Role of C-Reactive Protein and Procalcitonin in Differentiation of Tuberculosis from Bacterial Community Acquired Pneumonia

BACKGROUND/AIMS: We investigated the utility of serum C-reactive protein (CRP) and procalcitonin (PCT) for differentiating pulmonary tuberculosis (TB) from bacterial community-acquired pneumonia (CAP) in South Korea, a country with an intermediate TB burden. METHODS: We conducted a prospective study, enrolling 87 participants with suspected CAP in a community-based referral hospital. A clinical assessment was performed before treatment, and serum CRP and PCT were measured. The test results were compared to the final diagnoses. RESULTS: Of the 87 patients, 57 had bacterial CAP and 30 had pulmonary TB. The median CRP concentration was 14.58 mg/dL (range, 0.30 to 36.61) in patients with bacterial CAP and 5.27 mg/dL (range, 0.24 to 13.22) in those with pulmonary TB (p<0.001). The median PCT level was 0.514 ng/mL (range, 0.01 to 27.75) with bacterial CAP and 0.029 ng/mL (range, 0.01 to 0.87) with pulmonary TB (p<0.001). No difference was detected in the discriminative values of CRP and PCT (p=0.733). CONCLUSIONS: The concentrations of CRP and PCT differed significantly in patients with pulmonary TB and bacterial CAP. The high sensitivity and negative predictive value for differentiating pulmonary TB from bacterial CAP suggest a supplementary role of CRP and PCT in the diagnostic exclusion of pulmonary TB from bacterial CAP in areas with an intermediate prevalence of pulmonary TB.

Chest Computed Tomography (CT) Immediately after CT-Guided Transthoracic Needle Aspiration Biopsy as a Predictor of Overt Pneumothorax

BACKGROUND/AIMS: This study examined the correlation between pneumothorax detected by immediate post-transthoracic needle aspiration-biopsy (TTNB) chest computed tomography (CT) and overt pneumothorax detected by chest PA, and investigated factors that might influence the correlation. METHODS: Adult patients who had undergone CT-guided TTNB for lung lesions from May 2003 to June 2007 at Seoul National University Bundang Hospital were included. Immediate post-TTNB CT and chest PA follow-up at 4 and 16 hours after CT-guided TTNB were performed in 934 patients. RESULTS: Pneumothorax detected by immediate chest CT (CT-pneumothorax) was found in 237 (25%) and overt pneumothorax was detected by chest PA follow-up in 92 (38.8%) of the 237 patients. However, overt pneumothorax was found in 18 (2.6%) of the 697 patients without CT-pneumothorax. The width and depth of CT-pneumothorax were predictive risk factors for overt pneumothorax. CONCLUSIONS: CT-pneumothorax is very sensitive for predicting overt pneumothorax, and the width and depth on CT-pneumothorax are reliable risk factors for predicting overt pneumothorax.

Impact of Toxocariasis in Patients with Unexplained Patchy Pulmonary Infiltrate in Korea

Toxocariasis is one of the causes of pulmonary eosinophilic infiltrate that is increasing in Korea. This study was designed to identify the prevalence of toxocara seropositivity in patients with unexplained pulmonary patchy infiltrate and to evaluate associated factors. We evaluated 102 patients with unexplained pulmonary patchy infiltrate on chest computed tomography (CT) scan. As a control set, 116 subjects with normal chest CT were also evaluated. History of allergic disease, drug use, parasitic disease and raw cow liver intake were taken. Blood eosinophil count and total IgE level were measured. Specific serum IgG antibody to Toxocara canis larval antigen and specific IgG antibodies to 4 other parasites were measured by enzymelinked immunosorbent assay (ELISA). In the infiltrate group, 66.7% subjects were toxocara seropositive whereas 22.4% of the control group were seropositive (p< 0.001). In the infiltrate group, patients with a history of eating raw cow liver (odds ratio [OR], 7.8) and patients with eosinophilia (OR, 5.2) had a higher incidence of toxocara seropositivity. Thirty-five percent of toxocara seropositive patients with infiltrate exhibited migrating infiltrate and 48% had decreased infiltrate on the follow- up CT. We recommend that toxocara ELISA should be performed in patients with unexplained pulmonary patchy infiltrate, and that the eating of raw cow liver should be actively discouraged.

Correlation between Caloric Intake and Lung Function Parameters in Patients with Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

BACKGROUND: There are reports that food deprivation causes emphysematous changes in the lungs of rats and humans. However, the meaning of this phenomenon in patients with chronic obstructive pulmonary disease has not been evaluated. The aim of this study was to determine the correlations between the caloric intake and parameters of the lung function in patients with chronic obstructive pulmonary disease. METHODS: Patients with chronic obstructive pulmonary disease who had visited the respiratory clinic from March, 2006 for one year were enrolled in this study. The patients underwent pulmonary function tests, and a dietitian evaluated their nutritional intake using a food record method. RESULTS: There was no correlation between the total caloric intake and forced vital capacity (FVC, %predicted) or forced expiratory volume in one second (FEV1, %predicted). The total caloric intake showed a positive correlation with the diffusing capacity of carbon monoxide (DLCO %predicted, DLCO/VA %predicted), and a negative correlation with the total lung capacity (TLC, %predicted). Of the calories taken, only calories from protein intake correlated with the diffusing capacity of carbon monoxide (DLCO %predicted, DLCO/VA %predicted). CONCLUSION: The total caloric intake of patients with chronic obstructive pulmonary disease showed a positive correlation with the diffusing capacity of the lung, and a negative correlation with the total lung capacity. Further study on the linkage between the caloric intake and severity of emphysema is needed.

Correlation between Expiratory Increase of Lung Attenuation and Age and Smoking in the Subjects with Normal Inspiratory Low Dose CT and Pulmonary Function Test / 결핵및호흡기질환

BACKGROUND: The attenuation of the lung parenchyma increases on expiration as a consequence of decreased air in the lung. Expiratory CT scans have been used to show air trapping in patients with chronic airway disease and diffuse parenchymal disease and also in asymptomatic smokers. Although there have been several reports investigating the regional air trapping on a expiratory CT scan, there have been only a few reports evaluating the changes of whole lung attenuation with considering its clinical significance, and especially in healthy subjects. The purpose of this study was to evaluate the correlation of an expiratory increase of lung attenuation with age and smoking in healthy subjects. METHODS: Asymptomatic subjects who underwent a low dose chest CT scan as part of a routine check-up and who showed normal spirometry and a normal inspiratory CT scan were recruited for this study. We excluded the subjects with significant regional air trapping seen on their expiratory CT scan. Lung attenuation was measured at 24 points of both the inspiratory and expiratory CT scans, respectively, for 100 subjects. The correlations between an expiratory increase of the lung attenuation and the amount of smoking, the patient's age and the results of spirometric test were assessed. RESULTS: There were 87 men and 13 women included in this study. Their median age was 49.0 years old (range: 25~71). Sixty current smokers, 24 ex-smokers and 16 non-smokers were included. As age increased, the expiratory increase of lung attenuation was reduced at every measuring points (r=-0.297~-0.487, Pearson correlation). The statistical significance was maintained after controlling for the effect of smoking. Smoking was associated with a reduction of the expiratory increase of lung attenuation. But the significance was reduced after controlling for the patient's age. The FEV1, FVC, FEV1/FVC and FEF25~75% were not associated with an expiratory increase of lung attenuation. CONCLUSION: The expiratory increase of lung attenuation in subjects with a normal inspiratory CT scan was negatively correlated with age. It was also reduced in heavy smokers. It may reflect aging and the smoking related changes.

Correlation Between NT-proBNP and Pulmonary Arterial Pressure in COPD Patients / 결핵및호흡기질환

BACKGROUND: Pulmonary hypertension is one of the cardiovascular complications of in COPD. However, a diagnosis of pulmonary hypertension requires an invasive test, such as right heart catheterization. NT-proBNP is a cardiac hormone that is elevated when a cardiac volume or pressure overload is present. It was hypothesized that NT-proBNP might play a role in detecting of pulmonary hypertension in COPD patients. METHOD: The 31 COPD patients, who underwent all of NT-proBNP, echocardiography, and spirometry in Seoul National University Bundang Hospital during the period from November 2003 to July 2005, were retrospectively analyzed. RESULT: Of the 31 COPD patients, 9 patients had pulmonary hypertension. A significant positive correlation was observed between the NT-proBNP and pulmonary arterial pressure (r=0.589, p=0.002). However, there was no significant correlation observed between the FEV(1) and NT-proBNP and FEV(1) and pulmonary arterial pressure. CONCLUSION: NT-proBNP might indicate the presence of pulmonary hypertension in COPD patients.

Enhancement of Sensitivity of Human Lung Cancer Cell Line to TRAIL and Gefitinib by IGF-1R Blockade / 결핵및호흡기질환

BACKGROUND: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. METHODS: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). RESULTS: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. CONCLUSION: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.

Decreased Neutrophil Apoptosis in Patients with Sepsis is Related to the Activation of NF-kappaB / 결핵

BACKGROUND: Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-kappaB transcription factor, we hypothesized that nuclear factor-kappaB might be related to the reduced neutrophil apoptosis observed in sepsis. METHODS: Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches: by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-kappaB was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. RESULTS: We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-kappaB was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-kappaB activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-kappaB, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. CONCLUSION: These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-kappaB.

Polymorphisms of HLA-DRB1 and -DQB1 Genes in Korean Patients with Pulmonary Tuberculosis / 결핵

BACKGROUND: It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). METHODS: HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. RESULTS: Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. CONCLUSION: HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

The Effect of IkappaBalpha-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplation and Paclitaxel / 결핵

BACKGROUND: Some chemotherapeutic drugs induce NF-κB activation by degrading the IκBα protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting IκBα degradation would block NF-κB activation and result in increased tumor cell mortality in response to chemotherapy. METHODS: The "superrepressor" form of the NF-κB inhibitor was transferred by an adenoviral vector (Ad-IκBα-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MTT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. RESULTS: EMSA showed that IκBα-SR effectively blocked the NF-κB activation induced by cisplatin. Transduction with Ad-IκBα-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of IC50. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. CONCLUSION: The blockade of chemotherapeutics induced NF-κB activation by inducing Ad-IκBα-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of IκBα-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

Thoracic nodal staging in non-small cell lung cancer by FDG-PET / 결핵

BACKGROUND: Current non-invasive methods for evaluating the mediastinum by computed tomographic(CT) scan have limited sensitivity and specificity. The recently introduced PET was reported to be a more sensitive and specific method for the mediastinal staging of NSCLC(sensitivity:76-100%, specificity:81-100%) than CT or MRI. We assessed the usefulness of PET in the mediastinal staging of NSCLC. METHODS: We reviewed the medical records of NSCLC patients that had undertaken staging work-up by both CT and PET before thoracotomy between January 1997 and December 1998. A total of 23 patients were enrolled in the study(14 males and 7 females) with a mean age of 61±9 years. By comparing the clinical(CT and PET) and pathologic stagings, we evaluated the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET in thoracic nodal staging. RESULTS: Sensitivity, specificity, positive predicted value and negative predicted value were 38%, 40%, 25% and 50% respectively for computed tomography, and 50%, 60%, 30% and 69% for PET. The accuracy of FDG-PET in our study was lower than that reported by previous other studies. CONCLUSION: Tne addition of FDG-PET to CT scanning has limited benefit for the thoracic nodal staging of NSCLC, but its value in our study was lower than that observed by others.

The Histologic type of lung cancer in idiopathic pulmonary fibrosis : the difference according to the presence of fibrosis at cancer location / 결핵

BACKGROUND: It is well known that the prevalence of lung cancer is higher in idiopathic pulmonary fibrosis(IPF) patients than in the general population. This high prevalence is explained by the concept of 'scar carcinoma'. There have been several reports on the prevalence of histologic type of lung cancer in IPF with conflicting results. Despite of the high smoker rate in almost all previous reports, none considered the smoking history of patients. Therefore we performed a separate studies on fibrosis associated lung cancer and smoking associated lung cancer. The purpose of this study is to investigate the proportion of lung cancer in IPF that is fibrosis assiciated and to determine the most common histologic type in fibrosis associated lung cancer in IPF. METHODS: A retrospective review of medical records and radilolgic studies was performed for cases of lung cancer with IPF. We investigated smoking history, sequence of diagnosis of lung cancer and IPF, histologic type of lung cancer and the cancer location, especially whether the location is associated with fibrosis. To evaluate the proportion of fibrous associated lung cancer, the lung cancer in IPF were categorized according to the presence of fibrosis at cancer location. RESULTS: Fifty seven patients were subjects for this analysis. Six(11%) cases were diagnosed as lung cancer during follow-up for IPF, and both diseases were diagnosed simultaneously in the others. Ninety four percent of patients were smokers and the average smoking amount was 47.1±21.9 pack-year. Among the patients with IPF and lung cancer, 42(80.8%) cases were considered as 'fibrosis associated'. The remainder was 'not fibrosis associated' and probably was due to smoking etc. Although the most frequent histologic type was squamous cell carcinoma as a whole, adenocarcinoma was the prominent histologic type in 'fibrosis associated lung cancer.' CONCLUSION: Considering the proportion of 'fibrosis not associated lung cancer' in the patients with IPF and lung cancer, significant proportion of lung cancer in IPF may not be fibrosis induced. This may influence the distribution of histologic type of lung cancer in IPF.

The Usefulness of Serologic Diagnosis for Tuberculosis with Two Rapid Immunochromatographic Assay Devices / 결핵

BACKGROUND: Many diagnostic tests have developed to diagnose tuberculosis and other mycobacterial diseases but the diagnosis of tuberculosis relies largely on radiological findings and acid-fast staining of sputum and/or culture. Recently, new serologic diagnostic methods, which are safe and easy to use have been introduced into Korea. In this study, the usefulness of serologic diagnosis for tuberculosis and the disease pattern induced variation of the test were evaluated. METHODS: Serological assay was performed upon 108 patients with two test kits, the ICT tuberculosis and the BioSign(TM) TB, which are based upon a rapid immunochromatographic assay technique, capable of being interpreted within 15 minutes. The case groups consisted of 61 patients with active pulmonary tuberculosis(36 patients), extrapulmonary tuberculosis(3 patients), or both (22 patients). Control groups consisted of 47 patients with inactive old pulmonary tuberculosis (17 patients), nontuberculous pulmonary disease(16 patients) and nonpulmonary cardiac disease(14 patients). RESULTS: The diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ICT tuberculosis were 64.3%, 91.5%, 90.0% and 68.3% respectively. The diagnostic sensitivity, specificity, PPV and NPV of the BioSign(TM) TB were 76.5%, 95.3%, 94.1% and 78.8% respectively. Differences in sensitivity were not significant between patients with previous history of tuberculosis or patients without prior history of tuberculosis. The ICT tuberculosis test showed higher sensitivity in pulmonary tuberculosis patients (76.5%) than extrapulmonary tuberculosis patients (33.3%). There was no difference in sensitivity between patients with or without cavitary lesion by chest X-ray. CONCLUSION: Considering high specificity and PPV, serologic diagnosis using a rapid immunochromatographic assay device is another helpful diagnostic method in the diagnosis of tuberculosis, when combined with previous diagnostic methods such as chest X-ray, microbiologic study but it has limitation in terms of confirming the diagnosis for tuberculosis as the only diagnostic method because of relatively low sensitivity and NPV.