No abstract

Abdominal aortic aneurysm tissue and peripheral blood mononuclear cells (PBMC) of 41 consecutive subjects undergoing abdominal aortic aneurysm surgery were analyzed by polymerase chain reaction (PCR) for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori DNA. Twenty patients (49%) were positive for C. pneumoniae DNA-16 (39%) in both PBMC and aneurysm tissue, 3 (7.3%) in PBMC only, and 1 (2.4%) in the artery specimen only. Previous exposure to C. pneumoniae was confirmed in 19 (95%) of the 20 PCR positive subjects by C. pneumoniae-specific serology, using the microimmunofluorescence test. None was positive for H. pylori or M. pneumoniae DNA, either in the PBMC or in the artery specimens. In conclusion, carriage of C. pneumoniae DNA is common both in PBMC and in abdominal aortic tissue from patients undergoing abdominal aneurysm surgery. Blood PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the vascular wall.

The aim of our study was to evaluate the pharmacodynamic effects of 1-day treatment with formoterol, tiotropium and their combination in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Twenty-one (19 males, mean age 72+/-8 years, mean FEV1 38+/-14% of predicted values) patients with mild to moderate AECOPD were enrolled. Patients received formoterol (12 microg deliver via Modulite b.i.d.), tiotropium (18 microg dry powder capsules delivered via HandiHaler once daily), and their combination, in randomized sequence. Serial measurements of FEV1, FVC, IC, SpO2 and HR were performed over 24h. Formoterol, tiotropium, and their combination significantly improved the area under curves (AUCs) for FEV1, FVC and IC over 12 and 24h. The mean FEV1, FVC and IC AUC(0-12h) and AUC(0-24h) after formoterol and tiotropium combination were significantly higher than formoterol and tiotropium alone, whereas the differences between the two single drugs were not statistically significant. Formoterol, either alone or in combination with tiotropium, elicited a significantly faster onset of action, and combination elicited a greater maximum bronchodilation than both single drugs in terms of FEV1 and FVC. After 24h the bronchodilating effect of the three treatments disappeared, with the exception of the combination on FEV1. The results of this study have documented that, although the time course of the effects of evaluated drugs differs significantly from that in stable COPD, with a shorter bronchodilation both for tiotropium and formoterol, these two long-acting bronchodilators appear to also be complementary in mild to moderate AECOPD.

BackgroundAllergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum.ObjectivesTo test whether allergen-induced TH2 inflammatory markers can be reproducibly quantified by sensitive detection techniques in ultracentrifuged sputum and the effect of fluticasone (FP) on these endpoints.MethodsThirteen allergic asthmatics with dual allergen-induced airway responses, documented during a single-blind placebo run-in period, participated in a double-blind, two-period crossover study. Each period consisted of three consecutive days, separated by ≥3 weeks. Following randomization, subjects inhaled FP (500 µg bid, five doses total) or placebo. On Day 2 in each study period, allergen challenge was performed and airway response measured by forced expiratory volume in 1 sec (FEV1) until 7 h post-challenge. Sputum was induced 24 h pre-allergen and 7 and 24 h post-allergen. Sputum samples were split into two portions: TH2 biomarkers were quantified by Meso Scale multiplex platform following ultracentrifugation, and cell differentials were counted on Giemsa–May-Grünwald-stained cytospins. Allergen-induced changes in inflammatory endpoints were compared between FP and placebo using a mixed model ANCOVA.ResultsInhaled allergen induced dual airway responses in all subjects during both placebo periods with reproducible late asthmatic response (LAR) and increased sputum inflammatory biomarkers (IL-2, IL-4, IL-13, and eotaxin-1) and eosinophil counts. FP effectively blunted both the LAR and the inflammatory biomarkers.ConclusionsCombining novel, sensitive quantification methods with ultracentrifugation allows reproducible quantification of sputum biomarkers following allergen challenge, reversed by FP. This approach allows non-invasive identification of pharmacodynamic targets for anti-asthma therapies.