[Show abstract][Hide abstract] ABSTRACT: Whether the inflammatory biomarker procalcitonin provides prognostic information across clinical settings and different acute respiratory tract infections (ARI) is poorly understood. Herein, we investigated the prognostic value of admission procalcitonin levels to predict adverse clinical outcome in a large ARI population.
We analysed data from 14 trials and 4211 ARI patients to study associations of admission procalcitonin levels and setting specific treatment failure and mortality alone at 30 days. We used multivariable hierarchical logistic regression and conducted sensitivity analyses stratified by clinical settings and ARI diagnoses to assess the results' consistency.
Overall, 864 patients (20.5%) experienced treatment failure and 252 (6.0%) died. The ability of procalcitonin to differentiate patients with and without treatment failure was highest in the emergency department setting (treatment failure; area under the curve (AUC): 0.64 (95% confidence interval (CI): 0.61, 0.67), adjusted odds ratio (OR): 1.85 (95% CI: 1.61, 2.12), P <0.001 and mortality; AUC: 0.67 (95% CI: 0.63, 0.71), adjusted OR: 1.82 (95% CI: 1.45, 2.29), P <0.001). In lower respiratory tract infections, procalcitonin was a good predictor of identifying patients at risk for mortality (AUC: 0.71 (95% CI: 0.68, 0.74), adjusted OR: 2.13 (95% CI: 1.82, 2.49), P <0.001). In primary care and intensive care unit patients no significant associations of initial procalcitonin levels and outcome was found.
Admission procalcitonin levels are associated with setting specific treatment failure and provide most prognostic information in ARI in the emergency department setting.
Critical Care 12/2015; 19(1). DOI:10.1186/s13054-015-0792-1 · 4.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Vasoactive intestinal peptide (VIP) is the most abundant neuropeptide in the lung. VIP has been linked to pulmonary arterial hypertension and hypoxia.
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.
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).
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).
Increased serum VIP levels are associated with AE-COPD.
[Show abstract][Hide abstract] ABSTRACT: Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.
We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.
Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.
Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.
Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.
PLoS ONE 09/2015; 10(9):e0136549. DOI:10.1371/journal.pone.0136549 · 3.23 Impact Factor