Role of chest radiographs in early lung cancer detection.

BACKGROUND: Lung cancer is the second most common and the most fatal form of cancer. Although annual low-dose computed tomography is used as the primary method of cancer screening, it presents challenges regarding resources as well as potential health risks from radiation exposure. Chest radiography (CXR), though less effective, is used frequently and commonly. Moreover, often in clinical settings, CXR is the first imaging modality used; computed tomography is subsequently performed if abnormalities are detected on CXRs. This study examined whether controlling for distractors and time constraints, as well as side-by-side comparison of multiple CXRs in clinical settings can aid earlier detection of radiological abnormalities indicative of lung cancer lesions. METHODS: Thirty-two attending physicians in the Republic of Korea examined 1,750 radiographs of 50 lung cancer cases. Using "hot spot" technology, participants indicated the possible locations of cancer lesions on each radiograph. Subsequently, the same radiographs, cropped to focus the anatomical regions where lung cancers were diagnosed, were shown side-by-side to the participants. The participants were asked to identify the radiograph which first enabled the diagnosis of lung cancer and which first showed a possible lesion. RESULTS: Removal of systemic constraints alone significantly improved lesion identification by 221.72±9.69 days. Presenting radiographs side-by-side, cropped to relevant areas, had an additional significant and positive impact on cancer detection in both hidden and open areas on CXRs. Also, lesions were detected at smaller sizes and earlier than when actually diagnosed. CONCLUSIONS: CXR with improved methods and settings provides an easily accessible and low-risk imaging method for earlier detection of lung cancer compared to current clinical imaging settings. Further, this study demonstrates the potential effectiveness of programs that allow side-by-side comparisons of cropped areas of multiple radiographs to detect radiological abnormalities.

Measuring the Effects of Education in Detecting Lung Cancer on Chest Radiographs: Utilization of a New Assessment Tool.

This study was designed to evaluate the effect of group and individualized educational lectures to accurately interpret chest radiographs of lung cancer patients and to introduce a new educational tool in evaluating skills for reading chest radiographs. Utilizing "hotspot" technology will be instrumental in measuring the effect of education in interpreting chest radiographs. There were 48 participants in the study. Chest radiographs of 100 lung cancer patients and 11 healthy patients taken at various time points were used for evaluation. Using "hotspot" technology, lesions on each radiograph were outlined. Values were taken at baseline, after which the group received lectures. Several days later, they underwent exam 2. Exam 3 was conducted after individualized lectures. A final exam was taken after the participants underwent individualized training within 2 months. Scores significantly improved after the individual lessons (p < 0.001). This improvement in performance decreased in the final examination. Statistically significant differences were observed between exam 2 vs. exam 3 and exam 3 vs. the final exam (p < 0.001, p < 0.001). Participants demonstrated more improvement in detecting lesions in abnormal chest radiographs than in identifying normal ones. Although there was significant improvement in detecting abnormal radiographs by the end of the study (p < 0.001), no improvement was observed in detecting normal ones. We measured lung cancer detection rate using a new "hotspot" detection tool for chest radiographs. With the proposed scoring system, this tool could be objectively used in evaluating the educational effects.

Evaluation of Isothermal Target and Probe Amplification (iTPA) for the Detection of Mycobacterium Tuberculosis.

BACKGROUND: This study compared the diagnostic power of isothermal target and probe amplification (iTPA) with the existing real-time PCR for the detection of Mycobacterium tuberculosis (MTB). METHOD: The two molecular methods were performed using DNA extracted directly from lower respiratory tract samples, not from the culture broth. A total of 174 non-consecutive patients with suspected pulmonary tuberculosis were enrolled in this study. Acid-fast bacilli (AFB) stain and liquid culture with the BACTEC MGIT 960 system (Becton Dickinson Diagnostic, USA) were performed. Real-time PCR and iTPA methods were performed with the AdvanSure TB/NTM TaqMan assay (LG Lifescience, Korea) and the RapiDx® MTB test (RapleGene, Korea). RESULTS: Among 174 patients, 49 of 52 isolates were identified as MTB and 3 of 52 isolates were identified as non-tuberculous mycobacteria NTM. Based on the culture results, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.9%, 90.1%, 81.3%, and 98.2% for iTPA, and 95.7%, 91.0%, 80.4%, and 98.2% for real-time PCR, respectively. The agreement of iTPA was 83.0% with the AFB stain, 92.4% with the MGIT culture, and 94.2% with real-time PCR. Disagreement between the two molecular methods occurred in 10 patients. CONCLUSIONS: This study is the first to report the evaluation of iTPA conducted from direct specimens. Both iTPA and real-time PCR proved to be rapid, sensitive, and specific tools for the detection of MTB in clinical samples. The iTPA method for the MTB detection revealed a high concordance rate with real-time PCR.

A case of pulmonary metastasis of giant cell tumor of bone presenting as pulmonary arteriovenous malformation.

Although giant-cell tumor (GCT) of the bone was originally classified as a benign tumor, metastasis has been reported. The radiographic features usually comprise parenchymal solitary or multiple nodules that are round-to-oval nodular opacities of homogeneous density in patients with GCT. However, the patient described in this case presented with a hypervascular mass with feeding vessels and hemothorax, which are common features of pulmonary arteriovenous malformation. To the best of our knowledge, cases of pulmonary metastases presenting as a pulmonary arteriovenous malformation have not been reported. Here, we report a case of giant-cell tumor of the bone that exhibited histologically benign pulmonary metastases and mimicked an arteriovenous malformation.

A multicenter phase II study of belotecan, a new camptothecin analogue, in elderly patients with previously untreated, extensive-stage small cell lung cancer.

PURPOSE: Belotecan is a new camptothecin analogue and a potent topoisomerase I inhibitor. The aim of this phase II study was to investigate the efficacy and toxicity of belotecan in previously untreated elderly patients with small cell lung cancer (SCLC). METHODS: A total of 26 patients, aged ≥65 years, with previously untreated, extensive-stage SCLC were enrolled in the study. Belotecan was administered by daily intravenous infusion at 0.5 mg/m(2)/day for 5 consecutive days every 3 weeks. RESULTS: The overall response rate and disease control rate of chemotherapy on an intention-to-treat basis were 35 and 54 %, respectively. The median overall survival was 6.4 months, and the median time to progression was 2.8 months. The most common toxicity was hematologic. Grade 3 or 4 neutropenia occurred in 80.8 % of patients, and grade 3 or 4 thrombocytopenia in 15.3 %. Non-hematologic toxic effects of grade 3 or 4 were uncommon. CONCLUSION: Belotecan had modest efficacy and well-tolerated toxicity in previously untreated, elderly SCLC patients. Single belotecan could be a promising treatment option, considering its lower toxicity in elderly patients who are unsuitable candidates for platinum plus etoposide chemotherapy.

Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing.

Peptide nucleic acid (PNA)-mediated real-time PCR clamping has higher sensitivity than conventional direct sequencing for detecting mutations. Pleural effusion and serum may provide good samples in which to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. We studied 37 NSCLC patients with malignant pleural effusion. EGFR mutations were assessed by PNA clamping and direct sequencing using tumor tissues, cell blocks, pleural effusion, and serum. Concordance between PNA clamping and direct sequencing results, and the diagnostic performance of pleural effusion were investigated. The κ coefficients for the two methods were 0.68 (p = 0.0007), 0.91 (p < 0.0001), 0.75 (p < 0.0001) and -0.01 (p = 0.8639) for tissues, cell blocks, pleural effusion, and serum, respectively. The diagnostic performance of pleural effusion compared with the combination of tumor tissue and cell blocks showed 89% sensitivity, 100% specificity, positive predictive value of 100%, and negative predictive value of 95% by PNA clamping, and 67% sensitivity, 90% specificity, positive predictive value of 75%, and negative predictive value of 86% by directing sequencing. A patient in whom an EGFR mutation was identified in pleural effusion only by PNA clamping showed a significant response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. In contrast to the limited role of serum samples, pleural effusion had a diagnostic performance for the detection of EGFR mutations in NSCLC that was comparable to that of tumor tissues and cell blocks. The diagnostic performance of PNA clamping was good compared with that of direct sequencing. A more sensitive and accurate detection of EGFR mutations would benefit patients by allowing a better prediction of the response to EGFR-TKI treatment.

Protective effect of pravastatin on lipopolysaccharide-induced acute lung injury during neutropenia recovery in mice.

Although neutropenia recovery is associated with deterioration of preexisting acute lung injury (ALI), there are few reports of the preventive strategies. Statins have been found to attenuate inflammatory responses in murine models of lipopolysaccharide (LPS)-induced ALI. The aim of this study was to determine whether pravastatin could attenuate ALI during neutropenia recovery in mice. Cyclophosphamide was administered to mice to induce neutropenia. Mice were given intratracheal LPS 7 days after cyclophosphamide administration, after which pravastatin was administered by intraperitoneal injection. In order to study the effects of pravastatin, mice were killed on day 5. Pravastatin attenuated the pulmonary edema and histopathological changes of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-1ß, IL-6, and MPO in BAL fluids were also effectively inhibited by pravastatin. The expression levels of Toll-like receptor 4, nuclear factor kappa B, tumor growth factor-ß and matrix metalloproteinase-9 were significantly reduced by pravastatin. Taken together, pravastatin significantly attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the potential of pravastatin in the treatment of ALI during neutropenia recovery.

Prognostic factors in critically ill patients with hematologic malignancies admitted to the intensive care unit.

OBJECTIVE: Despite an improvement in the prognosis of patients with hematologic malignancies, the mortality of such patients transferred to the intensive care unit (ICU) is high. This study determined the predictors of mortality in a cohort of critically ill patients with hematologic malignancies admitted to the ICU. METHODS: We studied 227 critically ill patients with hematologic malignancies who were admitted to the ICU between April 2009 and December 2011. A cohort of consecutive patients with hematologic malignancies was reviewed retrospectively to identify clinically useful prognostic factors. RESULTS: The ICU mortality rate was 84.1%, and the in-hospital mortality rate was 89.9%. The ICU mortality was significantly higher in patients with acute leukemia than in those with other malignancies. A significant difference between survivors and nonsurvivors was found in neutropenia and its recovery during the ICU stay, presence of cardiac dysfunction, the need for an invasive mechanical ventilator, use of inotropic/vasopressor agents, platelet count, aspartate transaminase level, pH, and Acute Physiology And Chronic Health Evaluation II score. In the multivariate analysis, acute leukemia, need for invasive mechanical ventilator, use of inotropic/vasopressor agents, and Acute Physiology And Chronic Health Evaluation II scores were independently associated with a worse outcome in patients with hematologic malignancies admitted to the ICU. CONCLUSION: Higher mortality in patients with hematologic malignancies admitted to the ICU is associated with more severe illness, as reflected by higher organ failure scores or respiratory or hemodynamic instability. Mortality is higher in patients with acute leukemia as compared with other hematologic malignancies.

Clinical experience of rigid bronchoscopy in single center.

BACKGROUND: The aim of this study was to analyze clinical situations requiring rigid bronchoscopy and evaluate usefulness of rigid bronchoscopic intervention in benign or malignant airway disorders. METHODS: We retrospectively reviewed 29 patients who underwent rigid bronchoscopy from November 2007 to February 2011 at St. Paul's Hospital, The Catholic University of Korea School of Medicine. RESULTS: Of the 29 patients, the most frequent underlying etiology was benign stenosis of trachea (n=20). Of those 20 patients, 16 had post-intubation tracheal stenosis (PITS), 2 had tracheal stenosis due to inhalation burn (IBTS) and other 2 had obstructive fibrinous tracheal pseudomembrane (OFTP). Other etiologies were airway malignancy (n=6), endobronchial stenosis due to tuberculosis (n=2), and foreign body (n=1). For treatment, silicone stent insertion was done in 16 cases of PITS and IBTS and mechanical removal was performed in 2 cases of OFTP. In 6 cases of malignant airway obstruction mechanical debulking was performed and silicone stents were inserted additionally in 2 cases. Balloon dilatation and electrocautery were used in 2 cases of endobronchial stenosis due to tuberculosis. In all cases of stent, airway obstructive symptom improved immediately. Granulation tissue formation was the most common complication. CONCLUSION: Tracheal stenosis was most common indication and silicone stenting was most common procedure of rigid bronchoscopy in our center. Rigid bronchoscopic procedures, at least tracheal silicone stenting, should be included in pulmonary medicine fellowship programs because it is a very effective and indispensable method to relieve critical airway obstruction which needs training to learn.

The role of pentraxin-3 as a prognostic biomarker in paraquat poisoning.

Paraquat poisoning has been a public health problem in both the developing and developed countries. Pentraxin 3 is a member of the pentraxin family which is expressed as part of the acute-phase response that begins after injury, trauma, and infection. The aim of our study is to determine whether PTX3 levels can be a significant marker of pulmonary fibrosis and outcome of survival in paraquat poisoning. To measure the plasma paraquat level, we collected serum of the patients immediately after admission. EDTA plasma samples for checking the plasma PTX3 concentration were taken before and after the 1st hemoperfusion and after the 2nd hemoperfusion therapy. PTX3 concentrations in EDTA plasma were determined using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Plasma paraquat concentration was higher in survivors than in non-survivors (p<0.05). Maximal plasma PTX3 level was significantly higher in the pulmonary fibrosis group, and plasma PTX3 was significantly increased throughout hemoperfusion therapy (p<0.01). Moreover, increase in PTX3 was greater in non-survivors than survivors (p<0.05). Our results show that PTX3 is a useful biomarker of severity and outcome predictor in paraquat poisoning.

Prevalence, risk factors and survival of lung cancer in the idiopathic pulmonary fibrosis.

BACKGROUND: The aim of this study was to evaluate the prevalence, risk factors, and survival of lung cancer in patients with idiopathic pulmonary fibrosis (IPF). METHODS: IPF with lung cancer from tertiary hospitals consisted of 1685 patients who had been diagnosed between 2003 and 2007. We reviewed their medical records retrospectively to evaluate the prevalence, risk factors and prognosis of lung cancer in IPF patients. RESULTS: Among all patients with IPF, 114 cases (6.8%) had lung cancer with IPF. The incidence of lung cancer in patients with IPF was 1.03 persons per 100 person-year (25 patients/2408 years). Most cases of lung cancer (73/114, 68.9%) were located in IPF-associated areas; the lung cancer typically developed in peripheral and lower lobe areas. The study revealed that forced vital capacity (% predicted) at the initial diagnosis and development of lung cancer were independent prognostic factors in patients with IPF. CONCLUSIONS: Lung cancer in patients with IPF was significantly related with the IPF prognosis. An active evaluation should be performed in patients with IPF to detect lung cancer early.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis.

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Effect of nilotinib on bleomycin-induced acute lung injury and pulmonary fibrosis in mice.

BACKGROUND: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. OBJECTIVES: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. METHODS: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. RESULTS: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1ß and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-ß1 and PDGFR-ß. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-ß1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. CONCLUSIONS: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.

A multicenter phase II study of belotecan, a new camptothecin analogue, as a second-line therapy in patients with small cell lung cancer.

Belotecan (Camtobell, CKD602) is a new camptothecin derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this phase II study was to evaluate the efficacy and safety of single agent belotecan as a second-line therapy in patients with small cell lung cancer (SCLC). Patients who were previously treated for SCLC were entered into the study. Belotecan was given by daily intravenous infusion for five consecutive days, every three weeks. Twenty-five patients were enrolled in this study. On an intention-to-treat basis, belotecan induced an overall response rate of 24%, a median overall survival of 9.9 months, a median time to progression of 2.2 months, and a 1-year survival rate of 38.3%. Grade 3/4 neutropenia developed in 88.0% of patients and grade 3/4 thrombocytopenia in 40.0%. Nonhematologic toxicity of grade 3 or 4 was low. The results suggest that belotecan is relatively active and well tolerated as a second-line agent in patients with SCLC.

Inflammatory and remodeling events in asthma with chronic exposure to house dust mites: a murine model.

Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL- 13, and transforming growth factor-beta (TGF-beta) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-beta might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time.

Time sequence of airway remodeling in a mouse model of chronic asthma: the relation with airway hyperresponsiveness.

During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.

B cell-activating factor is a novel diagnosis parameter for asthma.

BACKGROUND: Asthma is a life-threatening immediate-type allergic disease. B cell-activating factor (BAFF) is a key regulator of B lymphocyte development and is required to generate and maintain the mature B cell pool. OBJECTIVES: To investigate the level of BAFF in the serum of asthma patients and the role of BAFF on T cells. METHODS: The BAFF level was measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMC) from asthma patients were analyzed by flow cytometry. T8.1 cells were used to test the role of BAFF on T cell-antigen-presenting cell (APC) conjugate formation. RESULTS: The BAFF level in patient serum was elevated relative to normal serum. Immunoglobulin E (IgE) concentration and the percentage of CD3+ T and CD19+ B cells vary according to the serum BAFF level. Patients with high BAFF and high IgE (group II) and those with high BAFF and low IgE (group III) show a high ratio of CD3+ T to CD19+ B cells, and the opposite is seen for patients with low BAFF and high IgE (group I) and those with low BAFF and low IgE (group IV). The addition of BAFF increased PBMC proliferation and T cell-APC conjugate formation. BAFF concentration in serum decreased after treatment with antiasthmatic drugs including glucocorticoids and immunosuppressants. CONCLUSION: These findings suggest that the serum BAFF level is high in both IgE-mediated asthma and non-IgE-mediated asthma and extend our knowledge about the fact that BAFF may play a stimulatory role on the proliferation of T cells. Thus, BAFF could be a parameter to monitor the severity of asthma symptoms.

Co-administration of vaccination with DNA encoding T cell epitope on the Der p and BCG inhibited airway remodeling in a murine model of chronic asthma.

Therapeutic modalities of airway remodeling in asthma have proved to be unsuccessful regarding reversing the previously established chronic airway changes. Recently, the potential of plasmid DNA to inhibit the Th2 immune response has been demonstrated in animal models of asthma. Bacillus Calmette-Guerin (BCG) immunization also induced immunomodulation, which appeared to be reliant on the properties of the interferon-gamma that was produced. Mice were immunized with house dust mite extract (HDM). At the 3 week point, we injected BCG subcutaneously into mice on three successive weeks. One week after the BCG injection, we immunized mice with the DNA plasmid encoding for murine T-cell epitope on Dermatophagoide pteronyssinus 2 thrice weekly. At 9 weeks after immunization, we measured airway responsiveness. Twenty four hours later, we performed bronchoalveolar lavage and histological examinations. Co-administration of DNA vaccination and BCG resulted in a partial suppression of the overproduction of goblet cells and the thickness of the peribronchial smooth muscle in ongoing allergic responses. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was reduced, and regarding the change of cytokines, the concentration of IL-4 was also decreased, but interferon-gamma was increased in the co-administration group, opposed to the asthma group. These results suggest that co-administration of vaccination with the DNA encoding T-cell epitope and BCG are effective regarding ongoing allergic response and might constitute an ideal method for combating allergic disease in the future.

Expression of vascular endothelial growth factor and hypoxia-inducible factor in the airway of asthmatic patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent proangiogenic cytokine, and it also increases vascular permeability. It is well known that VEGF levels are increased in the airway of asthmatic patients. Hypoxia-inducible factor (HIF) induces a rapid and strong increase in VEGF expression. OBJECTIVES: To evaluate the relationship between VEGF level and clinical characteristics and to determine whether VEGF expression is associated with HIF expression in asthmatic patients. METHODS: Bronchoscopy was performed on 30 asthmatic patients and 14 control subjects. The concentration of VEGF in the bronchoalveolar lavage fluid (BALF) was examined using enzyme-linked immunosorbent assay. We measured VEGF, HIF-1alpha, and HIF-2alpha expression on biopsy specimens by means of immunoreactivity. RESULTS: The VEGF level in the BALF was significantly higher in asthmatic patients than in controls. The VEGF level correlated with eosinophil counts in the BALF in asthmatic subjects (r = 0.501; P < .01). However, the VEGF level did not correlate with percentage of forced expiratory volume in 1 second and airway hyperresponsiveness. Asthmatic patients exhibited higher VEGF, HIF-1alpha, and HIF-2alpha immunoreactivity in the submucosa than did controls. Furthermore, VEGF expression correlated significantly with HIF-1alpha (r = 0.614; P = .02) and HIF-2alpha (r = 0.881; P = .001) expression. CONCLUSION: These findings suggest that VEGF may play an important role in inflammation and that VEGF level is related to HIF in bronchial asthma.