title: Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Manthei
authors.forename: E A
authors.initials: EA
authors.lastname: Schwantes
authors.forename: S K
authors.initials: SK
authors.lastname: Mathur
authors.forename: A G
authors.initials: AG
authors.lastname: Guadarrama
authors.forename: E A
authors.initials: EA
authors.lastname: Kelly
authors.forename: J E
authors.initials: JE
authors.lastname: Gern
authors.forename: N N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: L C
authors.initials: LC
authors.lastname: Denlinger
mesh_terms: D001249:Asthma / Q000175:diagnosis* / Q000209:etiology*; D003139:Common Cold / Q000150:complications* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D012372:ROC Curve; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A
keywords: TNF-α; VEGF; asthma; exacerbation; virus
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