Biomedical subjects

N F Adkinson

Publications and source records attributed to N F Adkinson.

At least 73 records · Page 4Linked to original sources

PubMed1990

Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis.

In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1-year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults.

Adolescent↗

PubMed1990

Ragweed IgE and IgG4 antibody in nasal secretions during immunotherapy.

We have developed sensitive amplified immunoassays for measurement of IgE and IgG4 ragweed (RW) antibodies in unconcentrated nasal washes. IgE to Amb a I (formerly antigen E) can be assayed to less than 0.1 ng/ml using IgE capture by anti-IgE on microtitre plates and an alkaline phosphatase-conjugated Amb a I with an amplification substrate technique. IgG4 to whole RW extract was assayed to less than 0.01 ng/ml by amplification ELISA using monoclonal anti-IgG4. Nasal washes (NW) (10 ml) and serum were obtained in December from 22 RW-sensitive patients before and after 1 and 2 yr of RW immunotherapy (IT), and assayed for Amb a I IgE or RW IgE and RW IgG4 antibodies Amb a I IgE could be measured in the NW of 15/22 pre IT, 19/22 at 1 yr IT, but only 3/10 at 2 yr IT (compared with pre-IT, P less than 0.05). Mean Amb a I IgE in NW was 0.66, 0.36 and 0.21 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Mean serum RW IgE, was 76, 55 and 27 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Amb a I IgE in nasal washes was correlated with RW IgE in serum (r = 0.56, P less than 0.001, n = 44). RW IgG4 was detectable in NW of 15/22 pre-IT, 18/22 at 1 yr IT and 9/10 at 2 yr IT (P-values greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Effects of hypoxia on leukotriene activity and vasomotor tone in isolated sheep lungs.

To determine whether hypoxic pulmonary vasoconstriction was associated with release of sulfidopeptide leukotrienes (SPLTs) from the lung, we measured SPLT activity by bioassay (guinea pig ileum) and radioimmunoassay in lymph, perfusate, and bronchoalveolar lavage (BAL) fluid from sheep lungs (n = 20) isolated and perfused in situ with a constant flow of autologous blood (100 ml.kg-1.min-1) containing indomethacin (60 micrograms/ml). The protocol consisted of three periods, each at least 1 h in duration. In experimental lungs, inspired O2 concentration (FIO2) was 28.2% in periods 1 and 3 and 4.2% in period 2. In control lungs, FIO2 was 28.2% throughout. Hypoxia increased pulmonary arterial pressure but did not alter peak tracheal pressure, lung lymph flow, or weight gain measured during the last 30 min of each period. SPLT activity was greatest in lung lymph and least in BAL fluid. Hypoxia did not alter SPLT activity in any fluid. Similar results were obtained in lungs not treated with indomethacin (n = 15). These data do not support the hypothesis that hypoxic pulmonary vasoconstriction is mediated by SPLTs.

Animals↗

PubMed1990

Mechanism of phosgene-induced lung toxicity: role of arachidonate mediators.

We have previously shown that phosgene markedly increases lung weight gain and pulmonary vascular permeability in rabbits. The current experiments were designed to determine whether cyclooxygenase- and lipoxygenase-derived mediators contribute to the phosgene induced lung injury. We exposed rabbits to phosgene (1,500 ppm/min), killed the animals 30 min later, and then perfused the lungs with a saline buffer for 90 min. Phosgene markedly increased lung weight gain, did not appear to increase the synthesis of cyclooxygenase metabolites, but increased 10-fold the synthesis of lipoxygenase products. Pre- or posttreatment with indomethacin decreased thromboxane and prostacyclin levels without affecting leukotriene synthesis and partially reduced the lung weight gain caused by phosgene. Methylprednisolone pretreatment completely blocked the increase in leukotriene synthesis and lung weight gain. Posttreatment with 5,8,11,14-eicosatetraynoic acid (ETYA), a nonmetabolized competitive inhibitor of arachidonic acid metabolism, or the leukotriene receptor blockers, FPL 55712 and LY 171883, also dramatically reduced the lung weight gain caused by phosgene. These results suggest that lipoxygenase products contribute to the phosgene-induced lung damage. Because phosgene exposure did not increase cyclooxygenase synthesis or pulmonary arterial pressure, we tested whether phosgene affects the lung's ability to generate or to react to thromboxane. Infusing arachidonic acid increased thromboxane synthesis to the same extent in phosgene-exposed lungs as in control lungs; however, phosgene exposure significantly reduced pulmonary vascular reactivity to thromboxane but not to angiotension II and KCl.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1990

Disassociation of the release of histamine and arachidonic acid metabolites from osmotically activated basophils and human lung mast cells.

Upon activation by most stimuli, basophils and human lung mast cells simultaneously release histamine and arachidonic acid metabolites. Hyperosmolar activation was examined, and both cell types were shown to release histamine but little or no leukotriene C4 or D4 (LTC4/D4) and, in the case of mast cells, little or no prostaglandin D2 (PGD2). In addition, hyperosmolar buffers were capable of preventing the formation of LTC4/LTD4 in basophils stimulated by anti-IgE when added simultaneously, or 2, 5, or 10 min after, the addition of anti-IgE. Catabolism of PGD2 and LTC4/D4 was not increased. Experiments with cell lysates demonstrated that intracellular formation, rather than secretion, was arrested in hyperosmolar buffers. We conclude that this selective inhibition of mediator production is a unique response of mast cells and basophils to osmotic activation. Although the mechanism of this selective cellular response is not clear, these in vitro observations have important therapeutic and pathophysiologic implications for the airway response to hyperosmolar stimuli.

Antibodies, Anti-Idiotypic↗

PubMed1990

Dry air-induced late phase responses in the canine lung periphery.

Although controversial, late phase responses in asthmatic subjects have been reported several hours after exercise. We previously showed that exposure to dry air increases collateral system resistance (Rcs) in the canine lung periphery, and produces acute airway responses analogous to those that characterize human exercise-induced asthma. We used a dual wedged bronchoscope technique in anaesthetized male mongrel dogs to monitor Rcs in: 1) control segments continuously exposed to 200 ml.min-1 of 5% CO2 in air and 2) dry air challenged segments exposed to 2000 ml.min-1 5% CO2 for 5 min. We examined Rcs at 5 min and approximately 5 h post-challenge in an attempt to document late phase airway obstruction. Five min after dry air challenge Rcs initially increased 114 +/- SE 22%; contralateral control segments remained unchanged (n = 9). Five hour post-challenge, Rcs in dry air exposed segments was elevated 81 +/- 20% above pre-challenge baseline (p less than 0.01); contralateral control segments did not change significantly over the 5 h period. Cell profile analyses of lavage samples at 5 hours revealed that neutrophils and eosinophils were significantly increased (p less than 0.03) in dry air challenged segments when compared to controls. Leukotriene C4/D4 concentration in lavage was correlated (p less than 0.02) with neutrophil infiltration. Thus, we conclude that the canine lung periphery represents a reproducible model of a dry air-induced late phase reaction.

Air↗

PubMed1989

Association of protamine IgE and IgG antibodies with life-threatening reactions to intravenous protamine.

Life-threatening reactions to intravenous protamine, administered to reverse heparin anticoagulation, have been reported with increasing frequency as a consequence of the escalating use of cardiac catheterization and coronary bypass surgery. Retrospective studies have shown that such reactions are more common in diabetic patients receiving daily subcutaneous injections of protamine-insulin preparations. To determine whether anti-protamine IgE or IgG antibodies might explain the increased risk for protamine reactions among patients with protamine-insulin-dependent diabetes, we conducted a case-control study of 27 patients (diabetic and nondiabetic) who had acute reactions to intravenous protamine and 43 diabetic patients who tolerated protamine without a reaction during diagnostic or surgical procedures. Cases and controls were grouped according to previous exposure to protamine-insulin preparations. In diabetic patients who had received protamine-insulin injections, the presence of serum antiprotamine IgE antibody was a significant risk factor for acute protamine reactions (relative risk, 95; P = 1.0 X 10(-5), as was antiprotamine IgG (relative risk, 38; P = 1.2 X 10(-5). No patients without previous exposure to protamine-insulin injections had serum protamine IgE antibodies. In this group, anti-protamine IgG antibody was a risk factor for protamine reactions (relative risk, 25; P = 0.0062). We conclude that in protamine-insulin-dependent diabetics, the increased risk of serious reactions when intravenous protamine was given appeared to be caused largely by antibody-mediated mechanisms. In nondiabetic subjects, the presence of protamine IgG was significantly associated with an increased risk of acute protamine reactions, although many nondiabetic subjects who had reactions had no IgG antibodies.

Adult↗

PubMed1989

The effect of cat removal on allergen content in household-dust samples.

To evaluate the effect of cat removal on cat-allergen content in the home, serial house dust samples were collected from 15 homes during a 9- to 43-week period after cat removal. Samples were obtained with a hand-held vacuum cleaner, and allergen content was quantitated by a radioimmunoassay specific for the major cat allergen, Fe1 d I. Baseline Fe1 d I content ranged from 7.8 Food and Drug Administration units per gram of dust to 436.7 U/gm (median 61.2 U/gm), consistent with levels found in homes with a pet cat. Fe1 d I levels declined gradually in most homes, and by 20 to 24 weeks after cat removal, eight of 15 reached levels consistent with levels found in control homes without cats. In two of those homes, allergen levels fell much more rapidly after aggressive environmental control measures were undertaken. In the other seven homes, however, the decline occurred at a much slower rate, with three homes demonstrating persistent elevations in Fe1 d I content for 20 or more weeks. These data demonstrate that the task of allergen elimination from an indoor environment is extremely difficult, even when the source of a specific allergen can be identified and removed.

Allergens↗

PubMed1989

Immunotherapy decreases skin sensitivity to cat extract.

In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients matched by intradermal skin test titration, leukocyte histamine release, and the doses of both cat extract and methacholine required for 20% fall in FEV1 were randomly assigned to one of the two treatment groups. Immunotherapy doses were increased to a maintenance dose of 4.56 Food and Drug Administration (FDA) units of Fel d I or if maintenance dose was less, to the highest tolerated dose. Before and during immunotherapy, we measured by intradermal titration the dose of cat extract, in FDA units of Fel d I equivalents, required for (1) 2+ end point (wheal diameter, greater than or equal to 10 mm; erythema diameter, 20 to 30 mm) and (2) 20 mm end point (erythema diameter, 20 mm). By prick skin test, we measured (1) the dose of cat extract that produced a wheal equal in area to that produced by histamine, 1 mg/ml, (2) the doses of cat extract that produced a wheal 22 mm2 in area, and (3) the sum of the wheal areas produced by five prick tests to 23.8, 7.1, 2.4, 0.7, and 0.2 FDA units per milliliter of Fel d I, respectively. After 1 year of treatment, in comparison to control patients, treated patients had significant increases in the ratio 1 year value/pretreatment value for the doses of cat extract required for intradermal test end points 1 and 2 (p less than 0.01), for prick test end point 1 (p less than 0.01), for end point 2 (p = 0.015), and significant decreases in this ratio for prick test end point 3 (p = 0.015). Treated patients also had significant increases in cat extract required for a 20% fall in FEV1 (p less than 0.01), in IgG antibodies toward whole cat extract, Fel d I and cat albumin (p less than 0.001), and in IgE antibodies toward whole cat extract, (p less than 0.01). Thus, a decrease in skin sensitivity to cat extract demonstrated by both intradermal and prick methods occurred in patients after 1 year of immunotherapy with cat extract at a time when bronchial sensitivity to cat extract was decreased and IgG and IgE antibodies toward cat extract were increased.

Allergens↗

PubMed1989

The pattern and kinetics in human skin of erythema and mediators during the acute and late-phase response (LPR).

To investigate the kinetics and pattern of allergenically induced mediator release in the human skin, we have studied 24 ragweed- and grass-allergic patients with a blister-chamber technique. Chambers sealed to the skin around a denuded area, formed by unroofing a blister, were challenged with 0.5 ml of either diluent or 10 or 100 times the concentration of allergen required for 4+ early intradermal reaction. Chamber fluids were removed hourly 1 to 8 hours after antigen challenge and examined for the presence of histamine, leukotriene C4 (LTC4), and prostaglandin D2 to compare inflammatory mediator levels with the clinical early response and late-phase response (LPR), as assessed by erythema around the chamber. An initial erythema developed rapidly and began to subside after 1 hour in all patients, but a late-phase local erythema and subcutaneous swelling around the chamber (i.e., greater than 2.5 cm, the outside diameter of the chamber) developed in 13/15 challenges only when the higher concentration of antigen was used. At both allergen concentrations, histamine levels peaked sharply at the first hour (20.6 +/- 2.3 ng/ml) and progressively declined during the next 4 hours by 75%, but remained above control levels for at least 7 hours. Despite high control values, LTC4 levels were significantly elevated (p less than 0.01) 4 to 6 hours after challenge. In visible reactions, maximal LPR around the chamber correlated with LTC4 levels obtained 6 and 7 hours after challenge (p less than 0.05). Prostaglandin D2 rose gradually in antigen-challenged chambers to a peak at 5 to 6 hours. Thus, early rises in histamine were temporally related to the immediate erythema, whereas the arachidonic acid metabolites from both cyclooxygenase and lipoxygenase pathways that appeared in the skin after allergen challenge followed kinetics that corresponded to the time course of cutaneous LPR.

Adolescent↗

PubMed1989

Responses to ragweed-pollen nasal challenge before and after immunotherapy.

To evaluate whether immunotherapy reduces mediator release after nasal challenge, we followed previously untreated patients with ragweed hay fever through 2 years (three seasons) of treatment. Eleven adult patients started immunotherapy after a season of symptom diaries and graded pretreatment challenges with 0.03, 0.3, 3.3, and 16.5 mg of ragweed pollen. Repeat challenges were performed when the treatment dosage reached 0.6, 12.4, and 24.8 micrograms of Amb a I (antigen E) equivalents per injection. After the 0.6 micrograms dose, there was little change, but after the larger doses, there was a significant reduction in histamine and tosylarginine methyl ester-esterase (TAME-esterase) release in two respects. More pollen was required before any mediator appeared, and the amount of mediator released at each stage of the challenge was reduced. There was no significant difference between the responses at the 12.4 and 24.8 micrograms treatment doses. Sneezing after challenge was not apparently changed after immunotherapy; however, patients' seasonal symptom-medication scores were reduced after treatment. These data set the optimal individual treatment dose of ragweed extract for immunotherapy at greater than 0.6 micrograms, but probably not more than 12.4 micrograms in terms of Amb a I equivalents.

Adolescent↗

PubMed1989

Attenuation of allergen sensitivity early in the course of ragweed immunotherapy.

During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.

Adolescent↗

PubMed1989

Rabbit F(ab')2 antihuman IgE is a universal skin test reagent in the evaluation of skin mast cell degranulation in vivo.

Antihuman IgE is often used to study basophil- and mast cell-mediator release in vitro but is infrequently used in vivo. To evaluate in vivo skin reactivity to anti-IgE, an affinity-purified rabbit F(ab')2 fragment of antihuman IgE was injected intradermally in 22 nonallergic and 27 allergic subjects. All 49 subjects (including a subject with less than 1 ng/ml of total serum IgE) had positive immediate cutaneous reactions to anti-IgE. Although total serum IgE level was weakly correlated (r = -0.51; p less than 0.005) with in vivo skin reactivity to anti-IgE for the entire population, allergic subjects did not have significantly increased skin reactivity compared to nonallergic subjects (p = 0.18), despite having higher total serum IgE levels (p less than 0.002). A late-phase cutaneous response (LPR) to anti-IgE occurred in 60% of the allergic and in 50% of the nonallergic subjects. Subjects with an LPR required approximately tenfold higher concentrations of anti-IgE to produce an immediate wheal of 10 mm compared to subjects who did not develop an LPR (p = 0.02), suggesting that the concentration of the stimulus injected is more important for the development of a LPR than the size of the immediate cutaneous response. Skin reactivity to codeine phosphate (a non-IgE-dependent secretagogue) was correlated with skin reactivity to anti-IgE (r = 0.47; p less than 0.05), suggesting that in vivo skin mast cell degranulation is partially a function of mast cell releasability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Barbiturate anesthetics inhibit thromboxane-, potassium-, but not angiotensin-induced pulmonary vasoconstriction.

Administration of the oxidant lipid peroxide tertiary butyl hydroperoxide (t-bu-OOH) in the isolated rabbit lung leads to acute pulmonary vasoconstriction, which is caused by the synthesis of thromboxane. The inhalational anesthetics, halothane, nitrous oxide, and cyclopropane, markedly enhance t-bu-OOH-induced pulmonary vasoconstriction and thromboxane production. The effects of the intravenous (iv) barbiturates thiopental and pentobarbital on t-bu-OOH-induced vasoconstriction were studied. Thiopental completely and pentobarbital partially blocked t-bu-OOH-induced vasoconstriction. Thiopental inhibited t-bu-OOH-induced synthesis of thromboxane and prostacyclin but pentobarbital did not. This inhibitory action of thiopental may be due to its antioxidant properties because similar inhibition has been observed of t-bu-OOH-induced thromboxane production with the antioxidants, vitamin E, or butylated hydroxylanisole. Thiopental and pentobarbital also inhibited the vasoconstriction induced by a thromboxane analog, epoxymethano prostaglandin H2 (U46619). Finally, both barbiturates partially inhibited the pulmonary vasoconstriction caused by potassium chloride, which requires calcium entry, but they did not inhibit the constriction caused by angiotensin II, which does not require calcium entry. These results suggest that pentobarbital and thiopental may block pulmonary vasoconstriction by inhibiting calcium entry.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1989

Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets.

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.

Animals↗

PubMed1989

Effect of pH on pulmonary vascular tone, reactivity, and arachidonate metabolism.

We studied the effects of perfusate pH on pulmonary vascular tone, reactivity, and thromboxane and prostacyclin synthesis in isolated buffer-perfused rabbit lungs. Extracellular acidosis did not affect base-line vascular tone, but alkalosis had a biphasic effect. Increasing the perfusate pH from 7.40 to 7.65 caused vasodilation, whereas raising pH to 7.70-8.10 caused vasoconstriction. Removing calcium (Ca2+) from the perfusate completely prevented the vasoconstriction caused by alkalosis. Perfusate pH strikingly affected pulmonary vascular reactivity. Acidosis inhibited the vasoconstriction caused by thromboxane and potassium chloride (KCl) but did not affect the response to angiotensin II. Alkalosis, in contrast, augmented the vasoconstriction caused by thromboxane and angiotensin II but reduced the vasoconstriction caused by KCl. Changes in pH also altered thromboxane and prostacyclin synthesis after the infusion of exogenous arachidonic acid (AA) or the endogenous release of AA by the lipid peroxide tert-butyl hydroperoxide.

Angiotensin II↗

PubMed1989

A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma.

Reproducibility of methacholine inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatics with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV1 greater than or equal to 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD20FEV1 using cumulative breath units (BU) were compared. The range of PD20FEV1 in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD20FEV1 less than 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Dexamethasone does not inhibit the release of mediators from human mast cells residing in airway, intestine, or skin.

Glucocorticoids are potent anti-inflammatory drugs that are widely used in the treatment of allergic disorders. Their actions are often species specific or cell-type specific. Previous studies have demonstrated that glucocorticoids inhibit mediator release from mast cells derived from the peritoneum of mouse or rat and from guinea pig lung, but not those residing in human lung parenchymal tissue. In the present study, we have analyzed the effect of overnight culture with dexamethasone (10(-6) to 10(-7)M) on the subsequent IgE-dependent release of mediators from human mast cells derived from airway tissue, intestine, and skin. Airway tissue was passively sensitized with antigen-specific, IgE-rich serum during the culture period and subsequently challenged with ragweed antigen E. Skin and intestinal mast cells were challenged with anti-IgE. Histamine and immunoreactive LTC4 and PGD2 release was monitored in all experiments. Prostaglandin E release was quantitated in the experiments using airway tissue. Dexamethasone treatment failed to inhibit the release of mast cell mediators from all three tissues, but it inhibited the antigen-induced release of immunoreactive PGE from other cells residing in airway tissue. These results confirm earlier studies of the effects of glucocorticoids on human lung parenchymal mast cells, but contrast with the inhibitory effects of steroids observed in murine mast cells and human basophils.

Adult↗