Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations
Summary Background Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood. Objective The aim of this analysis was to determine whether cytokine...
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| Veröffentlicht in: | Clinical and experimental allergy 2014-12, Vol.44 (12), p.1484-1493 |
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| creator | Manthei, D. M. Schwantes, E. A. Mathur, S. K. Guadarrama, A. G. Kelly, E. A. Gern, J. E. Jarjour, N. N. Denlinger, L. C. |
| description | Summary
Background
Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood.
Objective
The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations.
Methods
We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN‐α, IFN‐β, IFN‐γ, IFN‐λ1, IP‐10, TRAIL), cell recruiting (G‐CSF, IL‐1β, IL‐8, MCP‐1, MCP‐3, TNF‐α), polarizing (CXCL13, IL‐10, IL‐13, IL‐17, TSLP), and injury remodelling (fibronectin, IL‐33, MMP‐9, VEGF).
Results
The overall cytokine response induced during viral infections was not different between asthmatic and non‐asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF‐α and IL‐1β were 1.7‐, 5.1‐ and 4.7‐fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve‐defined thresholds, high VEGF and TNF‐α levels predicted a shorter time‐to‐exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively).
Conclusion and Clinical Relevance
Although they produce similar cytokine responses to viral infection as non‐asthmatics, asthmatics with higher levels of VEGF and TNF‐α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild‐to‐moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies. |
| doi_str_mv | 10.1111/cea.12387 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4247169</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1635023295</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4867-d7c01f80175458bae4bb4506da527d0a8cf6be061d852f48603c25954b59d5593</originalsourceid><addsrcrecordid>eNqNkctuEzEUhi0EoqF00RdAXsJiWt89s0GqQhKoqiCh3nbWGduTGiYzqT0T2sfiRfpMnZA2ggUSZ-OFv__TOfoROqTkiA5zbD0cUcZz_QKNKFcyY8O8RCNSSJHpvBB76E1K3wkhXBb5a7THJCWF0HqELueQoMY1rGHh8eVkNsXQOHw-n2YPv3Dt175O2PUxNAsMuIGujwNu29rhVfQu2A5D6m6WgP0dWB9L6ELbpLfoVQV18gdP7z66mE7Ox5-zs6-zL-OTs8yKXOnMaUtolROqpZB5CV6UpZBEOZBMOwK5rVTpiaIul6waIoRbJoerSlk4KQu-jz5uvau-XHpnfdMN-5lVDEuI96aFYP7-acKNWbRrI5jQVG0E758Esb3tferMMiTr6xoa3_bJUMUlYZwV8j9QpgspKd-gH7aojW1K0Ve7jSgxm8rMUJn5XdnAvvvzhB353NEAHG-Bn6H29_82mfHk5FmZbRMhdf5ul4D4wyjNtTRX85lRp1en364_KaP4I67Arvk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1627955135</pqid></control><display><type>article</type><title>Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Manthei, D. M. ; Schwantes, E. A. ; Mathur, S. K. ; Guadarrama, A. G. ; Kelly, E. A. ; Gern, J. E. ; Jarjour, N. N. ; Denlinger, L. C.</creator><creatorcontrib>Manthei, D. M. ; Schwantes, E. A. ; Mathur, S. K. ; Guadarrama, A. G. ; Kelly, E. A. ; Gern, J. E. ; Jarjour, N. N. ; Denlinger, L. C.</creatorcontrib><description>Summary
Background
Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood.
Objective
The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations.
Methods
We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN‐α, IFN‐β, IFN‐γ, IFN‐λ1, IP‐10, TRAIL), cell recruiting (G‐CSF, IL‐1β, IL‐8, MCP‐1, MCP‐3, TNF‐α), polarizing (CXCL13, IL‐10, IL‐13, IL‐17, TSLP), and injury remodelling (fibronectin, IL‐33, MMP‐9, VEGF).
Results
The overall cytokine response induced during viral infections was not different between asthmatic and non‐asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF‐α and IL‐1β were 1.7‐, 5.1‐ and 4.7‐fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve‐defined thresholds, high VEGF and TNF‐α levels predicted a shorter time‐to‐exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively).
Conclusion and Clinical Relevance
Although they produce similar cytokine responses to viral infection as non‐asthmatics, asthmatics with higher levels of VEGF and TNF‐α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild‐to‐moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/cea.12387</identifier><identifier>PMID: 25109477</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>asthma ; Asthma - diagnosis ; Asthma - etiology ; Common Cold - complications ; Common Cold - metabolism ; Cytokines - metabolism ; Disease Progression ; exacerbation ; Female ; Humans ; Male ; Nasal Lavage Fluid - immunology ; ROC Curve ; TNF-α ; Tumor Necrosis Factor-alpha - metabolism ; Vascular Endothelial Growth Factor A - metabolism ; VEGF ; virus</subject><ispartof>Clinical and experimental allergy, 2014-12, Vol.44 (12), p.1484-1493</ispartof><rights>2014 John Wiley & Sons Ltd</rights><rights>2014 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4867-d7c01f80175458bae4bb4506da527d0a8cf6be061d852f48603c25954b59d5593</citedby><cites>FETCH-LOGICAL-c4867-d7c01f80175458bae4bb4506da527d0a8cf6be061d852f48603c25954b59d5593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcea.12387$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcea.12387$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25109477$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manthei, D. M.</creatorcontrib><creatorcontrib>Schwantes, E. A.</creatorcontrib><creatorcontrib>Mathur, S. K.</creatorcontrib><creatorcontrib>Guadarrama, A. G.</creatorcontrib><creatorcontrib>Kelly, E. A.</creatorcontrib><creatorcontrib>Gern, J. E.</creatorcontrib><creatorcontrib>Jarjour, N. N.</creatorcontrib><creatorcontrib>Denlinger, L. C.</creatorcontrib><title>Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary
Background
Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood.
Objective
The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations.
Methods
We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN‐α, IFN‐β, IFN‐γ, IFN‐λ1, IP‐10, TRAIL), cell recruiting (G‐CSF, IL‐1β, IL‐8, MCP‐1, MCP‐3, TNF‐α), polarizing (CXCL13, IL‐10, IL‐13, IL‐17, TSLP), and injury remodelling (fibronectin, IL‐33, MMP‐9, VEGF).
Results
The overall cytokine response induced during viral infections was not different between asthmatic and non‐asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF‐α and IL‐1β were 1.7‐, 5.1‐ and 4.7‐fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve‐defined thresholds, high VEGF and TNF‐α levels predicted a shorter time‐to‐exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively).
Conclusion and Clinical Relevance
Although they produce similar cytokine responses to viral infection as non‐asthmatics, asthmatics with higher levels of VEGF and TNF‐α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild‐to‐moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies.</description><subject>asthma</subject><subject>Asthma - diagnosis</subject><subject>Asthma - etiology</subject><subject>Common Cold - complications</subject><subject>Common Cold - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Disease Progression</subject><subject>exacerbation</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Nasal Lavage Fluid - immunology</subject><subject>ROC Curve</subject><subject>TNF-α</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><subject>virus</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuEzEUhi0EoqF00RdAXsJiWt89s0GqQhKoqiCh3nbWGduTGiYzqT0T2sfiRfpMnZA2ggUSZ-OFv__TOfoROqTkiA5zbD0cUcZz_QKNKFcyY8O8RCNSSJHpvBB76E1K3wkhXBb5a7THJCWF0HqELueQoMY1rGHh8eVkNsXQOHw-n2YPv3Dt175O2PUxNAsMuIGujwNu29rhVfQu2A5D6m6WgP0dWB9L6ELbpLfoVQV18gdP7z66mE7Ox5-zs6-zL-OTs8yKXOnMaUtolROqpZB5CV6UpZBEOZBMOwK5rVTpiaIul6waIoRbJoerSlk4KQu-jz5uvau-XHpnfdMN-5lVDEuI96aFYP7-acKNWbRrI5jQVG0E758Esb3tferMMiTr6xoa3_bJUMUlYZwV8j9QpgspKd-gH7aojW1K0Ve7jSgxm8rMUJn5XdnAvvvzhB353NEAHG-Bn6H29_82mfHk5FmZbRMhdf5ul4D4wyjNtTRX85lRp1en364_KaP4I67Arvk</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Manthei, D. M.</creator><creator>Schwantes, E. A.</creator><creator>Mathur, S. K.</creator><creator>Guadarrama, A. G.</creator><creator>Kelly, E. A.</creator><creator>Gern, J. E.</creator><creator>Jarjour, N. N.</creator><creator>Denlinger, L. C.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201412</creationdate><title>Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations</title><author>Manthei, D. M. ; Schwantes, E. A. ; Mathur, S. K. ; Guadarrama, A. G. ; Kelly, E. A. ; Gern, J. E. ; Jarjour, N. N. ; Denlinger, L. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4867-d7c01f80175458bae4bb4506da527d0a8cf6be061d852f48603c25954b59d5593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>asthma</topic><topic>Asthma - diagnosis</topic><topic>Asthma - etiology</topic><topic>Common Cold - complications</topic><topic>Common Cold - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Disease Progression</topic><topic>exacerbation</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Nasal Lavage Fluid - immunology</topic><topic>ROC Curve</topic><topic>TNF-α</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><topic>virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manthei, D. M.</creatorcontrib><creatorcontrib>Schwantes, E. A.</creatorcontrib><creatorcontrib>Mathur, S. K.</creatorcontrib><creatorcontrib>Guadarrama, A. G.</creatorcontrib><creatorcontrib>Kelly, E. A.</creatorcontrib><creatorcontrib>Gern, J. E.</creatorcontrib><creatorcontrib>Jarjour, N. N.</creatorcontrib><creatorcontrib>Denlinger, L. C.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Manthei, D. M.</au><au>Schwantes, E. A.</au><au>Mathur, S. K.</au><au>Guadarrama, A. G.</au><au>Kelly, E. A.</au><au>Gern, J. E.</au><au>Jarjour, N. N.</au><au>Denlinger, L. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2014-12</date><risdate>2014</risdate><volume>44</volume><issue>12</issue><spage>1484</spage><epage>1493</epage><pages>1484-1493</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary
Background
Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood.
Objective
The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations.
Methods
We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN‐α, IFN‐β, IFN‐γ, IFN‐λ1, IP‐10, TRAIL), cell recruiting (G‐CSF, IL‐1β, IL‐8, MCP‐1, MCP‐3, TNF‐α), polarizing (CXCL13, IL‐10, IL‐13, IL‐17, TSLP), and injury remodelling (fibronectin, IL‐33, MMP‐9, VEGF).
Results
The overall cytokine response induced during viral infections was not different between asthmatic and non‐asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF‐α and IL‐1β were 1.7‐, 5.1‐ and 4.7‐fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve‐defined thresholds, high VEGF and TNF‐α levels predicted a shorter time‐to‐exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively).
Conclusion and Clinical Relevance
Although they produce similar cytokine responses to viral infection as non‐asthmatics, asthmatics with higher levels of VEGF and TNF‐α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild‐to‐moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25109477</pmid><doi>10.1111/cea.12387</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical and experimental allergy, 2014-12, Vol.44 (12), p.1484-1493 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | asthma Asthma - diagnosis Asthma - etiology Common Cold - complications Common Cold - metabolism Cytokines - metabolism Disease Progression exacerbation Female Humans Male Nasal Lavage Fluid - immunology ROC Curve TNF-α Tumor Necrosis Factor-alpha - metabolism Vascular Endothelial Growth Factor A - metabolism VEGF virus |
| title | Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations |
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