White Light Bronchoscopy Research Articles

Image-enhanced bronchoscopic evaluation of bronchial mucosal microvasculature in COPD.

BackgroundBronchial vascular remodeling is an underresearched component of airway remodeling in COPD. Image-enhanced bronchoscopy may offer a less invasive method for studying bronchial microvasculature in COPD.ObjectivesTo evaluate endobronchial mucosal vasculature and changes in COPD by image-enhanced i-scan3 bronchoscopy and correlate them pathologically by analyzing bronchial mucosal biopsies.MethodsThis case–control study analyzed 29 COPD patients (41.4% Global initiative for chronic Obstructive Lung Disease B [GOLD B] and 58.6% GOLD D) and ten healthy controls admitted at Alexandria Main University Hospital, Egypt. Combined high-definition white light bronchoscopy (HD WLB) with i-scan3 was used to evaluate endobronchial mucosal microvasculature. The vascularity was graded according to the level of mucosal red discoloration (ie, endobronchial erythema) from decreased discoloration to normal, mild, moderate, and severe increased red discoloration (G−1, G0, G+1, G+2, and G+3, respectively) and scored by three bronchoscopists independently. Bronchial mucosal biopsies were taken for microvascular density counting using anti-CD34 antibody as angiogenesis marker.ResultsDifferent grades of endobronchial erythema were observed across/within COPD patients using combined HD WLB + i-scan3, with significant agreement among scorers (P=0.031; median score of G+1 [G−1–G+2]) being higher in GOLD D (P=0.001). Endobronchial erythema significantly correlated with COPD duration, exacerbation frequency, and body mass index (P<0.05). Angiogenesis was significantly decreased among COPD patients versus controls (10.6 [8–13.3] vs 14 [11–17.1]; P=0.02). Mucosal surface changes (including edema, atrophy, and nodules) were better visualized by the combined HD WLB + i-scan3 rather than HD WLB alone.ConclusionCombined HD WLB + i-scan3 seems to be valuable in evaluating mucosal microvasculature and surface changes in COPD, which may represent vasodilatation rather than angiogenesis.

Evaluation of endobronchial ultrasound in the diagnosis of respiratory mucosal protrusions

To explore the white light bronchoscopic signs and ultrasound features of respiratory mucosal protrusions and to investigate the practical application value of endobronchial ultrasound. This study was a prospective observation. Endobronchial ultrasound was performed in 30 patients with respiratory mucosal protrusions, which were discovered by white light bronchoscopic examination in the Second Affiliated Hospital of Fujian Medical University on October 2013 to November 2014.The 43 lesions found in 30 patients were grouped into submucosal vascular lesions, mucosal thickening, and submucosal cysts based on the result of EBUS. Following white light bronchoscopy, signs such as respiratory mucosal protrusion location, shape, color and lustre, mucosal surface expansion and ultrasonic bronchoscopic image were recorded. We analyzed the results to explore the bronchoscopic signs and ultrasound features of different respiratory mucosal protrusions. Of the 43 respiratory mucosal protrusions by endobronchial ultrasound examination, 21 were submucosal vascular lesions, 19 showed mucosal thickening, and 3 were submucosal cysts. Morphologically, zoster protrusions, flat protrusions and semicircle protrusions were found in the submucosal vessel group, mucosal thickening group and cyst group. One nodular protrusion, 1 surface capillary expansion, and 2 mucosal surface pulsations were found in cases with submucosal vascular lesions. Submucosal vascular lesions were common causes of respiratory mucosal protrusions, for which biopsy should be cautious. White light bronchoscopy has limited value for diagnosing respiratory mucosal protrusions, while endobronchial ultrasound could be an important diagnostic tool for these lesions.

Convex probe EBUS for centrally located parenchymal lesions without a bronchus sign

BackgroundConvex probe endobronchial ultrasound (CP-EBUS) has proven safe and accurate for identifying malignancy and granulomatous disease affecting the mediastinum and hilum. For the diagnosis of parenchymal lung lesions, conventional techniques such as transbronchial biopsy, brush and lavage are useful, particularly when an airway leads directly to the lesion. For centrally located intraparenchymal lesions, CP-EBUS has been shown to be efficacious. ObjectiveTo expand on the existing literature in an effort to highlight the important diagnostic role of CP-EBUS in centrally located lesions, particularly those without a bronchus sign. MethodsIn our cohort of 430 patients undergoing CP-EBUS between 03/2009-03/2012, we retrospectively identified 32 who underwent transbronchial needle aspiration (TBNA) of a centrally located parenchymal lung lesion. All lesions were completely surrounded by lung parenchyma and not visualized during white light bronchoscopy. Diagnostic yield was determined and compared to conventional bronchoscopic biopsy techniques, when performed. ResultsThe mean lesion size was 25.6 mm and 24/32 (75%) lesions were located in the lower lobes. A definitive diagnosis was obtained in 27/32 (84.4%) of parenchymal lesions without a bronchus sign biopsied using CP-EBUS. CP-EBUS provided the exclusive method of diagnosis in 15/32 (46.9%) patients in this cohort. Most lesions (26/32) were diagnosed as non-small cell carcinoma. There were no procedural complications. ConclusionCP-EBUS is useful for diagnosing parenchymal lung abnormalities without a bronchus sign, extending its scope beyond mediastinal and hilar lymph nodes. It is imperative that physicians performing EBUS maintain this tool as a complement to conventional bronchoscopic techniques.

Real-time endoscopic Raman spectroscopy for in vivo early lung cancer detection.

Currently the most sensitive method for localizing lung cancers in central airways is autofluorescence bronchoscopy (AFB) in combination with white light bronchoscopy (WLB). The diagnostic accuracy of WLB+AFB for high grade dysplasia (HGD) and carcinoma in situ is variable depending on physician's experience. When WLB+AFB are operated at high diagnostic sensitivity, the associated diagnostic specificity is low. Raman spectroscopy probes molecular vibrations and gives highly specific, fingerprint-like spectral features and has high accuracy for tissue pathology classification. In this study we present the use of a real-time endoscopy Raman spectroscopy system to improve the specificity. A spectrum is acquired within 1 second and clinical data are obtained from 280 tissue sites (72 HGDs/malignant lesions, 208 benign lesions/normal sites) in 80 patients. Using multivariate analyses and waveband selection methods on the Raman spectra, we have demonstrated that HGD and malignant lung lesions can be detected with high sensitivity (90%) and good specificity (65%).

Clinical relevance of using autofluorescence bronchoscopy and white light bronchoscopy in different types of airway lesions

The aim of this study was to evaluate the sensitivity and specificity of autofluorescence bronchoscopy (AFB) according to the macroscopic appearance of airway lesions under white light bronchoscopy (WLB). The bronchoscopic findings of 708 patients, who were pathologically and clinically diagnosed with airway lesions and underwent both WLB and AFB, were analyzed. We recruited 708 patients for this study, of which 336 (47.5%) had benign lesions; 300 and 254 benign lesions were detected by AFB (specificity, 89.3%) and WLB (specificity, 75.6%), respectively. In 372 (52.5%) patients with bronchiogenic carcinoma, 356 and 235 lesions were identified by AFB (sensitivity, 95.7%) and WLB (sensitivity, 63.2%), respectively. The sensitivity and specificity of AFB for diagnosing lung cancer were higher than those of WLB (P < 0.05). Moreover, AFB showed high sensitivity for detecting lung cancer in cases in which WLB revealed hyperplasia, infiltration, and stenosis (P < 0.05). AFB combined with WLB could effectively improve the diagnosis of airway lesions.

430P Direct comparison of diagnostic accuracy between autofluorescence bronchoscopy (AFB) and AFB combined with white light bronchoscopy (AFB + WLB) for lung cancer and precancerous lesions: a systematic review and meta-analysis

430P Direct comparison of diagnostic accuracy between autofluorescence bronchoscopy (AFB) and AFB combined with white light bronchoscopy (AFB + WLB) for lung cancer and precancerous lesions: a systematic review and meta-analysis

Abstract A2-63: Airway gene-coexpression network rewiring in the presence of bronchial dysplasia and lung cancer

Abstract Lung cancer is a deadly disease, killing 160,000 a year in the US. The 5-year survival rate of lung cancer patients is invariably low, partially due to a lack of early diagnoses and limited access to CT screening programs during the early, most-curable stages of the disease. The urgent need for alternative early-stage diagnostics has been addressed in previous work, which focused on smoking- and lung cancer-specific gene expression alterations in cytologically normal airway epithelial cells. These lung cancer associated alterations have been shown to serve as a clinically relevant biomarker for the early detection of lung cancer. In this study, we have expanded upon this work by leveraging gene expression from airway epithelial cells collected in the presence of bronchial premalignant lesions. Specifically, we conducted network-based analyses to further explore alterations in bronchial gene coexpression (GCE) patterns in the uninvolved large airway of patients with tobacco-induced premalignancy and those with lung cancer. By studying airway GCE patterns present in patients with lung cancer and premalignancy, but absent in disease-free smokers, we hope to discover the earliest changes in process of lung carcinogenesis that may serve as novel targets for lung cancer treatment and prevention. Coexpression networks use expression-profile correlations to cluster genes to provide system-wide context for single genes implicated in a disease and elucidate the influence of interconnectedness of cellular components on phenotype. Here, we employed Weighted Gene Coexpression Network Analysis (WGCNA) to build GCE networks derived from cytologically normal airway epithelial cells obtained from current and former smokers with lung cancer (n=409), dysplastic airway lesions (n=121), and neither condition (n=412). Samples were collected from subjects undergoing white-light bronchoscopy as part of the AEGIS trial by Allegro Dx, or from subjects undergoing autofluorescence bronchoscopy in the British Columbia Lung Health Study. RNA was extracted from cells and profiled on microarrays or by mRNA-Seq. In order to detect and quantify reconfiguration of networks under different disease states, the Modular Differential Connectivity (MDC) measure was calculated to determine the degree of topological similarity between any pair of GCE modules. In addition, Fisher's Exact Test (FET) was used to calculate significance of gene-member overlap between pairs of GCE modules originating from disease networks to distinguish modules conserved in premalignancy and cancer. To identify modules conserved between disease states, but dissimilar from the healthy smoker modules, we focused on those with (a) significant overlap by FET, (b) non-differentiating premalignancy vs. cancer MDC and (c) differentiating normal vs. disease MDC. Hub genes within each network were identified based on intra-modular connectivity, a measure of module essentiality. We prioritized genes with increased connectivity upon entering the premalignant state that remained strong in the lung cancer network. We identified 16 module pairs conserved between disease states, i.e. cancer modules similarly connected (MDC FDR&amp;lt;0.05) and significantly overlapping (pFET&amp;lt;0.01) with premalignancy modules, one of which was weakly connected in the disease-free networks (MDC FDR&amp;lt;0.05). Functional annotation of these modules revealed associations with pathways and transcription factors implicated in carcinogenesis and cell proliferation. Furthermore, we identified two hub genes linked to pathways regulating cigarette smoke-induced signaling and inhibition of lung cancer cell growth. Integration of differential connectivity and GCE network analyses represents a novel approach to discovering pathways associated with early lung carcinogenesis. Our results suggest the occurrence of transcriptomic alterations that arise in patients with premalignancy and remain present in patients with lung cancer. Future work will include experimental validation of these findings. The computational approach outlined above may aid in the identification of candidate master regulators of early lung carcinogenesis that have potential utility both as indicators of increased lung cancer risk and as early-stage drug targets for chemoprevention or therapy. Citation Format: Anna Tassinari, Bin Zhang, Katrina Steiling, Duncan Whitney, Kate Porta, Stephen Lam, Marc Lenburg, Avrum Spira, Jennifer Beane. Airway gene-coexpression network rewiring in the presence of bronchial dysplasia and lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-63.

Abstract B1-17: Airway gene-coexpression network rewiring in the presence of bronchial dysplasia and lung cancer

Abstract Lung cancer is a deadly disease, killing 160,000 a year in the US. The 5-year survival rate of lung cancer patients is invariably low, partially due to a lack of early diagnoses and limited access to CT screening programs during the early, most-curable stages of the disease. The urgent need for alternative early-stage diagnostics has been addressed in previous work, which focused on smoking- and lung cancer-specific gene expression alterations in cytologically normal airway epithelial cells. These lung cancer associated alterations have been shown to serve as a clinically relevant biomarker for the early detection of lung cancer. In this study, we have expanded upon this work by leveraging gene expression from airway epithelial cells collected in the presence of bronchial premalignant lesions. Specifically, we conducted network-based analyses to further explore alterations in bronchial gene coexpression (GCE) patterns in the uninvolved large airway of patients with tobacco-induced premalignancy and those with lung cancer. By studying airway GCE patterns present in patients with lung cancer and premalignancy, but absent in disease-free smokers, we hope to discover the earliest changes in process of lung carcinogenesis that may serve as novel targets for lung cancer treatment and prevention. Coexpression networks use expression-profile correlations to cluster genes to provide system-wide context for single genes implicated in a disease and elucidate the influence of interconnectedness of cellular components on phenotype. Here, we employed Weighted Gene Coexpression Network Analysis (WGCNA) to build GCE networks derived from cytologically normal airway epithelial cells obtained from current and former smokers with lung cancer (n=409), dysplastic airway lesions (n=121), and neither condition (n=412). Samples were collected from subjects undergoing white-light bronchoscopy as part of the AEGIS trial by Allegro Dx, or from subjects undergoing autofluorescence bronchoscopy in the British Columbia Lung Health Study. RNA was extracted from cells and profiled on microarrays or by mRNA-Seq. In order to detect and quantify reconfiguration of networks under different disease states, the Modular Differential Connectivity (MDC) measure was calculated to determine the degree of topological similarity between pairs of GCE modules. In addition, Fisher's Exact Test (FET) was used to calculate significance of gene-member overlap between pairs of GCE modules originating from disease networks to distinguish modules conserved in premalignancy and cancer. To identify modules conserved between disease states, but dissimilar from the healthy smoker modules, we focused on those with (a) significant overlap by FET, (b) non-differentiating premalignancy vs. cancer MDC and (c) differentiating normal vs. disease MDC. Hub genes within each network were identified based on intra-modular connectivity, a measure of module essentiality. We prioritized genes with increased connectivity upon entering the premalignant state that remained strong in the lung cancer network. We identified 16 module pairs conserved between disease states, i.e. cancer modules similarly connected (MDC FDR&amp;lt;0.05) and significantly overlapping (pFET&amp;lt;0.01) with premalignancy modules, one of which was weakly connected in the disease-free networks (MDC FDR&amp;lt;0.05). Functional annotation of these modules revealed associations with pathways and transcription factors implicated in carcinogenesis and cell proliferation. Furthermore, we identified two hub genes linked to pathways regulating cigarette smoke-induced signaling and inhibition of lung cancer cell growth. Integration of differential connectivity and GCE network analyses represents a novel approach to discovering pathways associated with early lung carcinogenesis. Our results suggest the occurrence of transcriptomic alterations that arise in patients with premalignancy and remain present in patients with lung cancer. Future work will include experimental validation of these findings. The computational approach outlined above may aid in the identification of candidate master regulators of early lung carcinogenesis that have potential utility both as indicators of increased lung cancer risk and as early-stage drug targets for chemoprevention or therapy. Citation Format: Anna Tassinari, Bin Zhang, Katrina Steiling, Duncan Whitney, Kate Porta, Stephen Lam, Marc Lenburg, Avrum Spira, Jennifer Beane. Airway gene-coexpression network rewiring in the presence of bronchial dysplasia and lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-17.

Comparison of narrow band imaging to white light bronchoscopy for evaluation of histopathological biopsy

BackgroundIt is difficult to detect precancerous lesions such as dysplasia and carcinoma in situ (CIS) by conventional white light bronchoscopy (WLB). Narrow Band Imaging Bronchoscopy (NBI) has been reported to detect such lesions more readily. ObjectiveThe objective of the present study is to characterize the appearance of different airway mucosal lesions under NBI mode and to evaluate the role of NBI compared to WLB in diagnosis of premalignant and malignant lesions. Methods30 patients presented with radiological changes to chest department in Fayoum University Hospital. They were subjected to full airway examination by fiberoptic bronchoscopy first under WLB then under NBI. Biopsies were taken from susceptible lesions; pathological interpretation was performed. Results18 patients (60%) were proved by NBI to have invasive carcinoma compared to 11 patients (36.7%) by WLB. 3 patients (10%) were proved by NBI to have severe dysplasia/CIS compared to 6 patients (20%) by WLB. 3 patients (10%) were proved by NBI to have mild/moderate dysplasia compared to 4 patients (13.3%) by WLB (p value=0.03). The sensitivity of both WLB and NBI (76.9%) is better than WLB alone or NBI alone (9.1% and 57.1% respectively) in detecting premalignant lesions while the sensitivity of both WLB and NBI (52.6%) is less than WLB alone (55.6%) and better than NBI alone (26.7%) in detecting malignant lesions. ConclusionNBI can be used in combination with WLB to improve detection of premalignant lesions. It influences biopsy selection and therapeutic planning.

Abstract A55: Mapping the airways: The fate of bronchial epithelium in long term heavy smokers

Abstract Introduction: Although tumors of the bronchi account for a large percentage of the lung cancer burden, little is known about the status of the bronchial epithelium prior to transformation into invasive carcinoma. This report describes in situ cellular changes that occur in the central airways (bronchi and bronchioles) of long term heavy smokers screened by fluorescence bronchoscopy through the Colorado SPORE in Lung Cancer and includes results of recent intensive evaluation of selected sites of high grade lesions. Methods: Current and former tobacco smokers with a history of more than twenty pack years were asked to undergo fluorescence and white light bronchoscopy. Patients enrolled in clinical trials were offered follow-up bronchoscopy. Over 8900 bronchoscopic biopsies were obtained at abnormal or predetermined bronchial sites from 1373 subjects under IRB approved protocols between Jan-1993 and July-2014. Multiple same site biopsies were obtained from 290 individual. Biopsies from each site were serially sectioned, examined a multiple levels to identify abnormal epithelium throughout the biopsy tissue and graded for dysplasia on the 8 point scale of the WHO atlas, edition IV. Diagnostic H&amp;E images were archived in a digital repository that could be accessed through a digital tool, the Bronchial Map which allows for side by side comparison of digital images from different times and anatomical sites. Changes in histology score were quantified by subtracting later scores from earlier scores at same site. Clonality was assessed by TP53 sequencing in selected cases. Results: Squamous dysplasia of variable grade was found at 36% of sampled bronchial sites. In contrast to low grade lesions or normal epithelium, higher grade dysplasia often progressed or persisted. Persistent squamous dysplasia was associated with the development of squamous carcinoma (P&amp;lt;0.0001) but invasive carcinoma was rarely observed to develop at specific sites under observation. Four intensively followed cases illustrate the variable and unpredictable outcome of squamous dysplasia: Case 1. Fatal squamous carcinoma developed at a biopsy site that had exhibited grade 5 (moderate) dysplasia 14 years earlier. Case 2. Dysplasia grade improved following irradiation for an adjacent microinvasive squamous carcinoma. Case 3. High grade dysplasia (CIS) with a twice documented TP53 mutation was observed at the left upper lobe and was stable for several years under observation. An invasive squamous carcinoma with a different TP53 mutation subsequently developed on the right and proved fatal. Case 4. A high grade dysplastic lesion has intermittently persisted for several year without progressing to invasive carcinoma. Conclusions: 1. Squamous dysplasia is frequent and often persistent in the airways of heavy tobacco smokers 2. High grade dysplasia may persist for many years without progression to invasive carcinoma 3. Persistent dysplasia is associated with incident squamous carcinoma but the site of associated invasive tumor is frequently distant and unpredictable 4. Early intervention in progression of squamous lesions may require a combination of local and systemic treatment Supported by SPORE in Lung Cancer grant NCI CA580187 Citation Format: Wilbur A. Franklin, Daniel T. Merrick, Kathryn D. Matney, Robert Keith, Mormita Ghosh, Ichiro Nakachi, York E. Miller. Mapping the airways: The fate of bronchial epithelium in long term heavy smokers. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A55.

Abstract LB-092: Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator

Abstract Compared to the vigorous development of targeted drugs and some of them are already become one of the best treatment of choices in lung adenocarcinoma, squamous lung carcinoma has no definite targets and treatment outcome is not yet superior to lung adenocarcinoma. Demonstration of initial carcinogenesis is benefitial in two aspects: cancer prevention and development of its targets. Studying preneoplastic lesions of bronchus can answer those questions. Preneoplastic lesion, which is considered to have malignant potential, may develop into invasive cancer by escaping from host immune response. CD274 (programmed death-ligand 1, PD-L1) interacts with PD-1, is known to inhibit CD8+ cytotoxic T lymphocyte and induce apoptosis and, also to promote the differentiation of CD4+ T cells into regulatory T cells, so finally evade immune surveillance. We hypothesized that PD-L1 may work as an immune evader in preneoplastic lesion during its carcinogenesis. We performed white light and/or autofluorescence bronchoscopy in patients who have risk factor(s) of lung cancer or are suspected to have a lung cancer. Interestingly, PD-L1 was also overexpressed in preneoplastic lesions especially in severe dysplasia of the bronchus. This finding implies overexpression of PD-L1 can involve at early step of carcinogenesis. Further studies are needed to demonstrate the role of PD-L1 in preneoplastic bronchial lesion potential to develop invasive cancer. Citation Format: Hee Sun Park, Bo Mi Park, Dong Il Park, Chung Jae Uk, Jae Young Moon, Jung Sung Soo, Choong Sik Lee, Ju Ock Kim, Sun Young Kim, Jaseok Peter Koo. Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2015-LB-092

Early detection of central lung cancer: are we there yet?

Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and X-rays have been very disappointing in the detection and diagnosis of central (airways/endobronchial) lesions. Bronchoscopy with direct visualization and other supportive technologies has been the primary tool for the detection and surveillance of endobronchial precancerous and cancerous lesions. Early detection of lung cancer allows early interventions which has a survival benefit as shown by a 20% relative decrease in lung cancer specific mortality with low-dose computed tomography screening and high-risk groups [1]. CT screening of the thorax is able to detect lesions that are peripheral, central, and sub centimeter, however it is insensitive for detection of precancerous and early small cancerous lesions arising from the airways. The pathological progression from normal bronchogenic epithelium to squamous metaplasia followed by dysplasia and finally carcinoma in situ(CIS) is supported by sputum cytology studies as well as animal data [2,3], however other models such as multiple foci of precursor lesions that are produced throughout the respiratory epithelium may develop into carcinoma in situ as opposed to a stepwise progression of a single area [4]. Regardless, prompt detection of high-risk patients that offers early diagnosis of preinvasive lesions could allow for early intervention and improved survival. The use of white light bronchoscopy is the standard imaging tool for the diagnosis of central airway tumors. However, in the detection of precancerous lesions WLB has a low sensitivity and specificity [5,6]. Recent advances have allowed bronchoscopists to evaluate the airway with advanced high-resolution imaging modalities. The development of the ideal bronchoscopic imaging technique capable of detecting preinvasive lesions is ongoing. Currently autofluorescence bronchoscopy (AFB), narrow-band imaging(NBI), high magnification bronchovideoscopy (HMB), probe based confocal endomicroscopy (pCLE), optical coherence tomography (OCT), radial probe endobronchial ultrasonography (R-EBUS) and now high definition bronchoscopy (HD) with surface enhancement (i-scan) are all being studied or used in clinical practice to evaluate the airway. The ideal system would be able to detect and define preinvasive lesions so that not only are we able to preemptively treat these lesions but determine effectiveness of treatment with noninvasive or minimally invasive techniques. In this issue of Respiratory Research, van der Heijden and colleagues report a randomized blinded prospective study, which examined the use of 5 videobronchoscopy techniques in 29 patients in which the authors explore whether different modalities might lead to improved detection of suspicious vascular changes or suspected preinvasive lesions. In the previous literature, WLB combined with AFB increased the diagnostic accuracy for squamous dysplasia, CIS, and early lung cancer with a high sensitivity but resulted in a large number of false positives and unneeded biopsies [7,8]. Heijden and colleagues did show that HD bronchoscopy with i-scan improve detection of vascular changes over WLB and AFB however AFB did detect more preinvasive lesions over WLB and HD modes. Histological confirmation was not obtained in this study so it is difficult to discern whether there would be improved accuracy of HD modes over AFB. That said we agree that it is likely that improved images and image enhancement which are able to better identify vascular abnormalities could improve overall diagnostic yield. Further studies in which a potential combination of methods, which improve efficiency of the airway evaluation while also improving accuracy of diagnosis are needed to fully determine the clinical implications of these modalities. Finally, the bigger question remains, would early detection and treatment of precancerous lesions in the airway as a primary or a recurrent lesion changes the ultimate outcomes in patients.

Observation of the clinical application of auto-fluorescence bronchoscopy

Objective To investigate and analyze the clinical application of auto-fluorescence bronchoscopy (AFB). Methods 224 patients(M/F= 190/34)performed bronchoscopy were selected and randomly divided into the control group(n= 112,M/F= 96/16)and observation group(n= 112,M/F= 94/18).Patients of control group were performed white light bronchoscopy(WLB).Patients of observation group were performed WLB combined AFB.The primary endpoint was masculine rate of pathology biopsy and bleeding after biopsy.The retrospective analysis was performed. Results The masculine rate of carcinoma in situ of the observation group was 3.1%,which of the control group was 1.0%,the difference was statistically significant(χ2= 19.761,P 0.05). Conclusion AFB can improve site-specific accuracy of doubtful focus,improve masculine rate of pathology biopsy,and lessen bleeding after biopsy. Key words: Bronchoscopy/methods; Fluorescence; Biopsy; Diagnosis

Narrow-band imaging bronchoscopy improves assessment of tumor extent and affects therapeutic strategy for central lung cancer

To determine the sensitivity of narrow-band imaging bronchoscopy (NBI) in the assessment of tumor extent and therapeutic strategy. A total of 196 patients with imaging abnormalities for malignancy were examined with both white light bronchoscopy (WLB) and NBI (Olympus, EVIS LUCERA). Record the tumor infiltration, image and pathological results. There were 152 male and 44 female with a mean age of 58 years. In 22 patients (13.1%), NBI revealed greater tumor extent than WLB alone. And tumor margins were >1 cm wider on NBI examination than on WLB. In 19 patients (11.3%), that finding influenced further therapeutic course, leading to greater resection level (n = 14) or avoidance of surgery (n = 5). According to univariate analysis, tumor size > 30 mm and pathological type of squamous cell carcinoma were independent predictive factors (OR 3.13, 95% CI: 1.06-9.21, P = 0.038; OR 4.68, 95% CI: 1.02-21.58, P = 0.048). The diagnostic sensitivity of NBI group was 88.2%, specificity 83.3%, positive predictive value 98.1% and false predictive value 41.7%. And the diagnostic sensitivity of WLB group was 80.3%, specificity 55.6%, positive predictive value 94.7% and false predictive value 22.2%. The combined use of NBI bronchoscopy and conventional white-light examination has greater sensitivity and specificity for assessing tumor margins. And this technique also significantly improves the assessment of central lung cancer infiltration and influences the therapeutic strategy.

Quantization Methodology of Autofluorescence Bronchoscopy Image in the YUV System

背景与目的通过对不同病理类型的自荧光气管镜（autofluorescence bronchoscope, AFB）图像目标区域的YUV定量分析，确定区分不同疾病类型的最佳判别指标，探讨AFB在中央型支气管肺癌诊断中的价值。方法对研究对象进行白光气管镜+AFB检查，二者在镜下存在异常者行活检。并对荧光图像显示病变部位通过MATLAB图像测量软件进行YUV定量分析。根据正常支气管粘膜、炎症、低级别上皮样瘤变、高级别上皮样瘤变、浸润性癌的病理结果分组。研究各组与YUV值间的关系，所得数据采用SPSS 11.5软件进行统计学处理。结果Y值在浸润性癌和LGD组间存在统计学差异（P=0.040），在浸润性癌和炎症组也存在明显统计学差异（P < 0.001）。其他的各组间无统计学差异。U值在浸润性癌和HGD、LGD、炎症、正常支气管粘膜组之间存在统计学差异（P < 0.050），能较好鉴别正常粘膜及恶性病变。V值在浸润性癌和LGD组（P=0.003）、炎症组（P < 0.001）、正常支气管粘膜组（P < 0.001）存在统计学差异，能有效鉴别浸润性癌及良性疾病。V值在正常支气管粘膜组与HGD组（P=0.001）、炎症组（P=0.004）间比较也具有统计学差异。结论利用YUV色彩空间系统针对支气管和肺良恶性疾病鉴别有一定临床应用价值，为临床气管镜诊断肺癌及癌前病变提供有效科学依据。

Combination of narrow band imaging (NBI) and autofluorescence bronchoscopy (AFB) in the assessment of central lung cancer

To assess the diagnostic value of narrow-band imaging(NBI) in the diagnosis of central lung cancer. Patients (n = 153) suspected of having lung cancer underwent white light bronchoscopy(WLB), NBI and autofluorescence bronchoscopy(AFB) in turn. At least 3 biopsies in each case were taken from sites visualized as lesions. The sensitivity and specificity of NBI, AFB and combination of NBI and AFB were compared. There were 106 male (69.3%) and 47 female patients (30.7%). By NBI, 91 and 62 cases were positive and negative respectively. The sensitivity and specificity of NBI were 63.5% (87/137) and 75.0% (12/16) respectively. By AFB, 140 and 13 cases were positive and negative respectively. The sensitivity and specificity of AFB were 94.2% (129/137) and 87.5% (5/16) respectively. By NBI combined with AFB, 133 and 20 cases were positive and negative respectively, the sensitivity and specificity being 95.6% (131/137) and 87.5% (14/16) respectively. The difference of specificity between NBI plus AFB and AFB alone was significant (P < 0.01), but the difference of sensitivity between NBI plus AFB and AFB alone(P > 0.05) was not. The difference of specificity between NBI plus AFB and NBI alone was significant (P < 0.01), but the P value of specificity between NBI plus AFB and NBI was 0.03. Combination of NBI and AFB could increase the specificity of lung cancer diagnosis compared to AFB alone.

The clinical value of autofluorescence bronchoscopy for precancerous lesions in operable primary lung cancer patients

The aim of the present study is to show the role of autofluorescence bronchoscopy (AFB) compare with white light bronchoscopy (WLB) in detecting synchronous cancer and precancerous lesions in cases with operable primary lung cancer. Fourty-nine patients were included in the study. WLB findings were grouped as group 1 normal, group 2 erithema or edema, group 3 nodular lesions or mucosal abnormality. AFB findings were grouped as group 1 normal, group 2 light brownish abnormal areas, group 3 brownish abnormal areas. Biopsies were obtained from group 2 and 3 patients. In 12 (24.5%) of the patients no areas were suspected and no biopsies were taken. Twenty-six (53%) of 49 patients did not show abnormal biopsy results in any of the specimens. One (2%) patient had metaplasia, 1 (2%) patient had dysplasia, 1 (2%) patient had in situ carcinoma. The diagnostic accuracy rates for the detection of synchronous cancer and precancerous lesions using WLB and AFB were as follows respectively: sensitivity 77.8% vs. 100%; specificity 37.5% vs. 3%; positive predictive value 21.9% vs. 24.3%; negative predictive value 88.2% vs. 100%. The relative sensitivity of AFB to WLB is 1.28. This study demonstrated that, AFB is an effective method in detecting synchronous cancer and precancerous lesions because of its low specificity it is more likely to be complementary to WLB.

Comparison of autofluorescence imaging bronchoscopy and white light bronchoscopy for detection of lung cancers and precancerous lesions

BackgroundThe purpose of this paper was to compare the sensitivity, specificity, and overall diagnostic performance of autofluorescence imaging bronchoscopy (AFI) versus white light bronchoscopy (WLB) in the detection of lung cancers and precancerous lesions by meta-analysis.MethodsWe performed a literature search using the PubMed and EMBASE databases to identify studies published between March 1991 and March 2012. Article selection, quality assessment, and data extraction were then performed. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve of the summary receiver operating characteristic for AFI versus WLB were calculated using Stata version 12.0 software.ResultsSix studies were included in the meta-analysis. The pooled sensitivity of AFI and WLB was 0.89 (95% confidence interval [CI] 0.81–0.94) and 0.67 (95% CI 0.46–0.83) and the pooled specificity of AFI and WLB was 0.64 (95% CI 0.37–0.84) and 0.84 (95% CI 0.74–0.91), respectively. The diagnostic odds ratio for AFI and WLB was 14.5 (95% CI 3.76–55.63) and 10.9 (95% CI 3.12–38.21), and the area under the curve for AFI and WLB was 0.89 (95% CI 0.86–0.92) and 0.85 (95% CI 0.81–0.88), respectively. The pooled positive and negative likelihood ratios were 2.5 (95% CI 1.21–4.97) and 0.17 (95% CI 0.08–0.36) for AFI, and the corresponding values for WLB were 4.3 (95% CI 2.13–8.52) and 0.39 (95% CI 0.21–0.73). The pooled positive likelihood ratio for AFI and WLB was not higher than 10, and the pooled negative likelihood ratio for AFI and WLB was not lower than 0.1.ConclusionThe sensitivity of AFI is higher than that of WLB, while the specificity of AFI is lower than that of WLB. The overall diagnostic performance of AFI is slightly better than that of WLB in detecting lung cancers and precancerous lesions. AFI should find its place in routine bronchoscopic examination and may improve the diagnostic outcome on endoscopy.

Combination of narrow-band imaging and autofluorescence imaging videobronchoscopy in the assessment of lung cancer

背景与目的窄带成像（narrow-band imaging, NBI）与自荧光成像（autofluorescence imaging, AFI）是近几年临床诊断肺癌的支气管镜新技术。本研究旨在研究这两种技术的结合是否能提高肺癌诊断的敏感性和特异性。方法该项目共纳入137例疑似肺癌患者，所有患者的检查均基于Olympus Evis Lucera电子支气管镜系统，依次进行白光支气管镜（white light bronchoscopy, WLB）、窄带成像、自荧光成像检查，在每位患者镜下异常部位至少取3块组织送检。结果WLB的敏感性、特异性分别为56.6%和62.5%；NBI成像的敏感性、特异性分别为71.3%和75.0%；AFI敏感性、特异性分别为82.2%和25.0%；NBI联合AFI的敏感性、特异性分别为94.6%和87.5%。NBI+AFI与AFI相比，两者敏感性及特异性均有统计学差异（P < 0.01），与单用NBI相比，两者敏感性及特异性亦有统计学差异（P < 0.05）。结论NBI或AFI比WLB在肺癌诊断方面具有更好的敏感性，且联合使用NBI+AFI比其它任何一种单用技术具有更高的敏感性和特异性优势。

Value of Autofluorescence Imaging Videobronchoscopy in Detecting Lung Cancers and Precancerous Lesions: A Review

Bronchoscopy technology is a desirable method for detecting lung cancers arising in the central airways. Most early cancers and precancerous lesions are not visible on conventional white-light bronchoscopy (WLB). Autofluorescence bronchoscopy (AFB) is a newly developed technology that exploits the difference in autofluorescence intensity between normal and tumorous tissues to detect bronchial cancers and precancerous lesions. Several types of AFB systems have been used in clinical practice, and autofluorescence imaging videobronchoscopy (AFI) is one of these AFBs. In most of the studies on AFB other than AFI, AFB has provided a much higher sensitivity but a lower specificity than WLB. Regarding AFI, recent studies have reported controversial results on the sensitivity and specificity for detecting cancers and precancerous lesions, compared with WLB. In this paper we describe the working mechanisms and characteristics of AFBs, mainly AFI, and the diagnostic performance of AFI, compared with WLB, other AFBs, and narrow-band imaging, for detecting lung cancers and precancerous lesions.