disease, biochemical studies have been restricted to rat peritoneal mast cells and basophilic leukemia cells because they could be easily purified. We have used two new techniques of cell separation to purify human lung mast cells to 98% homogeneity. Lung cell suspensions were obtained by dispersion of chopped lung tissue with proteolytic enzymes. Mast cells were then purified from the suspensions by countercurrent centrifugal elutriation and affinity chromatography. The purified mast cells released both histamine and slow-reacting substance of anaphylaxis (SRS-A) (leukotriene C and D) during stimulation with goat anti-human IgE antibody. Moreover, these preparations were able to generate significant quantities of SRS-A (32 +/- 7 x 10(-17) LTD mole-equivalents/mast cell) at all stages of purification, indicating that a secondary cell is not necessary for the antigen-induced release of SRS.

Animals↗
PubMed1979

Effects of temperature, relative humidity, and mode of breathing on canine airway secretions.

Airway secretions were collected from the upper trachea of eight healthy nosebreathing mongrel dogs under general anesthesia, and the electrolytes and osmolality of these secretions were determined. Compared to plasma, secretions contained 15% higher Na+ and 33% higher Cl-, were 18% higher in osmolality, but had a lower Na+/Cl- throughout the 6-h experiments. When six nose-breathing dogs were exposed to air at 28.5 degrees C and 95% relative humidity, secretion osmolality became lower, but Na+/Cl- remained unchanged. In four other dogs, secretions approached the osmolality of plasma when inspired air was at 36.4 degrees C and 100% relative humidity. These secretions contained 22% higher Cl- and a lower Na+/Cl- than plasma. The differences between airway secretions and interstitial fluid suggest that secretions are formed by active Cl- transport. In another four dogs, secretion osmolality was higher with mouth breathing than breathing through the nose. Inasmuch as humidified and warmed air lowered and mouth breathing raised the osmolality of airway secretions, we postulate that the hyperosmolality of secretions results from water loss from the airway surface during conditioning of inspired air.

Animals↗
PubMed1979

Enrichment of albumin and IgG in the airway secretions of dogs breathing ozone.

A study was undertaken of the acute effect of the inhalation of ozone (1.0-1.5 ppm) on the concentration of proteins in the airway secretions harvested from the trachea of intact anesthetized dogs. Secretions were first collected during a control day during which room air was breathed. The dogs breathed ozone (1.0-1.5 ppm) on a second day. This protocol permitted each dog to serve as its own control. During the inhalation of ozone the concentration of total aqueous-soluble proteins, as well as of albumin and IgG were not significantly effected. However, when expressed as a percentage of total protein, both albumin and IgG were significantly enriched in the secretions. The quantitative changes of certain proteins in airway secretions may be an important reflection of the pulmonary response to ozone.

Administration, Intranasal↗
PubMed1979

In vitro studies of antigen-induced bronchospasm: effect of antihistamine and SRS-A antagonist on response of sensitized guinea pig and human airways to antigen.

Exposure of sensitized guinea pig tracheal rings or human bronchial strips to specific antigen in vitro resulted in a rapidly developing, prolonged contraction that was resistant to washing. Treatment of the tissue with diphenhydramine, a histamine H1 antagonist, before antigen delayed the onset and decreased the amplitude of the initial phase of the contraction but did not reduce the duration. Diphenhydramine treatment after development of the contraction did not relax the airway tissue. Antigen-induced histamine release from guinea pig trachea and from human bronchus was complete within the initial 15% of the duration of the contraction. Treatment of sensitized airway tissue with FPL 55712, a SRS-A antagonist, before antigen selectively inhibited the prolonged phase of the response. FPL 55712 administration after the development of antigen-induced contraction resulted in relaxation. These data suggest that both histamine and SRS-A are involved in the response of sensitized guinea pig and human airway tissue to antigen, with histamine mediating the early phase of the contraction and SRS-A primarily mediating the protracted phase.

Animals↗
PubMed1978

Nasal mucociliary clearance in man.

Nasal mucociliary clearance was measured in healthy young human subjects and tracheal clearance in the experimental animal under a wide variety of conditions. There is a broad range of clearance rates whether at standard ambient conditions (23 degrees C, 50% relative humidity) or in the face of a number of environmental variables. The degree to which those differences are attributable to the effectiveness of ciliary beating or the character of airway secretions is not known. Studies of tracheobronchial secretions simultaneous with clearance measurement in the anaesthetized dog have not yet provided a definite answer. Variations in upper respiratory defence mechanisms may bear some relationship to the aetiology of small airway disease in the lungs.

Adult↗
PubMed1978

Tracheobronchial secretions collected from intact dogs. I. Protein and mucous glycoprotein composition.

Tracheobronchial secretions (TBS) were collected in situ from intact, anesthetized dogs, and the protein composition and distribution were studied. TBS were separated into supernatant and pellet phases by centrifugation. The supernatant phase comprised 85%, by weight, of the secretory mixture; yet it contained only 58% of the total protein. Peptides of apparent molecular weights ranging from 16,000 to 154,000 daltons were present in the supernatant phase. Electrophoretic and immunochemical comparisons with canine serum suggested that certain of the peptides were of plasma origin including albumin, IgG, IgA, and IgM. Albumin and IgG comprised approximately 70% of the supernatant phase protein. Three percent of the total TBS protein was contributed by the peptide portion of mucous glycoproteins (mucins), and 97% of the mucin protein separated into the pellet phase. When compared to mucus collected from a canine tracheal pouch, TBS was less concentrated in mucins, and differences were observed in electrophoretic profiles between the two samples.

Animals↗