| 1. |
- Bergendal, Anna, et al.
(författare)
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Airway effects of salmeterol in healthy individuals
- 1995
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Ingår i: Pulmonary Pharmacology. - : Elsevier BV. - 0952-0600. ; 8:6, s. 283-288
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Kawikova, Ivana, et al.
(författare)
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Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction
- 1995
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 280:3, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects are associated with a local thromboxane A2 release.
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| 3. |
- Nwaru, Bright, et al.
(författare)
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Patterns of sensitization to furry animal allergen components in adult asthma and indicators of severity
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Whilst the role of allergen component sensitization in asthma has been investigated in children, studies in adults are lacking.Aim: To study the relationship between patterns of sensitization to furry animal allergen components and asthma, concomitant asthma/allergic rhinitis, and indicators of asthma severity in a population-representative adult sample.Methods: From the West Sweden Asthma Study, 2006 were clinically phenotyped, of which 1872 had Phadiatop analyzed. Those with IgE>0.35 kUA/L were then analyzed for specific cat (Fel d 1, 2, & 4), dog (Can f 1, 2, 3, & 5), and horse (Equ c 1) allergen components. Sensitization patterns were defined as mono-, double-, and poly-sensitization (i.e. >2 components). Outcomes were current asthma, current allergic rhinitis, concomitant asthma/rhinitis, and indicators of asthma severity.Results: Mono-, double-, and poly-sensitization to furry animal components were each associated with a substantial increased risk of asthma, allergic rhinitis, concomitant asthma/rhinitis, and ACT well-controlled asthma. Poly-sensitization was further associated with increased FeNo (β 0.43, 95%CI 0.18 to 0.68) and eosinophil (β 0.26, 95%CI 0.02 to 0.50) levels, and lower PD20 methacoline values (β -0.57, 95%CI -0.99 to -0.15). Sensitization patterns were not associated with asthma exacerbations, FEV1 values, emergency visits or oral steroid use, and neutrophil levels.Conclusion: Patterns of sensitization to furry animal allergen components are a good predictor of clinical outcomes and indicators of asthma severity in adults, but only poly-sensitization had impact on eosinophilic inflammatory markers of severity.
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