Jcw Mak

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.

Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics

Background Asthma is a disease associated with oxidative stress. The glutathione S‐transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported.

Elevated plasma TGF-β 1 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 (Pearsons 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.

Cigarette smoke induces differential alteration of AMP-activated protein kinase (AMPK) in rat heart

neutrophil elastase, metalloproteinases, and their inhibitors play an important role in the development of chronic obstructive pulmonary disease (CoPd), resulting in extensive tissue damage and malfunctioning of the airways. nearly fifty years after the protease-antiprotease imbalance hypothesis has been suggested for the cause of emphysema, it is still appealing, but it does not explain the considerable variation in the clinical expressions of emphysema. however, there are many recent research findings to support the imbalance hypothesis as will be shown in this review. Although limited, there might be openings for the treatment of the disease.

Transforming growth factor (TGF)-beta 1 gene common polymorphisms and plasma TGF-beta 1 levels in patients with lung cancer

for the 9th Congress of the Asian Pacific Society of Respirology 10–13 December 2004, Hong Kong Editors: Dr K.S. Chan Dr P.C. Wong A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF HOUSE DUST MITE IMMUNOTHERAPY IN ASTHMATIC PATIENTS IN CHINA HONGYU WANG1, XIAOPING LIN2, CHUANGLI HAO3, CHUNQING ZHANG1, BAOQING SUN1, JINGPING ZHENG1, PING CHEN2, JINYUN SHENG3, ADRIAN WU4, NANSHAN ZHONG1 1Guangzhou Institute of Respiratory Diseases, 2Shenyang General Military Hospital, 3Suzhou Children’s Hospital, 4Department of Medicine, The University of Hong Kong Background The purpose of this study was to determine if house dust mite immunotherapy is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. Methods This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6 to 45 years recruited from 3 different regions of Mainland China. Subjects were given a 52-week course of Alutard Der P (ALK-Abello, Horsholm, Denmark) treatment or placebo while the dose of inhaled corticosteroids (ICS) was maintained. Results 129 subjects (64 active) completed the study. The symptom scores began to diverge at week 25 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.003) and medication (P = 0.044) scores during the second half of the treatment period only in subjects who were taking ICS. Subjects on ICS also showed significant improvement in PEF after immunotherapy, but no difference in histamine PC20 was found. Serum ECP and blood eosinophils decreased after immunotherapy in subjects not using ICS. Skin test response decreased in immunotherapy subjects only, and Der P-specific IgE decreased in placebo but not immunotherapy subjects. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). Conclusions One year of immunotherapy with Alutard Der P significantly reduced symptoms and medication use in asthmatic subjects, particularly in those who were already using ICS. This was associated with a greater subjective improvement in asthma control. 002 Respirology (2004) 9, (Suppl.) A79–A164 ASSOCIATION OF TOTAL PLASMA IGE LEVELS AND ASTHMA IN ASIAN POPULATIONS WD ZHANG, XZ ZHANG, DW QIU, WC TAN Department of Medicine, National University of Singapore Background Previous studies demonstrated that high levels of serum IgE was associated with asthma and other allergic diseases. Objectives To determine and compare the total plasma IgE levels in both asthmatics and healthy controls in Chinese, Malay and Indian in Singapore. Methods Both 311 asthmatics (Chinese 150; Malay 74; Indian 87) and 355 healthy subjects (Chinese 156; Malay 98; Indian 101) were being participated in a genetic study of asthma. Total plasma IgE levels were determined by Enzyme-linked immunosorbent assay (ELISA). A binary logistic model was used to detect the association between total plasma IgE levels and asthma. Results Plasma total IgE was significantly higher in patients group than that of control group in each ethnicity (Chinese: P = 0.049; Malay: P = 0.002; Indian: P = 0.000). Plasma total IgE (Geometric mean) in Chinese (382 IU/ml) was significantly lower than that in Malay (584 IU/ml) and Indian (990 IU/ml) in the patient group (P = 0.000). However, there was no difference for plasma total IgE among Chinese (256 IU/ml), Malay (226 IU/ml) and Indian (323 IU/ml) (P = 0.385) in the control group. Conclusion High level of plasma total IgE may be a risk factor for asthma in Chinese, Malay and Indian. Total plasma IgE levels showed homogeneous among the three ethnicities. TIME TRENDS IN THE PREVALENCE OF ALLERGIC DISEASES IN GUANGZHOU CHILDHOOD HONGYU WANG, JINGPING ZHENG, NANSHAN ZHONG Guangzhou Institute of Respiratory Disease 510120 Guangzhou, China Objective To examine time trends in the prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood. Methods 3575 Children aged 13–14 years were randomly selected from ten middle schools in the four central districts of Guangzhou city in 2001. The selection followed the methods used for ISAAC Phase I in 1994–1995. All subjects completed the written questionnaire on asthma, rhinitis and eczema, then finished the video questionnaire about asthma. Results The response rate was 96%, 50.9% of them were female. With the written questionnaire /video questionnaire, the prevalence of wheezing ever, wheezing in the past year, wheezing related to exercise were 8.6%/5.9%, 4.8%/3.8%, 23.4%/11.3% respectively, revealed significantly higher than that were 6.2%/3.2%, 3.4%/2.0%, 17.4%/6.9% in the Phase I (P < 0.001). The prevalence of asthma ever were 4.6%, similar as 3.9% in the Phase I (P > 0.05). The positive response rate to all the questions related to rhinitis and eczema (P < 0.05) except eczema ever (P > 0.05) were significantly higher than that in Phase I. Conclusions The prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood were increasing during 7 years periods in Guangzhou. STUDY OF ROLE OF INSULIN AND INSULIN RECEPTOR IN ALLERGIC AIRWAY INFLAMMATION OF RATS YL MA, QY HE Department of Pulmonary Medicine People’s Hospital, Peking University, Beijing, P.R.C. 100044 Background Bronchial asthma and type 1 diabetes mellitus (IDDM) are rarely associated in the same subject although the mechanism is still unclear. Methods Streptozotocin and ovalbumin (OVA) were respectively used to induce diabetes mellitus and allergic airway inflammation. 64 male SD rats were divided into 8 groups: group A (asthma); group D (diabetes); group I (insulin treated); group AD (asthma + diabetes); group AI (asthma + insulin treated); group DI (diabetes + insulin treated); group ADI (asthma + diabetes + insulin treated); group C (control). Blood glucose measurements, serum insulin measurements, total and differential leukocyte counts of blood and BALF, HE stained paraffin section of lung tissue were carried out. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. Results After antigen challenge, rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. Serum insulin levels were higher in groups ADI, AI and A. Immunohistochemistrical staining revealed a diffused distribution pattern of insulin receptor in the lung tissue. Positive cells infiltrating in the lung were increased significantly in groups A, AI and ADI. In groups induced diabetes the expression of insulin receptor mRNA was elevated. Conclusion Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion was increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells were increased. 004 005 003 Saturday 5 April – Respiratory Nurses SIG Oral Presentations (1030–1200) Asthma A80 Respirology (2004) 9, (Suppl.)

Non-small cell lung cancer in Chinese is associated with disturbance in systemic antioxidants profiles

for the 9th Congress of the Asian Pacific Society of Respirology 10–13 December 2004, Hong Kong Editors: Dr K.S. Chan Dr P.C. Wong A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF HOUSE DUST MITE IMMUNOTHERAPY IN ASTHMATIC PATIENTS IN CHINA HONGYU WANG1, XIAOPING LIN2, CHUANGLI HAO3, CHUNQING ZHANG1, BAOQING SUN1, JINGPING ZHENG1, PING CHEN2, JINYUN SHENG3, ADRIAN WU4, NANSHAN ZHONG1 1Guangzhou Institute of Respiratory Diseases, 2Shenyang General Military Hospital, 3Suzhou Children’s Hospital, 4Department of Medicine, The University of Hong Kong Background The purpose of this study was to determine if house dust mite immunotherapy is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. Methods This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6 to 45 years recruited from 3 different regions of Mainland China. Subjects were given a 52-week course of Alutard Der P (ALK-Abello, Horsholm, Denmark) treatment or placebo while the dose of inhaled corticosteroids (ICS) was maintained. Results 129 subjects (64 active) completed the study. The symptom scores began to diverge at week 25 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.003) and medication (P = 0.044) scores during the second half of the treatment period only in subjects who were taking ICS. Subjects on ICS also showed significant improvement in PEF after immunotherapy, but no difference in histamine PC20 was found. Serum ECP and blood eosinophils decreased after immunotherapy in subjects not using ICS. Skin test response decreased in immunotherapy subjects only, and Der P-specific IgE decreased in placebo but not immunotherapy subjects. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). Conclusions One year of immunotherapy with Alutard Der P significantly reduced symptoms and medication use in asthmatic subjects, particularly in those who were already using ICS. This was associated with a greater subjective improvement in asthma control. 002 Respirology (2004) 9, (Suppl.) A79–A164 ASSOCIATION OF TOTAL PLASMA IGE LEVELS AND ASTHMA IN ASIAN POPULATIONS WD ZHANG, XZ ZHANG, DW QIU, WC TAN Department of Medicine, National University of Singapore Background Previous studies demonstrated that high levels of serum IgE was associated with asthma and other allergic diseases. Objectives To determine and compare the total plasma IgE levels in both asthmatics and healthy controls in Chinese, Malay and Indian in Singapore. Methods Both 311 asthmatics (Chinese 150; Malay 74; Indian 87) and 355 healthy subjects (Chinese 156; Malay 98; Indian 101) were being participated in a genetic study of asthma. Total plasma IgE levels were determined by Enzyme-linked immunosorbent assay (ELISA). A binary logistic model was used to detect the association between total plasma IgE levels and asthma. Results Plasma total IgE was significantly higher in patients group than that of control group in each ethnicity (Chinese: P = 0.049; Malay: P = 0.002; Indian: P = 0.000). Plasma total IgE (Geometric mean) in Chinese (382 IU/ml) was significantly lower than that in Malay (584 IU/ml) and Indian (990 IU/ml) in the patient group (P = 0.000). However, there was no difference for plasma total IgE among Chinese (256 IU/ml), Malay (226 IU/ml) and Indian (323 IU/ml) (P = 0.385) in the control group. Conclusion High level of plasma total IgE may be a risk factor for asthma in Chinese, Malay and Indian. Total plasma IgE levels showed homogeneous among the three ethnicities. TIME TRENDS IN THE PREVALENCE OF ALLERGIC DISEASES IN GUANGZHOU CHILDHOOD HONGYU WANG, JINGPING ZHENG, NANSHAN ZHONG Guangzhou Institute of Respiratory Disease 510120 Guangzhou, China Objective To examine time trends in the prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood. Methods 3575 Children aged 13–14 years were randomly selected from ten middle schools in the four central districts of Guangzhou city in 2001. The selection followed the methods used for ISAAC Phase I in 1994–1995. All subjects completed the written questionnaire on asthma, rhinitis and eczema, then finished the video questionnaire about asthma. Results The response rate was 96%, 50.9% of them were female. With the written questionnaire /video questionnaire, the prevalence of wheezing ever, wheezing in the past year, wheezing related to exercise were 8.6%/5.9%, 4.8%/3.8%, 23.4%/11.3% respectively, revealed significantly higher than that were 6.2%/3.2%, 3.4%/2.0%, 17.4%/6.9% in the Phase I (P < 0.001). The prevalence of asthma ever were 4.6%, similar as 3.9% in the Phase I (P > 0.05). The positive response rate to all the questions related to rhinitis and eczema (P < 0.05) except eczema ever (P > 0.05) were significantly higher than that in Phase I. Conclusions The prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood were increasing during 7 years periods in Guangzhou. STUDY OF ROLE OF INSULIN AND INSULIN RECEPTOR IN ALLERGIC AIRWAY INFLAMMATION OF RATS YL MA, QY HE Department of Pulmonary Medicine People’s Hospital, Peking University, Beijing, P.R.C. 100044 Background Bronchial asthma and type 1 diabetes mellitus (IDDM) are rarely associated in the same subject although the mechanism is still unclear. Methods Streptozotocin and ovalbumin (OVA) were respectively used to induce diabetes mellitus and allergic airway inflammation. 64 male SD rats were divided into 8 groups: group A (asthma); group D (diabetes); group I (insulin treated); group AD (asthma + diabetes); group AI (asthma + insulin treated); group DI (diabetes + insulin treated); group ADI (asthma + diabetes + insulin treated); group C (control). Blood glucose measurements, serum insulin measurements, total and differential leukocyte counts of blood and BALF, HE stained paraffin section of lung tissue were carried out. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. Results After antigen challenge, rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. Serum insulin levels were higher in groups ADI, AI and A. Immunohistochemistrical staining revealed a diffused distribution pattern of insulin receptor in the lung tissue. Positive cells infiltrating in the lung were increased significantly in groups A, AI and ADI. In groups induced diabetes the expression of insulin receptor mRNA was elevated. Conclusion Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion was increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells were increased. 004 005 003 Saturday 5 April – Respiratory Nurses SIG Oral Presentations (1030–1200) Asthma A80 Respirology (2004) 9, (Suppl.)