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Background: Epigallocatechin-3-gallate (EGCG), which has been shown to have potent antioxidant effect, comprises 80% of catechins in Chinese green tea. This study was to investigate whether cigarette smoke (CS) exposure would induce lung morphological changes and oxidative stress in the CS-exposed rat model, and whether Chinese green tea (Lung Chen tea with EGCG as its main active ingredient) consumption would alter oxidative stress in sera and lung leading to protection of CS-induced lung damage., Methods: Sprague-Dawley rats were randomly divided into four groups, i.e. sham air (SA), 4% CS, 2% Lung Chen tea plus SA or 4% CS. Exposure to SA or 4% CS was performed for 1h/day for 56 days in ventilated smoking chambers. Sera and lung tissues were collected 24h after last CS exposure for histology and all biochemical assays., Results: Airspace enlargement and goblet cell hyperplasia were observed after 56-day CS exposure alone, which were abolished in the presence of green tea consumption. Serum 8-isoprostane level was significantly elevated (p<0.01) as well as lung superoxide dismutase (SOD) and catalase activities in CS-exposed rats compared to SA-exposed rats (p<0.05), which returned to the levels of SA-exposed rats after Chinese green tea consumption., Conclusion: These results indicate that increased levels of systemic oxidative stress after CS exposure play an important role in the induction of lung damage. Chinese green tea may have the ability to suppress CS-induced oxidative stress that leads to protection of lung injury.

Background: Transforming growth factor-beta(1) (TGF-beta(1)), a multifunctional cytokine, has been implicated to be responsible for the increased deposition of extracellular matrix in the airways, and increased submucosal collagen expression in chronic obstructive pulmonary disease (COPD). We determined plasma TGF-beta(1) levels in patients with COPD and explored its association with common functional polymorphisms of TGF-beta(1) gene at C-509T and T869C in the development of COPD in a case-control study., Methods: Stable COPD patients who were ever smokers, and age and pack-years smoked matched healthy controls (n = 205 in each group) were recruited for measurement of plasma TGF-beta(1) levels using commercially available ELISA kit, and genotyped at C-509T and T869C functional polymorphisms of TGF-beta(1) gene using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)., Results: COPD patients had significantly elevated plasma TGF-beta(1) levels in comparison to healthy controls irrespective of the genotypes. Allele frequencies and genotype distributions at both polymorphic sites were not different among COPD patients or controls. TGF-beta(1) levels were inversely correlated (Pearson's correlation analysis) with FEV(1) (% predicted) (p < 0.001) and FVC (% predicted) (p < 0.001)., Conclusion: The findings of elevated plasma TGF-beta(1) levels in patients with COPD suggest that TGF-beta(1) may play a role in COPD pathogenesis. The C-509T and T869C functional polymorphisms of TGF-beta(1) gene do not represent a genetic predisposition to COPD susceptibility in Hong Kong Chinese patients.

The airway epithelium participates in chronic airway inflammation by expressing adhesion molecules that mediate the transmigration of neutrophils into the inflamed airways. We hypothesize that, in patients with bronchiectasis, cytokines in their bronchial secretions enhance the expression of intercellular cell adhesion molecule (ICAM-1) in the bronchial epithelium and thus contribute to sustained recruitment of neutrophils into the inflamed airways. In the present study, we investigated the effect of bronchial secretions on the regulation of ICAM-1 in bronchial epithelial cells, and its modulation by pharmacologic agents. The expression of ICAM-1 mRNA and protein in human bronchial epithelial cells upon exposure to sputum sol from subjects with bronchiectasis were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and ELISA, respectively. Modulating effects of dexamethasone, ibuprofen, MK-663 or triptolide on ICAM-1 regulation were investigated in vitro. We demonstrated that changes in ICAM-1 expression correlated with levels of TNF-alpha in the sputum sol, and treatment of sol samples with TNF-alpha antibodies attenuated both the increase in ICAM-1 mRNA and protein. The role of TNF-alpha was further demonstrated when TNF-alpha elicited dose dependent increase in ICAM-1 expression. The sputum effect could also be suppressed dose-dependently by pre-incubation of bronchial epithelial cells with dexamethasone, ibuprofen, MK-663 or triptolide. Evidence is thus provided for the upregulation of bronchial epithelial ICAM-1 expression by airway secretions in bronchiectasis and a specific role for TNF-alpha in the secretions. The success of drug attenuation of this upregulation provides insight into possible therapeutic paradigms in the management of the disease.

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.

It has been suggested that patients with bronchiectasis might have increased central microtubular orientation angle (CMOA), which leads to poor coordination of ciliary beating, and consequently impairment of airway defence. We have employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82). There was no significant difference in CMOA among patients according to the etiology of bronchiectasis, presence of nasal symptoms, or sputum status of Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e. those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had significantly lower CMOA than their counterparts (P<0.05). There was no correlation between CMOA with age, 24h sputum volume, exacerbation frequency, FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated with ciliary beat frequency (negative), and the percent of cilia showing ultrastructural or microtubular defects (P<0.05). Central microtubular orientation angle does not correlate with clinically important parameters, in contrary to the results reported by previously published smaller scale studies.

Persistent airway inflammation is an important pathogenetic factor in bronchiectasis, and interleukin (IL)-6 is among the mediators implicated in regulation of inflammation in bronchiectatic airways. We postulated that airway secretion with its constituents of cytokines and enzymes would provide an environment for perpetuation of inflammation in vivo. We aimed to determine the action of sputum from patients with bronchiectasis on IL-6 production from cultured normal human bronchial epithelial (NHBE) cells and its modulation by anti-inflammatory drugs in vitro. Cultures of NHBE cells were tested with (i) sputum of bronchiectatic patients, (ii) anti-tumor necrosis factor-alpha (TNF-alpha) pre-treated sputum, or (iii) recombinant human (rh)-TNF-alpha. Alternatively, NHBE cells were incubated with one of the anti-inflammatory drugs before treatment with sputum or rh-TNF-alpha. IL-6 produced into the medium was assayed by ELISA. Sputum in bronchiectasis stimulated IL-6 production from NHBE cells by 1.9 times. This was largely attributable to TNF-alpha as pre-incubation of sputum sol with anti-TNF-alpha almost neutralized the sputum effect. Apart from dexamethasone, the other drugs exerted inhibitory effects on IL-6 production. Ibuprofen suppressed sputum-stimulated IL-6 production to levels above control and effect levelled off at 50-100 microg/mi, contrasting the dose-dependent suppression to control level with MK-663 (0.1-10 microg/ml) and to sub-control levels with triptolide (20-1000 ng/ml). Our results support that sputum in bronchiectasis can stimulate IL-6 production from NHBE cells, and TNF-alpha is an important cytokine mediating the process. The suppressive effects observed with ibuprofen, triptolide and MK-663 warrant further study.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated., Methods: Double-blind placebo-controlled randomized study to evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical, Hong Kong) on patients, who had completed conventional treatment for advanced NSCLC., Results: Thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05) were recruited into each of the PSP and control arms. After 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications., Conclusion: PSP treatment appears to be associated with slower deterioration in patients with advanced NSCLC.