Comparison between specified percentage and fifth percentile criteria for spirometry interpretation in Thai patients

OBJECTIVES: The present study was conducted to determine the degree of agreement between the interpretation of spirometry using a specified percentage of predicted value (SPC) and the fifth percentile (FPC) as the cut off between normal and abnormal. METHODOLOGY: Spirometric values were collected for 1754 subjects attending the respiratory service at Siriraj Hospital between February 2000 and April 2001. These values included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, maximal mid-expiratory flow (FEF25-75%) and peak expiratory flow (PEF). A comparison of results between SPC and FPC was performed. The SPC cut-off values for FVC, FEV1, FEV1/FVC, FEF25-75% and PEF were 80% predicted, 80% predicted, 70%, 65% predicted and 80% predicted, respectively. The FPC cut-off values were calculated from reference equations for the Thai population. Inter-rater agreement was calculated as the kappa score. RESULTS: High kappa scores were obtained for FVC (0.84), FEV1 (0.88) and FEF25-75% (0.80). However, poor agreement was found for FEV1/FVC (0.72) and PEF (0.61). When the cut-off values for SPC were modified to 90% of predicted values for FEV1/FVC and to 65% of predicted values for PEF, agreement was substantially improved to 0.92 and 0.89, respectively. CONCLUSIONS: Interpretation by SPC using cut-off values of 80% predicted for FVC and FEV1 and 65% predicted for FEF25-75% resulted in good agreement with FPC. However, the SPC cut-off values for FEV1/FVC and PEF should be modified to 90% predicted and 65% predicted, respectively.     

Diagnostic value of gastric aspirate smear and polymerase chain reaction in smear-negative pulmonary tuberculosis

OBJECTIVE: The aim of this study was to determine the validity of acid-fast bacilli (AFB) smear and polymerase chain reaction (PCR) from gastric aspirates for the diagnosis of smear-negative pulmonary tuberculosis. METHODOLOGY: A cross-sectional study was conducted in a university hospital. One hundred and nine patients with suspected pulmonary tuberculosis in whom either sputum smears were negative or who were not producing sputum were recruited to the study. All patients underwent gastric aspiration after an overnight fast followed by standard fibreoptic bronchoscopy. Specimens were subjected to AFB smear, culture, and pathological examination. PCR was performed on culture filtrate after 1 week of incubation. RESULTS: Eight patients did not complete the follow-up schedule. Of the 101 patients with final outcomes, a diagnosis of pulmonary tuberculosis from microbiological evidence was established in 54 patients. The gastric aspirate smear, PCR, or either one of them was positive in 34, 30, and 39 tuberculosis patients, respectively. There were 13 false positive smears from 47 non-tuberculosis patients, with five resulting from non-tuberculous mycobacteria (NTM). The PCR was falsely positive in eight patients, five of whom had previous histories of tuberculosis. The overall sensitivity, specificity, positive predictive value, and negative predictive value of gastric aspirate examination by combined smear and PCR were 72, 58, 66, and 64%, respectively. CONCLUSIONS: Gastric aspiration is a useful tool for the diagnosis of smear-negative pulmonary tuberculosis warranting institution of antituberculosis treatment. Interpretation of the results should be cautious in those who have had tuberculosis in the past or who have been at risk for acquisition of NTM.     

Population pharmacokinetic modeling of the association between 63396C->T pregnane X receptor polymorphism and unboosted atazanavir clearance

Atazanavir (ATV) plasma concentrations are influenced by CYP3A4 and ABCB1, which are regulated by the pregnane X receptor (PXR; NR1I2). PXR expression is correlated with CYP3A4 in liver in the absence of enzyme inducers. The PXR single nucleotide polymorphism (SNP) 63396C→T (rs2472677) alters PXR expression and CYP3A4 activity in vitro, and we previously showed an association of this polymorphism with unboosted ATV plasma concentrations. The aim of this study was to develop a population pharmacokinetic analysis to quantify the impact of 63396C→T and diurnal variation on ATV clearance. A population analysis was performed with 323 plasma samples from 182 randomly selected patients receiving unboosted ATV. Two hundred fifty-nine of the blood samples were collected at random time points, and 11 patients had a full concentration-time profile at steady state. Nonlinear mixed effects modeling was applied to explore the effects of PXR 63396C→T, patient demographics, and diurnal variation. A one-compartment model with first-order absorption and lag time best described the data. Population clearance was 19.7 liters/h with interpatient variability or coefficient of variation (CV) of 21.5%. Homozygosity for the T allele for PXR 63396 was associated with a 17.0% higher clearance that was statistically significant. Evening dosing was associated with 34% higher bioavailability than morning dosing. Patient demographic factors had no effect on ATV clearance. These data show an association of PXR 63396C→T and diurnal variation on unboosted ATV clearance. The association is likely to be mediated through an effect on hepatic PXR expression and therefore expression of its target genes (e.g., CYP3A4, SLCO1B1, and ABCB1), which are known to be involved in ATV clearance.     

Diagnostic value of bronchoalveolar lavage and postbronchoscopic sputum cytology in peripheral lung cancer

Abstract The objective of this study was to evaluate the value of bronchoalveolar lavage (BAL) and postbronchoscopic sputum cytology in diagnosing peripheral lung cancer. We performed a prospective study in 55 patients with lesions on chest radiographs who were suspected of having lung cancer and had non-endoscopically visible lesions on fiberoptic bronchoscopy. The sequence of procedures in all cases was BAL and transbronchial forceps biopsy. The final diagnosis of these patients were primary lung cancer in 30 patients, metatastic lung cancer in five and benign diseases in 20. In the primary lung cancer group, BAL was positive for malignant cells in 14 of the 30 patients (46.7%). In seven (50%) of these patients, the cell type diagnosed by BAL agreed with the final diagnosis. The diagnostic yield of BAL was influenced by the size and segmental location of the lesion. Bronchoalveolar lavage provided a higher diagnostic yield (46.7%) than transbronchial biopsy (16.7%). In five patients with metastatic lung cancer and 20 patients with benign disease, BAL gave negative results in all. Postbronchoscopic sputum cytology was positive in only two of the 26 patients (7.7%) from whom samples could be obtained. Bronchoalveolar lavage cytology proved to be a valuable diagnostic tool in detecting peripheral, primary lung cancer. Postbronchoscopic sputum cytology provided no significant additional information.     

NRAMP1 and TNF-alpha polymorphisms and susceptibility to tuberculosis in Thais

OBJECTIVE AND BACKGROUND: Polymorphisms in the natural resistance-associated macrophage protein gene 1 (NRAMP1) and tumour necrosis factor (TNF)-alpha gene have been found to be associated with susceptibility to tuberculosis in different populations. However, the results are inconsistent. This study aimed to determine whether NRAMP1 and TNF-alpha variants are associated with tuberculosis in Thais. METHODS: Polymorphisms of NRAMP1 at INT4, D543N and the 3' untranslated region, and of TNF-alpha at +488, -238, and -308, were examined in 149 tuberculosis patients and 147 healthy controls. PCR using sequence-specific oligonucleotides and sequence-specific priming were used to genotype the NRAMP1 and TNF polymorphisms, respectively. RESULTS: There were no significant differences in the distribution of the genotype frequencies for the NRAMP1 and TNF-alpha polymorphisms between the patients and controls. CONCLUSIONS: The NRAMP1 and TNF-alpha genes are not associated with susceptibility to tuberculosis in Thais.     

Prevalence of bronchial hyperresponsiveness and asthma in the adult population in Thailand

OBJECTIVES: We conducted a nationwide cross-sectional survey of respiratory health in adults aged 20 to 44 years during 2001 to 2002 to determine the prevalence of bronchial hyperresponsiveness (BHR) and asthma in the adult Thai population. DESIGN: Subjects were selected by a multistage stratified random sampling. The stratification was done on geographic area, age group, and sex. Subjects were interviewed with questionnaires and underwent spirometric testing. Methacholine challenge tests were performed on all subjects without contraindication to determine BHR defined as the provocative concentration of methacholine producing a 20% fall in FEV(1) < or = 8 mg/mL. Definite asthma was defined as BHR present with any asthma symptom within the past 12 months or demonstrated reversible airflow obstruction. Current diagnosed asthma was defined as previous physician-diagnosed asthma and any asthma symptom within the past 12 months or currently receiving asthma medication. RESULTS: The study population was from 20 provinces of five geographic regions of Thailand and included 1,882 women and 1,572 men. The prevalence of BHR was 3.31% (95% confidence interval [CI], 2.68 to 3.94). However, if subjects with positive reversibility test results were included, the prevalence increased to 3.98% (95% CI, 3.30 to 4.67). The prevalence of definite asthma was 2.91% (95% CI, 2.32 to 3.50), whereas the prevalence of current diagnosed asthma by the questionnaire interview was 2.15% (95% CI, 1.66 to 2.63). The kappa index of the agreement between both definitions of asthma was 0.40, indicating poor to fair agreement. CONCLUSION: The prevalence of BHR and asthma in the adult Thai population is relatively low as compared with western countries.     

Tumor necrosis factor-alpha gene promoter polymorphism is not associated with smoking-related COPD in Thailand

OBJECTIVE: Susceptibility to COPD is, in part, genetically determined. Tumour necrosis factor (TNF)-alpha gene promoter polymorphisms have been investigated in different populations with inconsistent results. This study aimed to determine the genetic predisposition in Thai smoking-related COPD patients. METHODOLOGY: The polymorphism at position -308 of the TNF-alpha gene promoter was examined in 57 patients with smoking-related COPD, 67 smoker control subjects, and 116 control anonymous blood donors. Genomic DNA from peripheral blood lymphocytes was used for genotypic analysis by polymerase chain reaction with sequence specific primers. RESULTS: TNF-alpha-308*2 allele frequency was not significantly different between the population control subjects and the smoking-related COPD patients (4.7% vs. 7.9%, P= 0.14). This allele frequency was also not significantly different between smokers with and without COPD (7.9% vs. 7.5%, P= 0.46). CONCLUSIONS: Although it has been speculated that TNF-alpha might have a causal relationship with COPD, a role for the TNF-alpha gene promoter polymorphism in disease development in Thailand was not demonstrated.     

A simple C-reactive protein measurement for the differentiation between tuberculous and malignant pleural effusion

OBJECTIVE: The aim of this study was to determine the validity of pleural fluid C-reactive protein (CRP) concentrations and/or pleural fluid to serum CRP ratio for differentiating tuberculous pleuritis (TBP) from malignant pleural effusion (MPE) in patients presenting with lymphocytic exudative pleural effusions. METHODOLOGY: A cross-sectional study was conducted on 161 patients with pleural effusion who underwent diagnostic evaluation at Siriraj Hospital, Bangkok, Thailand, between April 2001 and March 2002. The complete biochemical analysis of pleural fluid, cultures of pleural fluid, and pathological examinations of pleural fluid and pleural tissue were performed. The CRP concentrations were then measured in stored sera and pleural fluid samples from patients with a lymphocytic exudative pleural effusion and with a definite diagnosis. RESULTS: Among the 148 patients with lymphocytic exudative pleural effusions, 55 were diagnosed with TBP, 60 with MPE, and 33 with non-specific pleuritis. Pleural fluid and serum CRP levels were significantly higher in the TBP group than in the MPE group (54.58 +/- 4.50 mg/L and 106.93 +/- 9.54 mg/L vs 12.66 +/- 3.52 mg/L and 49.66 +/- 8.84 mg/L, respectively, P < 0.001). The ratio of pleural fluid to serum CRP was significantly higher in the TBP group than in the MPE group (0.52 +/- 0.18 vs 0.30 +/- 0.16, P < 0.001). The optimum cut-off value for pleural fluid CRP level of > or =30 mg/dL had a sensitivity of 72% with 93% specificity, and the pleural fluid to serum CRP ratio cut-off value of 0.45 had a sensitivity of 60% with 89% specificity. A correlation between serum and pleural fluid CRP levels was observed in TBP patients but not in MPE patients. CONCLUSION: In patients presenting with lymphocytic exudative pleural effusion, a simple marker of raised pleural fluid CRP level may be helpful in discriminating between TBP and MPE.