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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Veröffentlicht in:PloS one 2015-03, Vol.10 (3), p.e0119325-e0119325
Hauptverfasser: 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
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container_title PloS one
container_volume 10
creator 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
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
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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&lt;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&lt;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 &amp; 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 &amp; 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&lt;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&lt;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 &amp; 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 &amp; 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 &amp; 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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&lt;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&lt;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>
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1932-6203
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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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