Sustained elevation of systemic oxidative stress and inflammation in exacerbation and remission of asthma.

Oxidative stress has been implicated in the pathogenesis of asthma. We aimed at investigating the biomarkers of oxidative stress, inflammation, and tissue damage in patients with asthma in acute exacerbation and remission. We recruited 18 asthmatics admitted to hospital with acute exacerbation and 18 healthy nonsmoking controls matched for age. We evaluated plasma levels of 8-isoprostane, C-reactive protein (CRP) and total matrix metalloproteinase- (MMP-) 9 by ELISA, and MMP-9 activity by zymographic analysis. Plasma levels of 8-isoprostane and CRP were significantly elevated in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls. The activities of pro-MMP-9 were also significantly higher in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls in parallel to plasma levels of total MMP-9. These data suggest that overproduction of MMP-9 along with highly elevated levels of oxidative stress and inflammation is implicated in asthma exacerbation and that measurements of these biomarkers can be a valid index in its management.

The role of circulating serotonin in the development of chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age. METHODS: The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA). RESULTS: The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108). CONCLUSION: Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.

Elevated plasma TGF-beta1 levels in patients with chronic obstructive pulmonary disease.

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.

Reference values of diffusing capacity of non-smoking Chinese in Hong Kong.

BACKGROUND AND OBJECTIVE: This study was conducted to define normal reference values and lower limits of normal (LLN) for single-breath carbon monoxide diffusing capacity (DLco) and DLco per unit of alveolar volume (Kco) for Chinese adults in Hong Kong. METHODS: Healthy non-smoking men and women aged 18-80 years were recruited by random digit dialing. DLco and Kco were measured according to American Thoracic Society standards. Reference equations were obtained by multiple linear regression; LLN were derived by distribution-free method for estimation of age-related centiles. RESULTS: Tests from 568 subjects (259 men, 309 women) were analysed. DLco declined with age in both genders, and increased with height and the interaction term of height and age in men and women, respectively. Considering Hb values did not improve the reference equations. Kco declined with age and increased with weight in both genders, while height and its interaction term with age were additional determinants in women. The reference DLco was lower than some Caucasian values, and was only explained partially by a smaller body size and alveolar volume in Chinese. The distribution-free method yielded better overall approximation to the fifth percentile compared with the traditional method of determining LLN. CONCLUSIONS: The equations for reference values and LLN of diffusing capacity derived in this study are of clinical relevance to Chinese subjects.

Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma.

BACKGROUND: The C-509T polymorphism of TGF-beta(1) gene has been associated with asthma and atopy in white populations. OBJECTIVE: We investigated the association between asthma and previously identified polymorphisms at C-509T and T869C of the TGF-beta(1) gene among 250 Chinese patients with asthma and 308 healthy controls in Hong Kong. METHODS: Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. RESULTS: There were no differences in the frequencies of genotypes and alleles between patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium (P < .01). Among atopic subjects, significant differences were found in genotype and allele frequencies for T869C polymorphism between patients and controls (P = .014 and P = .019, respectively), and individuals bearing the CC genotype were associated with increased risk for the development of asthma (odds ratio, 2.58; 95% CI, 1.17-5.66; P = .018) after adjusting for age, sex, and smoking status. Individuals with asthma bearing the CT genotype of the C-509T polymorphism had significantly increased risk for severe airflow obstruction compared with individuals who had mild obstruction (odds ratio, 4.00; 95% CI, 1.06-15.08; P = .035). CONCLUSION: Our results indicate that the polymorphisms at C-509T and T869C of the TGF-beta(1) gene are associated with asthma susceptibility in atopic subjects of the Hong Kong Chinese population, and the C-509T polymorphism may play a role in the pathogenesis of airflow obstruction.

Reactive oxidant species in asthma.

PURPOSE OF REVIEW: This overview summarizes some recent studies on the balance of oxidants to antioxidants in patients with asthma. The aim of the review is to compare studies on the changes in oxidants/antioxidants in stable asthma or in acute exacerbation of asthma. RECENT FINDINGS: Our review of the recent literature in this field seems to indicate conflicting findings. Increased release of reactive oxygen species such as superoxide anion and hydrogen peroxide has been reported in exhaled breath condensates and from circulating granulocytes, and from the bronchoalveolar lavage cells of patients with asthma. In asthma, bronchial obstruction is associated with an increased spontaneous and stimulus-induced production of oxygen free radicals. The primary defense against reactive oxygen species is endogenous antioxidants, which are found to be altered in asthma. A marked decrease in plasma antioxidant capacity occurs. Superoxide dismutase activity is higher in erythrocytes and serum of asthmatic than in normal subjects and is diminished in cells from lavage and brushing samples of patients with asthma. Higher level of erythrocyte catalase activity has only been found in Chinese asthmatic patients while decreased glutathione peroxidase activity has been well documented. SUMMARY: Since there are considerable discrepancies in erythrocyte or plasma antioxidant enzyme activity in patients with asthma, the problem at this time is attempting to sort out these conflicting results and to find their roles in the pathogenesis of asthma. There is good evidence that antioxidant compounds may have a potential role in the treatment of asthma, especially of asthma exacerbation.