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| 2. |
- Riise, Gerdt C., 1956, et al.
(author)
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Circulating cell adhesion molecules in bronchial lavage and serum in COPD patients with chronic bronchitis
- 1994
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In: Eur Respir J. - 0903-1936. ; 7:9, s. 1673-1677
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Journal article (peer-reviewed)abstract
- The initial phase of inflammation in bronchial asthma appears to be triggered by the expression of leucocyte-endothelial adhesion molecules on endothelial cell surfaces. Cell adhesion molecules (CAMs) cause adhesion of leucocytes to the endothelium prior to their subsequent extravasation into inflamed tissue. We wanted to determine whether circulating intercellular adhesion molecule-1 (cICAM-1) and circulating E-selectin (cE-selectin) could be detected in bronchial lavage fluid and serum in patients with stable chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Bronchoscopy and small volume bronchial lavage was performed in 19 patients with COPD and chronic bronchitis and in 13 control subjects. We found increased mean levels of cICAM-1 both in serum (481 micrograms.l-1) and in bronchial lavage (24 micrograms.l-1) in the COPD patients as compared to the controls (321 micrograms.l-1 in serum, 15 micrograms.l-1 in lavage). We also found higher mean levels of cE-selectin in serum from the COPD patients (86 micrograms.l-1) compared to controls (50 micrograms.l-1). The serum levels of cE-selectin correlated significantly with lung function measured as forced expiratory volume in one second (FEV1) in percentage of predicted. Patients with significant intrabronchial bacterial colonization had increased levels of serum cE-selectin. Our results indicate that cCAMs may reflect an upregulation of CAMs on endothelial and epithelial airway cells in COPD.
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| 3. |
- Arakawa, H, et al.
(author)
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Airway responses following intradermal sensitization to different types of allergens: ovalbumin, trimellitic anhydride and Dermatophagoides farinae
- 1995
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In: International Archives of Allergy and Immunology. - 1423-0097. ; 108:3, s. 274-280
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Journal article (peer-reviewed)abstract
- Sensitization of guinea pigs by intradermal injections of the occupational allergen trimellitic anhydride (TMA) in oily vehicle has been shown to be very reproducible. We studied the effect of intradermal sensitization with ovalbumin (OA) in oily vehicle on immune and airway responses in guinea pigs. We also compared airway responses to trimellitic anhydride or Dermatophagoides farinae (DF; mite) with those to OA in guinea pigs intradermally sensitized to respective allergens. Three to four weeks after sensitization, the animals were challenged with intratracheal instillation of these allergens. Intradermal injections with OA developed dose-dependently specific IgG1 antibodies to OA demonstrated by ELISA. In animals sensitized with different doses of OA in corn oil vehicle, a challenge with OA induced a reversely dose-dependent airflow obstruction and airway plasma exudation. In contrast, animals sensitized with OA in saline vehicle had dose-dependent airway responses to OA. Challenge with OA caused an immediate peak and subsequently persistent airflow obstruction, whereas this response to either TMA guinea pig serum albumin or Df was slowly progressive in animals sensitized to respective allergens. The animals sensitized to TMA or Df may show a different profile of airway responses following the challenge compared to OA. Intradermal sensitization may be a valuable method of sensitization for the development of an animal model of airway allergy to different types of allergens, including chemicals or mites.
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| 4. |
- Bergendal, Anna, et al.
(author)
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Airway effects of salmeterol in healthy individuals
- 1995
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In: Pulmonary Pharmacology. - : Elsevier BV. - 0952-0600. ; 8:6, s. 283-288
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Journal article (peer-reviewed)abstract
- The long-acting beta 2-agonist salmeterol has been shown in several in vitro studies to produce non-beta-mediated relaxant effects. The aim of the present study was to investigate whether these effects have any relevance in humans in vivo. Thirteen healthy individuals were studied in a randomized, double-blind, cross-over study on five separate days. The subjects were pre-treated orally with either propranolol 400 mg in order to block beta-adrenoceptor mediated effects or placebo. Two hours after drug intake, three increasing doses of salmeterol (25 + 50 + 100 micrograms), salbutamol (100 + 200 + 400 micrograms) or placebo were given from matched meter dose inhalers at 1-h intervals between doses. Specific airway conductance (sGAW) was measured in a body plethysmograph at the beginning of the experiment and 30 and 60 min after each inhaled dose of the beta-agonists. Salmeterol and salbutamol produced the same maximal increase in sGAW and had the same area under the dose-response curves. Pre-treatment with propranolol totally inhibited the effect of both drugs. In conclusion, salmeterol at clinically used doses did not produce any non-beta-mediated bronchodilating effect in normal individuals, measured as sGAW. Salmeterol and salbutamol showed the same efficacy but salmeterol was four times more potent than salbutamol.
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| 5. |
- Carlsson, L G, et al.
(author)
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Efficacy of cumulative doses of salbutamol administered via Turbuhaler or Diskhaler in patients with reversible airway obstruction
- 1998
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 53:7, s. 712-715
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Journal article (peer-reviewed)abstract
- The study aimed to estimate the relative dose potency of salbutamol inhaled via Turbuhaler and Diskhaler. The 24 adult patients participating had chronic reversible airway obstruction. The study was of a double-blind, double-dummy, crossover, randomized design. Five doses of salbutamol Turbuhaler, 50, 50, 100, 200, and 400 microg, were given on one study day at intervals of 30 min. On another study day, five doses of salbutamol Diskhaler, 200, 200, 400, 800, and 1600 microg, were given with the same interval. The treatment days were separated by a washout period of at least 24 h. The inhalation technique was standardized and supervised. Efficacy variables were recorded before and after each study dose. The primary efficacy variable was forced expiratory volume in 1 s (FEV1). When parallel and linear cumulative dose-response curves were statistically compared on a logarithmic scale, the dose potency of salbutamol Turbuhaler vs salbutamol Diskhaler was 1.99 (95% confidence interval 1.52-2.54). This study indicates that only half the dose of salbutamol is required via Turbuhaler as via Diskhaler for the same bronchodilating effect.
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| 6. |
- Ekberg-Jansson, A, et al.
(author)
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A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space
- 1999
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In: Respiratory Medicine. - 1532-3064. ; 93:8, s. 563-570
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Journal article (peer-reviewed)abstract
- In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+, helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+/CD3+8+ in BAL than in blood (3.4 vs 1.7; P = 0.001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment. We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.
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| 7. |
- Juniper, E F, et al.
(author)
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Asthma quality of life during 1 year of treatment with budesonide with or without formoterol
- 1999
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In: European Respiratory Journal. - 1399-3003. ; 14:5, s. 1038-1043
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Journal article (peer-reviewed)abstract
- The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting beta2-agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life. Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 microg budesonide, patients were randomized to either 200 microg (Bud200) or 800 microg budesonide (Bud800) in combination with either 24 microg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months. During the run-in, there was an improvement in AQLQ score (changes (delta) in overall score approximately 0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (delta=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51). Improvements in quality of life, which were greatest in the 800 microg budesonide plus 24 microg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience.
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| 8. |
- Löfdahl, Claes-Göran
(author)
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Corticosteroides
- 1998
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In: Revue des Maladies Respiratoires. - 0761-8425. ; 15, s. 42-42
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Journal article (peer-reviewed)
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| 9. |
- Löfdahl, Claes-Göran, et al.
(author)
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Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction
- 1997
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 10:11, s. 2474-2478
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Journal article (peer-reviewed)abstract
- Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.
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| 10. |
- Löfdahl, Claes-Göran, et al.
(author)
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Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients
- 1999
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In: BMJ. - 0959-8138. ; 319:7202, s. 87-90
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. DESIGN: Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. SETTING: 23 academic asthma centres in United States, Canada, and Europe. PARTICIPANTS: 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). INTERVENTIONS: Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. MAIN OUTCOME MEASURES: Last tolerated dose of inhaled corticosteroids. RESULTS: Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue. CONCLUSIONS: Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.
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