The safety and efficacy of alfentanil-based induction in bronchoscopy sedation: A randomized, double-blind, controlled trial.

BACKGROUND: Alfentanil in combination with propofol produces a synergistic sedative effect in patients undergoing flexible bronchoscopy (FB). However, the use of this combination is controversial due to the risk of cardiopulmonary depression. The aim of this study was to evaluate the proper induction regimen of alfentanil in propofol target-controlled infusion for FB sedation. METHODS: One hundred seventy-three patients were assigned randomly into 5 regimens: Group 1 and 2, alfentanil 2.5 and 5 µg/kg, respectively, immediately before propofol administration; Group 3 and 4, alfentanil 2.5 and 5 µg/kg, respectively, 2 minutes before propofol administration; and Group 5, propofol administration alone to achieve the observer assessment of alertness and sedation scale 3∼2. The bronchoscopists, physicians in charge of sedation, and patients were blind to the regimens. Adverse events, drug dose, induction, procedure and recovery time, cough severity, and propofol injection related pain were recorded. RESULTS: The patients in groups 2 and 4 required a lower dose of propofol (P = 0.031 and 0.019, respectively) and shorter time (P = 0.035 and 0.010) than group 5 for induction. Patients in group 2 experienced more hypoxemia than those in group 5 during induction (P = 0.031). The physician in charge of sedation scored a lower severity of cough in the patients in group 4 than in groups 3 and 5. There were no differences in terms of propofol injection related pain among the groups. CONCLUSION: Alfentanil 5 µg/kg given immediately before propofol infusion cannot be recommended. Further study is required to define conclusions about alfentanil 2.5 and 5 µg/kg because of the low power rating of subgroup in the present study.

Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due to exposure to harsh microenvironments. Hypoxia is known to induce expression of cytoprotective genes and also secretion of anti-inflammatory, anti-apoptotic and anti-fibrotic factors. Hypoxic preconditioning is thought to enhance the therapeutic potency and duration of survival of engrafted MSCs. In this work, we aimed to prolong the duration of survival of engrafted MSCs and to enhance the effectiveness of idiopathic pulmonary fibrosis transplantation therapy by the use of hypoxia-preconditioned MSCs. METHODS: Hypoxic preconditioning was achieved in MSCs under an optimal hypoxic environment. The expression levels of cytoprotective factors and their biological effects on damaged alveolar epithelial cells or transforming growth factor-beta 1-treated fibroblast cells were studied in co-culture experiments in vitro. Furthermore, hypoxia-preconditioned MSCs (HP-MSCs) were intratracheally instilled into bleomycin-induced pulmonary fibrosis mice at day 3, and lung functions, cellular, molecular and pathological changes were assessed at 7 and 21 days after bleomycin administration. RESULTS: The expression of genes for pro-survival, anti-apoptotic, anti-oxidant and growth factors was upregulated in MSCs under hypoxic conditions. In transforming growth factor-beta 1-treated MRC-5 fibroblast cells, hypoxia-preconditioned MSCs attenuated extracellular matrix production through paracrine effects. The pulmonary respiratory functions significantly improved for up to 18 days of hypoxia-preconditioned MSC treatment. Expression of inflammatory factors and fibrotic factor were all downregulated in the lung tissues of the hypoxia-preconditioned MSC-treated mice. Histopathologic examination observed a significant amelioration of the lung fibrosis. Several LacZ-labeled MSCs were observed within the lungs in the hypoxia-preconditioned MSC treatment groups at day 21, but no signals were detected in the normoxic MSC group. Our data further demonstrated that upregulation of hepatocyte growth factor possibly played an important role in mediating the therapeutic effects of transplanted hypoxia-preconditioned MSCs. CONCLUSION: Transplantation of hypoxia-preconditioned MSCs exerted better therapeutic effects in bleomycin-induced pulmonary fibrotic mice and enhanced the survival rate of engrafted MSCs, partially due to the upregulation of hepatocyte growth factor.

The potential regimen of target-controlled infusion of propofol in flexible bronchoscopy sedation: a randomized controlled trial.

OBJECTIVES: Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation. METHODS: After alfentanil bolus, initial induction Ce of propofol was targeted at 2 µg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 µg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded. RESULTS: The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 µg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 µg/ml, p = 0.005) and the Ce of procedures was higher at 0.5 µg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 µg/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 µg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively). CONCLUSION: Titration at 0.5 µg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01101477.

Asthma control in asthmatic patients treated for lung cancer.

BACKGROUND: The balance of the Th1 and Th2 immune response plays an important role in the regulation of the immune system and in general health. Tumor bearing hosts are supposed to have a balance shifting to the Th2 pathway, while a favorable Th1 anti-tumor pathway is induced in tumor-resected hosts. The clinical impacts of a tumor-related Th2 environment have not been clearly studied. The present study was conducted to test the hypothesis that nonsmall cell lung cancer (NSCLC) has an impact on control of asthma, a wellknown Th2-predominant inflammatory disease. METHOD: Thirty-eight patients with the diagnoses of both asthma and lung cancer were retrospectively enrolled. Patients were divided into two groups according to their response to lung cancer treatment, the responder group (complete regression, partial regression and stable disease) and non-responder group (progression of disease). Asthma control test (ACT) scores were analyzed one year before diagnosis, at the time of diagnosis of lung cancer, and at the time of re-staging after cancer treatment. RESULTS: All the asthmatics with lung cancer had worsening of their symptoms according to their ACT scores at the time of diagnosis of lung cancer compared to scores in the preceding year (21.6 ± 0.5 vs. 16.5 ± 0.8, n = 38, p < 0.001). The ACT scores in the responder group (17.3 ± 5.1) were significantly improved after effective lung cancer treatment (22.1 ± 1.8, n = 18, p < 0.01). However, the ACT scores in the non-responder group were even worse after disease progression (15.8 ± 5.0 vs. 11.6 ± 4.2, n = 18, p < 0.001). CONCLUSION: Our observations indicate that asthmatic patients with acquisition or progression of NSCLC may have worsening of their asthma control status. Those patients with good responses to cancer treatment had improved asthma control. These observations indicate that the Th2 pathway in lung cancer may be a contributing factor in asthma control, another Th2 predominant disorder. More sophisticated clinical and biological investigations are necessary to confirm the role of Th1/Th2 counterbalance in lung cancer in the clinical impact on related immune disorders.