The continued threat of tuberculosis.
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Biomedical subjects
Publications and source records attributed to S Y So.
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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 Boyden's 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)
Impaired pulmonary function is of prognostic importance in bronchiectasis. To assess the factors affecting pulmonary function in bronchiectasis, we studied the clinical features, atopic status, bronchial responsiveness, systemic inflammatory indices, and sputum characteristics including volume, purulence, leucocyte count, neutrophil chemotactic activity, elastolytic activity (EA) and bacteriology in 82 Chinese patients. The majority of patients had impaired spirometry with airflow obstruction but normal carbon monoxide diffusing capacity. Multivariate analysis showed that factors significantly associated with worse lung function were: bronchial hyperresponsiveness, concomitant asthma, higher serum globulin, higher peripheral leucocyte count, lower serum albumin, greater sputum volume, diffuse disease and older age. When subjects with clinical asthma were excluded, similar factors were identified, and in addition, longer duration of disease, presence of eosinophils in sputum and higher sputum EA were significantly related to worse spirometry. Most of the identified factors reflect a state of inflammation. Thus the findings suggest that persistent inflammation plays an important role in the deterioration of lung function in bronchiectasis.
Inhaled rather than oral antiasthmatic therapy is accepted as more advantageous but depends on patient technique and understanding. In 74 asthmatic outpatients, technique using metered-dose inhaler (MDI) was poor; in 56 patients inhaling beta-agonist, the mean peak expiratory flow rate (PEFR) increase was only 15 L/min (6%) greater than in 18 controls, p < 0.05, 95% confidence intervals 2-27 L/min or 2-11%. Tilting the head back and actuation "stopping" inspiration produced the least favorable PEFR responses; taken together, regression analysis yielded a statistically significant negative correlation with absolute or percentage PEFR change (R2 = 0.15; p < 0.02). Patients were unclear about which drugs to inhale as required or regularly. Among 19 patients reassessed inhaling beta-agonist, only 8 had baseline PEFR values within 10% of each other during both assessments. In the latter, the mean postinhalation PEFR increase was 36 L/min (or 13%) greater than the corresponding increase (or % change) at first assessment, p = 0.05 (0.08), 95% confidence intervals 0-73 L/min (-2 to 29%). Thus, MDI users should avoid tilting the head back, actuation stopping inhalation, and be more aware of prophylactic (steroid) versus symptomatic (beta-agonist) treatment.
To audit the clinical practice in drug treatment of bronchial asthma in Hong Kong, two questionnaire surveys were conducted in 1987 and 1992. The questionnaire was adapted from the 1984 European Audit. The response rate was 40% (248 of 615 mailings) in 1987 and 32% (207 of 652 mailings) in 1992. A total of 86% and 87% of responders were general practitioners (GP), respectively, and the others were chest physicians (CP). For treatment of acute severe asthma in adults, parenteral aminophylline was the first drug used by GP in 1987, whereas inhaled beta-agonist was used in 1992. Parenteral steroid was more often used by both GP and CP in 1992. In children, inhaled beta-agonist was always the first choice and parenteral steroid ranked higher in 1992, overtaking parenteral aminophylline. For maintenance therapy of chronic asthma in adults, inhaled beta-agonist ranked first in both surveys. Inhaled steroid has become much more popular with GP, ranking second in 1992, overtaking oral bronchodilators. With CP, inhaled steroid was already ranking second in 1987, and it was used as the first drug, as frequently as inhaled beta-agonist, in 1992. In children, in 1987, inhaled beta-agonist was the first drug of choice, and prophylactic drugs ranked lower than oral bronchodilators with both GP and CP. In 1992, cromoglycate and inhaled steroids were much more often used, so much so that among CP, inhaled steroid ranked first, just ahead of inhaled beta-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Eighty five Chinese patients with diffuse or localized bronchiectasis (non-cystic fibrosis) were studied regarding the prevalence of asthma. Twenty three of the 85 had concomitant asthma, diagnosed by history and reversibility on lung function testing either spontaneously or after bronchodilator. None fulfilled the diagnostic criteria of allergic bronchopulmonary aspergillosis (ABPA). Asthma preceded the onset of bronchiectasis in 13 patients and developed after long duration of bronchiectasis in seven, while the temporal onset could not be differentiated in three patients. Patients with both asthma and bronchiectasis had inferior spirometric values, higher prevalence of bronchial hyperresponsiveness to methacholine, higher prevalence of skin atopy, elevated serum immunoglobulin E (IgE), and more sputum eosinophilia, compared with their non-asthmatic counterparts. Possible mechanisms by which asthma and bronchiectasis predispose to each other include asthmatic obstruction contributing to development of bronchiectasis, and sensitization of airways with increased lability due to microbial colonization of the ectatic bronchial tree.
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 greater than or equal to 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.
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.
The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients.
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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.
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.
Inhaled drugs are now considered first line agents for the treatment of asthma, whereas oral beta-agonists, theophylline and its derivatives have been relegated to a secondary role. To determine whether current prescribing in Hong Kong conforms to these recommendations, we have evaluated anti-asthmatic drug utilization in the territory as reflected by 1984-86 drug sales (courtesy Medical and Health Department, Hong Kong). Sales/prescription statistics were also obtained from corresponding agencies of other governments and from published literature. If appropriate, data for comparison was expressed as defined daily doses (DDDs) per 1000 inhabitants per day. In contrast to the pattern of utilization in several developed nations, in Hong Kong (a) oral anti-asthmatic agents (particularly beta agonists) were more commonly utilized than inhaled drugs, and (b) inhaled therapy mainly consisted of non-selective beta-agonists, steroids being very rare. Further education is required to improve anti-asthmatic drug utilization patterns in the community.
Two cases of pleuropulmonary tuberculosis had local rib destruction simulating malignancy. There was no superficial abscess formation which was the usual clinical feature of rib tuberculosis. Computerized tomography was valuable in demonstrating and assessing the extent of skeletal involvement.
In areas where tuberculosis is endemic, clinicians managing immunocompromised patients (ICP) are confronted with the possibility of Mycobacterium tuberculosis as a pathogen. To determine the incidence and clinical pattern of, the diagnostic approach to, and potential therapeutic implications of pulmonary tuberculosis in this patient population, we reviewed 62 non-HIV infected ICP in Hong Kong who had bronchoscopy because of pulmonary infiltrates. Pulmonary tuberculosis was the second most common cause after bacterial infections. Clinical and radiographic presentations of 12 patients with tuberculosis were nonspecific. Flexible bronchoscopy for tuberculosis carried a diagnostic sensitivity of 91.7 percent. We conclude that for the non-HIV infected ICP from areas where tuberculosis is endemic: M tuberculosis should be suspected as the pathogen; radiographic findings are diagnostically not helpful; FB is a sensitive diagnostic test for tuberculosis and in smear-negative cases where tuberculosis is suspected, initiation of empiric anti-tuberculosis therapy should be considered while awaiting culture results.
Two manual laborers were exposed to dimethyl sulfate during work and sustained mucosal injury to the eyes and respiratory tract. In one of them, noncardiogenic pulmonary edema occurred and improved with high-dose methylprednisolone. On follow-up for 10 months, this patient developed persistent productive cough with no evidence of bronchiectasis or bronchial hyperreactivity.
Imipenem 2 g daily was administered intravenously to 40 evaluable patients with neutropenia and fever. Twenty-three patients had acute leukaemia and 17 malignant lymphoma. The overall response rate was 70.0%. Of the 14 patients with documented infection, 9 (64.3%) responded. Poorer responses were observed in patients with pneumonia (40%) or pseudomonal infection (50%). The response rate was significantly higher among patients with increasing neutrophil counts during therapy (P less than 0.02). Fungal infection was a common cause of treatment failure. Gastrointestinal side effects and skin rashes were occasionally seen. No patient developed central nervous system toxicity. Imipenem is a practical alternative to antibiotic combinations for management of neutropenic infection. However, careful monitoring is essential in the subgroups of patients with pneumonia or pseudomonal infections, who may require modifications of therapy.
Fifty patients with inoperable adenocarcinoma of the lung were randomized in a prospective study to receive either standard doses or high doses of 5-fluorouracil, adriamycin, and mitomycin-C (FAM versus Hi-FAM). The response/stabilization rate was 32% for FAM and 34% for Hi-FAM (P greater than 0.05), and the median survival was 27 weeks for FAM group and 24 weeks for Hi-FAM group (P greater than 0.05). Myelotoxicity was mild in FAM, but moderate to severe in Hi-FAM. It is concluded that Hi-FAM did not yield a higher response rate or median survival compared with FAM, but caused significantly more severe myelotoxicity.