Kwt Tsang

A pilot study of low-dose erythromycin in bronchiectasis

Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis.

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.

Bacteremia Caused by Escherichia coli producing Extended-spectrum Beta-lactamase: a Case-control Study of Risk Factors and Outcomes*

A case-control study was conducted in order to identify the risk factors associated with bloodstream infection caused by Escherichia coli producing extended-spectrum β-lactamase (ESBL) and to determine the outcomes of infected patients. Risk factors associated with ESBL production, according to univariate analysis, included a history of recent hospitalization [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.1-8.9; p < 0.001], severe underlying diseases (OR 15, 95% CI 4.4-51.5; p < 0.001), prior exposure to urinary catheters (OR 8.3, 95% CI 3.2-21.7; p < 0.001) and nosocomial (OR 14.1, 95% CI 6.1-32.8; p < 0.001) or urinary (OR 3.6, 95% CI 1.7-7.4; p < 0.001) origin of the bacteria. Multivariate analysis revealed that severe underlying diseases (OR 31.2, 95% CI 6.7-144; p < 0.001) and nosocomial (OR 16.5, 95% CI 5.6-49; p < 0.001) and urinary origins (OR 7.8, 95% CI 2.6-23.8; p < 0.001) of the bacteria were independently associated with ESBL production in bacteremic E. coli. Crude mortality in case patients was more than twice as high as that in controls (p = 0.04). Production of ESBL increased the risk of inappropriate initial therapy (OR 95.6, 95% CI 27.4-334.2; p < 0.001). Treatment failed in 4/7 case patients treated with ceftazidime to which the isolate was susceptible in vitro. Our findings have implications for the choice of empirical therapy in nosocomial urinary tract 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

Overexpression of matrix metalloproteinase‐8 and ‐9 in bronchiectatic airways in vivo

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP‐8 and MMP‐9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP‐8, MMP‐9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell·mm−2 of the lamina propria by using an image analysis system. There were significantly higher densities of MMP‐8 and MMP‐9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP‐8 and MMP‐9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP‐8 with neutrophil and MMP‐9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids

Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen‐stimulated cytokine‐secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme‐linked immunospot technology. Numbers of interferon‐gamma, interleukin (IL)‐2, IL‐4, IL‐10 and IL‐12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)‐stimulated IL‐10 secreting cells were increased in early SARS but fell during treatment. SAC‐induced IL‐12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL‐6 and tumour necrosis factor‐alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti‐inflammatory and antiviral therapies in order to limit cytokine impairment.

Risk factors associated with lung cancer in Hong Kong

The purpose of this study was to investigate the risk factors associated with lung cancer in Hong Kong. Three hundred and thirty-one histologically or cytologically proven consecutive cases of lung cancer and the same number of in- and out-patients without cancer matched for age and sex were recruited for this study using a detailed questionnaire completed by a trained interviewer. Smoking was the most important risk factor associated with lung cancer but the attributable risk (AR) was estimated to be 45.8% in men and 6.2% in women, considerably lower compared with those estimated in early 1980s. In addition, among women, exposure to environmental tobacco smoke (ETS) at work+/-at home and lack of education, were independent risk factors for lung cancer with adjusted odds ratio (OR) 3.60, (95% confidence interval (CI) 1.52-8.51) and OR 2.41 (95% CI 1.27-4.55), respectively. Among men, exposure to insecticide/pesticide/herbicide, ETS exposure at work or at home, and a family history of lung cancer and were independent risk factors with adjusted OR 3.29 (95% CI 1.22-8.9, OR 2.43, 95% CI 1.24-4.76 and OR 2.37, 95% CI 1.43-3.94, respectively). Exposure to incense burning and frying pan fumes were not significant risk factors in both sexes. A moderate or high consumption of fat in the diet was associated with increased risk in men but decreased risk in women. The results of this study suggested that as the prevalence of smoking declined, the influence of smoking as a risk factor for lung cancer decreased even further. Moreover, the contribution of other environmental, occupational and socioeconomic factors may be more apparent as etiological factors for lung cancer in a population with relatively high lung cancer incidence but low AR from active smoking.

Helicobacter pylori and upper gastrointestinal symptoms in bronchiectasis.

The recently reported increase in seroprevalence of Helicobacter pylori, the causative pathogen in peptic ulceration, in bronchiectasis is unexplained. Therefore, the association of antibodies directed against cytotoxin-associated gene A(CagA), whose expression indicates virulence of H. pylori, and upper gastrointestinal symptoms in patients with stable bronchiectasis and healthy volunteers evaluated. One hundred patients (mean +/- SD age 55.1+/-16.7 yrs) and 94 healthy asymptomatic subjects (54.6+/-7.6 yrs) underwent clinical and physiological assessment and serum levels of anti-H. pylori CagA were determined using standard clinical and enzyme-linked immunosorbent assay techniques. Samples were positive for anti-H. pylori CagA in 11.7% of controls and 24% of bronchiectatic subjects (p = 0.03). There was, however, no association between serum H. pylori CagA immunoglobulin G level and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), sputum volume, respiratory symptoms or upper respiratory gastrointestinal symptoms (p>0.05). Patients who suffered from acid regurgitation or upper abdominal distension had significantly lower FEV1 and FVC (as a percentage of the predicted value) compared to their counterparts. The results of anticytotoxin-associated gene A measurements in this study contrasted with the previous finding that anti-Helicobacter pylori immunoglobulin G correlated with sputum volume. These findings, therefore, suggest that Helicobacter pylori, should it have a pathogenic role in bronchiectasis, could act via noncytotoxin-associated gene A-mediated mechanisms, and, in this context, gastro-oesophageal reflux might be of importance in bronchiectasis.

Interstitial Lung disease in Systemic Sclerosis: An HRCT-clinical correlative study

Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=−0.43, p=0.008), FEV1 (forced expiratory volume) (r=–0.37, p=0.03), TLC (r=–0.47, p=0.003), and DLCO (r=–0.43, p=0.008); inflammatory index with DLCO (r=–0.43, p=0.008) and exercise tolerance (r=–0.39, p < 0.05); and fibrosis index with FVC (r=–0.31, p=0.05) and TLC (r=–0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Interstitial lung disease in systemic sclerosis.

PURPOSE To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. MATERIAL AND METHODS 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. RESULTS ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. CONCLUSION Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.