Mmw Chan-Yeung

Inhaled fluticasone in bronchiectasis: a 12 month study

Background: The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation. Methods: After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 μg twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion. Results: 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency ⩽2/year (p = 0.04), and sputum purulence score >5 (p = 0.03). Conclusions: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P aerurginosa infection.

Exhaled nitric oxide: the effects of age, gender and body size.

Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23, p = 0.02), weight (r = 0.34, p

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.

Asthma, atopy and tuberculin responses in Chinese schoolchildren in Hong Kong

BACKGROUND The prevalence rates of asthma and other atopic disorders have increased steadily in many developed countries over the past few decades. Recent epidemiological and animal studies have suggested that BCG vaccination might be beneficial in reducing the subsequent development of atopy. This study investigates the relationship between asthma, allergic symptoms, atopy, and tuberculin response in Chinese schoolchildren who received BCG vaccination at birth. METHODS A total of 3110 schoolchildren aged 10 years were recruited for the Hong Kong arm of the phase II International Study of Asthma and Allergies in Childhood. Of the 2599 children born in Hong Kong and vaccinated with BCG after birth, 2201 had tuberculin testing performed at a mean (SD) age of 8.4 (1.4) years. A random subsample of 980 children was also recruited for skin prick testing. RESULTS The prevalence rates of asthma ever, wheeze ever, current wheeze, current rhinoconjunctivitis, and current flexural eczema were not significantly different between tuberculin positive and negative subjects. The mean (SE) tuberculin response was 3.4 (0.2) mm in atopic subjects and 3.3 (0.2) mm in non-atopic subjects (difference not significant). Logistic regression analyses did not reveal any significant relationship between asthma ever, current wheeze, atopy, and positive tuberculin responses. CONCLUSIONS This study did not find any relationship between asthma, allergic symptoms, atopy, and positive tuberculin reactivity in Chinese schoolchildren vaccinated with BCG at birth.

Polymorphisms and functional activity in superoxide dismutase and catalase genes in smokers with COPD

Increased oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the risk of COPD and the substitution of alanine 16 with valine (Ala16Val) polymorphism of manganese-superoxide dismutase (Mn-SOD) and the cytosine to thymidine transition of nucleotide -262 (-262C>T) polymorphism of the catalase gene, and the activity of erythrocyte SOD and catalase. The subjects were stable COPD patient ever smokers (n = 165) and healthy controls, matched for age and cigarette consumption. Genotyping of Mn-SOD at Ala16Val and the catalase gene at -262C>T was performed, and the functional activity of SOD and catalase in erythrocytes determined. There were no significant differences in the distribution of the different genotypes or allele frequencies between patients and controls for both the Mn-SOD and catalase genes. Among healthy controls or COPD patients, no differences were observed in erythrocyte SOD and catalase activity, irrespective of genotype. Significantly higher erythrocyte catalase activity was found in COPD patients than in healthy controls. The T/T catalase genotype and Ala/Ala Mn-SOD genotype were uncommon in the present Chinese population. The increase in erythrocyte catalase activity in Chinese patients with chronic obstructive pulmonary disease probably indicates dysfunction of the oxidant/antioxidant defence system, but it is unclear whether this increase is compensatory or a pathogenic factor.

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.

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0–27.2) versus 48.7 (27.0–64.3) U·(ghaemoglobulin(Hb)-1), and higher GPx activity (175.2 (126.6–288.3) versus 49.2 (39.5–59.2) mU·(gHb)-1) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.

FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese.

BACKGROUND Forced expiratory volume in 3 seconds (FEV(3)) and 6 seconds (FEV(6)) could complement FEV(1) and forced vital capacity (FVC) for detecting airflow obstruction. OBJECTIVE To compare FEV(1)/ FEV(6) and FEV(3)/FVC with FEV(1)/FVC in the detection of airflow obstruction. METHOD Previous lung function data were re-analysed to establish reference values for FEV(3) and FEV(6). Data from a separate cohort of male smokers were used as test set. FEV(1), FEV(3), FEV(6), FVC, FEV(1)/FVC, FEV(1)/ FEV(6) and FEV(3)/FVC were regressed against age, standing height, weight and body mass index, and the mean and 95% confidence intervals for the lower limit of normal (LLN) values for these parameters were determined. RESULTS The percentage of smokers with airflow obstruction in the test population using FEV(1)/FVC < LLN was 15.0%, while using FEV(1)/ FEV(6) < LLN and FEV(3)/FVC < LLN they were respectively 18.5% and 18.1%. Using FEV(1)/FVC < LLN as reference, the sensitivity and specificity of FEV(1)/ FEV(6) < LLN in identifying airflow obstruction were 82.3% and 92.8%, while those for FEV(3)/FVC < LLN were 78.5% and 92.6%; the positive and negative predictive values were 67% and 96.7% for FEV(1)/ FEV(6) < LLN and 65.3% and 96% for FEV(3)/FVC < LLN. CONCLUSION FEV(3)/FVC < LLN and FEV(1)/ FEV(6) < LLN are comparable to FEV(1)/FVC < LLN for detecting airflow obstruction. FEV(3)/FVC < LLN could be useful in screening for airflow obstruction, while FEV(1)/ FEV(6) < LLN is useful in detecting airflow limitation in the elderly or in subjects with severe airflow obstruction.

Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS)

Systematic evaluation of treatment modalities for SARS is still needed The epidemic of severe acute respiratory syndrome (SARS) of 2003 caught the medical profession by surprise. The accumulated global total number of cases was 8098 with 774 deaths, a case-fatality ratio of 9.6%.1 Although the novel coronavirus (SARS-CoV) was discovered within weeks,2 treatment was inevitably empirical as controlled clinical trials were not possible during the epidemic of this new and serious illness. Many antiviral and immunomodulatory drugs, as well as other treatments such as convalescent patient plasma and traditional Chinese medicines, have been tried. Ribavirin and corticosteroids are by far the most widely used treatments for SARS. In the later phase of the epidemic lopinavir and ritonavir in combination were also used in Hong Kong. ### Ribavirin Ribavirin is used extensively for the treatment of SARS and was given to over 90% of patients in Hong Kong. It is a nucleoside analogue that has activity against a number of DNA and RNA viruses in vitro.3 The mechanism of action of ribavirin has been studied for decades and is still under active debate.4 In early March 2003, before the isolation of the SARS-CoV, many experts believed that the mysterious severe illness was due to an unknown virus and ribavirin was empirically given because of its broad spectrum antiviral activity. Furthermore, corticosteroids were increasingly prescribed for the treatment of SARS and some believed that such treatment would be dangerous if not covered with an antiviral agent. The published reports on the effectiveness of ribavirin were mostly retrospective case series with intrinsic methodological issues and it is difficult to draw conclusions. The major side effect of ribavirin is anaemia which occurs in 27–59% …

Effect of asthma self management programme on asthma morbidity and health care utilization in adult patients admitted to hospital with acute asthma in Hong Kong: A randomised controlled trial

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.)