title: Vasoactive Intestinal Peptide for Diagnosing Exacerbation in Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Vasoactive intestinal peptide (VIP) is the most abundant neuropeptide in the lung. VIP has been linked to pulmonary arterial hypertension and hypoxia.
  
  
  OBJECTIVE
  We aimed to assess circulating VIP levels at exacerbation and at stable chronic obstructive pulmonary disease (COPD) and to evaluate the diagnostic performance in a well-characterized cohort of COPD patients.
  
  
  METHODS
  The nested cohort study included patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV. Patients were examined at stable state and at acute exacerbation of COPD (AE-COPD), and dedicated serum was collected at both conditions. Serum VIP levels were determined by enzyme-linked immunosorbent assay. Diagnostic accuracy was analyzed by receiver operating characteristic curve and area under the curve (AUC).
  
  
  RESULTS
  Patients with acute exacerbation (n = 120) and stable COPD (n = 163) had similar characteristics at baseline. Serum VIP levels did not correlate with oxygen saturation at rest (p = 0.722) or at exercise (p = 0.168). Serum VIP levels were significantly higher at AE-COPD (130.25 pg/ml, 95% CI 112.19-151.83) as compared to stable COPD (40.07 pg/ml, 95% CI 37.13-43.96, p < 0.001). The association of increased serum VIP with AE-COPD remained significant after propensity score matching (p < 0.001). Analysis of the Youden index indicated the optimal serum VIP cutoff value as 56.6 pg/ml. The probability of AE-COPD was very low if serum VIP was ≤35 pg/ml (sensitivity >90%) and very high if serum VIP was ≥88 pg/ml (specificity >90%). Serum VIP levels presented a robust performance to diagnose AE-COPD (AUC 0.849, 95% CI 0.779-0.899).
  
  
  CONCLUSIONS
  Increased serum VIP levels are associated with AE-COPD.
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Jyotshna
authors.initials: J
authors.lastname: Mandal
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.forename: Luigi
authors.initials: L
authors.lastname: Costa
authors.forename: Lucas
authors.initials: L
authors.lastname: Boeck
authors.forename: Janko
authors.initials: J
authors.lastname: Rakic
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherr
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D057216:Propensity Score; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric; D014660:Vasoactive Intestinal Peptide / Q000097:blood*
chemical_list: D015415:Biomarkers; D014660:Vasoactive Intestinal Peptide