Vasoactive intestinal peptide for diagnosing exacerbation in chronic obstructive pulmonary disease

Introduction: Vasoactive Intestinal Peptide (VIP) is the most abundant neuropeptide in the lung. VIP has been linked to pulmonary arterial hypertension and hypoxia in Chronic Obstructive Pulmonary Disease (COPD). We aimed to assess circulating VIP levels at exacerbation and at stable COPD and to evaluate the diagnostic performance in a well-characterized cohort of COPD patients.

Methods: The nested cohort study included patients with GOLD stage II-IV. Patients were examined at stable state and at acute exacerbation COPD (AE-COPD), and dedicated serum was collected at both conditions. Serum VIP levels were determined by ELISA. Diagnostic accuracy was analyzed by receiver-operating characteristic (ROC) 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 56.6pg/ml. The probability of AE-COPD was very low if serum VIP was ≤35pg/ml (sensitivity > 90%) and very high if serum VIP was ≥88pg/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.