Willis Lam

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

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.

Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis

We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics. Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics. NCA was measured using modified Boydens technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate. All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state. At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05). All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state. A further week of antibiotics did not result in further decline of NCA or EA. Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again. In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels. Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of factors associated with bronchial hyperreactivity to methacholine in bronchiectasis

Nonspecific bronchial hyperreactivity (BHR) has been reported to occur in patients with bronchiectasis. To evaluate this further, we studied 77 patients with stable bronchiectasis (noncystic fibrosis) with special reference to the prevalence of BHR to methacholine (MCh), and its relation to lung function, sputum characteristics, concommitant asthma, and atopy. The concentration of MCh required to produce a fall of 20% in forced expiratory volume in 1 s (FEV1), PC20, was determined by Wright’s nebulization tidal breathing method. BHR defined by a PC20 ≤ 8 mg/ml was found in 21 of 47 (45%) subjects who underwent bronchial challenge. Presence of BHR was positively associated with low baseline spirometric values, diagnosis of asthma, long duration of disease, and elevated total IgE on univariant analysis, and was significantly related to FEV1/forced vital capacity (FVC) ratio and asthma on multiple regression analysis. Ten of the 21 hyperreactive subjects did not have clinical asthma, whereas all 11 of 22 subjects with clinical asthma who underwent bronchial challenge were hyperreactive. Among those with BHR, there was a positive correlation between PC20 and baseline FEV1. When patients were further classified into asthmatic and nonasthmatic subjects, a positive correlation between PC20 and FEV1 was seen only in those without asthma. Frequency of infective episodes and inflammatory score of sputum assessed by average daily volume, purulence, and leukocyte count did not differ significantly in the groups with and without BHR. These results suggest that BHR in patients with bronchiectasis is associated with coexistent asthma and worse spriometric values, and not with the severity of bronchial sepsis.

Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis. In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000×) when PA was cultured in 0.05, 0.5 and 5 µg·mL−1 of EM compared with control (absence of EM). Adherence density (20 SEM fields·log−1 inocular size) for PA obtained from no EM (56.8±43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 µg·mL−1 EM (21.5±17.56, 23.3±16.65, and 21.4±12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 µg·mL−1) had a significant reduction in its diagonal length, radius, height, volume and surface area. It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection.

Increasing use of inhaled steroids associated with declining asthma mortality.

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984–1986 and 1992–1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

Rising asthma mortality in young males in Hong Kong, 1976–85

The trend in asthma mortality in Hong Kong was estimated from published statistics for the years 1976-85. To avoid coding errors in death certifications, only asthma deaths in the age group 5-34 years were analysed. Mortality rose annually by an average of 10.5% in male (P less than 0.02), but not female asthmatics. Such an increase was not due to a change in coding as a result of the revision of the International Classification of Diseases in 1979, or an exchange of diagnostic labelling from other respiratory diseases. The exact causes for the increase in asthma mortality have yet to be determined.

Ofloxacin compared with amoxycillin in treating infective exacerbations in bronchiectasis

Forty-one hospitalized adult patients of bronchiectasis (non-cystic fibrotic) with infective exacerbations were entered into a randomized, double-blind, placebo-controlled study comparing ofloxacin (200 mg tid) and amoxycillin (1 g tid) both orally for ten days. In the ofloxacin group (20 patients), improvement in sputum purulence was excellent in 14, and fair in five patients with one failure. In the amoxycillin group (21 patients), improvement in sputum purulence was excellent in eight, fair in five and poor in eight patients. Mean drug levels on day 5 were 4.1 mg l-1 for serum (2 h post-dosage) and 4.0 mg l-1 for sputum for ofloxacin, and 18.4 mg l-1 for serum and 0.3 mg l-1 for sputum for amoxycillin. Ofloxacin thus yielded higher sputum concentration and appeared to be more effective and also better tolerated than amoxycillin in infective episodes of bronchiectasis.

The value of routine bronchial aspirate culture at fibreoptic bronchoscopy for the diagnosis of tuberculosis

We review the results of bronchial aspirate culture for mycobacteria sent routinely in a series of 1734 fibreoptic bronchoscopic procedures. The incidence of tuberculosis in the series was 8.3% (144 cases). Of these cases, a positive bronchial aspirate culture was obtained in 119 (82.6%) cases, and it was the exclusive means of diagnosis in 64 (44.4%). In 66% of these cases tuberculosis was not suspected at the time of bronchoscopy. Our results suggest that in an area with a high prevalence of tuberculosis, routine bronchial aspirate culture is a useful adjunct to diagnosis.