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Biomedical subjects

E Adelroth

Publications and source records attributed to E Adelroth.

33 records · Page 2Linked to original sources
PubMed1995

Effects of allergen challenge on eosinophils, eosinophil cationic protein, and granulocyte-macrophage colony-stimulating factor in mild asthma.

Allergen inhalation challenge is associated with increases in eosinophil number and activation, and provides a useful model for investigating airway inflammation in asthma. Limited information, however, is available on the effect of allergen challenge on cytokines regulating eosinophil function. We investigated allergen-induced changes in eosinophil number and activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine known to regulate eosinophil function in vitro. Seven subjects with mild atopic asthma and late asthmatic responses completed diluent- and allergen-inhalation challenges. Blood, bronchoalveolar lavage fluid (BALF), and biopsy samples were collected 24 h after challenge. Allergen inhalation caused a significant increase in eosinophils in BALF and biopsy samples. Eosinophil activation, as assessed by secretion of eosinophil cationic protein, and GM-CSF levels were significantly increased in BALF and bronchoalveolar lavage (BAL) cells. Allergen inhalation did not cause a significant change in eosinophil activation in biopsy tissue but did result in a significant decrease in GM-CSF in the tissue. Significant correlations were shown between the concentration of GM-CSF in BALF and the percentage of BAL eosinophils (Rs = 0.75, p = 0.05), severity of the late asthmatic response, and number of BAL eosinophils (Rs = 0.82, p = 0.02). A trend was seen between the late response and the concentration of GM-CSF in BALF. These results are consistent with the hypothesis that eosinophils, regulated by GM-CSF, contribute to allergen-induced decreases in airway function.

Adult↗
PubMed1995

Airway and lung elastic fibre is not reduced in asthma nor in asthmatics following corticosteroid treatment.

By morphometric investigation of the relative content of elastic and collagen fibres, we have tested the hypothesis that loss of elastic fibres in the conducting airways and lung parenchyma may reduce tissue elastic recoil, resulting in increased airway maximal closure and apparent increased responsiveness. The study groups comprised: Group A (n = 11) with relatively mild atopic asthma using inhaled bronchodilators prn (i.e. short-term corticosteroids users); Group B (n = 9) with more severe asthma requiring inhaled bronchodilators regularly, and daily inhaled glucocorticosteroids (i.e. longterm corticosteroid users); Group C (n = 12) normal healthy workers. Bronchial biopsy samples were taken from three sites from the left lung. Group A biopsy samples were taken before and after a 4 wk treatment period with inhaled corticosteroids (200 micrograms b.i.d.) and the relative elastic and collagen fibre content of a subepithelial zone was determined from electron micrographs. In a parallel study, the relative proportion of elastic fibre in post mortem lung tissue samples (inner aspect of the bronchial wall, alveolar wall, and points of attachment of surrounding alveoli to intrapulmonary bronchi) from subjects suffering a fatal asthma attack (n = 11), and non-asthmatic suffering sudden death (n = 9), were determined using Miller's elastic and eosin counterstain for light microscopy. In bronchial biopsies of normal subjects, 4.6 (SEM 1.1)% of subepithelial connective tissue was elastic fibre, similar to mild asthmatic subjects, 1.9 (SEM 0.48)%. Neither short-term (4 weeks) inhaled corticosteroid (200 micrograms b.i.d.) nor long-term (< 6 months) treatment with variable doses of inhaled steroids (100-1000 micrograms b.i.d.) significantly altered the elastic or collagen content of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs.

Inhaled corticosteroids are known to reduce components of the airway inflammation characteristic of asthma and improve airway hyperresponsiveness. However, the effect of inhaled corticosteroids on ozone-induced airway responses is unknown. Eight dogs inhaled budesonide [2.74 +/- 0.25 (SE) mg/day] or lactose powder twice daily for 7 days before inhaling ozone (3 ppm for 30 min) or dry air. Acetylcholine airway responsiveness was measured before and 1 h after ozone, followed by a bronchoalveolar lavage (BAL). The response to acetylcholine was expressed as the concentration causing an increase in lung resistance of 5 cmH2O.l-1.s above baseline (acetylcholine provocation concentration). Budesonide pretreatment significantly attenuated the ozone-induced increase in pulmonary resistance (P = 0.003) and neutrophil influx into BAL (P = 0.001) and significantly reduced BAL eosinophils (P = 0.026). However, budesonide pretreatment had no significant effect on ozone-induced airway hyperresponsiveness. After budesonide, the acetylcholine provocative concentration fell from 5.96 mg/ml (%SE 1.46) before to 1.11 mg/ml (%SE 1.63) after ozone (P = 0.006). After lactose, the acetylcholine provocative concentration fell from 5.34 mg/ml (%SE 1.40) before to 0.50 mg/ml (%SE 1.85) after ozone (P = 0.001). Dry air inhalation did not cause airway hyperresponsiveness (P = 0.68). These results suggest that ozone-induced airway hyperresponsiveness is steroid resistant and that airway neutrophils or eosinophils are not important in its pathogenesis.

Acetylcholine↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor, eosinophils and eosinophil cationic protein in subjects with and without mild, stable, atopic asthma.

Increasing evidence implicates the eosinophil as an important effector cell in asthma, but little is known regarding its regulation in vivo. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to regulate eosinophil function in vitro. We investigated the in vivo role of eosinophils and GM-CSF in mild asthma. We compared the number and function of eosinophils and the presence of GM-CSF in blood, bronchoalveolar lavage (BAL) and biopsy tissue obtained from eight mild, stable, atopic asthmatics and 10 nonasthmatics, five of whom were atopic and five nonatopic. Eosinophils were significantly increased in the blood, BAL and biopsy tissue from asthmatics. Activated eosinophils, assessed by immunostaining for the secreted form of eosinophil cationic protein (EG2), were also increased in asthmatic BAL cells and biopsy tissue. Significant increases in GM-CSF in BAL cells and biopsy tissue from asthmatics were also evident. Significant positive correlations existed between GM-CSF in BAL and EG2, and GM-CSF in biopsy tissue and BAL and biopsy eosinophils. Airway responsiveness was also significantly positively correlated with eosinophil number and activation, and with GM-CSF. These results demonstrate that there are increased numbers of activated eosinophils and GM-CSF is increased in patients with mild asthma. Furthermore, GM-CSF is correlated with eosinophil number and function in vivo and these indices are significantly correlated with airway function. These findings emphasize the importance of eosinophils, potentially regulated in vivo by GM-CSF, in contributing to the disordered airway function evident even in mild asthma.

Adult↗
PubMed1992

Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study.

We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline.

We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results.

Adult↗
PubMed1986

Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls.

Leukotrienes C4 and D4 may serve as chemical mediators in asthma. Although patients with asthma are known to be hyperresponsive to the bronchoconstrictive effects of histamine and methacholine, whether the same is true for the leukotrienes is controversial. We compared the airway responses to methacholine and to leukotrienes C4 and D4 in 12 asthmatic patients and 6 controls. We found that the patients were more responsive to the leukotrienes than the controls, and we observed a linear correlation between airway response to methacholine and that to leukotriene C4 (r = 0.68, P less than 0.01) and D4 (r = 0.79, P less than 0.001). However, relative to the airway response to methacholine, the response to the leukotrienes was much greater in the controls than in the patients. Furthermore, the asthmatic subjects who were most responsive to methacholine had the lowest relative airway response to both leukotrienes. Thus, the patients with the greatest airway responsiveness to methacholine paradoxically showed the lowest relative airway response to the leukotrienes. In contrast, this difference in relative airway responses has not been observed between methacholine and other bronchoconstrictor mediators, such as histamine. Although no adequate explanation for these observations has yet emerged, our data suggest that leukotrienes C4 and D4 are unique bronchoconstrictors with a possible role in the pathogenesis of asthma.

Adult↗
PubMed1986

Do physicians need objective measurements to diagnose asthma?

The frequency with which disagreement occurs between the clinician's diagnosis of asthma and the objective measurement of methacholine airway responsiveness is not known. We have examined this in 51 consecutive new adult patients presenting with symptoms consistent with asthma but with normal spirometry. Disagreement between the physician's assessment and the result of the methacholine test occurred in 20 patients (39%). Of these, 13 had a clinical diagnosis of asthma but normal responsiveness and 7 had an unexpected increase in methacholine responsiveness. There was no difference in the type of symptoms experienced whether or not there was agreement between the test and the physician's assessment. Thus, an objective measurement like a methacholine inhalation test is clinically useful when spirometry is normal. A normal methacholine test in the presence of symptoms suggestive of asthma should alert the physician to the need for further investigation.

Adult↗
PubMed1985

High dose inhaled budesonide in the treatment of severe steroid-dependent asthmatics. A two-year study.

Thirty-eight patients with chronic asthma requiring continuous oral corticosteroid treatment took part in a 2-year study. Budesonide, a new inhalation steroid with high topical activity and low systemic effects, was given in stepwise increasing doses from 200 micrograms daily up to 800-1600 micrograms daily and prednisolone doses were decreased gradually on an individual basis. After 2 years, 18 patients had been able to cease oral prednisolone treatment, 11 had decreased the dose by greater than or equal to 50%, three by less than or equal to 50% and two patients had increased their dose. At the end of the study the majority of patients (26) were using 800 micrograms budesonide daily and seven, 1200 micrograms or more daily. There were two dropouts, one due to local side effects and one to a severe pulmonary eosinophilia. Ten patients had local side effects in the form of hoarseness and/or sore throat, and 13 patients had steroid withdrawal symptoms such as arthralgia and myalgia. The asthma condition in all patients was improved, as indicated by the reduced need for hospital admissions. The results indicate that high doses of budesonide should be tried before starting maintenance therapy with oral steroids.

Administration, Intranasal↗
PubMed1982

Diagnosis of bronchial lesions by fiberoptic bronchoscopy combined with bronchography.

The combination of bronchoscopy and bronchography into a single procedure has facilitated the diagnosis of a wide variety of diseases. The technique is easily learned, morbidity is negligible, patient discomfort is minimal, and the number of examinations to which the patient is subjected is reduced. The technique is well suited for selective bronchography.

Adolescent↗
PubMed1982

Comparison between inhaled and oral corticosteroids in patients with chronic asthma.

Corticosteroid inhalants, beclomethasone dipropionate (BDP) and budesonide, were compared with each other and with oral prednisolone in patients with steroid dependent chronic bronchial asthma. In a first study in 23 patients the PEF values during 2 weeks' therapy with a supplementary dose of 200 or 800 micrograms of budesonide or 400 micrograms of BDP were found to be better than those noted during a preceding week with a supplementary dose of 30 mg prednisolone. In a following open study 31 patients on an initial maintenance therapy consisting of a standard dose of BDP and a mean daily dose of 9 mg prednisolone were treated with increasing (when necessary) doses of budesonide instead of BDP and decreasing (if possible) dose of prednisolone. After one year's treatment 21 patients were well controlled without oral prednisolone, and the mean prednisolone dose for the entire group was 2.5 mg a day. During the study lung function significantly improved in the subgroup of patients who were initially on the highest dose of oral prednisolone. In a third study in 17 patients the effects on lung function and on symptom scores were compared after a supplementary therapy with 10 or 20 mg oral prednisolone, or 400 or 800 micrograms budesonide. During such treatment the effect of 400 micrograms budesonide on PEF was the same as that of 10 mg prednisolone, and 800 micrograms budesonide and 20 mg prednisolone seemed to be equipotent. For corticosteroid dependent patients with severe asthma the introduction of budesonide seems to offer an improvement, allowing substantial reduction or withdrawal of oral prednisolone. This had not been possible earlier in such patients without deterioration of lung function and their clinical state. During treatment with budesonide lung function remained unchanged or improved.

Administration, Oral↗
PubMedDate not supplied

How to measure airway inflammation: bronchoalveolar lavage and airway biopsies.

Airway inflammation is a characteristic feature of asthma. Bronchoscopy with bronchoalveolar lavage (BAL) and/or mucosal airway biopsies has provided invaluable information about the nature of asthmatic inflammation. A common finding in all BAL studies in asthma is increased numbers or proportions of eosinophils even in subjects with mild disease. BAL cells in asthmatics demonstrate a cytokine profile consistent with a T helper2-like phenotype, with increased expression of interleukin (IL)-4 and IL-5. Endobronchial mucosal biopsies show loss of surface epithelium, thickening of the reticular layer of the basement membrane and an increased cellular infiltrate of mainly eosinophils, mast cells and T lymphocytes, and up-regulation of a number of cytokines. Recently, peripheral airways from asthmatics have been investigated, and even more intense inflammation has been described. However, in severe steroid-dependent asthmatics, intriguing differences in the type of inflammation have been described. The term 'airway remodelling' indicates structural changes seen in long standing asthma, where myofibroblasts might be of particular importance. BAL and mucosal biopsies are important tools in the investigation of airway inflammation in asthma.

Asthma↗