Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma
Background Combining inhaled corticosteroids with long-acting β2 -agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhance...
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| creator | Kelly, Margaret M., MB, PhD, FRCPC O'Connor, Terence M., MB, FRCPI Leigh, Richard, MB, PhD, FRCPC Otis, Joceline, MLT Gwozd, Carol, MLT Gauvreau, Gail M., PhD Gauldie, Jack, PhD O'Byrne, Paul M., MB, FRCPC, FRCPI |
| description | Background Combining inhaled corticosteroids with long-acting β2 -agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. Objective We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. Methods Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. Results Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. Conclusions The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol. |
| doi_str_mv | 10.1016/j.jaci.2009.09.011 |
| format | Article |
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However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. Objective We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. Methods Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. Results Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. Conclusions The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2009.09.011</identifier><identifier>PMID: 19969339</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Actins - drug effects ; Administration, Inhalation ; Adult ; Airway Remodeling - drug effects ; Allergy and Immunology ; Asthma ; Asthma - drug therapy ; Asthma - pathology ; Biological and medical sciences ; biopsy ; Bronchial Provocation Tests ; Bronchodilator Agents - administration & dosage ; bronchoscopy ; Budesonide - administration & dosage ; Chronic obstructive pulmonary disease, asthma ; Cross-Over Studies ; Double-Blind Method ; Drug Combinations ; Eosinophilia - drug therapy ; Ethanolamines - administration & dosage ; Female ; Formoterol Fumarate ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Immunopathology ; Inflammation - drug therapy ; inhaled glucocorticoids ; long-acting inhaled β-agonists ; Lymphocytes ; Male ; Medical sciences ; Microscopy, Electron, Transmission ; Muscle, Smooth - drug effects ; Pathogenesis ; Pneumology ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Sputum - cytology ; Sputum - drug effects ; Sputum - immunology</subject><ispartof>Journal of allergy and clinical immunology, 2010-02, Vol.125 (2), p.349-356.e13</ispartof><rights>American Academy of Allergy, Asthma & Immunology</rights><rights>2010 American Academy of Allergy, Asthma & Immunology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-eada15c6356df66f42d1f8e99f104c58f6d9240ab7844f1d4742a10303989d183</citedby><cites>FETCH-LOGICAL-c525t-eada15c6356df66f42d1f8e99f104c58f6d9240ab7844f1d4742a10303989d183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaci.2009.09.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22406080$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19969339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelly, Margaret M., MB, PhD, FRCPC</creatorcontrib><creatorcontrib>O'Connor, Terence M., MB, FRCPI</creatorcontrib><creatorcontrib>Leigh, Richard, MB, PhD, FRCPC</creatorcontrib><creatorcontrib>Otis, Joceline, MLT</creatorcontrib><creatorcontrib>Gwozd, Carol, MLT</creatorcontrib><creatorcontrib>Gauvreau, Gail M., PhD</creatorcontrib><creatorcontrib>Gauldie, Jack, PhD</creatorcontrib><creatorcontrib>O'Byrne, Paul M., MB, FRCPC, FRCPI</creatorcontrib><title>Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background Combining inhaled corticosteroids with long-acting β2 -agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. Objective We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. Methods Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. Results Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. Conclusions The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.</description><subject>Actins - drug effects</subject><subject>Administration, Inhalation</subject><subject>Adult</subject><subject>Airway Remodeling - drug effects</subject><subject>Allergy and Immunology</subject><subject>Asthma</subject><subject>Asthma - drug therapy</subject><subject>Asthma - pathology</subject><subject>Biological and medical sciences</subject><subject>biopsy</subject><subject>Bronchial Provocation Tests</subject><subject>Bronchodilator Agents - administration & dosage</subject><subject>bronchoscopy</subject><subject>Budesonide - administration & dosage</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Cross-Over Studies</subject><subject>Double-Blind Method</subject><subject>Drug Combinations</subject><subject>Eosinophilia - drug therapy</subject><subject>Ethanolamines - administration & dosage</subject><subject>Female</subject><subject>Formoterol Fumarate</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Immunopathology</subject><subject>Inflammation - drug therapy</subject><subject>inhaled glucocorticoids</subject><subject>long-acting inhaled β-agonists</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Electron, Transmission</subject><subject>Muscle, Smooth - drug effects</subject><subject>Pathogenesis</subject><subject>Pneumology</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Sputum - cytology</subject><subject>Sputum - drug effects</subject><subject>Sputum - immunology</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkt9rFDEQx4Mo9qz-Az5IQKQv3TPZZLMJiCCl_oCCD-pzyCWTmnM3OZNd7f33Zr2jhT4oDISQz3wnM99B6Dkla0qoeL1db40N65YQtV6C0gdoRYnqGyHb7iFa1QfaiJ6rE_SklC2pdybVY3RClRKKMbVCN5feg50KTh5vZgclxeAAm-iwT3lME-Q04BSxGQbI1xCbEN1swWET8m-zxxnKLsUC5RyH6AczjmYKKZ7_lbhlxuRgCPG6MtiU6ftonqJH3gwFnh3PU_Tt_eXXi4_N1ecPny7eXTW2a7upAeMM7axgnXBeCM9bR70EpTwl3HbSC6daTsyml5x76njPW0MJI0xJ5ahkp-jsoLvL6ecMZdJjKBaGwURIc9E974Tqe6n-TzImO6YIq-TLe-Q2zTnWNjTtCJdUErXotQfK5lRKBq93OYwm7zUlejFQb_VioF4M1EtQWpNeHKXnzQjuLuXoWAVeHQFTrBl8NtGGcsu1dRiCSFK5NwcO6nB_Bci62ACxOhdyNVy7FP79j7f30m31L9SKP2AP5a5fXVpN9Jdl1ZZNI4pQxknL_gDvYc33</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Kelly, Margaret M., MB, PhD, FRCPC</creator><creator>O'Connor, Terence M., MB, FRCPI</creator><creator>Leigh, Richard, MB, PhD, FRCPC</creator><creator>Otis, Joceline, MLT</creator><creator>Gwozd, Carol, MLT</creator><creator>Gauvreau, Gail M., PhD</creator><creator>Gauldie, Jack, PhD</creator><creator>O'Byrne, Paul M., MB, FRCPC, FRCPI</creator><general>Mosby, Inc</general><general>Elsevier</general><general>Elsevier Limited</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>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20100201</creationdate><title>Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma</title><author>Kelly, Margaret M., MB, PhD, FRCPC ; O'Connor, Terence M., MB, FRCPI ; Leigh, Richard, MB, PhD, FRCPC ; Otis, Joceline, MLT ; Gwozd, Carol, MLT ; Gauvreau, Gail M., PhD ; Gauldie, Jack, PhD ; O'Byrne, Paul M., MB, FRCPC, FRCPI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-eada15c6356df66f42d1f8e99f104c58f6d9240ab7844f1d4742a10303989d183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Actins - drug effects</topic><topic>Administration, Inhalation</topic><topic>Adult</topic><topic>Airway Remodeling - drug effects</topic><topic>Allergy and Immunology</topic><topic>Asthma</topic><topic>Asthma - drug therapy</topic><topic>Asthma - pathology</topic><topic>Biological and medical sciences</topic><topic>biopsy</topic><topic>Bronchial Provocation Tests</topic><topic>Bronchodilator Agents - administration & dosage</topic><topic>bronchoscopy</topic><topic>Budesonide - administration & dosage</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Cross-Over Studies</topic><topic>Double-Blind Method</topic><topic>Drug Combinations</topic><topic>Eosinophilia - drug therapy</topic><topic>Ethanolamines - administration & dosage</topic><topic>Female</topic><topic>Formoterol Fumarate</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Immunopathology</topic><topic>Inflammation - drug therapy</topic><topic>inhaled glucocorticoids</topic><topic>long-acting inhaled β-agonists</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Electron, Transmission</topic><topic>Muscle, Smooth - drug effects</topic><topic>Pathogenesis</topic><topic>Pneumology</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Sputum - cytology</topic><topic>Sputum - drug effects</topic><topic>Sputum - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelly, Margaret M., MB, PhD, FRCPC</creatorcontrib><creatorcontrib>O'Connor, Terence M., MB, FRCPI</creatorcontrib><creatorcontrib>Leigh, Richard, MB, PhD, FRCPC</creatorcontrib><creatorcontrib>Otis, Joceline, MLT</creatorcontrib><creatorcontrib>Gwozd, Carol, MLT</creatorcontrib><creatorcontrib>Gauvreau, Gail M., PhD</creatorcontrib><creatorcontrib>Gauldie, Jack, PhD</creatorcontrib><creatorcontrib>O'Byrne, Paul M., MB, FRCPC, FRCPI</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>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelly, Margaret M., MB, PhD, FRCPC</au><au>O'Connor, Terence M., MB, FRCPI</au><au>Leigh, Richard, MB, PhD, FRCPC</au><au>Otis, Joceline, MLT</au><au>Gwozd, Carol, MLT</au><au>Gauvreau, Gail M., PhD</au><au>Gauldie, Jack, PhD</au><au>O'Byrne, Paul M., MB, FRCPC, FRCPI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>125</volume><issue>2</issue><spage>349</spage><epage>356.e13</epage><pages>349-356.e13</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background Combining inhaled corticosteroids with long-acting β2 -agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. Objective We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. Methods Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. Results Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. Conclusions The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>19969339</pmid><doi>10.1016/j.jaci.2009.09.011</doi><tpages>8</tpages></addata></record> |
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| subjects | Actins - drug effects Administration, Inhalation Adult Airway Remodeling - drug effects Allergy and Immunology Asthma Asthma - drug therapy Asthma - pathology Biological and medical sciences biopsy Bronchial Provocation Tests Bronchodilator Agents - administration & dosage bronchoscopy Budesonide - administration & dosage Chronic obstructive pulmonary disease, asthma Cross-Over Studies Double-Blind Method Drug Combinations Eosinophilia - drug therapy Ethanolamines - administration & dosage Female Formoterol Fumarate Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunopathology Inflammation - drug therapy inhaled glucocorticoids long-acting inhaled β-agonists Lymphocytes Male Medical sciences Microscopy, Electron, Transmission Muscle, Smooth - drug effects Pathogenesis Pneumology Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Sputum - cytology Sputum - drug effects Sputum - immunology |
| title | Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma |
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