Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients
Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining...
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| Veröffentlicht in: | PloS one 2014-02, Vol.9 (2), p.e88567 |
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| creator | Wojewodka, Gabriella De Sanctis, Juan B Bernier, Joanie Bérubé, Julie Ahlgren, Heather G Gruber, Jim Landry, Jennifer Lands, Larry C Nguyen, Dao Rousseau, Simon Benedetti, Andrea Matouk, Elias Radzioch, Danuta |
| description | Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.
We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation. |
| doi_str_mv | 10.1371/journal.pone.0088567 |
| format | Article |
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We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0088567</identifier><identifier>PMID: 24533110</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Antibiotics ; Arachidonic acid ; Assessments ; Bioindicators ; Biology ; Biomarkers ; Biomarkers - blood ; Blood plasma ; C-reactive protein ; Cystic fibrosis ; Cystic Fibrosis - blood ; Development and progression ; Diabetes ; Disease Progression ; Docosahexaenoic acid ; Early intervention ; Fatty acids ; Fatty Acids, Unsaturated - blood ; Female ; Humans ; Identification methods ; Infections ; Inflammation ; Interleukin 8 ; Interleukins ; Interleukins - blood ; Kaplan-Meier Estimate ; Lipid Peroxidation ; Longitudinal Studies ; Lung diseases ; Lung Diseases - blood ; Lung Diseases - complications ; Lungs ; Macrophage inflammatory protein ; Macrophages ; Male ; Medical research ; Medicine ; Middle Aged ; Morbidity ; Mortality ; Omega 3 fatty acids ; Patient compliance ; Patients ; Peroxidation ; Polyunsaturated fatty acids ; Probability ; Proportional Hazards Models ; Prospective Studies ; Quality of Life ; Recurrence ; Respiratory function ; Respiratory Function Tests ; Risk assessment ; Risk Factors ; Spirometry ; Studies ; Thorax ; Time Factors ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - blood ; Unsaturated fatty acids ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - blood ; Young Adult</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e88567</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Wojewodka 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>2014 Wojewodka et al 2014 Wojewodka et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-7c9c3fdc00034ce848af52ad2bed06de8587f2509a1cb551c00ecaeaf4032ae73</citedby><cites>FETCH-LOGICAL-c692t-7c9c3fdc00034ce848af52ad2bed06de8587f2509a1cb551c00ecaeaf4032ae73</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/PMC3922941/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922941/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24533110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wojewodka, Gabriella</creatorcontrib><creatorcontrib>De Sanctis, Juan B</creatorcontrib><creatorcontrib>Bernier, Joanie</creatorcontrib><creatorcontrib>Bérubé, Julie</creatorcontrib><creatorcontrib>Ahlgren, Heather G</creatorcontrib><creatorcontrib>Gruber, Jim</creatorcontrib><creatorcontrib>Landry, Jennifer</creatorcontrib><creatorcontrib>Lands, Larry C</creatorcontrib><creatorcontrib>Nguyen, Dao</creatorcontrib><creatorcontrib>Rousseau, Simon</creatorcontrib><creatorcontrib>Benedetti, Andrea</creatorcontrib><creatorcontrib>Matouk, Elias</creatorcontrib><creatorcontrib>Radzioch, Danuta</creatorcontrib><title>Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.
We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antibiotics</subject><subject>Arachidonic acid</subject><subject>Assessments</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Blood plasma</subject><subject>C-reactive protein</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - blood</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Disease Progression</subject><subject>Docosahexaenoic acid</subject><subject>Early intervention</subject><subject>Fatty acids</subject><subject>Fatty Acids, Unsaturated - blood</subject><subject>Female</subject><subject>Humans</subject><subject>Identification methods</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interleukin 8</subject><subject>Interleukins</subject><subject>Interleukins - blood</subject><subject>Kaplan-Meier Estimate</subject><subject>Lipid Peroxidation</subject><subject>Longitudinal Studies</subject><subject>Lung diseases</subject><subject>Lung Diseases - blood</subject><subject>Lung Diseases - complications</subject><subject>Lungs</subject><subject>Macrophage inflammatory protein</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Omega 3 fatty acids</subject><subject>Patient compliance</subject><subject>Patients</subject><subject>Peroxidation</subject><subject>Polyunsaturated fatty acids</subject><subject>Probability</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Quality of Life</subject><subject>Recurrence</subject><subject>Respiratory function</subject><subject>Respiratory Function Tests</subject><subject>Risk assessment</subject><subject>Risk Factors</subject><subject>Spirometry</subject><subject>Studies</subject><subject>Thorax</subject><subject>Time Factors</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - 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The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.
We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24533110</pmid><doi>10.1371/journal.pone.0088567</doi><tpages>e88567</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-02, Vol.9 (2), p.e88567 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1497405665 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Antibiotics Arachidonic acid Assessments Bioindicators Biology Biomarkers Biomarkers - blood Blood plasma C-reactive protein Cystic fibrosis Cystic Fibrosis - blood Development and progression Diabetes Disease Progression Docosahexaenoic acid Early intervention Fatty acids Fatty Acids, Unsaturated - blood Female Humans Identification methods Infections Inflammation Interleukin 8 Interleukins Interleukins - blood Kaplan-Meier Estimate Lipid Peroxidation Longitudinal Studies Lung diseases Lung Diseases - blood Lung Diseases - complications Lungs Macrophage inflammatory protein Macrophages Male Medical research Medicine Middle Aged Morbidity Mortality Omega 3 fatty acids Patient compliance Patients Peroxidation Polyunsaturated fatty acids Probability Proportional Hazards Models Prospective Studies Quality of Life Recurrence Respiratory function Respiratory Function Tests Risk assessment Risk Factors Spirometry Studies Thorax Time Factors Tumor necrosis factor Tumor Necrosis Factor-alpha - blood Unsaturated fatty acids Vascular endothelial growth factor Vascular Endothelial Growth Factor A - blood Young Adult |
| title | Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T13%3A57%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Candidate%20markers%20associated%20with%20the%20probability%20of%20future%20pulmonary%20exacerbations%20in%20cystic%20fibrosis%20patients&rft.jtitle=PloS%20one&rft.au=Wojewodka,%20Gabriella&rft.date=2014-02-12&rft.volume=9&rft.issue=2&rft.spage=e88567&rft.pages=e88567-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0088567&rft_dat=%3Cgale_plos_%3EA478806120%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1497405665&rft_id=info:pmid/24533110&rft_galeid=A478806120&rft_doaj_id=oai_doaj_org_article_2793943f2127415e8008b604a02cb010&rfr_iscdi=true |