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- Holgate, S. T., et al.
(författare)
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Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma
- 2004
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 34:4, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need. Objective This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma. Methods After a run-in period when an optimized fluticasone dose (greater than or equal to1000 mug/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed. Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a greater than or equal to50% dose reduction (P=0.001). Fluticasone dose reduction to less than or equal to500 mug/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo. Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
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| 4. |
- Joos, GF, et al.
(författare)
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Indirect airway challenges
- 2003
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 21:6, s. 1050-1068
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Arakawa, H, et al.
(författare)
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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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Ingår i: International Archives of Allergy and Immunology. - 1423-0097. ; 108:3, s. 274-280
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Arakawa, H, et al.
(författare)
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Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 259:3, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 +/- 3 g: 2 weeks) and adult guinea pigs (512 +/- 5 g: 11 weeks). In the same animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in RL in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in RL did not change with age (leukotriene D4 > U-46619 > acetylcholine). In immature animals, the peak RL after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 8. |
- Arvidsson, P, et al.
(författare)
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Exudation of plasma and production of thromboxane in human bronchi after local bradykinin challenge
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:5, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Plasma exudation has been suggested to be an important component of the inflammatory response in asthma. Bradykinin elicits many of the features of asthma, including bronchoconstriction, cough, plasma exudation and mucus secretion. In an attempt to quantify local plasma exudation, we have employed a novel low-trauma technique with the aim of challenging and lavaging a central part of the bronchial tree, by selecting a medium sized bronchus. A fibreoptic bronchoscopy was performed in non-smoking healthy volunteers. The instrument was placed proximally in the right upper lobe bronchus. A plastic catheter, equipped with an inflatable latex balloon, was inflated with air (2-4 cmH2O). A solution (100 microl of either two different concentrations of bradykinin: 0.09 and 0.9 mg ml(-1) or normal saline) was instilled through the catheter and distal to the balloon. Eight minutes later a lavage procedure with 10 ml of saline was performed through the catheter. The procedure was then repeated twice, with the other solutions, but from the lingular and middle lobe bronchi. All solutions were given in a blinded fashion, and two different studies were performed. Lavage concentrations of albumin and IgG were quantified as measurements of plasma exudation. In our first study we found that bradykinin challenge significantly increased concentrations of albumin and IgG. In study two, there was no numeric increase in plasma proteins after local bradykinin challenge, but the concentration of thromboxane was significantly increased in lavages from bradykinin-challenged bronchi. Thus, local bronchial administration of bradykinin has the capacity to induce exudation of large plasma macromolecules into the bronchial lumen, as well as local thromboxane production.
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