A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia.

The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non-inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.

Elevated platelets enhance cancer cell migration, promote hematogenous metastasis and associate with a poor prognosis in advanced non-small cell lung cancer cases.

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration . Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets (81.7±0.45% vs 41.0±3.50%, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, 4.33±0.33 vs 0.33±0.33, P=0.01; in SPC-A1, 2.67±0.33 vs 0.00±0.00, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (>200x109/L, 3 months versus ≤200x109/L, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases.

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

High p27 expression is associated with a better prognosis in East Asian non-small cell lung cancer patients.

BACKGROUND: The role of the anti-apoptotic protein p27 in non-small cell lung cancer (NSCLC) remains controversial. To clarify its association with survival in NSCLC, we performed a systematic review of the literature with meta-analysis. METHODS: Trials were selected for further analysis if they provided an independent assessment of p27 in NSCLC and reported the analysis of survival data based on p27 status. A total of 11 trials, which comprised 1646 patients, provided sufficient information for the meta-analysis. Sensitivity analyses were conducted using histology, disease stage and ethnicity. RESULTS: The combined hazard ratio (HR) of 1.50 (95% CI=1.15-1.97; P<0.001 for heterogeneity) suggested that high p27 expression has a favorable impact on survival. When the studies were restricted to those of East Asian populations, patients that expressed high levels of p27 showed a better survival rate (HR 1.73, 95% CI=1.36-2.21; P=0.169 for heterogeneity) than those that did not express high levels of p27. In addition, the heterogeneity and publication bias disappeared. CONCLUSION: In NSCLC, high p27 expression is associated with a better prognosis among East Asians.

Beta(2)-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population.

Association and linkage studies of beta2-adrenergic receptor (beta2AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta2AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions -47, -20, 46, 79, and 252) of beta2AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta2AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV1) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV1 (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV1 (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype -47 T/-20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta2AR SNPs or beta2AR haplotype.

[A randomized, double-blind, placebo-control study of once-daily inhaled tiotropium in chronic obstructive pulmonary disease].

OBJECTIVE: To compare the efficacy and safety between tiotropium capsule and placebo in a 12-week treatment in patients with chronic obstructive pulmonary disease (COPD). METHODS: A multi-center, randomized, double-blind, and placebo-control clinical trial was conducted in 205 patients with stable COPD. They were randomized into inhaled tiotropium 18 µg once daily or placebo, lasting for 12 weeks. The spirometry was conducted at baseline, 6 and 12 weeks after treatment. RESULTS: A total of 205 patients with stable stage I or II COPD were randomized to tiotropium and placebo groups. The improvement rate of clinical symptom in the tiotropium group was 25.2% (26/103) after a 12 week treatment, but that of the control group was 4.9% (5/102). The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in the tiotropium group increased (0.2 ± 0.3) L and (19.2 ± 29.1)% after the 12 week therapy, but only (0.0 ± 0.2) L and (0.8 ± 18.2)% in the placebo group. The rate of adverse reaction in the tiotropium group was 7.8% (8/103), but in the placebo group was 12.8% (13/102). The difference between the 2 groups was not significant. All adverse reactions were mild, including dry mouth and sore throat. CONCLUSIONS: This trial confirmed that tiotropium powder 18 µg once daily relieved dyspnea, prevented aggravation and improved pulmonary function, clinical symptoms and life quality. Tiotropium was a safe and effective once-daily anticholinergic bronchodilator as first-line maintenance therapy in COPD.

[Effects of curcumin on apoptosis of pulmonary fibroblasts from rats].

OBJECTIVE: To investigate the effect of curcumin on apoptosis of pulmonary fibroblasts from rats and the molecular mechanisms. METHODS: Twenty 6 week old male SD rats were randomly divided into 2 groups with 10 rats in each group: the normal control group (NLF) and the model group (MLF). The pulmonary fibrosis models were made by intratracheally instillation of bleomycin. The rats were sacrificed on the 28 day of experiment, and the pathologic changes of the lung tissues were investigated. Fibroblasts were derived from lung tissues and were cultured in vitro. Then the cells were treated with curcumin at different concentrations (5, 10, 20 and 40 micromol/L). TUNEL staining was used to detect apoptosis. The Caspase-3 and Caspase-8 expression of each group were determined by flow cytometry (FCM). The expression changes of apoptosis-regulating proteins of Caspase-9 in cells were examined by immunohistochemical staining. RESULTS: In the MLF group treated with 4 different concentrations of curcumin for 12 h, apoptotic morphological changes were observed in the cells. Apoptotic index (AI) was (30.17 +/- 0.53)%, (37.20 +/- 0.25)%, (45.12 +/- 0.31)%, (51.90 +/- 0.27)% respectively, which were significantly higher than that of the control group without curcumin (4.59 +/- 0.19)%. The expression of Caspase-3 was (53.1 +/- 0.7)%, (60.5 +/- 0.6)%, (69.1 +/- 0.9)%, (74.9 +/- 0.7)%, which were significantly higher than that of the control group (5.5 +/- 0.8)%. The expression of Caspase-8 were (37.2 +/- 0.5)%, (46.8 +/- 0.4)%, (56.5 +/- 0.3)%, (67.3 +/- 0.3)%, which were significantly higher than that of the control group (4.6 +/- 0.6)%. The expression of Caspase-9 were (39.38 +/- 0.88)%, (47.51 +/- 0.24)%, (57.75 +/- 0.63)%, (68.36 +/- 0.29)%, which were significantly higher than that of the control group (4.92 +/- 0.34)%. Curcumin did not induce apoptosis of NLF, the expressions of Caspase-3, Caspase-8, Caspase-9 being not statistically different from that of the control group without curcumin. CONCLUSIONS: Curcumin can induce apoptosis of pulmonary fibroblasts in rats with bleomycin-induced pulmonary fibrosis and the mechanism may be related to the activation of Caspase-3, Caspase-8, and Caspase-9.

MDM2 309 T/G polymorphism is associated with lung cancer risk among Asians.

Published data on the association between MDM2 309 T/G polymorphism and lung cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight studies including 6063 cases and 6678 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with GG variant genotype in recessive model when all the eligible studies were pooled into the meta-analysis (OR=1.17; 95% CI=1.02-1.34; P(heterogeneity)=0.06). In the subgroup analysis by ethnicity, significantly increased risks were found among Asians for TG versus TT (OR=1.20; 95% CI=1.05-1.37; P(heterogeneity)=0.30), GG versus TT (OR = 1.34; 95% CI=1.01-1.79; P(heterogeneity)=0.03) and dominant model (OR=1.26; 95% CI=1.11-1.43; P(heterogeneity)=0.14). However, no significant associations were found in both Europeans and Africans for all genetic models. This meta-analysis suggests that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.

[Effect of curcumin on the expression of collagen type I protein and transforming growth factor-beta1 mRNA in pulmonary fibrosis rats].

OBJECTIVE: To study the effects of curcumin on the expressions of collagen type I protein and transforming growth factor-beta1 mRNA in lung tissues of rats with pulmonary fibrosis. METHODS: 96 male SD rats were randomly divided into four groups with 24 rats in each group: the normal control group, the model group, the prednisone treated group, and the curcumin treated group. Pulmonary fibrosis was induced by intra-bronchial injection of bleomycin A5. From the 15(th) day after bleomycin administration, rats in the prednisone treated group and the curcumin treated group were given prednisone (5 mg/kg) or curcumin (300 mg/kg) respectively once daily by intragastric administration. In the same way, rats in the normal control group and the model group were given 1% Sodium Carboxymethyl Cellulose (10 ml/kg) once daily. The histological changes of lung tissue were evaluated by Haematoxylin-eosin (HE) and Masson's trichrome. The rats were randomly sacrificed on the 21(st), 28(th), 42(nd) and 56(th) day after bleomycin administration. The type I collagen expression was analyzed by immunohistochemistry. The transforming growth factor-beta(1) (TGF-beta(1)) mRNA expression of lung was detected by the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Pulmonary fibrosis in the curcumin treated group was significantly reduced as compared with the model group and the prednisone treated group on the 42(nd) and 56(th) day (P < 0.05). The expression of type I collagen protein in the curcumin treated group was significantly decreased than that in the model group and the prednisone treated group on the 28(th), 42(nd) and 56(th) day after bleomycin administration (P < 0.05). The TGF-beta(1) mRNA expression in the curcumin treated group was 0.61 +/- 0.09 and 0.48 +/- 0.16 respectively on the 21(st) and 28(th) day after bleomycin administration (P < 0.05). It was significantly decreased than that in the model group on the 21(st), 28(th) day after bleomycin administration and lower as compared with the prednisone treated group on the 21(st) day (P < 0.05). CONCLUSION: Curcumin could suppress BLM-induced pulmonary fibrosis in rats at the fibrosing stage, with the possible mechanism of inhibiting the synthesis and deposition of type I collagen protein and depressing the overexpression of TGF-beta(1) mRNA. The therapeutic effect of curcumin on pulmonary fibrosis is better than prednisone.

[Primary natural killer/T cell lymphoma of the lung: two cases report and clinical analysis].

OBJECTIVE: To describe the clinical and pathological features of primary NK/T cell lymphoma of the lung. METHODS: Two cases of primary NK/T cell lymphoma of the lung were reported, and the clinical, radiological and pathological characteristics of the disease were discussed with literature review of 3 cases. RESULTS: Most patients presented with fever, cough and dyspnea, and antibiotics were ineffective. Radiographic findings included solitary or multiple nodules and consolidation, unilateral orbilateral pleural effusions (4/5), without hilar or mediastinal adenopathy. Ebstein-Barr virus was positive in cases patients (3/5). Histopathology revealed a great deal of abnormal lymphocyte infiltration, which were angio-centric with marked tissue putrescence and angio-destruction. Immunophenotyping showed CD56(+), CD3(+), perform (+), T-cell intracytoplasmic antigen-1(+) and/or GranB(+), but CD20(-). Most patients died of respiratory failure in half a year (4/5). CONCLUSION: Primary NK/T cell lymphoma of the lung is rare, but should be considered when patients present with lung shadows and fever non-responsive to antibiotics, decreased WBC and increased LDH.

[The effect of curcumin on bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: To observe the effect and mechanism of curcumin on pulmonary fibrosis induced by bleomycin in rats. METHODS: Fifty-four SD rats were randomly divided into 3 groups, 18 rats each group. The control group received a single intratracheal dose of 2 ml/kg of sterile physiological saline at day 0, and from 14 d, 0.5 ml/kg of sterile physiological saline intraperitoneally every day. The bleomycin group received a single intratracheal dose of 5 mg/kg of bleomycin A(5), and from 14 d, 0.5 ml/kg of suspension of 6% alcohol and 6% polyethylene glycol intraperitoneally every day. The curcumin group received a single intratracheal dose of 5 mg/kg of bleomycin A(5), and from 14 d, 50 mg/kg of curcumin (suspended in 6% alcohol and 6% polyethylene glycol) intraperitoneally every day. Six rats in each group were killed at day 17, 21, 28 in batches. The sections of lungs were stained with hematoxylin-eosin (HE) and Masson's trichrome to evaluate the severity of alveolitis and pulmonary fibrosis. The content of hydroxyproline and the expression of transforming growth factor-beta(1) (TGF-beta(1)) mRNA, interferon-gamma (IFN-gamma) mRNA in lung tissues were analyzed. The concentration of TGF-beta(1) and IFN-gamma in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: (1) The scores of alveolitis in the curcumin group and the bleomycin group at day 28 were 1.3 +/- 0.5, 2.0 +/- 0.9, respectively, the difference being significant (q = 3.26, P < 0.05). (2) The scores of pulmonary fibrosis in the curcumin group and the bleomycin group were 1.3 +/- 0.5, 1.8 +/- 0.4 at day 21, and 1.2 +/- 0.4, 2.2 +/- 1.0 at day 28, the difference being significant between the two groups (q = 3.33, 4.00, all P < 0.05). (3) The content of hydroxyproline in lung tissues in the curcumin group and the bleomycin group were (1.75 +/- 0.36) microg/g, (2.47 +/- 0.24) microg/g at day 28, the difference being significant (q = 7.20, P < 0.01). (4) The concentration of TGF-beta(1) in BALF in the curcumin group and the bleomycin group were (20 +/- 3) ng/L, (39 +/- 7) ng/L at day 21, and (24 +/- 4) ng/L, (40 +/- 7) ng/L at day 28, all being statistically different between the two groups (q = 5.30, 6.27, all P < 0.05). (5) The expression of TGF-beta(1) mRNA in lung tissues in the curcumin group and the bleomycin group were 0.51 +/- 0.11, 0.59 +/- 0.13 at day 21, and 0.50 +/- 0.07, 0.64 +/- 0.11 at day 28, all being not statistically different between the two groups (q = 1.55, 3.13, all P > 0.05). (6) The concentrations of IFN-gamma in BALF in the curcumin group and the bleomycin group were 0.49 +/- 0.17, 0.50 +/- 0.08 at day 21, and 0.52 +/- 0.15, 0.52 +/- 0.11 at day 28, all being not statistically different between the two groups (q = 1.85, 2.03, all P > 0.05). (7) The expression of IFN-gamma mRNA in the curcumin group and the bleomycin group were (28 +/- 5) ng/L, (35 +/- 13) ng/L at day 21, and (30 +/- 11) ng/L, (39 +/- 13) ng/L at day 28, no significant difference between the two groups (q = 0.17, 0.00, all P > 0.05). CONCLUSIONS: Curcumin can alleviate alveolitis and pulmonary fibrosis induced by bleomycin in rats, possibly through its inhibition of TGF-beta(1).

[Primary pulmonary involvement of NK/T-cell lymphoma: report of two cases with literature review].

OBJECTIVE: To describe the imaging, clinical and pathological features of primary pulmonary involvement of NK/T-cell lymphoma. METHODS: The imaging, clinical and pathological features of 2 patients with primary pulmonary involvement of NK/T-cell lymphoma were retrospectively analyzed. RESULTS: The 2 cases (both young women) of NK/T-cell lymphoma were confirmed with CT-guided percutaneous needle lung biopsy and the lung was the primary involved site. They presented similar clinical features, including fever, dry cough, and progressive tachypnea with hypoxia. Bilateral pulmonary parenchymal nodular consolidations with bilateral pleural fluid were detected at admission chest CT scanning. Air bronchogram and halo signs were found in both the cases. The plasma Epstein-Barr virus (EBV) DNA level was 3.65 x 10(5) copies/ml and 1000 copies/ml respectively. The disease deteriorated progressively and the patients survived only 40d and 66d respectively. CONCLUSION: The lungs may be the primary involved sites of NK/T-cell lymphoma and the prognosis is grim.

[Effect of interferon-gamma on bleomycin induced pulmonary fibrosis in rats].

OBJECTIVE: To observe the effects of interferon-gamma (IFN-gamma) on lung injury induced by bleomycin and its mechanism. METHODS: Sixty-six SD rats were randomly divided into three group: the normal control group (group N, n=24), the bleomycin group (group B, n=24) and IFN-gamma treatment group (group I, n=18). The degree of lung injury and the concentrations of tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured. RESULTS: The degree of lung injury in group I was severer than group B, but with no significant difference. The concentration of TNF-alpha in BALF on 17, 21, 28 days and in serum on 21 and 28 days were significantly increased after IFN-gamma administration compared with group N and group B (all P<0.05). The concentration of IFN-gamma in BALF and serum increased on 21 and 28 days in group I (all P<0.05). CONCLUSION: IFN-gamma might aggravate lung injury induced by bleomycin, and it might attribute to an increase in TNF-alpha.