Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients: A Randomized, Controlled Trial
Publication Date
May 07, 2013
Journal
PLOS ONE
Authors
Lisette I. Z. Kunz, Jolanda Strebus, Simona E. Budulac, Therese S. Lapperre, et al
Volume
8
Issue
5
Pages
e63430
DOI
https://dx.plos.org/10.1371/journal.pone.0063430
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0063430
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23667615
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646783
Europe PMC
http://europepmc.org/abstract/MED/23667615
Web of Science
000319654700142
Scopus
84877147602
Mendeley
http://www.mendeley.com/research/inhaled-steroids-modulate-extracellular-matrix-composition-bronchial-biopsies-copd-patients-randomiz
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Mendeley 1927 Apr 08:06 UTC

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{"title"=>"Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients: A Randomized, Controlled Trial", "type"=>"journal", "authors"=>[{"first_name"=>"Lisette I. Z.", "last_name"=>"Kunz"}, {"first_name"=>"Jolanda", "last_name"=>"Strebus"}, {"first_name"=>"Simona E.", "last_name"=>"Budulac"}, {"first_name"=>"Therese S.", "last_name"=>"Lapperre"}, {"first_name"=>"Peter J.", "last_name"=>"Sterk"}, {"first_name"=>"Dirkje S.", "last_name"=>"Postma"}, {"first_name"=>"Thais", "last_name"=>"Mauad"}, {"first_name"=>"Wim", "last_name"=>"Timens"}, {"first_name"=>"Pieter S.", "last_name"=>"Hiemstra"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0063430", "issn"=>"1932-6203", "isbn"=>"1932-6203", "pmid"=>"23667615"}, "id"=>"6b50cc4d-3554-34f2-a744-cb9eb061fde6", "abstract"=>"RATIONALE: Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD. We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD.\\n\\nOBJECTIVE: To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD.\\n\\nMETHODS: We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31-54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively. Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content. Percentage and density of stained area were calculated by digital image analysis.\\n\\nRESULTS: 30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo. Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04). There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins.\\n\\nCONCLUSIONS: These data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD. This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD. Smoking status is not associated with bronchial extracellular matrix proteins.\\n\\nTRIAL REGISTRATION: ClinicalTrials.gov NCT00158847.", "link"=>"http://www.mendeley.com/research/inhaled-steroids-modulate-extracellular-matrix-composition-bronchial-biopsies-copd-patients-randomiz", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>13}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Brazil"=>1, "United Kingdom"=>1}, "group_count"=>1}
Scopus 1802 Jan 14:15 UTC

Scopus | Further Information

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Figshare 4518 Apr 07:38 UTC

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1055586", "https://ndownloader.figshare.com/files/1055588", "https://ndownloader.figshare.com/files/1055597", "https://ndownloader.figshare.com/files/1055598"], "description"=>"<div><p>Rationale</p><p>Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD. We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD.</p><p>Objective</p><p>To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD.</p><p>Methods</p><p>We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31–54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively. Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content. Percentage and density of stained area were calculated by digital image analysis.</p><p>Results</p><p>30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo. Increased collagen I staining density correlated with increased post-bronchodilator FEV<sub>1</sub> after inhaled steroids treatment (Rs = 0.45, p = 0.04). There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins.</p><p>Conclusions</p><p>These data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD. This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD. Smoking status is not associated with bronchial extracellular matrix proteins.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href=\"http://tinyurl.com/ct6ebl2\" target=\"_blank\">NCT00158847</a></p></div>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders", "steroids", "modulate", "extracellular", "matrix", "bronchial", "biopsies", "copd", "controlled"], "article_id"=>699337, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063430.s001", "https://dx.doi.org/10.1371/journal.pone.0063430.s002", "https://dx.doi.org/10.1371/journal.pone.0063430.s003", "https://dx.doi.org/10.1371/journal.pone.0063430.s004"], "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhaled_Steroids_Modulate_Extracellular_Matrix_Composition_in_Bronchial_Biopsies_of_COPD_Patients_A_Randomized_Controlled_Trial_/699337", "title"=>"Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients: A Randomized, Controlled Trial", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-05-07 02:35:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055584"], "description"=>"<p>Panel A presents post-bronchodilator FEV<sub>1</sub> (% predicted) and panel B shows PC<sub>20</sub> (in doubling dose).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders", "collagen", "baseline"], "article_id"=>699335, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_percentage_collagen_type_I_at_baseline_and_lung_function_parameters_/699335", "title"=>"Correlation between percentage collagen type I at baseline and lung function parameters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-07 02:35:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055585"], "description"=>"<p>Patient characteristics for current smokers and ex-smokers with COPD and groups treated with placebo and fluticasone (only compliant patients). Bronchial biopsies were available at baseline of 64 (elastic fibers), 56 (versican), 61 (decorin), 61 (collagen I) and 64 (collagen III) patients. After 30 months, bronchial biopsies of 32 compliant patients were available, tissue from 29 (elastic fibers), 26 (versican), 27 (decorin), 28 (collagen I) and 28 (collagen III) patients had sufficient surface area for analysis (≥0.09 mm<sup>2</sup>) (fluticasone and placebo groups combined). Data are presented as mean (SD) or median (IQR), unless otherwise stated. Methacholine PC<sub>20</sub>: provocative concentration of methacholine that causes a 20% decrease in FEV<sub>1</sub>, expressed as mean doubling doses. Part of the data have been published previously <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Lapperre1\" target=\"_blank\">[17]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Lapperre2\" target=\"_blank\">[22]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Kunz1\" target=\"_blank\">[27]</a>.</p>*<p>p<0.05 compared to current smokers (two tailed unpaired t-tests).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders"], "article_id"=>699336, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_at_baseline_/699336", "title"=>"Patient characteristics at baseline.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-07 02:35:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055583"], "description"=>"<p>Percentage (upper panel) and density (lower panel) of stained area in bronchial biopsies is presented. Ex-smokers are presented as open circles, current smokers as closed circles. Horizontal bars represent medians. No significant differences were found for all studied extracellular matrix proteins (both percentage stained area and density).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders", "stained", "baseline", "ex-smokers", "smokers"], "article_id"=>699334, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_and_density_of_stained_area_at_baseline_of_ex_smokers_and_smokers_with_COPD_/699334", "title"=>"Percentage and density of stained area at baseline of ex-smokers and smokers with COPD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-07 02:35:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055580"], "description"=>"<p>Percentage (upper panel) and density (lower panel) of stained area in bronchial biopsies is presented. Open figures: baseline percentage stained area, closed figures: percentage stained area after 30 months. Horizontal bars represent medians.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders", "stained", "placebo", "fluticasone", "ecm"], "article_id"=>699331, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_and_density_of_stained_area_for_placebo_and_fluticasone_for_all_ECM_proteins_/699331", "title"=>"Percentage and density of stained area for placebo and fluticasone for all ECM proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-07 02:35:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055582"], "description"=>"<p>Both values represent values after 30 months minus values at baseline. Closed circles represent fluticasone treated subjects, open circles represent placebo treated subjects.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders", "post-bronchodilator", "collagen"], "article_id"=>699333, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_change_in_post_bronchodilator_FEV_1_L_and_change_in_density_of_collagen_I_/699333", "title"=>"Correlation between change in post-bronchodilator FEV<sub>1</sub> (L) and change in density of collagen I.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-07 02:35:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1055578"], "description"=>"<p>The same bronchial biopsy section is shown for the histochemical staining for elastic fibers (A) and the immunohistochemical stainings for versican (B), decorin (C), collagen type I (D) and collagen type III (E). Original magnification 200×.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "microbiology", "Molecular cell biology", "Extracellular matrix", "Extracellular matrix composition", "Diagnostic medicine", "pathology", "anatomical pathology", "histopathology", "Pulmonology", "Chronic obstructive pulmonary diseases", "Smoking related disorders"], "article_id"=>699329, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Lisette I. Z. Kunz", "Jolanda Strebus", "Simona E. Budulac", "Therese S. Lapperre", "Peter J. Sterk", "Dirkje S. Postma", "Thais Mauad", "Wim Timens", "Pieter S. Hiemstra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063430.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Examples_of_immuno_histochemical_stainings_/699329", "title"=>"Examples of (immuno)histochemical stainings.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-07 02:35:29"}
PMC Usage Stats 115717 Jan 18:18 UTC

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"25", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
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  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
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  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
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  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
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Relative Metric 7167510 May 17:02 UTC

Relative Metric

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F1000Prime 120 Jan 12:51 UTC

F1000Prime | Further Information

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