Wah-Kit Lam

Rapid diagnosis of suspected pulmonary tuberculosis by fiberoptic bronchoscopy

Fiberoptic bronchoscopy was performed on 65 patients suspected of having active pulmonary tuberculosis, who were either sputum smear-negative or had no sputum to test. Bronchial aspirate was smear positive in 25 of 65 patients (38%); postbronchoscopy sputum was smear positive in 15 of 60 (37%) and there was bronchial biopsy evidence of tuberculosis in 33 of 57 (58%). Biopsy was particularly useful; it provided the exclusive diagnosis in 12% of cases. When the 3 methods were combined, a diagnosis of tuberculosis was made within 3-4 days in 42 of 65 patients (65%). Taking culture results into consideration, we made a definitive diagnosis in 61 of 65 patients (94%). Thirteen patients had atypical radiographic shadows and 7 had unsuspected co-existing bronchogenic carcinoma. No major complication developed after bronchoscopy. Our results are compared with those of 3 other reported series.

Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients.

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.

EVIDENCE THAT RESPIRATORY TRACT IS MAJOR RESERVOIR FOR EPSTEIN-BARR VIRUS

Exfoliated cells harvested from bronchial washings of 53 patients with suspected bronchogenic carcinoma were tested by means of DNA dot hybridisation using the cloned large internal repeat (IR) sequence of Epstein-Barr virus (EBV) genome as a probe. 25 of these patients gave positive results. Since the patients had diseases that were not related to the virus, this finding suggests that the lower respiratory tract is a major reservoir for EBV. Attempts at cellular localisation of the virus revealed only an occasional cell which harboured the viral genome or expressed viral capsid antigens. These cells could not account for the quantity of the viral DNA detected in bronchial washings. Moreover, patients had similar profiles of serum EBV antibodies whether they were positive or negative for EBV DNA by dot hybridisation. These findings are compatible with a state of viral latency in which cells harbour a low copy number of the viral genome. Viral expression rarely occurs in these cells, which seem to elicit a minimum host immune response. If it is assumed that each latently infected cell harbours a maximum of approximately 30 EBV genomes (which is the lower limit of detection by the in-situ hybridisation method used in this study), the findings suggest that a considerable proportion of the exfoliative cells from the lower respiratory tract, of the order of 0.1-16%, harbour latent EBV.

The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer. Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination. Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91 versus 58%) at detecting these lesions, but less specific (26 versus 50%). A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.

Clinical profiles of Chinese patients with diffuse panbronchiolitis

BACKGROUND Diffuse panbronchiolitis (DPB), characterised by progressive sinobronchial sepsis, is well characterised in Japanese subjects but not in other ethnic groups. The experience with DPB in seven Chinese patients is described and the clinical profiles compared with those of Japanese subjects. METHODS Seven Chinese patients (three women; mean (SD) age 48(18.6) years, all never smokers) who attended a teaching hospital centre and fulfilled the diagnostic criteria for DPB were assessed prospectively for clinical, radiological, lung function, microbiological, and other “characteristic” laboratory parameters. RESULTS Lung function assessment showed a typical obstructive pattern (n = 5) and air trapping (n = 7). Typical bronchiolar infiltration by lymphocytes and plasma cells and accumulation of foamy macrophages in the intraluminal tissue were detected in open lung biopsy specimens (n = 2). Chest radiographs and high resolution computed tomographic scans revealed hyperinflation, diffuse nodules, bronchial thickening and dilatation, peripheral hypoattenuation, and bronchiolectasis. Radiological improvement, manifest as a reduction in nodular density and bronchial thickening, and persistence of other abnormalities such as air trapping were not accurately depicted by the classical Nakata or Akira classifications. The other “characteristic” features such as HLA-B54, IgG subclass deficiency, raised CD4/CD8 T lymphocyte ratio, cold haemagglutinaemia, raised IgA, IgG, and rheumatoid factor were not present. Treatment with erythromycin led to excellent responses in symptoms, lung function indices, and the radiological picture. A review of the non-Japanese cases in the literature reveals that this absence of typical “additional features” in DPB might also be applicable to non-Japanese patients. CONCLUSIONS We report the only series of non-Japanese Mongoloid patients with well characterised DPB who had uncharacteristic investigation profiles. This experience should help other clinicians in the investigation and management of DPB in non-Japanese patients.

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.

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.

Ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy.

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.

Effect of calcium antagonists on allergen‐induced asthma

The protective effect of inhaled verapamil (estimated dose 2‐4 mg) and sub‐lingual nifedipine (20 mg) against allergen‐induced asthma were each assessed by the administration of calcium antagonists 30 min before bronchial provocation tests using Dermatophagoides pteronyssinus extracts on eight young perennial asthmatics. Neither drug changed the basal forced expiratory volume in one second (FEV1) or the provocation dose of allergen required to cause a 20% fall in FEV1 (PD20 FEV1). That calcium antagonists are ineffective in preventing allergen‐induced asthma suggest indirectly that mechanism other than mediator release from mast cells may also be involved.

Pulmonary sequelae of treatment for breast cancer: A prospective study

PURPOSE To prospectively study the effects of loco-regional radiotherapy in women with breast cancer. METHODS AND MATERIALS Thirty consecutive patients with breast resection underwent clinical, lung function, radiographic, and thoracic high-resolution computed tomography evaluation before and at 1, 3, 6, and 12 months after adjuvant radiotherapy. Chemotherapy was also administered to 15 patients. RESULTS Nineteen patients reported mild respiratory symptoms at 1 month, which resolved completely at 6 months after radiotherapy. Opacities were present on 80% of chest radiographs and in all patients on high-resolution computed tomography by 3 months. These opacities became compact and persisted on high-resolution computed tomography at 12 months. Lung function indices, including FEV1, FVC, TLC, and DLCO, progressively declined after radiotherapy, and was irreversible at 12 months (p < 0.05). Patients who received chemotherapy did not have significantly different lung function indices compared with their counterparts at all time points (p > 0.05). CONCLUSIONS Our results have shown that adjuvant loco-regional radiotherapy, a common practice in breast cancer treatment, is associated with irreversible reduction in lung function parameters. These changes are accompanied by radiological evidence of persistent lung injury. Further studies should be performed to evaluate the incidence and long-term pulmonary sequelae of current treatment for breast cancer.