Fluticasone inhibits but does not reverse allergen-induced structural airway changes
Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensi...
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Veröffentlicht in: | American journal of respiratory and critical care medicine 2001-03, Vol.163 (3), p.674-679 |
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creator | VANACKER, Nele J PALMANS, E. L. S KIPS, Johan C PAUWELS, Romain A |
description | Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized BN rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling. |
doi_str_mv | 10.1164/ajrccm.163.3.2004160 |
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L. S ; KIPS, Johan C ; PAUWELS, Romain A</creator><creatorcontrib>VANACKER, Nele J ; PALMANS, E. L. S ; KIPS, Johan C ; PAUWELS, Romain A</creatorcontrib><description>Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized BN rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/ajrccm.163.3.2004160</identifier><identifier>PMID: 11254522</identifier><language>eng</language><publisher>New York, NY: American Lung Association</publisher><subject>Allergens - immunology ; Allergens - pharmacology ; Androstadienes - pharmacology ; Animals ; Anti-Asthmatic Agents - pharmacology ; Biological and medical sciences ; Bronchoalveolar Lavage Fluid ; Carbachol - pharmacology ; Cholinergic Agents - pharmacology ; Fibronectins - metabolism ; Fluticasone ; Lung - anatomy & histology ; Lung - drug effects ; Lung - immunology ; Lung - metabolism ; Male ; Medical sciences ; Pharmacology. 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L. S</creatorcontrib><creatorcontrib>KIPS, Johan C</creatorcontrib><creatorcontrib>PAUWELS, Romain A</creatorcontrib><title>Fluticasone inhibits but does not reverse allergen-induced structural airway changes</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized BN rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.</description><subject>Allergens - immunology</subject><subject>Allergens - pharmacology</subject><subject>Androstadienes - pharmacology</subject><subject>Animals</subject><subject>Anti-Asthmatic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Bronchoalveolar Lavage Fluid</subject><subject>Carbachol - pharmacology</subject><subject>Cholinergic Agents - pharmacology</subject><subject>Fibronectins - metabolism</subject><subject>Fluticasone</subject><subject>Lung - anatomy & histology</subject><subject>Lung - drug effects</subject><subject>Lung - immunology</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Respiratory system</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLxDAUhYMojq9_IBIQ3HXMq0m7lMEXDLhRcBduk9uZDJ12TFrFf29liq7uWXznwP0IueRszrlWt7CJzm3nXMu5nAvGFNfsgJzwXOaZKg07HDMzMlOqfJ-R05Q2jHFRcHZMZpyLXOVCnJDXh2bog4PUtUhDuw5V6BOthp76DhNtu55G_MSYkELTYFxhm4XWDw49TX0cXD9EaCiE-AXf1K2hXWE6J0c1NAkvpntG3h7uXxdP2fLl8Xlxt8yclLzPjCuAS-NkDVgJ4RVontemNAYNVlCXDH2VM40FiEIqDd4wXdd56SvIvUZ5Rm72u7vYfQyYersNyWHTQIvdkKzRZTG-Wo6g2oMudilFrO0uhi3Eb8uZ_bVp9zbtaNNKO9kca1fT_lBt0f-XJn0jcD0BkBw0dYTWhfTHlbIQUskfGVSAoQ</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>VANACKER, Nele J</creator><creator>PALMANS, E. L. S</creator><creator>KIPS, Johan C</creator><creator>PAUWELS, Romain A</creator><general>American Lung Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010301</creationdate><title>Fluticasone inhibits but does not reverse allergen-induced structural airway changes</title><author>VANACKER, Nele J ; PALMANS, E. L. S ; KIPS, Johan C ; PAUWELS, Romain A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-7c8a137c3faeb22d4a615f7977e7ebaf90edb506e8a28346ad706ff59dba5d6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Allergens - immunology</topic><topic>Allergens - pharmacology</topic><topic>Androstadienes - pharmacology</topic><topic>Animals</topic><topic>Anti-Asthmatic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Bronchoalveolar Lavage Fluid</topic><topic>Carbachol - pharmacology</topic><topic>Cholinergic Agents - pharmacology</topic><topic>Fibronectins - metabolism</topic><topic>Fluticasone</topic><topic>Lung - anatomy & histology</topic><topic>Lung - drug effects</topic><topic>Lung - immunology</topic><topic>Lung - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Respiratory system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VANACKER, Nele J</creatorcontrib><creatorcontrib>PALMANS, E. L. S</creatorcontrib><creatorcontrib>KIPS, Johan C</creatorcontrib><creatorcontrib>PAUWELS, Romain A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VANACKER, Nele J</au><au>PALMANS, E. L. S</au><au>KIPS, Johan C</au><au>PAUWELS, Romain A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluticasone inhibits but does not reverse allergen-induced structural airway changes</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>163</volume><issue>3</issue><spage>674</spage><epage>679</epage><pages>674-679</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized BN rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.</abstract><cop>New York, NY</cop><pub>American Lung Association</pub><pmid>11254522</pmid><doi>10.1164/ajrccm.163.3.2004160</doi><tpages>6</tpages></addata></record> |
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subjects | Allergens - immunology Allergens - pharmacology Androstadienes - pharmacology Animals Anti-Asthmatic Agents - pharmacology Biological and medical sciences Bronchoalveolar Lavage Fluid Carbachol - pharmacology Cholinergic Agents - pharmacology Fibronectins - metabolism Fluticasone Lung - anatomy & histology Lung - drug effects Lung - immunology Lung - metabolism Male Medical sciences Pharmacology. Drug treatments Rats Rats, Inbred BN Respiratory system |
title | Fluticasone inhibits but does not reverse allergen-induced structural airway changes |
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