Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation
Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation. Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL...
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description | Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.
Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.
BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p |
doi_str_mv | 10.1371/journal.pone.0119325 |
format | Article |
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Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.
BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.
Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119325</identifier><identifier>PMID: 25822228</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Adults ; Aged ; Aged, 80 and over ; Alveoli ; Biopsy ; Bronchiectasis ; Bronchiectasis - metabolism ; Bronchiectasis - pathology ; Bronchoalveolar lavage ; Bronchoalveolar Lavage Fluid - cytology ; Bronchoalveolar Lavage Fluid - microbiology ; Bronchus ; Case-Control Studies ; Cell activation ; Chronic infection ; Chronic obstructive pulmonary disease ; Cystic fibrosis ; Cytokines ; Drug dosages ; Female ; Fibrosis ; Gene expression ; Haemophilus influenzae - isolation & purification ; Health aspects ; Health services ; Helper cells ; Hospitals ; Humans ; Immunity ; Infection ; Infections ; Inflammation ; Interleukin 1 ; Interleukin 23 ; Interleukin 8 ; Interleukins - genetics ; Interleukins - metabolism ; Leukocytes (neutrophilic) ; Lymphocytes T ; Male ; Medicine ; Microbiology ; Microbiota ; Middle Aged ; Neutrophils ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - isolation & purification ; Respiratory tract ; Th17 Cells - metabolism ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0119325-e0119325</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Chen et al 2015 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3d1c64f75e61f45939910081e0eabc73d6deba79de11d4dc07d5957a71dbaf363</citedby><cites>FETCH-LOGICAL-c692t-3d1c64f75e61f45939910081e0eabc73d6deba79de11d4dc07d5957a71dbaf363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379018/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379018/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25822228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Beekman, Jeffrey M.</contributor><creatorcontrib>Chen, Alice C-H</creatorcontrib><creatorcontrib>Martin, Megan L</creatorcontrib><creatorcontrib>Lourie, Rohan</creatorcontrib><creatorcontrib>Rogers, Geraint B</creatorcontrib><creatorcontrib>Burr, Lucy D</creatorcontrib><creatorcontrib>Hasnain, Sumaira Z</creatorcontrib><creatorcontrib>Bowler, Simon D</creatorcontrib><creatorcontrib>McGuckin, Michael A</creatorcontrib><creatorcontrib>Serisier, David J</creatorcontrib><title>Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.
Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.
BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.
Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adults</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alveoli</subject><subject>Biopsy</subject><subject>Bronchiectasis</subject><subject>Bronchiectasis - metabolism</subject><subject>Bronchiectasis - pathology</subject><subject>Bronchoalveolar lavage</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Bronchoalveolar Lavage Fluid - microbiology</subject><subject>Bronchus</subject><subject>Case-Control Studies</subject><subject>Cell activation</subject><subject>Chronic infection</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Cystic fibrosis</subject><subject>Cytokines</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Haemophilus influenzae - isolation & purification</subject><subject>Health aspects</subject><subject>Health services</subject><subject>Helper cells</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunity</subject><subject>Infection</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 23</subject><subject>Interleukin 8</subject><subject>Interleukins - genetics</subject><subject>Interleukins - metabolism</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medicine</subject><subject>Microbiology</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Neutrophils</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - isolation & purification</subject><subject>Respiratory tract</subject><subject>Th17 Cells - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-L1DAQx4so3rn6H4gWBNGHrknTJu2LsBz-WDg40NPXME3SbZZssybp6f73pre9Yyv3YFuYdvqZbzKTmSR5idESE4Y_bO3gejDLve3VEmFck7x8lJyPNqM5Io9P3s-SZ95vESpJRenT5Cwvqzxe1XkiVnIwIe1tn4mDD1qkrW6c9dqn0fSi00oEGD_jIzpwIIJy2iuZNocUtPsNh9QMOx23kl53mKV7CN3ojKC-gaBt_zx50oLx6sVkF8mPz5-uL75ml1df1hery0zQOg8ZkVjQomWlorgtyprUNUaowgopaAQjkkrVAKulwlgWUiAmy7pkwLBsoCWULJLXR929sZ5P9fEcU8ooxUVeRmJ9JKSFLd87vQN34BY0v3VYt-HgYhGM4jlWjDFUtDSXhSgBJAAtANUFqiVjKmp9nFYbmp2SQvXBgZmJzv_0uuMbe8MLwmqEqyjwbhJw9tegfOA77YUyBnplh9t9VzmpEB4ze_MP-nB2E7WBmIDuWxvXFaMoXxW4RoTmsRcWyfIBKt5S7bSIzdTq6J8FvJ8FRCaoP2EDg_d8_f3b_7NXP-fs2xO2U2BC560Zxpbxc7A4giI2pneqvS8yRnychbtq8HEW-DQLMezV6QHdB901P_kLVPsEnA</recordid><startdate>20150330</startdate><enddate>20150330</enddate><creator>Chen, Alice C-H</creator><creator>Martin, Megan L</creator><creator>Lourie, Rohan</creator><creator>Rogers, Geraint B</creator><creator>Burr, Lucy D</creator><creator>Hasnain, Sumaira Z</creator><creator>Bowler, Simon D</creator><creator>McGuckin, Michael A</creator><creator>Serisier, David J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150330</creationdate><title>Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation</title><author>Chen, Alice C-H ; Martin, Megan L ; Lourie, Rohan ; Rogers, Geraint B ; Burr, Lucy D ; Hasnain, Sumaira Z ; Bowler, Simon D ; McGuckin, Michael A ; Serisier, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-3d1c64f75e61f45939910081e0eabc73d6deba79de11d4dc07d5957a71dbaf363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adults</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alveoli</topic><topic>Biopsy</topic><topic>Bronchiectasis</topic><topic>Bronchiectasis - metabolism</topic><topic>Bronchiectasis - pathology</topic><topic>Bronchoalveolar lavage</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Bronchoalveolar Lavage Fluid - microbiology</topic><topic>Bronchus</topic><topic>Case-Control Studies</topic><topic>Cell activation</topic><topic>Chronic infection</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Cystic fibrosis</topic><topic>Cytokines</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Haemophilus influenzae - isolation & purification</topic><topic>Health aspects</topic><topic>Health services</topic><topic>Helper cells</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunity</topic><topic>Infection</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Interleukin 1</topic><topic>Interleukin 23</topic><topic>Interleukin 8</topic><topic>Interleukins - genetics</topic><topic>Interleukins - metabolism</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medicine</topic><topic>Microbiology</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Neutrophils</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Alice C-H</au><au>Martin, Megan L</au><au>Lourie, Rohan</au><au>Rogers, Geraint B</au><au>Burr, Lucy D</au><au>Hasnain, Sumaira Z</au><au>Bowler, Simon D</au><au>McGuckin, Michael A</au><au>Serisier, David J</au><au>Beekman, Jeffrey M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-30</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0119325</spage><epage>e0119325</epage><pages>e0119325-e0119325</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.
Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.
BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.
Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25822228</pmid><doi>10.1371/journal.pone.0119325</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-03, Vol.10 (3), p.e0119325-e0119325 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1667661425 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Adolescent Adult Adults Aged Aged, 80 and over Alveoli Biopsy Bronchiectasis Bronchiectasis - metabolism Bronchiectasis - pathology Bronchoalveolar lavage Bronchoalveolar Lavage Fluid - cytology Bronchoalveolar Lavage Fluid - microbiology Bronchus Case-Control Studies Cell activation Chronic infection Chronic obstructive pulmonary disease Cystic fibrosis Cytokines Drug dosages Female Fibrosis Gene expression Haemophilus influenzae - isolation & purification Health aspects Health services Helper cells Hospitals Humans Immunity Infection Infections Inflammation Interleukin 1 Interleukin 23 Interleukin 8 Interleukins - genetics Interleukins - metabolism Leukocytes (neutrophilic) Lymphocytes T Male Medicine Microbiology Microbiota Middle Aged Neutrophils Pseudomonas aeruginosa Pseudomonas aeruginosa - isolation & purification Respiratory tract Th17 Cells - metabolism Tumor necrosis factor-TNF |
title | Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation |
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