Role of sensory innervation and mast cells in neurogenic plasma protein exudation into the airway lumen

Abstract Neurogenic inflammation in the airways involves both mucosal oedema and plasma protein exudation into the airway lumen. We aimed to investigate the mechanism of exudation of plasma proteins into the airway lumen. Neurogenic inflammation was induced in anaesthetized Sprague-Dawley rats by electrical stimulation of both vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as ¹²⁵I-albumin extravasation into both the airway wall and tracheobronchial lavage fluid. Following vagal stimulation, tracheobronchial lavages were analysed for albumin, total protein, histamine, immunoreactive substance P (SP), and immunoreactive calcitonin gene-related peptide (CGRP). Vagal stimulation rapidly increased vascular permeability in the airway mucosa and induced exudation of plasma proteins into the tracheobronchial fluid. Pretreatment with capsaicin inhibited both neurogenic vascular permeability and movement of albumin into the airway lumen. SP and CGRP were detectable in basal lavages (1.37 ± 0.12 ng/mL and 2.17 ± 0.21 ng/mL, respectively) and the concentration of SP fell by 43% following treatment with capsaicin. Following vagal stimulation, concentrations of both SP and CGRP decreased significantly. Although basal tracheobronchial lavages contained histamine, vagal stimulation did not increase the histamine concentration. These results indicate that both neurogenic vascular permeability and plasma protein exudation into the airway lumen results from activation of capsaicin-sensitive sensory nerves and the reaction is not associated with mast cell activation.     

Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard‐risk cytogenetics

Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well‐known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38⁺ CD45^‐cells and examined their relationship with cytogenetic risk. Patients had an average follow‐up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut‐off of circulating PCs for defining poor prognosis to be 41. Patients with high‐risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC < 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression‐free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard‐risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC < 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard‐risk cytogenetics confirmed that the co‐presence of circulating PCs ≥ 41, older age, Durie‐Salmon stage >I and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two‐colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard‐risk cytogenetics.