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Biomedical subjects

L Greiff

Publications and source records attributed to L Greiff.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of topical budesonide and levocabastine on nasal symptoms and plasma exudation responses in seasonal allergic rhinitis.

This study compares the effects of two topical nasal treatments for allergic rhinitis, budesonide and levocabastine, on symptom development during seasonal pollen exposure. Additionally, the protective effects of drug treatments on allergen-challenge-induced responses (symptoms and microvascular exudation of plasma) are examined late into the pollen season. Forty-four patients with seasonal allergic rhinitis to birch pollen participated in this single-blind, randomized, and placebo-controlled study. Topical nasal treatment with either levocabastine (200 microg b.i.d.; n = 16), budesonide (200 microg b.i.d.; n = 16), or placebo (n = 12) was instituted before the start of the pollen season and continued for 5 weeks until the end of the birch pollen season. The participants kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges with increasing doses of a birch pollen extract (10[2], 10[3], and 10[4] SQ-U) were carried out both before, when patients were asymptomatic and without treatment, and late into the pollen season. A nasal lavage followed each challenge, and the lavage fluid levels of albumin were measured as an index of the acute inflammatory response of the allergic mucosa. The birch pollen season was rather mild, producing only small increases in nasal symptoms. Budesonide treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to levocabastine (P<0.05), while levocabastine treatment did not differ significantly from placebo. Ocular symptoms and use of rescue medication did not differ between placebo and the active treatments. At the end of the pollen season, both treatments reduced allergen-challenge-induced nasal symptoms compared to placebo (P<0.01). Only budesonide reduced allergen-challenge-induced increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in comparison with placebo). The results suggest that budesonide reduces both seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is effective against allergen-challenge-induced symptoms also during the season. In addition, the topical steroid treatment, but not the antihistamine, inhibits the inflammatory exudation evoked by allergen challenge in patients with active seasonal disease.

Administration, Intranasal↗
PubMed1998

Demonstration of mast-cell chemotactic activity in nasal lavage fluid: characterization of one chemotaxin as c-kit ligand, stem cell factor.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Allergens↗
PubMed1998

Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects.

BACKGROUND: A number of studies have shown that beta 2 agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus in animal airways. Whether clinical doses of beta 2 agonists inhibit plasma exudation in human bronchial airways is unknown. METHODS: In order to explore the microvascular permeability and its potential inhibition by beta 2 agonists in human bronchial airways a dual induction method was developed: plasma exudation induced by histamine inhalation followed by sputum induction by hypertonic saline (4.5%) inhalation. Sixteen healthy subjects received formoterol (18 micrograms) in a placebo controlled, double blind, crossover study. Sputum was induced on five occasions: once at baseline and four times after histamine challenge (30 minutes and eight hours after both formoterol and placebo treatments). Sputum levels of alpha 2-macroglobulin were determined to indicate microvascular-epithelial exudation of bulk plasma. RESULTS: Histamine induced plasma exudation 30 minutes after placebo was considerably greater than at baseline (median difference 11.3 micrograms/ml (95% confidence interval 0.9 to 90.0)). At 30 minutes after formoterol the effect of histamine was reduced by 5.1 (0.9 to 61.9) micrograms/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formoterol was not demonstrated. CONCLUSION: This study shows for the first time an anti-exudative effect of a beta 2 agonist in healthy human bronchial airways. Through its physical and biological effects, plasma exudation is of multipotential pathogenic importance in asthma. If the present findings translate to disease conditions, it suggests that an anti-exudative effect may contribute to the anti-asthmatic activity of formoterol.

Adrenergic beta-Agonists↗
PubMed1998

Plasma-derived proteins in airway defence, disease and repair of epithelial injury.

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.

Animals↗
PubMed1998

Effects of orally inhaled budesonide in seasonal allergic rhinitis.

It has previously been demonstrated that topical nasal treatment with glucocorticosteroids has significant effects on the bronchial airways. Less is known about effects on nasal disease by topical bronchial treatment with these drugs. The present study examined effects on nasal allergic disease of inhaled budesonide (avoiding nasal deposition of the drug). Patients with seasonal allergic rhinitis, but without asthma, were thus given inhalations of budesonide (600 microg b.i.d.) or placebo. The aim of the design was to allow the study of eosinophilic airway disease in a part of the airway other than the directly treated locus. Moderate to high birch pollen levels were recorded during the study season, and nasal symptoms were significantly increased in both treatment groups, although they were milder in patients receiving budesonide than in the placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of eosinophil cationic protein as well as blood eosinophils were increased during the season (p<0.05), but these increases were prevented by the inhaled budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly elevated in the placebo group but did not differ between patients receiving placebo and budesonide. Budesonide prevented the seasonal development of increased bronchoconstrictor responses to methacholine challenge (p<0.05). In conclusion, budesonide reduced the seasonal eosinophilia both in the circulation and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects, inhaled budesonide produces clinically significant anti-inflammatory effects in the entire airways, including the nasal mucosa, which is not exposed topically to the drug. We suggest that nasal and systemic anti-eosinophil actions are produced at commonly employed dose levels of orally inhaled budesonide.

Administration, Inhalation↗
PubMed1997

Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo.

Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.

Administration, Topical↗
PubMed1997

Permeation of polysucrose 15000 across the human nasal mucosa in vivo.

Studies of the nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15,000 (approx. 14,700 Da), to predict the mucosal permeation of inhalational allergens. PS 15,000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.

Adult↗
PubMed1997

The "nasal pool"-device for challenge and lavage of the nasal mucosa in children: histamine-induced plasma exudation responses.

The accessibility of the nasal airway allows important examination of the airway mucosa in health and disease. However, the current methods for nasal challenge and lavage in children suffer from several shortcomings. In the present study, we have assessed the utility of a recently developed "nasal pool"-device in 7-9 year old children, and explored the ability of the nasal mucosa of these school-children to mount a plasma exudation response (lumenal entry of bulk plasma). Isotonic saline was instilled and maintained (1 min) as a "pool" in the unilateral nasal cavity. Recovery of the "pool" (lavage fluids) was determined. Concomitant challenge and lavage was then performed by exposing the nasal mucosa to a "pool" of isotonic saline and histamine (40-400 micrograms/ml) for 2 min. "Pool" fluids were analysed for alpha 2-macroglobulin as an index of microvascular-epithelial exudation of bulk plasma. The school-children successfully managed to carry out nasal lavages as well as concomitant histamine challenges and lavages with the "nasal pool"-device. The recovery of the nasal lavage fluids was almost quantitative (> 85%) and thus well reproducible. Histamine produced significant exudation of bulk plasma (alpha 2-macroglobulin). We suggest that the "nasal pool"-device is well suited for challenge and lavage of the nasal airway mucosa in children above 6 years of age, and conclude that lumenal entry of multipotent humoural protein-systems may be an important first line respiratory defence mechanism in children.

Child↗
PubMed1997

Effects of inhaled histamine, methacholine and capsaicin on sputum levels of alpha 2-macroglobulin.

BACKGROUND: Plasma exudation-derived proteins and peptides contribute significantly to inflammation in the airway mucosa in vivo. In the guinea pig trachea both histamine and the neurogenic stimulant capsaicin produce acute mucosal tissue distribution and luminal entry of bulk plasma, whereas cholinergic agonists fail to produce this effect. Of these agents, only histamine induces mucosal exudation of plasma in human nasal airways. The exudative effect of the above agents on human bronchi remains unknown. METHODS: The bronchial exudative responses to inhalation of histamine, methacholine, and capsaicin were examined in two groups of healthy volunteers. Sputum was induced on three occasions in each study group by inhalation of hypertonic saline (4.5%) given as an aerosol for 40 minutes using an ultrasonic nebuliser. The second and third occasions were preceded by histamine and capsaicin challenges in the first study group, and by histamine and methacholine challenges in the second study group. Histamine and methacholine were given in cumulative doses (total doses 3160 micrograms, respectively) or until a 20% reduction in forced expiratory volume in one second (FEV1) was achieved. Cumulative doses of capsaicin were inhaled until coughing prevented the subjects from drawing a full breath. Sputum levels of alpha 2-macroglobulin (729 kDa) were measured as an index of mucosal exudation of bulk plasma. RESULTS: Histamine increased mean (SE) sputum levels of alpha 2-macroglobulin from 2.72 (1.01) micrograms/ml (95% confidence interval (CI) 0.49 to 4.94) to 18.38 (8.03) micrograms/ml (95% CI 0.49 to 36.27) in the first group, and from 1.66 (0.84) micrograms/ml (95% CI -0.18 to 3.49) to 9.43 (3.63) micrograms/ml (95% CI 1.59 to 17.27) in the second group. In contrast, capsaicin evoked no exudation (sputum levels of alpha 2-macroglobulin 1.21 (0.28) micrograms/ml (95% CI 0.59 to 1.83)) and methacholine produced a minor increase in sputum levels of alpha 2-macroglobulin (2.90 (0.92) micrograms/ml (95% CI 0.90 to 4.89)). CONCLUSIONS: These results indicate that histamine is a useful agent for studying bronchial exudative responsiveness in man and that exudative effects are only of marginal importance in the cough and bronchoconstriction produced by capsaicin and methacholine.

Administration, Inhalation↗
PubMed1997

Reduced airway absorption in seasonal allergic rhinitis.

The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.

Absorption↗
PubMed1997

Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of alpha 2-macroglobulin into human nasal airways.

BACKGROUND: Oral anti-histamine drugs are widely used in the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become available also for topical treatment. OBJECTIVE: The present study, involving healthy subjects, examined the effect of topical azelastine on luminal entry of alpha 2-macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The effect was compared to a clinical dose of the oral anti-histamine cetirizine and to placebo treatments. METHODS: Placebo and azelastine (0.254 mg per nasal cavity) were delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10 mg) were given as single doses in a placebo-controlled (double-dummy), double-blind, and cross-over design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12, and 24 h after each treatment. The nasal mucosal surface was lavaged after each challenge. The lavage-fluid levels of alpha 2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored. RESULTS: Histamine (40-400 micrograms/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400 micrograms/mL histamine-induced mucosal exudation of plasma from 1-12 h after treatment. In addition, cetirizine reduced the 40 micrograms/mL histamine-induced mucosal exudation of plasma 24 h after treatment. Differences between the two treatments were not evident regarding nasal symptoms. CONCLUSION: Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action of antihistamines. We conclude that topical azelastine is suited for b.i.d. therapy and that neither the exudative process nor watery secretion may impede the efficacy or the duration of action of this nasal drug.

Administration, Intranasal↗
PubMed1997

Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways.

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.

Administration, Intranasal↗
PubMed1996

Skin plasma exudation and vasodilatation monitored by external detection of conversion electrons.

We have examined the plasma exudation response of inflammation in guinea pig skin by a noninvasive method and have evaluated the influence of vasodilatation. Indium radionuclides have been used to label plasma and blood and conversion electrons have been detected by an external detector. Transferrin (79,600 Da) was labeled by 111In or 113mIn in vivo and red blood cells were labeled by 111In in vitro. These tracers were given to separate groups of anesthetized guinea pigs and baseline activities were recorded from shaved skin surface areas. Skin prick tests with histamine and saline were performed and time-activity curves were recorded. The measurements with 111In-transferrin and 111In-labeled red blood cells demonstrated that histamine produced dose-dependent accumulation of plasma (up to a 6.5-fold increase) and blood (up to a 2.0-fold increase) in the skin. Hence, about one-third of accumulation of plasma induced by histamine may be explained by vasodilatation. With 113mIn-transferrin as plasma tracer greater effects of histamine were recorded, probably reflecting that the measurements also included deeper sections of the skin. We conclude that the intensity of accumulation of plasma in skin inflammation can be monitored by external detection of conversion electrons from 111In- and 113mIn-transferrin, and that the influence of vasodilatation can be estimated by detection of 111In-labeled red blood cells.

Animals↗
PubMed1996

Plasma exudation in the skin measured by external detection of conversion electrons.

A novel technique for measurement of plasma exudation in the skin is described. Transferrin labelled in vivo with indium-113m is used as a plasma tracer. The conversion electrons from 113mIn are detected with a polystyrene crystal mounted on a photomultiplier tube. Owing to the short range of the electrons in tissue, background radiation from tracer circulating in underlying tissue will be very small, allowing plasma exudation in the skin to be detected with a high signal to noise ratio. The characteristics of the detector system are described in model experiments using sheets of mylar to simulate soft tissue. The acute inflammatory response to histamine provocation was studied in guinea pig skin. A dose-related increase in count rate representing vasodilatation and plasma exudation was detected over the skin after histamine provocation. The electron radiation system appears suitable for detection of low levels of superficial radioactivity and for pathophysiological studies of the skin.

Animals↗
PubMed1996

Day-night differences in mucosal plasma proteins in common cold.

Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.

Adult↗
PubMed1995

Mechanisms of nasal hyper-reactivity.

Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivities in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the "increased absorption permeability theory", are disputed.

Allergens↗