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Stephen T Holgate - One of the best experts on this subject based on the ideXlab platform.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Angel Fowlertaylor, John G Matthews, William W Busse, Stephen T HolgateAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with impr...
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Efficacy and safEty of a rEcombinant anti Immunoglobulin E Antibody omalizumab in sEvErE allErgic asthma
Clinical & Experimental Allergy, 2004Co-Authors: Stephen T Holgate, Jean Bousquet, A G Chuchalin, J Hebert, Jan Lotvall, G Persson, Kian Fan Chung, Huib A M Kerstjens, H Fox, J ThirlwellAbstract: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. (LEss)
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Efficacy and safEty of a rEcombinant anti Immunoglobulin E Antibody omalizumab in sEvErE allErgic asthma
Clinical & Experimental Allergy, 2004Co-Authors: Stephen T Holgate, Jean Bousquet, A G Chuchalin, J Hebert, Jan Lotvall, Kian Fan Chung, Huib A M Kerstjens, J Thirlwell, G B Persson, G Della CioppaAbstract: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 (> or =1000 microg/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 > or =50% dosE rEduction (P=0.001). FluticasonE dosE rEduction to < or =500 microg/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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Efficacy of omalizumab an anti Immunoglobulin E Antibody in patiEnts with allErgic asthma at high risk of sErious asthma rElatEd morbidity and mortality
Current Medical Research and Opinion, 2001Co-Authors: Stephen T Holgate, Jean Bousquet, Sally E Wenzel, Jordi CastellsagueAbstract:SummaryAim: Add-on thErapy with omalizumab, an anti-Immunoglobulin E Antibody, is EffEctivE in improving disEasE control in patiEnts with allErgic asthma of varying sEvErity. ThE aim of thE prEsEnt study was to dEtErminE thE Efficacy of omalizumab in a subgroup of patiEnts at high risk of sErious asthma-rElatEd morbidity and mortality.MEthods: A mEta-analysis was pErformEd of thrEE randomisEd, doublE-blind, placEbo-controllEd studiEs (studiEs 1, 2 and 3) that EnrollEd 1412 patiEnts with modEratE or sEvErE allErgic asthma, all rEquiring daily trEatmEnt with inhalEd corticostEroids (ICS). Omalizumab was administErEd subcutanEously EvEry 2 or 4 wEEks at a total 4-wEEkly dosE of at lEast 0.016mg/kg/IgE [IU/ml]. Each study consistEd of a 16-wEEk stEroid-stablE phasE and a 12-16-wEEk stEroid-rEduction phasE, followEd by a 24-wEEk ExtEnsion phasE (studiEs 1 and 2 only). ThE primary outcomE mEasurE was thE annualisEd ratE of significant asthma ExacErbation EpisodEs (sAEEs) during thE stEroid-stablE phasE for thE ...
William W Busse - One of the best experts on this subject based on the ideXlab platform.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Weibin Bao, Angel Fowlertaylor, John G Matthews, William W BusseAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with improvEmEnt in airway hypErrEsponsivEnEss to mEthacholinE. This study shows antiinflammatory EffEcts of omalizumab trEatmEnt and providEs cluEs for mEchanisms whErEby omalizumab rEducEs asthma ExacErbations and othEr asthma outcomEs in morE sEvErE asthma. ThE lack of EffEct of omalizumab on mEthacholinE rEsponsivEnEss suggEsts that IgE or Eosinophils may not bE causally linkEd to airway hypErrEsponsivEnEss to mEthacholinE in mild to modEratE asthma.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Angel Fowlertaylor, John G Matthews, William W Busse, Stephen T HolgateAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with impr...
Ratko Djukanovic - One of the best experts on this subject based on the ideXlab platform.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Weibin Bao, Angel Fowlertaylor, John G Matthews, William W BusseAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with improvEmEnt in airway hypErrEsponsivEnEss to mEthacholinE. This study shows antiinflammatory EffEcts of omalizumab trEatmEnt and providEs cluEs for mEchanisms whErEby omalizumab rEducEs asthma ExacErbations and othEr asthma outcomEs in morE sEvErE asthma. ThE lack of EffEct of omalizumab on mEthacholinE rEsponsivEnEss suggEsts that IgE or Eosinophils may not bE causally linkEd to airway hypErrEsponsivEnEss to mEthacholinE in mild to modEratE asthma.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Angel Fowlertaylor, John G Matthews, William W Busse, Stephen T HolgateAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with impr...
Fan K Chung - One of the best experts on this subject based on the ideXlab platform.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Weibin Bao, Angel Fowlertaylor, John G Matthews, William W BusseAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with improvEmEnt in airway hypErrEsponsivEnEss to mEthacholinE. This study shows antiinflammatory EffEcts of omalizumab trEatmEnt and providEs cluEs for mEchanisms whErEby omalizumab rEducEs asthma ExacErbations and othEr asthma outcomEs in morE sEvErE asthma. ThE lack of EffEct of omalizumab on mEthacholinE rEsponsivEnEss suggEsts that IgE or Eosinophils may not bE causally linkEd to airway hypErrEsponsivEnEss to mEthacholinE in mild to modEratE asthma.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Angel Fowlertaylor, John G Matthews, William W Busse, Stephen T HolgateAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with impr...
John G Matthews - One of the best experts on this subject based on the ideXlab platform.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Weibin Bao, Angel Fowlertaylor, John G Matthews, William W BusseAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with improvEmEnt in airway hypErrEsponsivEnEss to mEthacholinE. This study shows antiinflammatory EffEcts of omalizumab trEatmEnt and providEs cluEs for mEchanisms whErEby omalizumab rEducEs asthma ExacErbations and othEr asthma outcomEs in morE sEvErE asthma. ThE lack of EffEct of omalizumab on mEthacholinE rEsponsivEnEss suggEsts that IgE or Eosinophils may not bE causally linkEd to airway hypErrEsponsivEnEss to mEthacholinE in mild to modEratE asthma.
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EffEcts of trEatmEnt with anti Immunoglobulin E Antibody omalizumab on airway inflammation in allErgic asthma
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Ratko Djukanovic, Susan J Wilson, Monica Kraft, Nizar N Jarjour, Mark D Steel, Fan K Chung, Angel Fowlertaylor, John G Matthews, William W Busse, Stephen T HolgateAbstract:IgE plays an important rolE in allErgic asthma. WE hypothEsizEd that rEducing IgE in thE airway mucosa would rEducE airway inflammation. Forty-fivE patiEnts with mild to modEratE pErsistEnt asthma with sputum Eosinophilia of 2% or morE wErE trEatEd with humanizEd monoclonal Antibody against IgE (omalizumab) (n = 22) or placEbo (n = 23) for 16 wEEks. OutcomEs includEd inflammatory cElls in inducEd sputum and bronchial biopsiEs, and mEthacholinE rEsponsivEnEss. TrEatmEnt with omalizumab rEsultEd in markEd rEduction of sErum IgE and a rEduction of IgE+ cElls in thE airway mucosa. ThE mEan pErcEntagE sputum Eosinophil count dEcrEasEd significantly (p < 0.001) from 6.6 to 1.7% in thE omalizumab group, a rEduction significantly (p = 0.05) grEatEr than with placEbo (8.5 to 7.0%). This was associatEd with a significant rEduction in tissuE Eosinophils; cElls positivE for thE high-affinity Fc rEcEptor for IgE; CD3+, CD4+, and CD8+ T lymphocytEs; B lymphocytEs; and cElls staining for intErlEukin-4, but not with impr...
