Relationship between estimated pretest probability and accuracy of automated Mycobacterium tuberculosis assay in smear-negative pulmonary tuberculosis.

BACKGROUND: The AMPLICOR assay (Roche; Branchburg, NJ), a rapid direct amplification test for Mycobacterium tuberculosis, has only been licensed for use in smear-positive respiratory specimens. However, many patients with pulmonary tuberculosis (PTB) have smear-negative disease. The clinical utility of this test in patients with smear-negative PTB is unknown. OBJECTIVE: To evaluate the effect of pretest probability of PTB estimated by chest physicians on the accuracy of the AMPLICOR assay in patients with smear-negative PTB. DESIGN AND METHODS: A prospective study of consecutive patients suspected of having smear-negative PTB. Two chest physicians estimated the pretest probability of active disease (high, intermediate, and low categories). Respiratory specimens were examined with radiometric broth medium cultures and with the AMPLICOR assay for M tuberculosis. The decision on a final diagnosis of PTB was blinded to the AMPLICOR results. RESULTS: Active PTB was diagnosed in 25 of 441 patients (5.7%). The AMPLICOR assay had an overall sensitivity of 44% and a specificity of 99%. Results of the assay were negative in seven patients with culture-negative PTB. The proportions of patients in the high, intermediate, and low pretest groups were 4.5%, 19.7%, and 75.7%, respectively. The incidence of PTB for each group was 95%, 3.4%, and 0.9%, respectively. The sensitivities of the AMPLICOR assay in the three groups of patients were 47%, 33%, and 33%, respectively, while the specificities were 100%, 98%, and 99%, respectively. CONCLUSIONS: In patients suspected of having smear-negative PTB, the following conclusions were drawn: (1) the incidence of active PTB was low; (2) pretest estimates accurately discriminated between patients with high and low risk of PTB; (3) the risk of PTB was overestimated in the intermediate group; and (4) the utility of the AMPLICOR assay in the intermediate-risk group may be limited by the overestimation of disease prevalence and low test sensitivity. Further studies are needed on the role of the AMPLICOR assay in better selected patients with an intermediate risk of having smear-negative PTB.

Early discharge of patients hospitalized with acute asthma: a controlled study.

There is no consensus on the optimal length of stay and timing of release from hospital in patients admitted with acute asthma. We hypothesize that it might be safe to discharge patients from hospital once they have responded clinically to intensive anti-asthma treatment. In a non-randomized prospective controlled study, we compared two discharge protocols in consecutive patients admitted for acute severe exacerbations of bronchial asthma. Patients in group A were discharged after remission of signs and symptoms and those in group B after improvement but before complete remission of signs and symptoms. Peak expiratory flow rates (PEFR) were monitored but were not used as discharge criteria for either group. Patients with complicating disease and who were likely to be non-compliant were excluded. The length of hospital stay (LOS) and best PEFR at discharge were significantly lower in group B (87 admissions) than group A (80 admissions). The mean (+/-SD) LOS was 1.8(+/- 1) days vs. 3.5(+/- 1.4) days and best PEFR was 58(+/- 17)% predicted versus 71(+/- 15)% predicted respectively (P < 0.001 for both variables). No patient in either group relapsed within 4 weeks of discharge from hospital. We concluded that the release of asthmatics who respond promptly to intensive treatment and are compliant with medication despite incomplete resolution of symptoms, signs and PEFR at the time of discharge from hospital may not be associated with increased risk of early relapse.

Asthma in the elderly--a more severe disease.

OBJECTIVE: To determine the severity of asthma in the elderly compared to the younger asthmatics. DESIGN: Cross-sectional study. SETTING: University outpatient asthma clinic. SUBJECTS: Asthmatics seen over a 6 month period in 1997. RESULTS: There were 154 patients and 16% were elderly (> 65 years) asthmatics. The elderly asthmatics were on significantly more anti-asthmatic medications (2.3 +/- 1.1 vs. 1.6 +/- 0.9, p < 0.001), and their clinical severity was significantly worse than their younger counterparts (Step 2.2 +/- 1.2 vs. 1.7 +/- 1.0, p < 0.001). Near-fatal asthma episodes were also more common in the elderly asthmatics (39% vs 13%, chi 2 test p < 0.01). CONCLUSIONS: Elderly asthmatics appear to have more severe asthma as evidenced by the increase in near-fatal episodes, and their increased clinical severity.

Hospitalised low-risk community-acquired pneumonia: outcome and potential for cost-savings.

Fine et al. from USA have identified a sub-group of patients with community-acquired pneumonia (CAP) with a low risk of mortality and suggested that it may be cost-effective to manage them as outpatients. The aims of this study were: to evaluate the outcome of low risk CAP patients that were hospitalised in our local setting, and to gauge the number of such patients in order to estimate the potential cost-savings by treating them as outpatients, as well as the safety of such an approach. All patients with CAP admitted to our hospital from 1 April 1997 to 1 March 1998 were enrolled into this prospective cohort study. Low-risk patients were identified, and their hospital outcome compared with other patients. Hospitalisation charges were obtained from the Finance Department. There were 226 patients with CAP. The average age was 64 years with a range of 12 to 96 years. The median hospital stay was 6 days. Mortality was 13.7%. 16.8% required admission to the ICU; none of these were low-risk patients. There were 47 (21%) low-risk patients, and there was no mortality in this group. They had significantly shorter hospital stay (6.4 days versus 10 days) and lower hospitalisation charges ($2,160 versus $5,770) compared to other CAP patients. Only one low-risk patient had a positive blood culture. In conclusion, nearly one-fifth of our CAP admissions consisted of low-risk patients that experienced no mortality, and required a significantly shorter hospitalisation. The management of such patients who are young (< or = 50 years), with no serious co-morbidities in an outpatient setting may be a cost-effective strategy, and this group of patients consumed 9% of the total hospitalisation charges for CAP.

Empirical treatment with fibrinolysis and early surgery reduces the duration of hospitalization in pleural sepsis.

The efficacy of three different treatment protocols was compared: 1) simple chest tube drainage (Drain); 2) adjunctive intrapleural streptokinase (IP-SK); and 3) an aggressive empirical approach incorporating SK and early surgical drainage (SK+early OP) in patients with pleural empyema and high-risk parapneumonic effusions. This was a nonrandomized, prospective, controlled time series study of 82 consecutive patients with community-acquired empyema (n=68) and high-risk parapneumonic effusions (n=14). The following three treatment protocols were administered in sequence over 6 years: 1) Drain (n=29, chest catheter drainage); 2) IP-SK (n=23, adjunctive intrapleural fibrinolysis with 250,000 U x day(-1) SK); and 3) SK+early OP (n=30, early surgical drainage was offered to patients who failed to respond promptly following initial drainage plus SK). The average duration of hospital stay in the SK+early OP group was significantly shorter than in the Drain and IP-SK groups. The mortality rate was also significantly lower in the SK+early OP than the Drain groups (3 versus 24%). It was concluded that an empirical treatment strategy which combines adjunctive intrapleural fibrinolysis with early surgical intervention results in shorter hospital stays and may reduce mortality in patients with pleural sepsis.

Efficacy of the conventional diagnostic approach to pulmonary tuberculosis.

OBJECTIVE: The aim of this study was to evaluate the efficacy of the current clinical approach to the diagnosis of culture positive pulmonary tuberculosis (PTB) in hospitalised adult patients. METHOD: We examined the case records and chest X-rays (CXR) of 199 adult patients with culture positive PTB diagnosed from 1993 to 1995. Patients were divided into two groups: early treatment (ET) and delayed treatment (DT) of PTB. DT were patients who received treatment only after respiratory specimens had returned with positive culture results. We also compared the CXR of the DT group with a group of age, sex matched patients who did not have PTB (control). Usual CXR pattern for PTB was defined as: upper lobe acinar shadows, upper lobe cavitation or miliary pattern. RESULTS: There were 199 patients with a mean age of 56 (19). One patient was HIV antibody positive and 27% were diabetics. There were 143 (72%) patients in the ET group and 56 (28%) in the DT group. The ET group was significantly younger and more likely to show usual features and cavitary disease on the CXR than the DT group. The diabetic patients had significantly more frequent cavitation than non-diabetics. When compared to a control group without PTB, the DT group was significantly more likely to show usual CXR pattern and less likely to have a clear CXR. CONCLUSIONS: The conventional approach to the diagnosis of PTB is reasonably accurate and efficient enough for the majority of patients. The delay in the diagnosis and treatment of PTB was more common among elderly patients, patients with negative smear results and atypical CXR features. If PTB is suspected in elderly patients, an early decision should be made between empiric treatment and further diagnostic testing.

Population based standards for pulmonary function in non-smoking adults in Singapore.

Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data (n = 406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20-79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore.

Controlled trial of intrapleural streptokinase in the treatment of pleural empyema and complicated parapneumonic effusions.

OBJECTIVE: To compare the efficacy of adjunctive intrapleural streptokinase (SK) with simple closed chest tube drainage (Drain) in the treatment of empyemas and complicated parapneumonic effusions. METHOD: This was a controlled study of 52 patients (mean age, 57 years; 41 men) with pleura space sepsis. Forty patients (77%) had empyema and 12 had complicated parapneumonic effusions. Twenty-nine patients were treated with Drain only while 23 received, in addition, repeated daily SK, 250,000 U in saline solution (mean, 5.3 days). RESULTS: The two groups of patients had comparable degrees of peripheral blood leukocytosis, frequency of loculated effusions, pleural fluid pH, and lactate dehydrogenase levels. Infective organisms were isolated in 54% of which 32% were anaerobic and 21% were polymicrobial infections. The incidence of surgical decortication was 17% and mortality was 15%. A significantly larger volume of pleural fluid was drained from patients in the SK treatment group (2.0 [1.5] L) than those in the Drain treatment group (1.0 [1.01] L). There were no significant differences, however, between the two treatment groups in terms of duration before defervescence, duration of hospital stay, the need for surgical intervention, or mortality rates. CONCLUSION: We conclude that thrombolytic therapy increased the volume of fluid drained from pleural empyemas but did not markedly reduce morbidity and mortality.

Treatment of complicated parapneumonic effusions and pleural empyema: a four-year prospective study.

We studied prospectively the microbiologic findings, management, including the use of intrapleural streptokinase to improve pleural drainage, and outcome of 33 patients with complicated parapneumonic effusions (6) frank empyema (27) treated by our unit over a 4-year period. The mean age was 61 years, with more male (26) than female (7) patients. Seventy-nine percent of the patients had some form of underlying illness, especially chronic lung disease (46%), followed by diabetes mellitus (23%). Fifteen percent of the pleural collections were loculated. Pleural fluid cultures were positive in 58%, Staph aureus and Kleb pneumoniae being the most prevalent aerobic isolates. The incidence of anaerobic isolates was 32%. Besides empirical antibiotics, all patients had drainage of the pleural collections at diagnosis. Four patients were treated with needle aspiration; 28 (85%) required thoracostomy tube drainage for a mean of 8 days, 5 of these went on to surgical decortication. Thirteen patients received intrapleural streptokinase (SK) to facilitate drainage, with significant increase in the volume drained. The mean duration of stay for the whole group was 22 days. The administration of intrapleural SK did not significantly shorten the duration of hospital stay. There were six deaths (18%), none as a direct result of the empyema. We describe a therapeutic approach to parapneumonic effusions and empyema which tailors the interventional modality to the clinical stage of disease.

Detection of Mycobacterium tuberculosis in sputum, pleural and bronchoalveolar lavage fluid using DNA amplification of the MPB 64 protein coding gene and IS6110 insertion element.

Two gene sequences specific for Mycobacterium tuberculosis were evaluated for the diagnosis of pulmonary tuberculous (PTB) in pleural fluid (PF), bronchoalveolar lavage fluid (BAL) and sputum (Sp). The 240 bp sequence (nts 460-700) coding for the MPB 64 protein coding gene and the 123 bp IS6110 insertion element present in multiple copies in the mycobacterial genome were amplified using the polymerase chain reaction. Fifty-nine clinical specimens were studied. The diagnosis of PTB was confirmed by positive M. tuberculosis cultures in 14 specimens, and by the presence of characteristic histological features of granuloma and Langerhan's giant cells on pleural biopsy in 3 PF specimens through cultures for M. tuberculosis were negative. The remaining 42 specimens were obtained from patient's with non-tuberculosis pulmonary infections or malignancy, and these served as negative controls. Our results showed that the IS6110 insertion element and MPB 64 gene sequence were detected in all 14 culture positive PTB cases, although detection of the latter sequence required both DNA amplification and oligonucleotide hybridization. There was however one false positive specimen with the MPB 64 detection protocol. More importantly, both the MPB 64 sequence and IS6110 insertion element protocols were unable to detect M. tuberculosis DNA in the 3 PF samples diagnosed by histological characteristics on pleural biopsy and culture negative. We conclude that DNA amplification for M. tuberculosis-specific sequences is a useful method for rapid diagnosis of PTB in culture positive specimens. However, the false negative results with TB culture negative cases of tuberculosis pleurisy, limits its usefulness for the diagnosis of tuberculous pleurisy.

Pulmonary blastoma in an adult presenting as a chronic loculated effusion: a diagnostic problem.

A 33 year old woman posed a diagnostic problem for two years with recurrent left sided chest pain and radiographic features suggestive of a loculated effusion. Diagnosis was finally made at thoracotomy which revealed an encapsulated cystic mass. Histological examination confirmed a rare monomorphic pulmonary blastoma.

Idiopathic lipoid pneumonia in an adult treated with prednisolone.

The treatment of lipoid pneumonia, an uncommon chronic lung condition, is generally conservative. We describe a patient with idiopathic lipoid pneumonia who was successfully treated with oral steroids with improvement of chest radiographic abnormalities.

Moraxella catarrhalis respiratory infection in adults.

Moraxella catarrhalis (MC) is an upper respiratory tract commensal which may also be pathogenic. In this report we examined the clinical features, microbiology and therapeutic response in 30 consecutive adult patients with pneumonia who had MC isolated in the sputum. The mean age was 66 years with an equal sex ratio. Most patients gave a history of cigarette smoking (77%) and had underlying pulmonary diseases (73%). Dyspnea and productive cough were the most common complaints (87%). Fever was a manifestation in 60% of patients. Chest X-ray features of pneumonia were noted in 78% of patients while leucocytosis (> 11,000/mm3) was evident in 70%. While all isolates were susceptible to tetracycline, 70% were resistant to penicillin/ampicillin by in-vitro testing. Three patients died, two from their underlying illnesses and one from myocardial infarct. We believe that MC isolated in sputum cultures from symptomatic adults with underlying respiratory diseases should be treated as a pathogen. The short term prognosis is good.

Prospective study of the aetiology of adult community acquired bacterial pneumonia needing hospitalisation in Singapore.

A prospective survey of 96 consecutive adult patients with community acquired pneumonia requiring hospitalisation was carried out at National University Hospital, Singapore. Causative pathogens were identified in 58% of patients. Mycobacterium tuberculosis was the most common pathogen (21%), followed by Streptococcus pneumoniae (12%), Haemophilus influenzae (5.2%), Mycoplasma pneumoniae (5.2%) and Staphylococcus aureus (4.2%). Gram-negative organisms (apart from Haemophilus influenzae) were found in 10% of pneumonia patients. More than half of the patients had pre-existing illness, the most common was diabetes mellitus (21%).