[Show abstract][Hide abstract] ABSTRACT: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment.
Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations.
There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE' (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy.
CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information.
[Show abstract][Hide abstract] ABSTRACT: Exposure to high ambient levels of nitrogen dioxide (NO2) enhances the bronchial inflammatory reaction to allergen in humans. We tested whether this NO2 effect occurs also in the upper airways.
Sixteen allergic subjects with rhinitis and mild asthma were exposed at rest to either purified air or 500 microg/m3 NO2 for 30 minutes, followed 4 hours later by a nasal allergen challenge. Nasal lavage was performed before air/NO2 exposure, before allergen challenge, and 1, 4 and 18 hours after allergen challenge. Symptoms were recorded.
The percentage of eosinophils and neutrophils, eosinophil cationic protein, and myeloperoxidase were similar after exposure to air + allergen and to NO2 + allergen. We noticed a tendency to increased sneezing the day after exposure to NO2 + allergen.
The priming effect of an ambient brief NO2 exposure on subsequent allergic response was not noticeable in activation of inflammatory cells and mediators in the upper airways.
No preview · Article · Nov 2005 · American Journal of Rhinology
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of asthma is complex and engages cascades of events in the cytokine network. We, therefore, investigated the impact of bronchial allergen challenge in humans on the cytokine profile of circulating lymphocytes. Peripheral blood samples from 10 patients with allergic asthma were collected before and 24 h after allergen provocation. Patients who mounted a late-phase reaction were designated dual responders opposite to single responders. Whole blood cells were stimulated by mitogen and intracellular interleukin (IL)-4 and interferon (IFN)-gamma were detected by flow cytometry. The allergen challenge induced a decrease in IL-4+CD4+ cells in the patients (P = 0.05), and a significant decrease (P < 0.05) in IFN-gamma+CD4+ cells was noted in single, but not dual, responders. In addition, there was a significant difference (P < 0.01) with respect to the changes in the IFN-gamma+CD4+ cells comparing dual and single responders. No corresponding changes were observed in CD8+ cells. The data suggest a possible on-going traffic of IFN-gamma and IL-4+CD4+ lymphocytes into the bronchial mucosa in relation to an allergen challenge and generate the hypothesis that a difference exists between single and dual responders in this respect. Because the CD4+IFN-gamma-producing cells have the capacity to downregulate the T-helper type 2 response, a reduced capacity in this aspect might contribute to the pathophysiology in dual responders.
Full-text · Article · Aug 2005 · Scandinavian Journal of Immunology
[Show abstract][Hide abstract] ABSTRACT: Counting eosinophils in induced sputum seems to be a better way to survey disease activity than indirect clinical assessments of airway inflammation, such as pulmonary function measurement. The conventional analysis of induced sputum, however, is time-consuming and requires skilled personnel, which have restricted its use.
To determine whether measuring eosinophil cationic protein (ECP) levels in the entire sputum sample could replace the method of counting eosinophils and measuring ECP levels in the supernatant only to establish a clinically more applicable method of studying the intraindividual changes in eosinophilic activity in induced sputum.
In 13 patients with mild, nonsymptomatic allergic asthma, sputum was induced before and 24 hours after allergen challenge. The entire sputum sample was diluted with 0.1% dithiothreitol, incubated, and divided into 2 parts. One part was processed according to the conventional method, and released ECP levels in the supernatant were measured. The second part was treated with a lysing reagent. Cell debris was separated, and total (intracellular and extracellular) ECP levels in the solution were measured.
We found good correlation between total ECP levels in the entire sputum sample and released ECP levels in the supernatant before (r = 0.97) and 24 hours after (r = 0.99) allergen challenge (P < .01 for both). We also found a good correlation between the changes in total and released ECP levels (r = 0.99; P < .01).
Total ECP concentration seems to reflect the eosinophilic inflammatory changes in asthma and might be a useful tool in clinical practice.
No preview · Article · Jul 2005 · Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology
[Show abstract][Hide abstract] ABSTRACT: Exposure to high ambient levels of nitrogen dioxide (NO2) enhances the airway reaction in humans to allergen, measured as decreased pulmonary function. We tested whether this NO2 effect is associated with an increased inflammatory response to allergen in the airways. To mimic real-life conditions, in which exposure to high ambient levels of NO2 occurs only during short periods of time but often several times a day, we used a repeated-exposure model. On day 1, 18 subjects with allergic asthma were exposed, in randomized order, to purified air or to 500 microg/m3 NO2 for 15 min, and on day 2 for 2 x 15 min. Allergen was inhaled 3-4h after the NO2 exposures on both days. Symptoms, pulmonary function, and inflammatory response in sputum and blood were measured daily. Eosinophil cationic protein in both sputum and blood increased more from day 1 to day 3 after NO2+allergen than after air+allergen, whereas eosinophil counts did not differ. The change in myeloperoxidase was significantly greater after NO2+allergen than after air+allergen in blood but not in sputum. This finding was not accompanied by raised levels of neutrophils in sputum and blood. Symptoms and pulmonary function were equally affected by NO2+allergen and air+allergen. We conclude that two to three brief exposures to ambient levels of NO2 can prime circulating eosinophils and enhance the eosinophilic activity in sputum in response to inhaled allergen. This might be an important mechanism by which air pollutants amplify the inflammatory reactions in the airways.
No preview · Article · Feb 2005 · Environmental Research
[Show abstract][Hide abstract] ABSTRACT: Air pollution constitutes an important factor for asthma aggravation, and there is increased concern about respiratory health effects of common air pollutants. The purpose of this study was to examine how exposure to a high ambient concentration nitrogen dioxide (NO2) prior to a bronchial allergen challenge modulated the inflammatory response in the bronchi. Thirteen subjects with mild asthma and allergy were exposed at rest to either purified air or 500 microg x m 3 NO2 for 30 min, followed 4 h later by an allergen inhalation challenge. The exposures (NO2 or air) were performed in random order and at least 4 weeks apart. Lung function during NO2/air exposure and allergen challenge was measured by plethysmography, and then hourly by portable spirometry after exposures. Subjective symptoms were recorded during and after exposure. Bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 19 h after allergen challenge. NO2+allergen enhanced the percentage of neutrophils in both BW and BAL compared to air+allergen (BW 19 vs. 11, P=0.05; BAL 3 vs. 1, P=0.02 median values). The levels of eosinophil cationic protein (ECP) in BW was higher after NO2+allergen compared to air+allergen (90 vs. 3.6 microg/l; P=0.02, median values). There was no NO2-associated effect on symptoms or pulmonary function. These data suggest that ambient NO2 can enhance allergic inflammatory reaction in the airways without causing symptoms or pulmonary dysfunction.
Full-text · Article · Dec 2002 · Respiratory Medicine
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess whether air pollution in road tunnels would promote asthmatic reactions in persons with mild allergic asthma. Twenty volunteers with mild allergic asthma were exposed, inside a car, for 30 min in a Stockholm city road tunnel. As a control, the subjects were exposed to much lower pollution levels in a suburban area. Four hours after the exposure, the subjects inhaled a low dose of allergen. Asthmatic reaction during the early phase was measured as the increase in specific airway resistance 15 min after allergen inhalation and during the late phase as the decrease in lung function forced expiratory volume in one second 3-10 h after allergen inhalation. Asthma symptoms and drug use were monitored up to 18 h after allergen inhalation. The median nitrogen dioxide level during exposure was 313 microg x m-3 (range 203-462). The median levels of particles with 50% cut-off aerodynamic diameters of 10 (PM10) and 2.5 microm (PM2.5) were 170 (range 103-613) and 95 (range 61-218) micro x m-3, respectively. Subjective symptoms during tunnel exposure were not pronounced. However, subjects exposed to tunnel N02 levels of > or = 300 microg x m-3 had a significantly greater early reaction, following allergen exposure, as well as lower lung function and more asthma symptoms during the late phase, compared to control. Also, subjects with PM2.5 exposure > or = 100 microg x m-3 had a slightly increased early reaction compared to control. In conclusion, exposure to air pollution in road tunnels may significantly enhance asthmatic reactions to subsequently inhaled allergens.
Full-text · Article · May 2000 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: Important aims of the study were to investigate whether an educational program (the 'Asthma School') directed by a nurse led to improved knowledge of the disease, to improved self-medication and self-management and to improved, self-rated, functional status. A total of 32 patients (6 males, 26 females, mean age 43 years) was included. The following methods were used to collect the data before and one year after the Asthma School was completed; two study-specific questionnaires for collecting demographic data and measuring different aspects of the patients' knowledge of the disease and its treatment, monthly diary cards, lung-function tests (FEV1) and the Sickness Impact Profile (SIP) questionnaire. The main results of the study were an improved knowledge of the disease and its treatment, better self-management, i.e. more frequent use of the peak expiratory flow meter (PEF-meter) and use of inhaled bronchodilators on an as-required basis, fewer patients on sick-leave and a better, self-rated, physical health status. However, in spite of these encouraging results, the lungfunction was found to be unaffected, no pronounced changes in the use of asthma drugs could be found and the patients' need for medical care remained the same.
Preview · Article · May 1999 · International Journal of Nursing Studies
[Show abstract][Hide abstract] ABSTRACT: Asthma tends to affect mucociliary clearance, as assessed from measurements in large airways. However, there is no knowledge about clearance in the smallest airways of the tracheobronchial region in acute exacerbation of asthma.
The aim of the study was to investigate clearance from the bronchiolar region in patients with allergic asthma in a situation resembling a mild acute exacerbation of the disease. We also aimed to compare clearance data with corresponding data found for healthy subjects and asthmatics on therapy.
Tracheobronchial clearance was studied twice in 9 patients with mild asthma of the allergic type after inhalation of 6 microm (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. At one exposure, inhalation was performed 4 h after bronchial provocation with an allergen the patients were allergic to. The second exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h.
All patients demonstrated an early asthmatic reaction of varying degree after bronchial provocation. There was significant clearance of radioaerosol in each 24-hour period for both exposures, with the possible exception of the period between 24 and 48 h for the provocation exposure, with similar fractions of retained particles at all points of time. The retained fractions were significantly larger compared to a group of healthy subjects and asthmatics on regular treatment with anti-inflammatory drugs.
Our results indicate that in allergic asthmatics a bronchial allergen provocation with an early asthmatic reaction does not significantly influence overall clearance from the bronchiolar region. However, in the present group of patients, retention in small ciliated airways was significantly higher compared to healthy subjects and asthmatics on regular treatment.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.
Full-text · Article · Aug 1998 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: We investigated whether exposure to a low level (490 micrograms/m3) of nitrogen dioxide (NO2) affects bronchial responsiveness to allergen and enhances allergen-induced increase in airway responsiveness to histamine. Eighteen subjects with asthma and allergy to pollen were exposed at rest to either purified air or NO2 for 30 min followed 4 h later by an allergen inhalation challenge. Responsiveness to histamine was measured the day after. Lung function during NO2 exposure and allergen challenge was measured by plethysmography and after exposure by a portable spirometer hourly. The order of exposure to NO2 and air was randomized and separated by at least 2 wk. The asthmatic reaction during the late phase was enhanced by NO2, and peak expiratory flow after allergen challenge was on average 6.6% lower (p = 0.02) after NO2 than after air exposure. The number of subjects having a late asthmatic reaction (fall in FEV1 > 15%) was seven after air and 10 after NO2 (NS). Peripheral blood samples were analyzed for differential cell counts before and after NO2/allergen and serum levels of eosinophil cationic protein (ECP). NO2 effect on lung function was neither associated with an increase in eosinophil numbers nor with ECP levels. NO2 did not affect lung function before allergen challenge, early asthmatic reaction, and allergen-induced increase in responsiveness to histamine. These results indicate that short exposure to an ambient level of NO2 followed several hours later by allergen inhalation enhances allergen-induced late asthmatic reaction.
No preview · Article · Mar 1997 · American Journal of Respiratory and Critical Care Medicine
[Show abstract][Hide abstract] ABSTRACT: The response of peripheral neutrophils was studied in 16 patients with allergic asthma after challenge with birch/grass pollen allergen, in order to identify inflammatory markers associated with only the early asthmatic reaction and those associated with both early and late asthmatic reactions. The allergen challenge proceeded until the patients had an early asthmatic reaction with 100% increase in specific airway resistance. Bronchoconstriction after allergen challenge was monitored hourly over 9 h and finally after 18 h, by measurement of the forced expiratory volume in 1 s. Seven patients had a late reaction, defined as a decrease in forced expiratory volume in 1 s of more than 15%. Blood samples were taken before and 18 h after challenge. After allergen challenge (18 h) the blood concentration of neutrophils in patients with a late asthmatic reaction was 1.4 times higher than before challenge and there was a tendency for increased Fc gamma receptor-mediated chemiluminescence. Lewis X-antigen (CD 15), which is associated with endothelial adhesion and extravasation, significantly decreased at the same time. Neutrophils were incubated with the tetrapeptide arginine-glycine-aspartate-serine before and 18 h after allergen challenge. Both patient groups showed an increased Fc gamma receptor-mediated chemiluminescence and a decreased Fc gamma receptor membrane expression following allergen challenge, suggesting a preactivation. In conclusion, patients with a dual asthmatic reaction show a sustained primed inflammatory response and primed neutrophils compared with patients with only an early reaction when measured after the decline of clinical symptoms provoked by allergen challenge.
No preview · Article · Feb 1997 · International Journal of Clinical & Laboratory Research
[Show abstract][Hide abstract] ABSTRACT: The time-kinetics of NO2 induced effects on bronchial responsiveness are poorly known as most observations have been made shortly after exposure. The aim of this study was to measure nonspecific bronchial responsiveness, lung function and inflammatory markers at different times after NO2 exposure in asthmatics. Nineteen subjects with mild asthma were exposed to either purified air or 488 micrograms.m-3 (0.26 ppm) NO2 for 30 min during intermittent exercise. Airway responsiveness to histamine, specific airway resistance (sRaw) and thoracic gas volume (TGV) were measured 30 min, 5 h, 27 h and 7 days after exposure. Peripheral blood inflammatory mediators and the expression of an adhesion molecule, (Mac1) on granulocytes, were analysed 30 min and 27 h after exposure. Bronchial responsiveness to histamine was significantly increased 5 h after NO2 exposure when compared to air (median provocative dose of histamine required to cause 100% increase of sRaw ((PDsRaw,100%) 110 micrograms after NO2 exposure vs 203 micrograms on air). There was a tendency for an increase after 30 min, which was nonsignificant (median PDsRaw,100% 100 vs 153 micrograms). NO2 exposure did not affect sRaw, but TGV was significantly reduced after exposure. We found an increased expression of Mac-1 on granulocytes 30 min after NO2 exposure when compared to pre-exposure values. No effect was seen on tryptase, eosinophil cationic protein (ECP), or myeloperoxidase (MPO). These results suggest that exposure to an ambient level of NO2 causes a delayed effect on bronchial responsiveness in asthmatics. The increased expression of an adhesion molecule in peripheral blood may indicate a NO2-induced priming of human granulocytes.
Preview · Article · May 1996 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: Ground-level ozone is formed in complex atmospheric photochemical reactions between nitrogen oxides and hydrocarbons. The levels are highest in summertime and outside city centers. Elevated concentrations of ground-level ozone is mainly due to chemical reactions of emissions of volatile organic compounds and nitrogen oxides. The average concentrations of ground-level ozone occurring in non-urban areas in western Europe range from 40 to 70 μg.m-3. One-hour maximum values may reach 300 μg.m-3 in central Europe and 200 μg.m-3 in Sweden. Numerous studies, ranging from experimental studies with laboratory animals to controlled studies with humans to epidemiologic studies, have been performed on the health effects of ozone. In animal experiments, morphological effects on lung tissue, effects on host defense mechanisms, inflammation, fibrosis and tumors have all been induced by the inhalation of ozone. The lowest concentration tested that has given rise to these effects is 200 μg.m-3. It led to hyperplastic changes, proinflammatory changes, and sensitization to allergens. In chamber exposure studies of 1- to 6-h duration, respiratory symptoms and pulmonary effects such as lung function decrements, increased airway responsiveness, and inflammatory reactions have all been demonstrated in humans. These effects have occurred even at the lowest concentration tested, 160 μg.m-3 for 6 h. Reduced lung function at 1-h maximum daily values of 160 μg.m-3 has also been found in epidemiologic studies, and some reports indicate effects at even lower levels. Other effects of ozone seen in epidemiologic studies include respiratory symptoms, hospital admissions, and emergency room visits for respiratory conditions, all of which correlated with daily 1-h maximum values of 240 μg.m-3 and lower. From these data on humans, and with the use of a safety factor of 2, a 1-h guideline value of 80 μg.m-3 is recommended. This level is also intended to protect against health effects in the most sensitive sections of the population. The proposed guideline level is currently exceeded and should be regarded as a goal for action to avoid adverse health effects in the future. The experimental and epidemiologic basis for a risk assessment concerning long-term exposure is much weaker than for short-term exposure, and no explicit long-term guideline value is recommended. However, the proposed short-term guideline would probably offer some protection against potential effects of ozone following long-term exposure.
[Show abstract][Hide abstract] ABSTRACT: Mouth and throat, and regional lung deposition was estimated in fifteen asthmatic subjects for 3.6-microns (aerodynamic diameter) radiolabeled polytetrafluoroethylene (Teflon) particles inhaled at 0.5 L/s with and without added external resistance. Radioactivity was measured by a profile scanner. Behavior of the pharynx and larynx was assessed by fiberoptic laryngoscopy. Mean mouth and throat deposition was 22% (range, 13 to 47%) and 33% (range, 12 to 84%) with and without resistance (p < 0.05), respectively. A marked reduction in mouth and throat deposition (range, 20 to 44%), with a corresponding increase in lung deposition, was observed especially in the six subjects with mouth and throat deposition values > 30% at inhalation without resistance. Furthermore, a small (mean 8%) but significant (p < 0.05) increase in peripheral lung deposition, estimated as retention at 24 h, was found at inhalation with increased resistance. The fiberoptic examination showed wide intersubject variability in the pharynx and larynx, with tendencies toward higher mouth and throat deposition with pharyngeal narrowing, and significantly (p < 0.05) lower lung retention with laryngeal narrowing. Our results show that an external resistance reduces mouth and throat deposition and increases deposition and retention of aerosol particles in the lungs in asthmatic individuals.
No preview · Article · Aug 1995 · American Journal of Respiratory and Critical Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Variability in airway conductance (Gaw) and lung volume (TGV) was studied in 26 subjects with moderately severe asthma during a 9-week period. Specific airway conductance (SGaw) was calculated as Gaw:TGV. There was considerable inter-individual variability in airway conductance, and a smaller variability in TGV. Airway conductance (SGaw) showed an eight-fold difference and TGV a three-fold difference between smallest and largest values. The intra-individual variability was less, with a range of +/- 55% (SGaw) and +/- 12% (TGV) of the grand mean, respectively. The error of the method contributed only marginally to the variations in airway conductance. These data for spontaneous variability of conductance facilitate, for example, the assessment of the clinical importance of changes in lung function seen after exposure to air pollutants in chamber studies. Furthermore, the substantial inter-individual variability in conductance argues against comparing samples of asthmatic subjects in polluted and non-polluted areas, and in favour of prospective studies of cohorts of subjects with asthma.
No preview · Article · Jun 1995 · Clinical Physiology
[Show abstract][Hide abstract] ABSTRACT: We previously studied the deposition of inhaled particles in the mouth and throat of asthmatic patients, and found large, reproducible differences among subjects. In the present study, we examined whether anatomical and/or functional differences in the pharynx and larynx could underlie this interindividual variation. Deposition in the mouth and throat, and in the lung was estimated in 16 asthmatic subjects after inhalation of 3.6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at a flow rate of 0.5 l.s-1 with maximally deep breaths. Radioactivity was measured by external scanning over head and neck, lungs and stomach, immediately after the inhalation. Radioactivity in the lungs was also measured 24 h later. A measure of the total amount of particles deposited in the mouth and throat was obtained from the added activities in mouthwash, head and neck, and stomach, immediately after the inhalation of the test particles. Pharynx and larynx function was examined by fibreoptic laryngoscopy performed during a corresponding inhalation procedure. Deposition in the mouth and throat varied widely among the subjects, ranging 9-76% (median 12%). We found two subpopulations, 13 subjects in the range 9-34%, and 3 subjects with > 70% deposition. Deviations in pharyngeal configuration during inhalation were significantly related to high mouth and throat deposition, whereas functional differences in the larynx were not. Our study shows that mouth and throat deposition may be extremely high in some asthmatics, and that pharyngeal configuration affects deposition of particles in the mouth and throat.
Full-text · Article · Aug 1994 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: 1. Adrenoceptor subtype function was studied in isolated adipocytes obtained by subcutaneous fat biopsies from nine patients with mild asthma. The biopsies were taken before and after 7 days treatment with 25 mg of prednisolone given orally. Lipolytic activity after stimulation with various adrenergic agent was measured, using glycerol release as an index of lipolysis. The number of beta 1- and beta 2-adrenoceptor binding sites was determined in radioligand binding experiments and beta 1- and beta 2-adrenoceptor mRNA levels were measured with a solution hybridization assay. 2. Lipolytic sensitivity (ED50) to isoprenaline, a non-selective beta-adrenoceptor agonist, increased 50-fold after treatment (P = 0.04). Sensitivity to terbutaline, a selective beta 2-adrenoceptor agonist, increased 25-fold (P = 0.01), whereas the ED50 values for dobutamine, a selective beta 1-adrenoceptor agonist, did not change significantly. Likewise, the sensitivity to the alpha 2-adrenoceptor agonist, clonidine, and to the drugs acting at post-receptor levels did not change significantly. Basal and maximum lipolytic rates on stimulation were not altered by the treatment. 3. The number of beta 2-adrenoceptor binding sites increased by 60% after treatment (P < 0.05), whereas the beta 1-adrenoceptor binding sites were not affected. The affinity of each receptor subtype for the displacing ligand, ICI 118.551, was not significantly altered by steroids. No significant changes were demonstrated in either beta 1- or beta 2-adrenoceptor mRNA levels. 4. Thus, glucocorticoids selectively increase beta 2-adrenoceptor density and function in patients with asthma, studied by using subcutaneous fat cells as an experimental model.
No preview · Article · Aug 1993 · Clinical Science
[Show abstract][Hide abstract] ABSTRACT: Ten subjects with asthma inhaled 3.6 micron particles labeled with 111In in air and in a helium-oxygen mixture (He-O2) at 0.5 and at 1.2 L/s. Lung retention was measured after zero and after 24 h, and the percentage 24-h retention (Ret24) was taken to represent the fraction deposited in the alveolar part of the lung. For both inhalation rates, Ret24 was significantly higher when particles were inhaled with He-O2 than with air. The increase in Ret24 seemed to be larger in subjects with asthma than in healthy persons earlier studied. Ret24 was correlated with changes in both large and small airways, especially when the particles were inhaled with He-O2. Our data suggest that inhalation of drugs in He-O2 might be of therapeutic value when treating patients with severely obstructed airways.
No preview · Article · Apr 1993 · The American review of respiratory disease