Current Issue : October - December Volume : 2016 Issue Number : 4 Articles : 5 Articles
Background: Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute\nexacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery.\nPirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was\nconducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative\nAE-IPF patients with lung cancer.\nMethods: Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone\nwas dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks\nof 1200-mg/day administration. The primary endpoint was nonââ?¬â??AE-IPF rate during postoperative days 0ââ?¬â??30, compared\nto the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF\nwere confirmed by an independent review committee.\nResults: From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both\npirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39\npatients (94.9 % [95 % confidential interval: 82.7ââ?¬â??99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 %\nconfidential interval: 85.5ââ?¬â??99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient,\nafter AE-IPF; no other grade 3ââ?¬â??5 adverse events were observed Conclusions: Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer\nsurgery in IPF patients....
Background: Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is\nassociated with worse health status, and increased hospitalisation and mortality. Long-acting bronchodilators, either\nalone or in combination, have been shown to improve exercise intolerance. However, none of these studies were\ndesigned with physical activity as primary outcome.\nThis study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 Ã?¼g once\ndaily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with\nmoderate-to-severe COPD.\nMethods: In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received\nIND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods). Eligible patients\nwere ââ?°Â¥40 years of age, current or ex-smokers (smoking history ââ?°Â¥10 pack-years), with post-salbutamol forced\nexpiratory volume in 1 s (FEV1) 40ââ?¬â??80 % predicted, and FEV1:forced vital capacity <0.70.\nThe co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure. Key\nsecondary endpoints were average number of steps per day and the duration of at least moderate activity per\nday. Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.\nResults: A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 %\npredicted), with 183 (94.3 %) completing the study.\nCompared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001),\nactivity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day\n(difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity\n(difference 4.4 min, p = 0.264). IND/GLY was associated with statistically significant improvements versus placebo\nin peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days. The incidence of treatment-emergent\nadverse events was 22.8 % with IND/GLY and 22.9 % with placebo.\nConclusions: In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient\neducation or lifestyle advice, improved daily physical activity levels. This suggests that IND/GLY has the potential\nto impact two of the main clinical concerns in the care of patients with COPD....
Background: Recent studies have suggested that eosinophils may have a direct effect on airway smooth muscle\ncells (ASMC), causing their proliferation in patients with asthma, but the precise mechanism of the interaction\nbetween these cells remains unknown. We propose that changes in Wnt signaling activity and extracellular matrix\n(ECM) production may help explain these findings. Therefore, the aim of this study was to investigate the effect of\neosinophils from asthmatic and non-asthmatic subjects on Wnt-5a, transforming growth factor �²1 (TGF-�²1), and\nECM protein (fibronectin and collagen) gene expression and ASMC proliferation.\nMethods: A total of 18 subjects were involved in the study: 8 steroid-free asthma patients and 10 healthy subjects.\nPeripheral blood eosinophils were isolated using centrifugation and magnetic separation. An individual co-culture\nof eosinophils with human ASMC was prepared for each study subject. Adhesion of eosinophils to ASMC (evaluated\nby assaying eosinophil peroxidase activity) was determined following various incubation periods (30, 45, 60, 120,\nand 240 min). The expression of Wnt-5a, TGF-�²1, and ECM protein genes in ASMC was measured using quantitative\nreal-time polymerase chain reaction (PCR) after 24 h of co-culture. Proliferation of ASMC was measured using the\nAlamar blue method after 48 h and 72 h of co-culture with eosinophils.\nResults: Eosinophils from asthmatic subjects demonstrated increased adhesion to ASMC compared with\neosinophils from healthy subjects (p < 0.05) in vitro. The expression of Wnt-5a, TGF-�²1, collagen, and fibronectin\ngenes in ASMC was significantly higher after 24 h of co-culture with eosinophils from asthmatic subjects, while\nco-culture of ASMC with eosinophils from healthy subjects increased only TGF-�²1 and fibronectin gene expression.\nASMC proliferation was augmented after co-culture with eosinophils from asthma patients compared with\nco-culture with eosinophils from healthy subjects (p < 0.05).\nConclusions: Eosinophils enhance Wnt-5a, TGF-�²1, fibronectin, and collagen gene expression in ASMC and\npromote proliferation of these cells in asthma....
Background: Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the\nonce-daily long-acting �²2-agonist olodaterol 5 �¼g and 10 �¼g on constant work-rate cycle endurance in patients\nwith moderate to very severe chronic obstructive pulmonary disease.\nMethods: Patients received placebo, olodaterol 5 �¼g once daily (QD) and olodaterol 10 �¼g QD in a randomised\norder for 6 weeks each, with a 2-week washout period in between. The primary end point was change in\nendurance time during constant work-rate cycle ergometry to symptom limitation at 75 % maximal work capacity\nafter 6 weeks of treatment (2 h post-dose), based on log10-transformed data. Key secondary end points were\ninspiratory capacity at isotime and intensity of breathing discomfort at isotime.\nResults: 151 and 157 patients were randomised and treated in Studies 1222.37 and 1222.38, respectively, with 147\nand 154 being included in the full analysis sets. Mean endurance time at week 6 was increased compared to\nplacebo by 14.0 % (Study 1222.37; p < 0.001) and 11.8 % (Study 1222.38; p < 0.01) with olodaterol 5 �¼g, and by\n13.8 % (Study 1222.37; p < 0.001) and 10.5 % (Study 1222.38; p < 0.01) with olodaterol 10 �¼g. Inspiratory capacity at\nisotime increased with olodaterol 5 �¼g (Study 1222.37, 0.182 L, p < 0.0001; Study 1222.38, 0.084 L, p < 0.05) and\n10 �¼g (Study 1222.37, 0.174 L; Study 1222.38, 0.166 L; both studies, p < 0.0001), and breathing discomfort was\nsignificantly reduced in Study 1222.37 (olodaterol 5 �¼g, 0.77 Borg units, p < 0.001; olodaterol 10 �¼g, 0.63 Borg units,\np < 0.01) but not Study 1222.38.\nConclusions: These studies provide further characterisation of the efficacy of olodaterol, showing that\nimprovements in airflow (forced expiratory volume in 1 s) are associated with increases in inspiratory capacity and\nimprovements in exercise endurance time....
Background: Six-minute walk test (6MWT) is routinely performed in chronic thromboembolic pulmonary hypertension\n(CTEPH) before pulmonary endarterectomy (PEA). However, the clinical relevance of heart rate response (Ã?â?HR) and\nexercise-induced oxygen desaturation (EID) during 6MWT is remaining unknown.\nMethods: Patients undergoing PEA in our center between 03/2013-04/2014 were assessed prospectively with\nhemodynamic and exercise parameters prior to and 1 year post-PEA. Patients with symptomatic chronic\nthromboembolic disease (mean pulmonary artery pressure (mPAP) <25 mmHg) and clinical relevant obstructive\npulmonary disease were excluded. The following definitions were used: Ã?â?HR = (peak HR - resting HR), percent heart\nrate reserve (HRR) = (peak HR ââ?¬â??rest HR)/(220 - age - rest HR) x 100 and EID=SpO2 ââ?°Â¤88 %.\nResults: Thirty-seven patients (of 116 patients screened) with mPAP of 43.2 Ã?± 8.7 mmHg, pulmonary vascular resistance\n(PVR) of 605.5 Ã?± 228.7 dyn*s/cm5, cardiac index (CI) of 2.4 Ã?± 0.5 l/min/m2 and a 6MWT-distance of 404.7 Ã?± 148.4 m and\na peak VO2 of 12.3 Ã?± 3.4 ml/min/kg prior to PEA were included. Baseline Ã?â?HR during 6MWT was significantly associated\nwith PVR 1 year post-PEA using linear regression analysis (r = 0.43, p = 0.01). Multivariate analysis indicated an\nassociation of HRR during 6MWT and residual PH with a hazard ratio of 1.06 (95 % Confidence interval for\nhazard ratio 0.99ââ?¬â??1.14, p = 0.08). EID was observed commonly during 6MWT but no correlations to outcome\nparameters were found.\nConclusions: This is the first prospective study to describe an association of Ã?â?HR during 6MWT with pulmonary\nhemodynamics 1 year post-PEA. Our preliminary results indicate that HRR derived from 6MWT is of clinical\nsignificance. EID was commonly observed, albeit failed as a significant prognostic factor....
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