Current Issue : October - December Volume : 2015 Issue Number : 4 Articles : 6 Articles
Background: Airway resistance (RAW) and specific airway conductance (sGAW) are measures that reflect the patency\nof airways. Little is known of the variability of these measures between different lung diseases. This study\ninvestigated the contribution of RAW and sGAW to a diagnosis of obstructive airways disease and their role in\ndifferentiating asthma from COPD.\nMethods: 976 subjects admitted for the first time to a pulmonary practice in Belgium were included. Clinical\ndiagnoses were based on complete pulmonary function tests and supported by investigations of physicians�\ndiscretion. 651 subjects had a final diagnosis of obstructive diseases, 168 had another respiratory disease and 157\nsubjects had no respiratory disease (healthy controls).\nResults: RAW and sGAW were significantly different (p < 0.0001) between obstructive and other groups. Abnormal\nRAW and sGAW were found in 39 % and 18 % of the population, respectively, in which 81 % and 90 % had\ndiagnosed airway obstruction. Multiple regression revealed sGAW to be a significant and independent predictor of\nan obstructive disorder. To differentiate asthma from COPD, RAW was found to be more relevant and statistically\nsignificant. In asthma patients with normal FEV1/FVC ratio, both RAW and sGAW were more specific than sensitive\ndiagnostic tests in differentiating asthma from healthy subjects.\nConclusions: RAW and sGAW are significant factors that contribute to the diagnosis and differentiation of obstructive\nairways diseases...
Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and\nsymptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung\ntissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure\n(Ppa) is achieved during the early symptomatic stage, indicating that the elevation of the mean Ppa is primarily driven\nby the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage.\nRecently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined\nby the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate\nthat intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage\nof the disease.\nHowever, many questions remain. For instance, how does the pulmonary hemodynamics change during the\ncourse of the disease, and what drives the development of severe PAH? Although it is generally acknowledged\nthat both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary\narterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the\nrecent histopathological concepts of PAH with respect to the progression of the lung vascular disease....
Background: Human lung mast cells (HLMCs) infiltrate the airway epithelium and airway smooth muscle (ASM) in\nasthmatic airways. The mechanism of HLMC adhesion to both cell types is only partly defined, and adhesion is not\ninhibited by function-blocking anti-Kit and anti-stem cell factor (SCF) antibodies. Our aim was to identify adhesion molecules\nexpressed by human mast cells that mediate adhesion to human ASM cells (HASMCs) and human airway epithelial cells.\nMethods: We used phage-display to isolate single chain Fv (scFv) antibodies with adhesion-blocking properties from rabbits\nimmunised with HLMC and HMC-1 membrane proteins.\nResults: Post-immune rabbit serum labelled HLMCs in flow cytometry and inhibited their adhesion to human BEAS-2B\nepithelial cells. Mast cell-specific scFvs were identified which labelled mast cells but not Jurkat cells by flow cytometry.\nOf these, one scFv (A1) consistently inhibited mast cell adhesion to HASMCs and BEAS-2B epithelial cells by about\n30 %. A1 immunoprecipitated Kit (CD117) from HMC-1 lysates and bound to a human Kit-expressing mouse mast cell\nline, but did not interfere with SCF-dependent Kit signalling.\nConclusion: Kit contributes to human mast cell adhesion to human airway epithelial cells and HASMCs, but may utilise\na previously unidentified adhesion domain that lies outside the SCF binding site. Targeting this adhesion pathway\nmight offer a novel approach for the inhibition of mast cell interactions with structural airway cells, without detrimental\neffects on Kit signalling in other tissues....
Purpose The expression of the neutrophil high-affinity\nFc-gamma receptor (CD64) can be used as a diagnostic\nmarker for bacterial infection and sepsis. The aims of this\nstudy were to determine the diagnostic accuracy of CD64\ncompared to C-reactive protein (CRP) and white blood cell\ncount (WBC) in patients hospitalized with acute exacerbations\nof COPD (AECOPD) and to investigate the kinetics\nof CD64 expression.\nMethods The present study is a prospective, single-centre\nobservation study. Blood samples were collected from\npatients hospitalized with AECOPD at admission and after\n6, 24 and 48 h. Retrospective reviews on the patients�\nmedical records were performed blinded to the CD64\nresults. The CD64 was measured using the Leuko64 kit\nfrom Trillium Diagnostics, LLC (Maine, USA) with the\nCELL-DYN Sapphire Haematology System (Abbott Laboratories,\nIllinois, USA). Diagnostic accuracy of the CD64,\nCRP and WBC was compared using a receiver operating\ncharacteristic (ROC) curve analysis.\nResults A total of 113 patients were included. Thirty-six\npatients (32 %) had pulmonary infiltrate on chest X-ray at\nadmission (PI). The CD64 was higher in samples from\npatients with AECOPD and PI than those without PI at\nadmission (median 1.25 vs. 0.60, p = 0.002) and during\n48 h of follow-up. The area under the ROC curve of CD64,\nCRP and WBC was 0.69, 0.73 and 0.64, respectively,\n(p = 0.42 for the test of difference).\nConclusion Neutrophil CD64 expression has about the\nsame diagnostic accuracy as CRP in diagnosing pneumonia\nin patients hospitalized with AECOPD, but does not add to\nthe diagnostic accuracy of CRP and WBC count....
Background: A Phase II, multicentre, randomised, double-blind, placebo-controlled, crossover trial comparing the\n24-h forced expiratory volume in 1 s (FEV1) time profile after 3 weeksââ?¬â?¢ treatment with once-daily (QD) or twice-daily\n(BID) olodaterol (at the same total daily dose) versus placebo delivered via RespimatÃ?® in patients with moderate to\nsevere asthma.\nMethods: Patients were randomised to different sequences of olodaterol with 2-week washout, either as a total\ndaily dose of 5 ?g (5 ?g QD [AM] or 2.5 ?g BID) or placebo, or 10 ?g (10 ?g QD [AM] or 5 ?g BID) or placebo.\nPrimary end point was FEV1 area under the curve from 0 to 24 h (AUC0ââ?¬â??24) response (defined as change from study\nbaseline FEV1) after 3 weeks. Key secondary end points were FEV1 AUC0ââ?¬â??12 and AUC12ââ?¬â??24 responses.\nResults: Two hundred and six patients received treatment. All olodaterol treatments demonstrated statistically\nsignificant improvements in FEV1 AUC0ââ?¬â??24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment\ndifference versus placebo was 0.191 L for olodaterol 2.5 ?g BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for\n5 ?g QD (95 % CI 0.111, 0.189), 0.228 L for 5 ?g BID (95 % CI 0.190, 0.266) and 0.209 L for 10 ?g QD (95 % CI 0.170,\n0.247). These results were supported by the key secondary end points. Olodaterol 5 ?g QD provided numerically lower\nmean values for 24-h bronchodilation than olodaterol 2.5 ?g BID (p = 0.0465), with no statistically significant difference\nbetween treatment with olodaterol 10 ?g QD and 5 ?g BID. No relevant differences in morning and evening peak\nexpiratory flow or Asthma Control Questionnaire scores at 3 weeks were observed between different doses and\nregimens. Adverse events were generally mild to moderate and comparable between groups.\nConclusions: All doses and dose frequencies provided adequate 24-h bronchodilation superior to placebo. Based on\nthe results of this study, it would be reasonable to include both posologies of 5 ?g olodaterol daily (5 ?g QD or 2.5 ?g\nBID, both delivered in two puffs per dose from the RespimatÃ?® inhaler) in subsequent studies. Further studies are\nnecessary to confirm the optimum dosing regimen in asthma. No safety concerns were identified....
Background: Long acting bronchodilators are the standard of care in the management of chronic obstructive\npulmonary disease (COPD). The aim of this study was to investigate the efficacy and safety of V0162, a novel\nanticholinergic agent with bronchodilator properties, in preclinical models and in patients with COPD.\nMethods: Guinea pigs were used to evaluate the impact of V0162 on the acetylcholine or histamine-induced\nbronchoconstriction. V0162 was also investigated in an allergic asthma model on ovalbumin-sensitized guinea pig.\nFor clinical investigations, healthy volunteers were included in a dose-escalation, randomized, placebo-controlled\nphase I study to determine the maximal tolerated dose, followed by a randomized, placebo-controlled, cross-over\nphase II study in patients with COPD. V0162 was given via inhalation route. The objectives of the phase I/II study\nwere to assess the safety and efficacy of V0162, in terms of bronchodilation and reduction in hyperinflation.\nResults: Preclinical results showed that V0162 was able to prevent bronchoconstriction induced either by\nacetylcholine or histamine. V0162 reversed the bronchoconstriction and airway inflammation caused by ovalbumin\nchallenge in sensitized guinea pigs. In the healthy volunteers study, 88 subjects were enrolled: 66 received V0162\nand 22 received placebo. No particular safety concerns were raised. The maximal tolerated dose was not reached\nand the dose escalation was stopped at 2400 ?g. A total of 20 patients with COPD were then enrolled. All patients\nreceived a single-dose of V0162 1600 ?g and of placebo in two alternating periods. In COPD patients, V0162\ndemonstrated a significant increase in FEV1 compared with placebo (148 �± 137 ml vs. 36 �± 151 ml, p = 0.003).\nThis bronchodilatory effect was corroborated by a reduction in hyperinflation. There was a trend toward dyspnea\nrelief (change in visual analog scale at 22 h, ?15.1 �± 26.0 mm vs.- 5.3 �± 28.8 mm with placebo, p = 0.054). No serious\nadverse events (AEs) were reported. Most common AEs were productive and non-productive cough, dyspnea\nand pruritus.\nConclusions: V0162 improved pulmonary function and tended to improve dyspnea in patients with COPD over\nmore than 24 h. The slight plasmatic exposure observed might support the good safety profile....
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