Breath markers of oxidative stress in patients with unstable angina

Cardiac chest pain is accompanied by oxidative stress, which generates alkanes and other volatile organic compounds (VOCs). These VOCs are excreted in the breath and could potentially provide a rational diagnostic marker of disease. The breath methylated alkane contour (BMAC), a 3-dimensional surface plot of C4-C20 alkanes and monomethylated alkanes, provides a comprehensive set of markers of oxidative stress. In this pilot study, we compared BMACs in patients with unstable angina pectoris and in healthy volunteers. Breath VOCs were analyzed in 30 patients with unstable angina confirmed by coronary angiography and in 38 age-matched healthy volunteers with no known history of heart disease (mean age +/- SD, 62.7 +/- 12.3 years and 62.5 +/- 10.0, not significant). BMACs in both groups were compared to identify the combination of VOCs that provided the best discrimination between the 2 groups. Forward stepwise entry discriminant analysis selected 8 VOCs to construct a predictive model that correctly classified unstable angina patients with sensitivity of 90% (27 of 30) and specificity of 73.7% (28 of 38). On cross-validation, sensitivity was 83.3% (25 of 30) and specificity was 71.1% (27 of 38). We conclude that the breath test distinguished between patients with unstable angina and healthy control subjects.     

Effect of oxygen on breath markers of oxidative stress.

Supplemental oxygen is often administered to induce hyperoxia in nonhypoxic patients for indications such as chest pain, despite lack of evidence of clinical benefit. Induced hyperoxia is potentially toxic, since it may increase oxidative stress and peroxidative damage to deoxyribonucleic acid, lipids and proteins. The aim of this study was to establish whether supplemental oxygen induces oxidative stress in nonhypoxic subjects. Breath markers of oxidative stress were measured in 31 healthy subjects before and after breathing 28% oxygen at 2.0 L x min(-1) via nasal prongs for 30 min while resting. The criterion standard of oxidative stress was the breath methylated alkane contour (BMAC), a three-dimensional plot of the alveolar gradients of C4-C20 alkanes and monomethylated alkanes produced by lipid peroxidation. Volatile organic compounds (VOCs) in breath were assayed by gas chromatography and mass spectroscopy, and the BMACs before and after oxygenation were compared. Following oxygenation, there was a significant increase in mean volume under the curve of the BMAC and in alveolar gradients of three VOCs: 3-methyltridecane, 3-methylundecane and 5-methylnonane. Breath markers of oxidative stress were significantly increased in normal volunteers breathing supplemental oxygen for 30 min.     

Volatile biomarkers of pulmonary tuberculosis in the breath

Pulmonary tuberculosis may alter volatile organic compounds (VOCs) in breath because Mycobacteria and oxidative stress resulting from Mycobacterial infection both generate distinctive VOCs. The objective of this study was to determine if breath VOCs contain biomarkers of active pulmonary tuberculosis. Head space VOCs from cultured Mycobacterium tuberculosis were captured on sorbent traps and assayed by gas chromatography/mass spectroscopy (GC/MS). One hundred and thirty different VOCs were consistently detected. The most abundant were naphthalene, 1-methyl-, 3-heptanone, methylcyclododecane, heptane, 2,2,4,6,6-pentamethyl-, benzene, 1-methyl-4-(1-methylethyl)-, and cyclohexane, 1,4-dimethyl-. Breath VOCs were assayed by GC/MS in 42 patients hospitalized for suspicion of pulmonary tuberculosis and in 59 healthy controls. Sputum cultures were positive for Mycobacteria in 23/42 and negative in19/42 patients. Breath markers of oxidative stress were increased in all hospitalized patients (p<0.04). Pattern recognition analysis and fuzzy logic analysis of breath VOCs independently distinguished healthy controls from hospitalized patients with 100% sensitivity and 100% specificity. Fuzzy logic analysis identified patients with positive sputum cultures with 100% sensitivity and 100% specificity (95.7% sensitivity and 78.9% specificity on leave-one-out cross-validation); breath VOC markers were similar to those observed in vitro, including naphthalene, 1-methyl- and cyclohexane, 1,4-dimethyl-. Pattern recognition analysis identified patients with positive sputum cultures with 82.6% sensitivity (19/23) and 100% specificity (18/18), employing 12 principal components from 134 breath VOCs. We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between "sick versus well" i.e. between normal controls and patients hospitalized for suspicion of pulmonary tuberculosis, and between infected versus non-infected patients i.e. between those whose sputum cultures were positive or negative for Mycobacteria.     

Diagnosis of peripheral lung cancer with three echoic features via endobronchial ultrasound

BACKGROUND: Endobronchial ultrasonography (EBUS) is useful in localizing peripheral lung lesions. Previous reports have revealed that several characteristic echoic patterns correlate well with the histopathologic findings of benign and malignant lesions. Therefore, EBUS may be also useful in the differential diagnosis of malignant lesions of the lung. OBJECTIVE: To assess the feasibility of EBUS in the differential diagnosis between malignant and benign lesions by the following three characteristic echoic features indicating malignancy: continuous margin; absence of a linear-discrete air bronchogram; and heterogeneous echogenicity. METHOD: EBUS images from 224 patients who undergone bronchoscopy for a peripheral lung lesion were analyzed. The sensitivity and specificity for each echoic feature or in combination in diagnosing malignancy or benignity were determined. RESULT: Continuous margin, absence of linear-discrete air bronchogram, and heterogeneous echogenicity are three echoic features indicating malignancy. The absence of linear-discrete air bronchogram has the highest sensitivity in the diagnosis of malignancy (91.9%), but the lowest specificity (62.4%). By contrast, a well-defined margin has the highest specificity (93.1%), but the lowest sensitivity (27.6%). The sensitivity and specificity for heterogeneous echogenicity are intermediate (65.0% and 90.1%, respectively). The negative predictive value for the malignancy of a lesion with none of these three echoic features is 93.7%. The positive predictive value for malignancy of a lesion with any two of the three echoic features is 89.2%. CONCLUSION: These results indicate that EBUS is useful as an adjunct in lung cancer diagnosis, especially when peripheral lung lesions are not visible in traditional bronchoscopy.     

Lung cancer screening

PURPOSE OF REVIEW: Advances in imaging technologies and biomarker research offer hope that the incidence and mortality of lung cancer can be reduced by screening similar to what have been achieved for cancer of the cervix, breast, and colon. RECENT FINDINGS: Spiral computed tomography with multitrack scanners and autofluorescence bronchoscopy offer unprecedented sensitivity to detect lung cancer even during the preinvasive stage. The high sensitivity of these tests, however, is associated with a low specificity. Better selection of individuals at highest risk of lung cancer using biomarkers in sputum, blood, or exhaled breath, as well as a better understanding of genetic susceptibility, may improve their positive predictive values, minimize unnecessary downstream investigations or treatment, as well as reduce screening costs. SUMMARY: Improvement in the performance of sputum, exhaled breath, or blood biomarkers holds promise as the first screening step to identify individuals at highest risk of lung cancer beyond what age and smoking could predict to select those who would obtain the most benefits from spiral computed tomography or autofluorescence bronchoscopy as localization tools.     

白光联合荧光支气管镜在肺癌早期诊断中作用的临床评价

目的评价白光联合荧光支气管镜在肺癌早期诊断中的价值。方法将支气管镜检查的患者分普通白光电子支气管镜组（白光组）和荧光电子支气管镜组（联合组）,采用刷检和／或钳夹方法取得标本组织送检,对比两组对肺癌组织检查结果的差异。结果入选患者87例,白光组和联合组分别45例、42例,最终两组分别确诊肺癌23例和26例。其中自光组与联合组的一次性检出率分别为73．9％、88．5％,两者有统计学差异（P〈0．05）。镜下判断恶性的准确性,白光组的敏感率、特异率、阳性预告值和阴性预告值分别82．1％、71．4％、85．1％和66．7％,而联合组分别是92．5％、46．7％、75．8％和77．8％。结论采用白光联合荧光检查的荧光支气管镜,对肺癌病灶的检出具有高敏感性、低特异性的特点,对气道粘膜癌变的早期检出具有一定的优势。     

Effect of influenza vaccination on oxidative stress products in breath

Viral infections cause increased oxidative stress, so a breath test for oxidative stress biomarkers (alkanes and alkane derivatives) might provide a new tool for early diagnosis. We studied 33 normal healthy human subjects receiving scheduled treatment with live attenuated influenza vaccine (LAIV). Each subject was his or her own control, since they were studied on day 0 prior to vaccination, and then on days 2, 7 and 14 following vaccination. Breath volatile organic compounds (VOCs) were collected with a breath collection apparatus, then analyzed by automated thermal desorption with gas chromatography and mass spectroscopy. A Monte Carlo simulation technique identified non-random VOC biomarkers of infection based on their C-statistic values (area under curve of receiver operating characteristic). Treatment with LAIV was followed by non-random changes in the abundance of breath VOCs. 2, 8-Dimethyl-undecane and other alkane derivatives were observed on all days. Conservative multivariate models identified vaccinated subjects on day 2 (C-statistic = 0.82, sensitivity = 63.6% and specificity = 88.5%); day 7 (C-statistic = 0.94, sensitivity = 88.5% and specificity = 92.3%); and day 14 (C-statistic = 0.95, sensitivity = 92.3% and specificity = 92.3%). The altered breath VOCs were not detected in live attenuated influenza vaccine, excluding artifactual contamination. LAIV vaccination in healthy humans elicited a prompt and sustained increase in breath biomarkers of oxidative stress. A breath test for these VOCs could potentially identify humans who are acutely infected with influenza, but who have not yet developed clinical symptoms or signs of disease.     

The diagnostic efficiency of multislice CT virtual bronchoscopy in detecting endobronchial tumors

In this study, the diagnostic efficiency of virtual bronchoscopy, which is a new and helpful method to conventional fiberoptic bronchoscopy, has been investigated for endobronchial lung tumors and its clinical applications are discussed. 36 patients with clinically suspected lung cancer (28 males, 8 females, mean age 61; range from 39 to 74) underwent multislice computed tomography (MSCT) virtual bronchoscopy and then conventional bronchoscopy on the same day. For all patients, investigators were uninformed about results of conventional bronchoscopy. Sensitivity, specificity, positive and negative predictive values of virtual bronchoscopy were calculated using conventional bronchoscopy results as standard reference values. In 12 patients, conventional bronchoscopy did not show pathologic findings. In 24 cases pathologic findings were detected; mucosal infiltration was observed in three cases, vegetating lesions were detected in 21 cases. Review of these 21 cases demonstrated preocclusive stenosis in five and various degrees of luminal stenosis in 16 cases. All 21 tumoral lesions observed with conventional bronchoscopy were also detected with virtual bronchoscopy. Retrospective evaluation of six lesions visualized with virtual bronchoscopy but not detected with conventional bronchoscopy showed that they consisted of highly viscous mucous secretion. No abnormalities were detected on both conventional and virtual bronchoscopy in six patients. Three mucosal infiltrations observed on conventional bronchoscopy were not visualised on virtual bronchoscopy. The sensitivity of MSCT virtual bronchoscopy was 88% and specificity was 50% which is concordant with the literature. Positive predictive value, negative predictive value and accuracy was found 78%, 66% and 75%, respectively.     

Detection of lung cancer by sensor array analyses of exhaled breath

RATIONALE: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. OBJECTIVES: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. METHODS: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. MAIN RESULTS: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. CONCLUSION: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.     

A randomized trial of CT fluoroscopic-guided bronchoscopy vs conventional bronchoscopy in patients with suspected lung cancer

BACKGROUND: Prior case series have shown promising diagnostic sensitivity for CT scan-guided bronchoscopy. METHODS: This was a prospective randomized trial comparing CT scan-guided bronchoscopy vs conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes. All procedures were performed using a protocolized number of passes for forceps, transbronchial needles, and brushes. Cytologists and pathologists were blinded as to bronchoscopy type. Patients with negative results underwent open surgical biopsy (for nodules or lymph nodes) or were observed for >/= 2 years if they had a nodule < 1 cm in size. RESULTS: Fifty patients were enrolled into the study (CT scan-guided bronchoscopy, 26 patients; conventional bronchoscopy, 24 patients). Two patients, one from each arm, dropped out of the study. Ultimately, 36 patients were proven to have cancer, and 27 of these patients (75%) had their diagnosis made by bronchoscopy. The sensitivity for malignancy of CT scan-guided bronchoscopy vs conventional bronchoscopy for peripheral lesions was similar (71% vs 76%, respectively; p = 1.0). The sensitivity for malignancy of CT guided bronchoscopy vs conventional bronchoscopy for mediastinal lymph nodes was higher (100% vs 67%, respectively) but did not reach statistical significance (p = 0.26). On a per-lymph-node basis, there was a trend toward higher diagnostic accuracy with CT scan guidance (p = 0.09). The diagnostic yield was higher in larger lesions (p = 0.004) and when CT scanning confirmed target entry (p = 0.001). CONCLUSION: We failed to demonstrate a significant difference between CT scan-guided bronchoscopy and conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes. Further study of improved steering methods combined with CT scan guidance for the diagnosis of lung cancer in peripheral lesions is warranted.     

Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy

To evaluate the diagnostic usefulness of simultaneous determinations of 4 tumor markers (carcinoembryonic antigen, calcitonin, creatinine kinase-BB, and DNA), we studied 31 patients with lung cancer, 22 with benign lung disease, and 15 normal volunteers as control subjects. The measurements were made by radioimmunoassay in bronchoalveolar lavage (BAL) and in serum obtained on the same day. The results showed that in serum, only CEA levels were significantly higher in malignancy; in lavage fluids, all 4 markers were abnormally high in cancer patients when compared with control subjects (p less than 0.05); there was no correlation between the levels in lavage and those in the bloodstream. When the mean levels in lavage of the normal control subjects were designated as the limits for a positive test, significant association was found between malignancy and abnormally elevated marker concentration (p less than 0.01). The particular combination of CEA-BAL greater than 35 ng/mg, CEA-serum greater than 4 ng/ml, and calcitonin-BAL greater than 120 pg/mg taken together with the results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant and benign lung disease. The sensitivity of the bronchoscopy procedure increased from 50 to 89%, with at least 2 positive markers, and had a specificity of 71%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%. We conclude that tumor marker levels in lavage are a useful aid in the diagnosis of malignancy in patients undergoing bronchoscopy.     

Accuracy of F-18 fluorodeoxyglucose positron emission tomography for the evaluation of malignancy in patients presenting with new lung abnormalities: a retrospective review.

STUDY OBJECTIVE: To evaluate the accuracy of positron emission tomography (PET) in determining the presence of malignancy in patients presenting with new lung findings, either as an incidental finding or after treatment of a primary carcinoma. DESIGN: A retrospective review of the PET database of our hospital from April 29, 1997, to March 20, 1999, identified 196 patients referred for the evaluation of new lung findings, either as an incidental finding or following definitive treatment of a primary carcinoma. The diagnosis of either malignancy or a benign condition was established in 71 patients. This was determined by either histopathology from biopsy, or by subsequent imaging demonstrating disease progression, resolution, or stability of the initial lung findings. RESULTS: In patients presenting with new lung findings without a history of carcinoma (n = 37), the sensitivity and specificity of PET was 95% and 82%, respectively. In this population, the negative predictive value was 93% and the positive predictive value was 86%. PET was less sensitive and specific for evaluating metastatic or recurrent disease in patients previously treated for carcinoma. In patients presenting with a previously treated primary lung cancer (n = 13), the sensitivity of PET was 70%, with a specificity of 67%. The negative predictive value was only 40% and the positive predictive value was 88% in this subset of patients. In patients with an extrapulmonary primary carcinoma presenting with new lung nodules (n = 21), the sensitivity and specificity of PET was 92% and 63%, respectively. In this population, the negative predictive value was 83% while the positive predictive value was 80%. Of the 71 total cases for which follow-up data were available, there were 5 false-negative cases and 7 false-positive cases, for an overall sensitivity of 88%, specificity of 75%, negative predictive value of 81%, and positive predictive value of 84%. CONCLUSIONS: The sensitivity of PET is highest for the evaluation of new malignancy in patients without a known primary carcinoma. PET is less sensitive for evaluating metastatic or recurrent disease.     

Impact of sampling procedures on the results of breath analysis

The impact of different sampling techniques on the results of breath analysis was to be assessed in this study. Alveolar, mixed expiratory and time-controlled samples were collected from ten volunteers and from eight lung cancer patients. Breath sampling was visually controlled by means of capnometry. PCO(2) and 13 VOCs were determined. Mixed expiratory sampling yielded 25% lower concentrations of CO(2) and blood-borne VOCs. Time-controlled sampling generated high variation of results. Ratios C(alv)/C(mixed) were >1.5 for CO(2), acetone and isoprene, and <1 for isopropanol, 2-butanone and hexanal. Acetonitrile, butane, dimethylsulfide, pentane, butanal, benzene and hexane showed 1.5 > C(alv)/C(mixed) > 1. The ratio C(alv)/C(mixed) of CO(2), acetone and isoprene was different in healthy volunteers and lung cancer patients. Alveolar samples showed the highest concentrations of endogenous and lowest concentration of exogenous substances. Sampling can impact results in breath analysis. Valuable information can be obtained from ratios of alveolar and mixed expired concentrations.     

PET/CT联合多项检查在肺癌诊断中的价值

目的探讨PET/CT联合肿瘤标志物与电子支气管镜检查在肺癌诊断中的应用价值,并进行对比分析。方法收集2011年5月~2012年5月在我院PET/CT中心检查发现肺部病变患者68例,对纳入患者均进行了肿瘤标志物、电子支气管镜检查或经皮肺穿或手术取组织行病理学检查。结果 68例患者中,电子支气管镜、PET/CT、PET/CT联合肿瘤标志物检测对肺癌诊断的灵敏度、特异度及准确度分别为62.2%、93.5%及76.4%;81.8%、74.9%及77.9%;91.9%、77.4%及85.3%。结论电子支气管镜检查的特异度较PET/CT显像检查高,而灵敏度较PET/CT显像检查低,二者的准确度基本相近,PET/CT与血清肿瘤标志物检测联合应用后可使灵敏度、特异度、准确度均有提高,可减少误诊或漏诊的发生。     

Volatile biomarkers in the breath of women with breast cancer

We sought biomarkers of breast cancer in the breath because the disease is accompanied by increased oxidative stress and induction of cytochrome P450 enzymes, both of which generate volatile organic compounds (VOCs) that are excreted in breath. We analyzed breath VOCs in 54 women with biopsy-proven breast cancer and 204 cancer-free controls, using gas chromatography/mass spectroscopy. Chromatograms were converted into a series of data points by segmenting them into 900 time slices (8 s duration, 4 s overlap) and determining their alveolar gradients (abundance in breath minus abundance in ambient room air). Monte Carlo simulations identified time slices with better than random accuracy as biomarkers of breast cancer by excluding random identifiers. Patients were randomly allocated to training sets or test sets in 2:1 data splits. In the training sets, time slices were ranked according their C-statistic values (area under curve of receiver operating characteristic), and the top ten time slices were combined in multivariate algorithms that were cross-validated in the test sets. Monte Carlo simulations identified an excess of correct over random time slices, consistent with non-random biomarkers of breast cancer in the breath. The outcomes of ten random data splits (mean (standard deviation)) in the training sets were sensitivity = 78.5% (6.14), specificity = 88.3% (5.47), C-statistic = 0.89 (0.03) and in the test sets, sensitivity = 75.3% (7.22), specificity = 84.8 (9.97), C-statistic = 0.83 (0.06). A breath test identified women with breast cancer, employing a combination of volatile biomarkers in a multivariate algorithm.     

肺癌患者呼出气体中特征性挥发性有机化合物的研究

目的 筛选肺癌患者呼出气体中特征性挥发性有机化合物(VOCs),并探讨其对肺癌诊断的价值.方法 收集2007年2月至2009年8月在浙江大学医学院附属邵逸夫医院呼吸内科住院治疗的55例肺癌患者、21例肺部良性病变患者及30名住院健康体检者的呼出气体,采用固相微萃取联合气相色谱技术检测受试者呼出气体中的VOCs,比较分析各组的VOCs,筛选肺癌患者的特征性VOCs.结果 肺癌组45例检出庚醛(82%),肺部良性病变组1例检出庚醛(5%),健康组1名检出庚醛(3%),肺部良性病变组庚醛检出比例与健康组比较,差异无统计学意义(χ~2=0.06,P>0.05);将上述两组合并为非肺癌组,肺癌组庚醛检出比例明显高于非肺癌组(χ~2=65.06,P<0.05);庚醛的出峰情况与患者的年龄、性别、吸烟程度、肺癌分期及组织类型均无关(χ~2值为1.06～3.30,均P>0.05).结论 庚醛可能为肺癌患者的特征性VOCs之一,检测呼出气体中的VOCs对诊断肺癌可能具有一定的临床价值.     

Critical evaluation of the gallium-67 scan for surgical patients with lung cancer

Seventy-five patients with lung cancer underwent a gallium scan and thoracotomy with total mediastinal nodal dissection. Evaluation of mediastinal lymph nodes by means of the gallium scan showed a sensitivity of 23 percent (3/13), a specificity of 82 percent (31/38), an accuracy of 67 percent (34/51), a positive predictive valve of 30 percent (3/10), and a negative predictive value of 76 percent (31/41) in those patients whose primary tumors demonstrated uptake of radioactive gallium. The low sensitivity was due to an inability to detect microscopic disease in mediastinal lymph nodes. The specificity was decreased by gallium-67 uptake in enlarged inflamed nodes that contained no metastases. These results do not support the use of the gallium scan in the selection of patients with lung cancer for thoracotomy.     

A comparison of cytology and fluorescence in situ hybridization for the detection of lung cancer in bronchoscopic specimens

STUDY OBJECTIVES: To determine the relative sensitivity and specificity of cytology and fluorescence in situ hybridization (FISH) for the detection of lung cancer in bronchoscopically obtained specimens. DESIGN: Cytology and FISH were performed on brushing and washing specimens obtained from patients undergoing bronchoscopy for suspected lung cancer. FISH utilized the LAVysion probe set (Abbott Molecular; Des Plaines, IL), which contains locus-specific probes to 5p15, 7p12 (EGFR), 8q24 (C-MYC), and a centromeric probe to chromosome 6. SETTING: Single-center, academic, tertiary medical center. PARTICIPANTS: One hundred thirty-seven patients referred for bronchoscopy for suspicion of lung cancer. INTERVENTIONS: Cytology and FISH were performed on bronchoscopic brushings and washings. MEASUREMENTS AND RESULTS: One hundred thirty-seven patients undergoing bronchoscopy had pathology, FISH, and cytology results. FISH and cytology were performed on 123 washing and 78 brushing specimens. Sensitivities of FISH and cytology were 71% and 51% (p = 0.007), respectively, for brushing specimens, and 49% and 44% (p = 0.541) for washing specimens. When FISH and cytology results were combined, sensitivities were 75% and 61%, respectively, for brushing and washing specimens, which was significantly better (p < 0.001) than cytology alone. Specificities of FISH and cytology for patients with negative findings at the time of initial bronchoscopy were 83% and 100% (p = 0.125), respectively, for brushing specimens, and 95% and 100% (p = 0.500) for washing specimens. CONCLUSIONS: These findings show that FISH is significantly more sensitive than conventional cytology for detecting lung cancer in bronchial brushing specimens; when combined with cytology, FISH can improve the diagnostic sensitivity of detecting malignancy in bronchial brushing and washing specimens.     

Role of (99m)tc-hexakis-2-methoxy-isobutylisonitrile in the diagnosis and staging of lung cancer

BACKGROUND: Preliminary studies have shown that (99m)Tc-hexakis-2-methoxyisobutylisonitrile (MIBI) is an interesting tracer for various tumors. The aim of this study was to determine the feasibility of using (99m)Tc-MIBI as a diagnostic and staging procedure for lung cancer. METHODS: We prospectively compared the results of biopsy with (99m)Tc-MIBI imaging in patients with potentially resectable lung lesions (stages IIIA or lower). In the patients with radiopharmaceutical uptake, the staging provided by CT was compared with that obtained with (99m)Tc-MIBI. RESULTS: Ninety-nine of the 116 patients examined had lung cancer. For the diagnosis of malignancy, the specificity of (99m)Tc-MIBI was 100%, sensitivity was 89.8%, positive predictive value was 100%, negative predictive value was 62.9%, and accuracy was 91.4%. In the 87 patients with radiopharmaceutical uptake in their lung cancer, the values for the specificity and sensitivity of (99m)Tc-MIBI in the detection of mediastinal lymph node metastases were 100% and 54.5%, respectively. The corresponding values for CT in the same patients were 87.6% and 63.3%, respectively. The difference in specificity is statistically significant (p = 0.011). CONCLUSIONS: This study demonstrates that (99m)Tc-MIBI provides significant diagnostic and staging information in patients with lung lesions. The high specificity and positive predictive value of (99m)Tc-MIBI suggest that this radiopharmaceutical could be a very useful tool for the diagnosis of lung cancer, especially in consideration of its low costs and wide availability.     

组胺与乙酰甲胆碱支气管激发试验的诊断价值及不良反应比较

目的：比较组胺支气管激发试验(His-BPT)与乙酰甲胆碱支气管激发试验(Mch-BPT)的诊断价值及不良反应差异,为临床激发药物的选择提供参考。方法招募哮喘患者28例(哮喘组)、感染后咳嗽(cough post infection,CPI)患者23例(CPI 组)及健康志愿者21名(正常对照组)。所有受试者按照随机自身交叉对照原则分别进行 His-BPT 与 Mch-BPT,比较两种试验的灵敏度、特异度及不良反应差异。结果① His-BPT 与 Mch-BPT 的灵敏度分别为90%和83%;特异度分别为89%和100%;准确度分别为89%和93%;阳性预测价值分别为84%和100%;阴性预测价值分别为93%和90%。②His-BPT 的 ROC 曲线下面积为0.959(95% CI ：0.916~1.001),P <0.01;Mch-BPT 的 ROC 曲线下面积为0.957(95% CI ：0.901~1.013),P <0.01;③哮喘组不良反应以咳嗽(His-BPT：64.29%, Mch-BPT：50%, P =0.10)、咽干(His-BPT：57.14%, Mch-BPT：35.71%,P =0.17)、气紧(His-BPT：82.14%,Mch-BPT：78.57%,P =0.92)与胸闷(His-BPT：32.14%,Mch-BPT：25%,P =0.40)为主;CPI 组以咳嗽(His-BPT：66%,Mch-BPT：44%,P <0.01)、咽干(His-BPT：43%,Mch-BPT：57%,P =0.47)以及气紧(His-BPT：22%,Mch-BPT：19%,P =0.40)为主;正常对照组中 His-BPT 的咳嗽(67%)及声嘶发生率(29%)显著均高于Mch-BPT (咳嗽：38%,P <0.01;声嘶发生率：5%,P =0.05)。结论两种激发试验均对哮喘有较高的诊断价值,Mch-BPT 特异度较高但敏感度稍逊,His-BPT 不良反应比例略高,两者均无发生严重不良反应,故两者均适合在临床上推广使用。