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Biomedical subjects

W W Busse

Publications and source records attributed to W W Busse.

At least 163 records · Page 9Linked to original sources
PubMed1990

Superoxide generation by hypodense eosinophils from patients with asthma.

Low density, or hypodense eosinophils (HE) are found in increased numbers in asthma. Since HE have been reported to have increased inflammatory potential and correlate with the severity of airway obstruction, it has been suggested that this subpopulation of eosinophils may contribute to the asthma process. However, investigations to define the function of HE in asthma have been limited. In this study, pure populations of both HE and normal dense eosinophils were isolated from the peripheral blood of seven patients with asthma, and functional activity of these cells was determined by measuring superoxide (O2-) generation to several activators. Compared to normal dense eosinophils, HE generated significantly more O2- when activated with the chemotactic peptide FMLP or opsonized zymosan; however, these differences were small. In contrast, no difference was observed in O2- production between normal- and low-density eosinophils from asthma patients when stimulated by phorbol myristate acetate (PMA) or the calcium ionophore A23187. Furthermore, both eosinophil populations, and corresponding neutrophil isolates, from asthma patients generated significantly more O2- than control granulocytes when activated by PMA. When stimulated by calcium ionophore, all three eosinophil populations released equivalent amounts of O2-, which were, however, higher than from both neutrophil suspensions. Compared to increased activity found in some other hypereosinophilic conditions, blood HE in asthma do not necessarily have enhanced function. This suggests that eosinophil heterogeneity extends not only to cell density but is also reflected in cell function and that these cell variations are dependent on many factors, including the function assessed, source of cells (normal versus patients with some diseases), and stimulus used.

Adult↗
PubMed1989

The relationship between plasma histamine concentrations and bronchial obstruction to antigen challenge in allergic rhinitis.

Antigen activation of pulmonary mast cells causes mediator release and airway obstruction in allergic patients with asthma. Concomitant measurements of airway mediators and pulmonary function are technically difficult, even with bronchoalveolar lavage. Thus, a procedure was developed to evaluate further the relationship between mediator release, as measured by plasma histamine concentrations, and airway obstruction in patients with allergic rhinitis challenged with inhaled ragweed antigen. At an initial challenge, the cumulative antigen dose to decrease the FEV1 by approximately 20% was determined. Approximately 4 weeks later, the entire predetermined cumulative antigen dose to decrease the FEV1 by approximately 20% was administered in five consecutive inhalations with simultaneous monitoring of plasma histamine. We found the percent fall in FEV1 (24.3 +/- 2.3 versus 30.4 +/- 4.0; p greater than 0.05; n = 7) was similar whether antigen was administered by a cumulative or single-dose challenge. With the single-dose antigen challenge and monitoring blood samples frequently, we found plasma histamine (picograms per milliliter) values to increase from 73 +/- 17 to 1071 +/- 377 (p = 0.022) with peak value 5 minutes after challenge. Furthermore, we found that the intensity of airway obstruction to antigen corresponded to both the patient's baseline airway responsiveness to histamine and the absolute changes in plasma histamine after antigen challenge. Thus, the degree of airway obstruction to inhaled antigen is determined by both the intensity of the allergic reaction (as reflected by the plasma histamine value) and bronchial responsiveness.

Adult↗
PubMed1989

The relationship between viral infections and onset of allergic diseases and asthma.

The pathogenesis of both allergic diseases and asthma remains an unsolved mystery. Of considerable interest, and perhaps insight, into this problem are clinical observations that viral illnesses play an important role in the allergic diathesis. Conclusive evidence to establish a relationship linking viral illnesses to clinical allergy has yet to be established. Nonetheless, recent observations in this arena are intriguing to scientist and clinician alike. The following discussion reviews recent investigations that evaluate the relationship between viral illnesses and development of allergic disease and asthma.

Animals↗
PubMed1989

The effect of parainfluenza 3 infection on guinea pig basophil and lung mast cell histamine release.

The guinea pig infected with parainfluenza 3 (P-3) has provided an animal model to study mechanisms of virus-induced asthma and airway hyperreactivity. Evidence to identify the mechanisms by which P-3 infection enhances airway hyperreactivity, however, has not been established. The present study evaluated the effect of P-3 infection on histamine release (HR) from isolated peripheral blood guinea pig basophils and lung mast cells. Basophil HR was determined in animals made basophilic with 13 daily intraperitoneal injections of sheep blood. On Day 10 of the sensitization, blood was obtained from all animals, and leukocyte HR was determined to sheep gammaglobulin (SG), which served as the secretagogue. After these baseline studies, the animals were separated into two groups; one was insufflated with P-3 virus and the other with growth medium that did not contain virus. Four days later, animals were killed, basophils and lung mast cells were isolated, HR was determined, and lung tissue was cultured for the presence of virus. In basophils isolated from animals proven to be infected with P-3 virus, we found significantly more histamine released in response to the lower doses of SG and a significant shift in the -log EC50 dose of this antigen causing HR in these cells. Experiments conducted with the calcium ionophore A23187 as the basophil secretagogue in the same experimental design did not demonstrate similar HR findings. Furthermore, a defect in calcium disposition did not account for the enhanced HR from basophils isolated from infected animals. HR from pulmonary mast cells was similar in cells isolated from P-3-infected and control insufflated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The appearance of hypodense eosinophils in antigen-dependent late phase asthma.

Although peripheral blood eosinophils (EOS) of low density are increased in patients with asthma, the mechanisms contributing to their presence are not well established. The following study evaluated the effect of an antigen bronchoprovocation (BP) on the percentage of circulating hypodense eosinophils (HE) in asthma. EOS density was measured by centrifugation of peripheral blood granulocytes over multiple discontinuous density Percoll gradients in samples taken immediately before and 24 h after antigen BP. We found that the percentage of peripheral blood HE (density less than 1.095 g/ml) increased significantly (p less than 0.02) over baseline values (78.9 +/- 4.8% versus 53.3 +/- 8.2%, mean +/- SEM, n = 11) when evaluated 24 h after antigen BP but only in patients who experienced both an immediate (IAR) and late phase asthma reaction (LAR). No significant change in the percentage of HE was observed in asthma subjects who had only an early asthma response to inhaled antigen (n = 6). In an expanded population of allergic asthmatics (n = 38), a significant correlation was found between the percent peripheral blood HE and disease severity as represented by the percent predicted FEV1 (r = -0.56, p = 0.003). These data suggest that in vivo activation of asthma by inhaled antigen increases the proportion of peripheral blood EOS that are hypodense but only in those patients with both an IAR and LAR. Furthermore, we also conclude that the percentage of HE better reflects the severity of asthma than the concentration of total peripheral blood eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.

Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness.

Adult↗
PubMed1988

Pathogenesis and pathophysiology of nocturnal asthma.

Nocturnal wheezing is a major component of asthma. This article reviews the many factors (allergen exposure, sleep, airway cooling, diminished clearance of mucous secretions) that have been identified as contributing to nocturnal asthma. Also discussed are recent data suggesting that diurnal variations in hormone concentrations and in autonomic nervous system control are possible mechanisms of nocturnal asthma. Decreased epinephrine secretion and increased vagal tone during sleep not only cause airway obstruction but may also enhance bronchial reactivity. These changes in the modulation of airway smooth muscle tone produce bronchial obstruction, which, in turn, accentuates ventilation-perfusion mismatch and increases hypoxia.

Allergens↗
PubMed1988

Twelve-hour bronchodilation in asthma with a single aerosol dose of the anticholinergic compound glycopyrrolate.

Anticholinergic aerosols provide effective bronchodilation in some patients with obstructive lung disease. Glycopyrrolate is a quaternary ammonium anticholinergic compound that is poorly absorbed from mucus membranes, thus reducing anticholinergic side effects. In 20 adult patients with asthma, we evaluated bronchodilation to a single administration of metered-dose glycopyrrolate aerosol (GA) to ascertain its onset and duration of action along with evaluation of safety. In this randomized, double-blind, placebo-controlled, single-dose, crossover trial, bronchodilation was evaluated on five separate occasions to either placebo or a GA dose of 80, 240, 480, or 960 micrograms. Baseline spirometry for each patient on each visit was similar (mean FEV1 +/- SD of 62.2 +/- 13.6% predicted). After aerosol dosing, spirometry was measured at 30 minutes and then at hourly intervals up to 12 hours. Compared to placebo, metered-dose aerosols of 240, 480 and 960 micrograms elicited significantly greater bronchodilation at each test time. Furthermore, significant bronchodilation was noted within 30 minutes of dosing and was sustained for at least 12 hours. Bronchodilation with the 480 and 960 micrograms dose was equal, and both were greater than 240 micrograms. A subset of four asthma patients with baseline FEV1 values less than 50% predicted did not have a bronchodilating response with GA. No notable side effects occurred. Thus, a single aerosol dose of GA provides clinically significant, safe 12-hour bronchodilation in patients with asthma without severe airway obstruction (i.e., FEV1 greater than 50% predicted).

Adult↗
PubMed1988

Hypodense eosinophils in allergic rhinitis.

Based on density, function, and membrane receptors, peripheral blood eosinophils are a heterogeneous population of cells. Importantly, hypodense eosinophils (HE) are metabolically more active and likely to contribute to tissue injury. In the following study, peripheral blood from patients with allergic rhinitis (AR) was evaluated for the presence of HE. To accomplish this, blood was obtained from patients with ragweed AR, granulocytes were isolated and fractionated by continuous density Percoll gradients, and the density distribution of these cells was determined after centrifugation. A significantly higher percentage of peripheral blood eosinophils were hypodense (defined as density less than 1.081 gm/ml) in patients with AR when these patients were compared to control subjects, 30.0 +/- 5.0% versus 9.0 +/- 1.9%, p less than 0.01. Moreover, we also noted that an increased percentage of HE was found more often in patients with moderate-to-severe AR than in subjects with none-to-mild disease (p less than 0.01). These data suggest that the appearance of HE in the circulation may relate to the development of allergic symptoms. Furthermore, our observations suggest that the HE, because of its enhanced metabolic activity and now its association with more symptomatic hay fever, may participate in the pathophysiology of AR.

Adult↗
PubMed1988

Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma.

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction.

Adult↗
PubMed1988

The presence of hypodense eosinophils and diminished chemiluminescence response in asthma.

Although peripheral blood eosinophilia is a prominent feature of asthma, the contribution of eosinophils to asthma has yet to be fully comprehended. Furthermore, study of isolated eosinophil function in asthma has been complicated by difficult purification methods and, now, the presence of hypodense eosinophils. In our study, eosinophils were isolated from normal subjects and patients with asthma. Two principal evaluations were performed: (1) a comparison of the density-gradient profiles on peripheral blood leukocytes from normal subjects and patients with asthma and (2) a comparison of the chemiluminescence (CL) response with normal dense eosinophils from these two study groups. Granulocyte preparations were initially isolated from Ficoll-Hypaque gradients and were then applied to a continuous Percoll density gradient. In asthma, 40.8 +/- 5.8% of the peripheral blood eosinophils were hypodense (defined as a density less than 1.081 gm/ml), whereas normal subjects had only 9.1 +/- 1.9% of this subpopulation (p less than 0.01). Functional assessment of purified (greater than 90%) normal dense eosinophils was made by measurement of CL to opsonized zymosan particles and the soluble stimulus phorbol myristate acetate. In asthma, eosinophil CL to zymosan, but not phorbol myristate acetate, was significantly less. Differences in eosinophil CL between normal subjects and subjects with asthma did not correlate with the severity of airway obstruction or the peripheral blood eosinophil count. The reasons for the appearance of hypodense eosinophils and diminished metabolic activity in asthma are not established but raise the possibility that their presence represents previous eosinophil activation.

Adult↗
PubMed1988

Stimulus-dependent differences in superoxide anion generation by normal human eosinophils and neutrophils.

The role of eosinophils in allergic and hypersensitivity diseases has yet to be fully established and remains limited by techniques to isolate the eosinophil in high purity. Consequently, most studies that evaluate and characterize eosinophil function are conducted with isolates from patients with hypereosinophilia. There is, however, evidence to suggest that isolates from such patients do not represent normal function. Now, with new techniques to isolate and purify eosinophils from normal subjects without eosinophilia, metabolic function of the normal eosinophil can be assessed. To accomplish this, granulocytes from healthy volunteers were separated by continuous density Percoll gradients into populations of purified eosinophils (90.3 +/- 1.9%) and neutrophils (98.2 +/- 0.4%). Superoxide (O2-) generation was measured with a microassay of superoxide dismutase-inhibitable cytochrome c reduction in response to several soluble and particulate agonists. Normal eosinophils generated significantly more O2- in response to either phorbol myristate acetate or calcium ionophore A23187 than their matched neutrophil fractions. In contrast, differences in granulocyte response to zymosan and chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine, were dependent on the presence of cytochalasin B (CB) in the reaction. N-formyl-methionyl-leucyl-phenylalanine-stimulated eosinophils generated less O2- in the absence of CB but similar amounts in the presence of CB, compared to neutrophils. Activation by zymosan in the presence of 10% autologous serum generated similar amounts of O2- in all the cell populations when CB was present; however, in the absence of CB, neutrophils produced less O2- when they were compared to eosinophils. Therefore, normal eosinophils respond differently to some activators, compared to neutrophils, and these differences may prove significant as the contribution of eosinophils to inflammation becomes established.

Adolescent↗
PubMed1988

Release of lysosomal enzyme beta-glucuronidase from isolated human eosinophils.

The human eosinophil contains lysosomal enzymes that can contribute directly to tissue injury and inflammation. Characterization of lysosomal-enzyme release from the eosinophil has been largely limited to isolates from patients with hypereosinophilia. Because eosinophils from such individuals may not demonstrate normal functional responses, we established a method to obtain purified, normal human eosinophils with a Percoll gradient. With this method, it is possible to isolate eosinophils (95.5 +/- 3.9%) and neutrophils (greater than 99%) in high purity from normal subjects. With these granulocyte isolates, we evaluated and compared release of the lysosomal enzyme, beta-glucuronidase (BG), after cell activation with opsonized zymosan particles. Neutrophils released 33.0 +/- 1.2% (mean +/- SEM; n = 5) of total BG (30 minutes of incubation with zymosan), whereas eosinophil secretion was 24.2 +/- 1.7% (n = 5). The fungal metabolite, cytochalasin B (CB), which inhibits microfilament activity, enhanced BG secretion from neutrophils (33.0 +/- 1.2% to 42.8 +/- 2.8% with CB; p less than 0.01). In contrast, CB had no effect on eosinophil BG release. Interestingly, BG content in eosinophils is 101.2 +/- 3.9 micrograms phenolphthalein per 10(6) cells per 18 hours, which compares to a neutrophil level of 51.0 +/- 3.2 (p less than 0.001). Thus, although eosinophils and neutrophils release a similar percentage of total cellular BG on stimulation with zymosan particles, the absolute amount of enzyme per cell is greater in the eosinophil than in the neutrophil. Study of eosinophil function promises to elicit a more complete insight into its contribution to tissue injury.

Cell Separation↗