Utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions

Utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions Gaozhe Wang, Yan Jin, Kunlong Xiong, Xiaoyan Jin, Linfeng Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3038489/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: Bronchoscopy is currently the most commontechnique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. Methods: We conducted a retrospective studyin a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions. Results: A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3% (95% confidence interval [CI]: 53.1%-67.1%), which was higher than that of patients with WLB alone (45.2%, 95% CI: 38.2-52.4%) ( P = 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100%, 95% CI: 95.5-100% versus 69.6%, 95% CI: 59.6-78.1%), positive predictive value (100%, 95% CI: 96.1-100% versus 74.3%, 95% CI: 65.5-81.7%) and negative predictive value (56.3%, 95% CI: 48.8-63.6% versus 39.4%, 95% CI: 32.3-47.0%). Conclusion: Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions. AFB Mucous Early diagnosis Lung cancer Figures Figure 1 Introduction Lung cancer is a substantial challenge; it has high incidence and mortality rates, and it accounted for 12 to 13% of new cancer cases and approximately 22% of cancer-related deaths in the United States in 2021 [1] . Methods for diagnosing lung cancer have progressed due to medical research [2-10] . However, patients with lung cancer are often diagnosed at advanced stages, of which 30% are at stage III and 40% are at stage IV, thus emphasizing the need fir earlier diagnosis and more efficacious therapy [4-5] . Routine imaging examinations, such as chest X-ray (CXR) and chest tomography (CT), are useful for lung cancer diagnosis, as they can nip malignancy in the bud by prompting a timely surgical procedure [6-7] . However, radiologic examinations such as CXR or CT cannot solve all the problems, especially in the early stage of lung cancer without obvious space occupation. Therefore, these approaches need to be combined with other auxiliary examination methods to enhance diagnosis. Among them, the advent of bronchoscopy, including white light bronchoscopy (WLB) and autofluorescence bronchoscopy (AFB), has been beneficial for the diagnosis of lung cancer [8-10] . Since most lung cancers originate from the bronchial mucosa epithelium or bronchial mucous glands, bronchoscopy has become increasingly essential for early lung cancer diagnosis through direct observation and tissue biopsies [11-12] . Chest CXR and CT have restricted application due to their limited capability to identify preinvasive bronchial lesions (PBLs), such as dysplastic bronchial epithelium and carcinoma in situ (CIS), in lung cancer diagnosis [13] . Conventional bronchoscopy can perform biopsy, lavage and brush inspection under the operating mode of WLB [14] . The identification of these PBLs was difficult to achieve through conventional bronchoscopy on direct bronchoscopic inspection and sampling. AFB is a new type of bronchoscope designed for careful examination of bronchial mucosa and is now widely used in combination with WLB examinations [9] . It is a safe technique with fluorescent emission signals at green (520 nm) and red (>630 nm). Normal mucosal tissue in bronchi reflects these signals and appears green in color, while PBL or invasive cancer tissue absorbs the green fluorescence and turns the reflected light magenta [15] . Thus, AFB can be used to screen central intraepithelial risks for lung cancer, such as moderate or severe dysplasia, CIS, and microinvasive carcinoma. AFB can not only be utilized for the definite diagnosis of tumors but also help to determine the surgical scope or other therapeutic schedules and contribute to the treatment and monitoring of lung cancer patients with recurrence after surgery, radiotherapy and chemotherapy [16-17] . Wang et al . [18] found that WLB combined with AFB could further improve the positive rate of lung cancer diagnosis for patients with lung nodules or lung masses, and the overall positive rate increased from 60.5% to 86.8%. It should be noted that most studies concerning the usefulness of AFB in patients with bronchial visible lesions. However, few studies have been conducted to study the utility of AFB in those with bronchial mucosal lesions. Therefore, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. Methods Study Design and Subjects This is a retrospective cohort study conducted in Ningbo First Hospital. The protocol of our study was approved by the Ningbo First Hospital’s Ethics Committee. All participants included in this study provided informed consent. We screened the subjects who had underwent WLB- and AFB-guided biopsies from 2018 to 2021, and all participants had histologically confirmed cases. To explore the role of AFB in early mucosal lesions of the bronchi, only patients with early mucosal lesions were enrolled, and those with obvious space-occupying lesions in the bronchi were excluded. In the present study, abnormalities under WLB microscopy were defined as mucosal hyperemia, edema, thickening with a rough or heave surface, color change, and vascular aggregation or distortion, while abnormalities under AFB microscopy were defined as lesions appearing magenta in color under fluorescent light. The clinical information of the patients, such as age, sex, smoking history, bronchoscopic findings and pathological examination results, was collected from the hospital electronic medical record system. Bronchoscopy The equipment systems used in this study are WLB (BF-240; Olympus, Tokyo, Japan) and VIS LUCERA (CV-260SL) Self-fluorescence Imaging System (Olympus, Tokyo, Japan). The tracheoscopy procedures involved in this study were performed by qualified and skilled physicians. Each patient was informed about the procedure in detail before tracheoscopy. Under local anesthesia, we performed WLB according to the patients’ chest CT images and recorded the macroscopic findings during WLB. Next, we repeated the examination after changing the WLB mode to AFB mode with the bronchoscope still in the trachea and captured the suspicious tissue. After the suspicious lesions were captured, the biopsy was conducted immediately. Biopsy tissues were sent for pathological examination. In addition, during the tracheoscopy, the physician also determined whether to perform local lavage and brush examination or further operations, such as transbronchial lung biopsy (TBLB) or transbronchial needle aspiration (TBNA), according to the condition of each patient. Statistical Analysis For statistical description, categorical variables are presented as n (%), and continuous variables are expressed as the means ± standard deviations or medians with interquartile ranges determined by data distribution. Comparisons between the AFB-guided biopsy group and the WLB group were made by the chi-square (X 2 ) test. A P value < 0.05 was considered statistically significant. Data analyses were performed by SPSS software 20.0 (SPSS Inc., Chicago, IL, USA). Results A total of 301 patients who received WLB and AFB-guided biopsies were included in the present study. The characteristics of the enrolled participants are shown in Table 1. Of the 301 patients, 213 were males and 88 were females, with a mean age of 64 years (25-83 years). A total of 171 patients (56.8%) were current or former smokers with a pack-years of 25 (Table 1). Through the biopsy specimens, whose histopathological diagnosis was confirmed by two specialists in pathology, 199 patients were confirmed as atypical hyperplasia or cancerous mucosa, including 12 cases of atypical hyperplasia, 58 cases of squamous cell carcinoma, 81 cases of adenocarcinoma, 27 cases of small cell carcinoma, 15 cases of carcinosarcoma, and 6 cases of cancer cells that could not be histologically classified. Other benign pathological diagnoses included pulmonary nodules (1 case), chronic mucosal inflammation (91 cases), granuloma (8 cases) and fungal infection (2 cases) (Table 1). The benign lesions are only represented in mucosal hyperemia, edema, thickening with rough or heave surface, color change, and vascular aggregation or distortion under WLB, while the malignant lesions can be represented in mucosal color changes under AFB. The fluorescent magenta changes in the mucosa under AFB had a good indication of early mucosal lesions, as shown in Figure 1. Under WLB, there was no obvious difference between benign lesions (Figure 1A) and malignant lesions (Figure 1C), which are easily misdiagnosed. Under AFB, malignant lesions (Figure 1D) showed magenta changes, while benign lesions (Figure 1B) only showed slight magenta changes in part. The sensitivity of AFB-guided biopsy for premalignant and malignant lesion detection (60.3%, 95% CI: 53.1-67.1%) was significantly higher than that of WLB (45.2%, 95% CI: 38.2-52.4%) ( P = 0.0026) (Table 2). In addition, compared with the WLB group, the AFB-guided biopsy group was found to have a significantly higher specificity (100%, 95% CI: 95.5-100% versus 69.6%, 95% CI: 59.6-78.1%; P = 0), positive predictive value (100%, 95% CI: 96.1-100% versus 74.3%, 95% CI: 65.5-81.7%; P = 0) and negative predictive value (56.3%, 95% CI: 48.8-63.6% versus 39.4%, 95% CI: 32.3-47.0%; P = 0.0013). The negative likelihood ratio value was 0.40 (95% CI: 0.33-0.47) in the AFB-guided biopsy group and 0.78 (95% CI: 0.68-0.90) in the WLB group (Table 2). These findings strongly suggest that AFB-guided biopsy can improve the detection rate of premalignant bronchial lesions in high-risk individuals. Discussion The prognosis of lung cancer is closely associated with its stage, and detecting cancers at the early stage together with subsequent radical surgery aimed at complete resection is the only curative treatment option for the majority of patients with lung cancer. Due to the application of new bronchoscopic technologies, the updating of equipment and the publication of molecular studies, the rate of detection and surgical treatment for early lung cancer is increasing, and the survival rate of lung cancer is continuously rising [19-20] . However, only approximately 20% of patients with newly diagnosed lung cancer will receive potentially curative treatment in clinical practice [21] . Despite great progress in treating lung cancer, the overall survival rate for lung cancer and the 5-year survival rate of patients with advanced lung cancer remain only 20% and 10-15%, respectively [22-24] . One promising approach is the identification of lung cancer at an early stage. Bronchoscopy is extremely important for the diagnosis of pulmonary diseases, especially bronchial lesions [25] . Since the advent of the first generation of AFB in the early 20th century, the value of AFB in the diagnosis of malignant lung lesions has been constantly evaluated in clinical research [26-29] . Until now, most clinical trials have concentrated on the diagnostic value of AFB in lungs with highly suspicious lesions, such as pulmonary nodules or masses. It should be noted particularly that our study focused on the utility of fluorescence-guided biopsy among patients without bronchial visible lesions and bronchial mucosal lesions. The results from our study showed that the sensitivity of AFB-guided biopsy (60.3%, 95% CI 53.1-67.1%) for premalignant and malignant lesion detection was significantly higher than that of WLB alone (45.2%, 95% CI 38.2-52.4%), with a good specificity (100%, 95% CI: 95.5-100% versus 69.6%, 95% CI: 59.6-78.1%), positive predictive value (100%, 95% CI: 96.1-100% versus 74.3%, 95% CI: 65.5-81.7%) and negative predictive value (56.3%, 95% CI: 48.8-63.6% versus 39.4%, 95% CI: 32.3-47.0%). These results suggested that AFB-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions. The differential diagnosis of lung cancer may not be difficult in patients with obvious bronchial space-occupying lesions. The most novel aim of this study was to investigate AFB-guided biopsy among patients with bronchial mucosal lesions. WLB relies only on the appearance of differences in tissue thickness, mucosal swelling, mucosal roughness, bleeding, and subsequent biopsy and brush examination to distinguish cancerous tissue from normal tissue. However, these tissue and mucosal changes can occur in both benign bronchial lesions and malignant bronchial lesions under WLB examination, making it difficult for WLB to yield a definitive clinical diagnosis. Thus, the ability of WLB to diagnose early mucous and submucous carcinomas is very limited, and mucosal inflammation, congestion and other factors may interfere with the final diagnosis [30] . It has been reported that detecting preinvasive lesions using WLB is particularly difficult even for an experienced bronchoscopist, and only 29% of patients with bronchial CIS lesions were visible using WLB [31] . As a method that makes use of the inherent properties of fluorescent emission signals to evaluate mucosal tissues, AFB was developed for the detection of bronchial dysplastic lesions and early lung cancers. AFB has an advantage over WLB and should be more sensitive in theory, as previously reported [32-35] . The American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (2nd edition) have shown that the pooled sensitivity of WLB and AFB combined with WLB for intraepithelial neoplasia detection on a per-lesion basis was 40% and 80%, respectively [36] . ACCP recommended AFB use in situations such as normal chest radiographs with carcinoma on sputum cytology, CIS, or severe dysplasia. However, AFB has a lower specificity in lung cancer detection than WLB. Sun et al . [27] showed that the specificity of AFB combined with WLB was 35% lower than that of WLB alone. The reason for this low specificity may be attributed to the difficulty of AFB in distinguishing preinvasive bronchial lesions from some other bronchial mucosal changes, such as bronchitis [37] . Fluorescence-guided biopsy can compensate for the low specificity of AFB, and our study showed that the specificity of AFB-guided biopsy (100%, 95% CI: 95.5-100%) was significantly higher than that of WLB alone (69.6%, 95% CI: 59.6-78.1%) in the detection of lung cancer without obvious space occupation. Therefore, through the recognition of color differences under fluorescence, the properties of mucosa can be preliminarily determined, and the sensitivity of biopsy can be consequently improved. In summary, the findings from our study demonstrated that fluorescence-guided biopsy had a higher sensitivity and specificity than WLB alone in patients with bronchial mucosal lesions. Therefore, fluorescence-guided biopsy is a novel modality serving as a useful adjunct to WLB for the early detection of bronchial carcinogenesis. Declarations Ethics approval and informed consent Our research followed ethical principles from the Declaration of Helsinki and the Good Clinical Practice guidelines from the International Conference on Harmonization. Participants or their representatives gave informed consent, fully understanding the research's purpose, potential risks and benefits, and their right to withdraw without consequences. Ethical approvals for this study were obtained from the ethics committee of The First Affiliated Hospital of Ningbo University (2020-R229). Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests All authors declare no competing interests. Funding This work was supported by the program for the science and technology 2025 major project of Ningbo (2019B10037). Authors' contributions WG, JY, and XK collected the epidemiological and clinical data. WG, JY and XK processed statistical data. WG, JY, XK, JX, LC and WL summarized all data. WG, LC and WL drafted the manuscript, LC and WL reviewed the final manuscript. Acknowledgements We would like to acknowledge the science and technology 2025 major project of Ningbo for their funding and support. We are grateful for their guidance and resources throughout the project. References 1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin 2021, 71(1) : 7-33. 2. Blumenthal GM, Karuri SW, Zhang H, et al. Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. 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Clinical characteristics and final diagnosis of included patients Characteristic Enrolled patients (n= 301) Age (mean± SDs) 64 （ 64.3± 10.85 ） Sex Male (n, %) 213 （ 70.8% ） Female (n, %) 88 （ 29.2% ） Smoking condition (n, %) Smoker 171 （ 56.8% ） Pack-years (mean± SDs) 25 (25.28± 31.33) Nonsmoker 130 （ 43.2% ） Malignancy 199 （ 66.1% ） Atypical hyperplasia 12 Squamous cell carcinomas 58 Adenocarcinoma 81 Small cell carcinoma Carcinosarcoma 27 15 Histological classification failed 6 Benign lung disease 100 （ 33.2% ） Pulmonary nodules 1 Granulomatous 8 Chronic mucosal inflammation 91 Infectious disease 2 （ 0.7% ） Fungal infection 2 Table 2. Comparison of the diagnostic rate between the WLB group and AFB guide for cancerous and precancerous lesions Statistics WLB Fluorescence-guided biopsy P value True positive (n) 90 120 - False positive (n) 31 0 - False negative (n) 109 79 - True negative (n) 71 102 - Sensitivity (95% CI) 45.2% (38.2-52.4%) 60.3% (53.1-67.1%) 0.0026* Specificity (95% CI) 69.6% (59.6-78.1%) 100% (95.5-100%) 0* Positive likelihood ratio 1.48(1.06-2.07) Infinity - Negative likelihood ratio 0.78 (0.68-0.90) 0.40 (0.33-0.47) - Positive predictive value 74.3% (65.5-81.7%) 100% (96.1-100%) 0* Negative predictive value 39.4% (32.3-47.0%) 56.3% (48.8-63.6%) 0.0013* CI, confidence interval; * P < 0.05; likelihood ratios were calculated by the conventional estimation method. Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3038489","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":213398343,"identity":"21f29603-80e5-4de7-8a5f-04276077a3b4","order_by":0,"name":"Gaozhe Wang","email":"","orcid":"","institution":"Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Gaozhe","middleName":"","lastName":"Wang","suffix":""},{"id":213398344,"identity":"5b5f98f7-f0cf-4aa9-8b67-f03f1718cc30","order_by":1,"name":"Yan Jin","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Jin","suffix":""},{"id":213398345,"identity":"a8f3b833-a358-44a1-8df4-b042140d805e","order_by":2,"name":"Kunlong Xiong","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Kunlong","middleName":"","lastName":"Xiong","suffix":""},{"id":213398346,"identity":"abf67849-d28a-4593-8134-9d43d6c92c28","order_by":3,"name":"Xiaoyan Jin","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Jin","suffix":""},{"id":213398347,"identity":"82704de1-50bf-4261-b559-cadf5c7ae9da","order_by":4,"name":"Linfeng Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYDACdsaHDxIq2OTY2NsPEKmFmdnY4MMZPmM+njMJRGsxk5zZJpc4T8LBgDgdBoeZGaR52MzS2yQYEhh+VGwjTosxD09abpt04wHGnjO3CWsxO8x/IJlH4lhum8yBBGbGNqK0MDMc5jH4n84mkWBAtBbGxhkJbAnEa7E/zMzM8OEAm2EbMJAPEuUXyfZm9h+J/9jk5dvbDz74UUGEFhRwgET1o2AUjIJRMApwAQARRDgZ0s1cRAAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":true,"prefix":"","firstName":"Linfeng","middleName":"","lastName":"Wang","suffix":""},{"id":265123062,"identity":"a0cdc774-df34-418f-96f2-8fffb8ab0166","order_by":5,"name":"Chenwei Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApklEQVRIiWNgGAWjYBACg/s9jJ95KiTk+InWYnHjDLM0zxkLY8kGYrXY3Mhh4+Ztq0jcQIKWM2zMvPMkGDcwMD98dIMYLWb3e9iYc7dJMJszsBkb5xClBWQLUAubZQMPmzRRWoyBfmHOnSPBY3CAWC2GIO//bZCQIEULMJDnHJMwkGwm1i8G9/sffuapqavvZ29++JgoLQjATJryUTAKRsEoGAX4AACNDTAK0jTZrAAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":true,"prefix":"","firstName":"Chenwei","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2023-06-08 10:44:29","currentVersionCode":2,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3038489/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-3038489/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49191879,"identity":"fffd5961-65b7-4dfe-9d5b-f5da6e0a8bda","added_by":"auto","created_at":"2024-01-04 20:34:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1276845,"visible":true,"origin":"","legend":"\u003cp\u003eThe representative appearance of benign lesions (A and B) and malignant lesions (C and D) under white light bronchoscopy examination (A and C) and autofluorescence bronchoscopy examination (B and D).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3038489/v2/ffe138a2c6a46ea810e917c1.jpg"},{"id":49192083,"identity":"4bb1b295-baf1-427c-b54e-809a2715178e","added_by":"auto","created_at":"2024-01-04 20:42:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":433585,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3038489/v2/36b5f66f-a0a7-41fe-ab1e-b5bee11fd45e.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eUtility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLung cancer is a substantial challenge; it has\u0026nbsp;high incidence and mortality\u0026nbsp;rates, and it accounted for 12 to 13% of new cancer cases and\u0026nbsp;approximately\u0026nbsp;22% of cancer-related\u0026nbsp;deaths\u0026nbsp;in the United States\u0026nbsp;in\u0026nbsp;2021\u003csup\u003e[1]\u003c/sup\u003e. Methods for diagnosing lung cancer have progressed due to medical research\u003csup\u003e[2-10]\u003c/sup\u003e. However, patients with lung cancer\u0026nbsp;are\u0026nbsp;often diagnosed at advanced stages, of which 30%\u0026nbsp;are\u0026nbsp;at stage III and 40%\u0026nbsp;are\u0026nbsp;at stage IV, thus emphasizing the need fir earlier diagnosis and more efficacious therapy\u003csup\u003e[4-5]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRoutine imaging examinations, such as chest X-ray (CXR) and chest tomography (CT), are useful for lung cancer diagnosis, as they can nip malignancy in the bud\u0026nbsp;by\u0026nbsp;prompting a timely surgical procedure\u003csup\u003e[6-7]\u003c/sup\u003e. However, radiologic examinations\u0026nbsp;such as\u0026nbsp;CXR or CT cannot solve all the problems, especially in the early stage of lung cancer without obvious space occupation. Therefore, these approaches\u0026nbsp;need\u0026nbsp;to be combined with other auxiliary examination methods to enhance diagnosis. Among them, the advent of bronchoscopy, including white light bronchoscopy (WLB) and autofluorescence\u0026nbsp;bronchoscopy (AFB), has been beneficial for the diagnosis of lung cancer\u003csup\u003e[8-10]\u003c/sup\u003e. Since most lung cancers originate from the bronchial mucosa epithelium or bronchial mucous glands, bronchoscopy\u0026nbsp;has become\u0026nbsp;increasingly essential for early lung cancer diagnosis through direct observation and tissue biopsies\u003csup\u003e[11-12]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChest CXR and CT\u0026nbsp;have\u0026nbsp;restricted application due to their limited capability to identify\u0026nbsp;preinvasive\u0026nbsp;bronchial lesions (PBLs), such as dysplastic bronchial epithelium and carcinoma in situ (CIS), in lung cancer diagnosis\u003csup\u003e[13]\u003c/sup\u003e.\u0026nbsp;Conventional\u0026nbsp;bronchoscopy can perform biopsy, lavage and brush inspection under the operating mode of WLB\u003csup\u003e[14]\u003c/sup\u003e. The identification of these\u0026nbsp;PBLs\u0026nbsp;was difficult to achieve through conventional bronchoscopy on direct bronchoscopic inspection and sampling. AFB is a new type of bronchoscope designed for careful examination of bronchial mucosa and\u0026nbsp;is\u0026nbsp;now widely used\u0026nbsp;in combination\u0026nbsp;with WLB examinations\u003csup\u003e[9]\u003c/sup\u003e.\u0026nbsp;It is\u0026nbsp;a safe technique with fluorescent emission signals at green (520 nm) and red (\u0026gt;630 nm). Normal\u0026nbsp;mucosal tissue in bronchi reflects these signals and appears green in color, while PBL or invasive cancer tissue absorbs the green fluorescence and turns the reflected light magenta\u003csup\u003e[15]\u003c/sup\u003e. Thus, AFB can be used to screen central intraepithelial risks for lung cancer, such as moderate or severe dysplasia, CIS, and microinvasive carcinoma.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAFB can not only be utilized\u0026nbsp;for\u0026nbsp;the definite diagnosis of\u0026nbsp;tumors\u0026nbsp;but also help to determine\u0026nbsp;the\u0026nbsp;surgical scope or other therapeutic schedules\u0026nbsp;and\u0026nbsp;contribute to the treatment and monitoring\u0026nbsp;of\u0026nbsp;lung cancer patients with recurrence after surgery, radiotherapy and chemotherapy\u003csup\u003e[16-17]\u003c/sup\u003e. Wang \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e[18]\u003c/sup\u003e found that WLB combined with AFB could further improve the positive rate of lung cancer diagnosis for patients with lung nodules or lung masses, and the overall positive rate increased from 60.5% to 86.8%. It should be noted that most studies concerning the usefulness of AFB in patients with bronchial visible lesions. However, few studies have been conducted to study the utility of AFB in those with bronchial mucosal lesions. Therefore, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Subjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective cohort study conducted in Ningbo First Hospital. The protocol of our study was approved by the Ningbo First Hospital\u0026rsquo;s Ethics Committee. All participants included in this study provided informed consent.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe screened the subjects who had underwent WLB- and AFB-guided biopsies\u0026nbsp;from 2018 to 2021,\u0026nbsp;and all participants had\u0026nbsp;histologically\u0026nbsp;confirmed\u0026nbsp;cases.\u0026nbsp;To\u0026nbsp;explore the role of AFB in early mucosal lesions of the bronchi, only patients with early mucosal lesions were enrolled,\u0026nbsp;and those with obvious space-occupying lesions\u0026nbsp;in the bronchi were excluded. In the present study, abnormalities under WLB microscopy were defined as mucosal hyperemia, edema, thickening with\u0026nbsp;a\u0026nbsp;rough or heave surface, color change, and vascular aggregation or distortion, while abnormalities under AFB microscopy were defined as lesions appearing magenta in color under fluorescent\u0026nbsp;light.\u0026nbsp;The clinical information of the patients, such as age, sex, smoking history, bronchoscopic findings and pathological examination results,\u0026nbsp;was\u0026nbsp;collected from the hospital electronic medical record system.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBronchoscopy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe equipment systems used in this study are WLB (BF-240; Olympus, Tokyo, Japan) and VIS LUCERA (CV-260SL) Self-fluorescence Imaging System (Olympus, Tokyo, Japan). The tracheoscopy procedures involved in this study were performed by qualified and skilled physicians. Each patient\u0026nbsp;was\u0026nbsp;informed about the procedure in detail before tracheoscopy. Under local\u0026nbsp;anesthesia, we performed WLB according to the patients\u0026rsquo; chest CT\u0026nbsp;images and\u0026nbsp;recorded the macroscopic findings during WLB. Next, we repeated the examination after changing the WLB mode to AFB mode with the bronchoscope still in the trachea and captured the suspicious tissue.\u0026nbsp;After the suspicious lesions were captured, the biopsy was conducted immediately. Biopsy tissues were sent for pathological examination. In addition, during the tracheoscopy, the physician also determined whether to perform local lavage and brush examination or further operations, such as transbronchial lung biopsy (TBLB) or transbronchial needle aspiration (TBNA), according to the condition of each patient.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor statistical description, categorical variables\u0026nbsp;are\u0026nbsp;presented as n (%),\u0026nbsp;and continuous variables\u0026nbsp;are\u0026nbsp;expressed as\u0026nbsp;the means \u0026plusmn;\u0026nbsp;standard deviations or medians with interquartile ranges\u0026nbsp;determined\u0026nbsp;by data distribution.\u0026nbsp;Comparisons\u0026nbsp;between the AFB-guided\u0026nbsp;biopsy group\u0026nbsp;and the WLB group\u0026nbsp;were\u0026nbsp;made by\u0026nbsp;the chi-square (X\u003csup\u003e2\u003c/sup\u003e) test. A \u003cem\u003eP value\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant. Data analyses were performed by SPSS software 20.0 (SPSS Inc., Chicago, IL, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of\u0026nbsp;301 patients\u0026nbsp;who\u0026nbsp;received\u0026nbsp;WLB\u0026nbsp;and\u0026nbsp;AFB-guided biopsies\u0026nbsp;were included in the present study. The characteristics of\u0026nbsp;the\u0026nbsp;enrolled participants\u0026nbsp;are\u0026nbsp;shown in Table 1. Of the 301 patients, 213 were males and 88 were females, with a mean age of 64 years (25-83 years).\u0026nbsp;A total of\u0026nbsp;171 patients (56.8%) were current or former smokers with a pack-years of 25 (Table 1).\u0026nbsp;Through the biopsy specimens, whose histopathological diagnosis was confirmed by two specialists in pathology, 199 patients were confirmed as\u0026nbsp;atypical hyperplasia\u0026nbsp;or cancerous mucosa, including 12 cases of atypical hyperplasia, 58 cases of squamous cell carcinoma, 81 cases of adenocarcinoma, 27 cases of small cell carcinoma, 15 cases of carcinosarcoma, and 6 cases of cancer cells that could not be histologically classified. Other benign pathological\u0026nbsp;diagnoses\u0026nbsp;included pulmonary nodules (1 case), chronic mucosal inflammation (91 cases), granuloma (8 cases) and fungal infection (2 cases) (Table 1).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe benign lesions are only represented in mucosal hyperemia, edema, thickening with rough or heave surface, color change, and vascular aggregation or distortion under WLB, while the malignant lesions can be represented in mucosal color changes under AFB. The fluorescent magenta changes in the mucosa under AFB had a good indication of early mucosal lesions, as shown in Figure 1. Under WLB, there was no obvious difference between benign lesions (Figure 1A) and malignant lesions (Figure 1C), which\u0026nbsp;are easily\u0026nbsp;misdiagnosed. Under AFB, malignant lesions (Figure 1D) showed magenta changes,\u0026nbsp;while benign lesions (Figure 1B) only showed slight magenta changes in part.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe sensitivity of AFB-guided\u0026nbsp;biopsy for premalignant and malignant\u0026nbsp;lesion\u0026nbsp;detection (60.3%,\u0026nbsp;95% CI: 53.1-67.1%) was significantly higher than that of WLB (45.2%,\u0026nbsp;95% CI: 38.2-52.4%) (\u003cem\u003eP\u003c/em\u003e= 0.0026) (Table 2).\u0026nbsp;In addition, compared with\u0026nbsp;the\u0026nbsp;WLB group,\u0026nbsp;the\u0026nbsp;AFB-guided\u0026nbsp;biopsy group was found to have\u0026nbsp;a\u0026nbsp;significantly higher\u0026nbsp;specificity (100%,\u0026nbsp;95% CI: 95.5-100% \u003cem\u003eversus\u003c/em\u003e 69.6%,\u0026nbsp;95% CI: 59.6-78.1%; \u003cem\u003eP\u003c/em\u003e= 0), positive predictive value (100%,\u0026nbsp;95% CI: 96.1-100% \u003cem\u003eversus\u003c/em\u003e 74.3%,\u0026nbsp;95% CI: 65.5-81.7%; \u003cem\u003eP\u003c/em\u003e= 0) and negative predictive value (56.3%,\u0026nbsp;95% CI: 48.8-63.6% \u003cem\u003eversus\u003c/em\u003e 39.4%, 95% CI: 32.3-47.0%; \u003cem\u003eP\u003c/em\u003e= 0.0013). The negative likelihood ratio value was 0.40 (95% CI: 0.33-0.47) in the AFB-guided biopsy group and 0.78 (95% CI: 0.68-0.90) in the WLB group (Table 2). These findings strongly suggest that AFB-guided biopsy can improve the detection rate of premalignant bronchial lesions in high-risk individuals.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe prognosis of lung cancer is closely associated with its stage,\u0026nbsp;and\u0026nbsp;detecting cancers at the early stage together with\u0026nbsp;subsequent\u0026nbsp;radical surgery aimed at complete resection is the only curative treatment option for the majority of patients with lung cancer. Due to the application of new bronchoscopic technologies, the updating of equipment and the publication of molecular\u0026nbsp;studies, the rate of detection and surgical treatment for early lung cancer is increasing, and the survival rate of lung cancer is continuously rising\u003csup\u003e[19-20]\u003c/sup\u003e. However,\u0026nbsp;only\u0026nbsp;approximately\u0026nbsp;20% of patients with newly diagnosed lung cancer will receive potentially curative treatment in clinical practice\u003csup\u003e[21]\u003c/sup\u003e.\u0026nbsp;Despite\u0026nbsp;great progress in treating lung cancer, the overall survival rate for lung cancer and the 5-year survival rate of patients with advanced lung cancer remain only 20% and 10-15%, respectively\u003csup\u003e[22-24]\u003c/sup\u003e.\u0026nbsp;One promising approach is the identification of lung cancer at an early stage.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBronchoscopy is extremely important for the diagnosis of pulmonary diseases, especially bronchial lesions\u003csup\u003e[25]\u003c/sup\u003e. Since the advent of the first generation of AFB in the early 20th century, the value of AFB in the diagnosis of\u0026nbsp;malignant\u0026nbsp;lung lesions has been constantly evaluated in clinical\u0026nbsp;research\u003csup\u003e[26-29]\u003c/sup\u003e. Until now, most clinical trials\u0026nbsp;have\u0026nbsp;concentrated on the diagnostic value of AFB in\u0026nbsp;lungs\u0026nbsp;with highly suspicious lesions,\u0026nbsp;such as pulmonary nodules or masses. It should be noted particularly that our study focused on the utility of fluorescence-guided biopsy among patients without bronchial visible\u0026nbsp;lesions\u0026nbsp;and bronchial mucosal lesions.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results from our study showed that\u0026nbsp;the sensitivity of AFB-guided\u0026nbsp;biopsy (60.3%,\u0026nbsp;95% CI\u0026nbsp;53.1-67.1%) for premalignant and malignant\u0026nbsp;lesion\u0026nbsp;detection was significantly higher than that of WLB alone (45.2%,\u0026nbsp;95% CI\u0026nbsp;38.2-52.4%), with a good specificity\u0026nbsp;(100%,\u0026nbsp;95% CI: 95.5-100% \u003cem\u003eversus\u003c/em\u003e 69.6%,\u0026nbsp;95% CI: 59.6-78.1%), positive predictive value\u0026nbsp;(100%,\u0026nbsp;95% CI: 96.1-100% \u003cem\u003eversus\u003c/em\u003e 74.3%,\u0026nbsp;95% CI: 65.5-81.7%)\u0026nbsp;and negative predictive value\u0026nbsp;(56.3%,\u0026nbsp;95% CI: 48.8-63.6% \u003cem\u003eversus\u003c/em\u003e 39.4%, 95% CI: 32.3-47.0%). These results suggested that AFB-guided biopsy can serve as an important adjunct to WLB for\u0026nbsp;the\u0026nbsp;differential diagnosis of lung cancer in patients with bronchial mucosal lesions.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe differential diagnosis of lung cancer may not\u0026nbsp;be\u0026nbsp;difficult in patients\u0026nbsp;with obvious\u0026nbsp;bronchial space-occupying lesions. The most novel\u0026nbsp;aim\u0026nbsp;of this study was to investigate\u0026nbsp;AFB-guided\u0026nbsp;biopsy among\u0026nbsp;patients with bronchial mucosal lesions. WLB\u0026nbsp;relies\u0026nbsp;only on the\u0026nbsp;appearance of differences\u0026nbsp;in tissue thickness, mucosal swelling, mucosal roughness, bleeding, and\u0026nbsp;subsequent\u0026nbsp;biopsy and brush examination to distinguish cancerous tissue from normal tissue. However, these tissue and mucosal changes can occur in both benign bronchial lesions and malignant bronchial lesions under WLB examination,\u0026nbsp;making it\u0026nbsp;difficult for WLB to yield a definitive clinical diagnosis. Thus, the ability of WLB to diagnose early mucous and submucous carcinomas is very limited,\u0026nbsp;and\u0026nbsp;mucosal inflammation, congestion and other factors may interfere with the final diagnosis\u003csup\u003e[30]\u003c/sup\u003e. It has been reported that detecting preinvasive lesions using WLB is particularly difficult even for an experienced bronchoscopist,\u0026nbsp;and\u0026nbsp;only 29% of patients with bronchial CIS lesions were visible using WLB\u003csup\u003e[31]\u003c/sup\u003e.\u0026nbsp;As a method that makes use of the inherent properties of fluorescent emission signals to evaluate mucosal tissues, AFB was developed for the detection of bronchial dysplastic lesions and early lung cancers. AFB has an advantage over WLB and should be more sensitive\u0026nbsp;in theory, as previously reported\u003csup\u003e[32-35]\u003c/sup\u003e. The American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (2nd edition) have\u0026nbsp;shown\u0026nbsp;that the\u0026nbsp;pooled\u0026nbsp;sensitivity of WLB and AFB combined with WLB for intraepithelial neoplasia detection on a per-lesion basis was 40% and 80%, respectively\u003csup\u003e[36]\u003c/sup\u003e. ACCP recommended AFB use in\u0026nbsp;situations\u0026nbsp;such as normal chest radiographs with carcinoma on sputum cytology, CIS, or severe dysplasia. However, AFB has a lower specificity in lung cancer detection than WLB.\u0026nbsp;Sun \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e[27]\u003c/sup\u003e showed\u0026nbsp;that\u0026nbsp;the specificity of AFB combined with WLB was 35% lower than\u0026nbsp;that of\u0026nbsp;WLB alone. The reason for this low specificity may be attributed to the difficulty of AFB in\u0026nbsp;distinguishing\u0026nbsp;preinvasive bronchial lesions from some other bronchial mucosal changes, such as\u0026nbsp;bronchitis\u003csup\u003e[37]\u003c/sup\u003e. Fluorescence-guided biopsy can compensate for the low specificity of AFB,\u0026nbsp;and\u0026nbsp;our study showed\u0026nbsp;that\u0026nbsp;the specificity of AFB-guided biopsy\u0026nbsp;(100%,\u0026nbsp;95% CI: 95.5-100%) was\u003cem\u003e\u0026nbsp;\u003c/em\u003esignificantly higher\u003cem\u003e\u0026nbsp;\u003c/em\u003ethan\u0026nbsp;that of\u0026nbsp;WLB alone (69.6%,\u0026nbsp;95% CI: 59.6-78.1%) in the detection of lung cancer\u0026nbsp;without obvious space occupation. Therefore, through the recognition of color\u0026nbsp;differences\u0026nbsp;under fluorescence, the properties of mucosa can be preliminarily determined,\u0026nbsp;and the sensitivity of biopsy can be\u0026nbsp;consequently\u0026nbsp;improved.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn summary, the findings from our study demonstrated that fluorescence-guided biopsy had a higher sensitivity and specificity than WLB alone in patients with bronchial mucosal lesions. Therefore, fluorescence-guided biopsy is a novel modality serving as a useful adjunct to WLB for the early detection of bronchial carcinogenesis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and informed consent\u003c/p\u003e\n\u003cp\u003eOur research followed ethical principles from the Declaration of Helsinki and the Good Clinical Practice guidelines\u0026nbsp;from the International Conference on Harmonization. Participants or their representatives gave\u0026nbsp;informed consent, fully understanding the research\u0026apos;s purpose, potential risks and benefits, and their right to withdraw without consequences.\u0026nbsp;Ethical approvals for this study were obtained from the ethics committee of The First Affiliated Hospital of Ningbo\u0026nbsp;University (2020-R229).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;datasets used and/or\u0026nbsp;analyzed during the\u0026nbsp;current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the program for the science and technology 2025 major project of Ningbo (2019B10037).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWG, JY, and XK collected the epidemiological and clinical data. WG, JY and XK processed statistical data. WG, JY, XK, JX, LC and WL summarized all data. WG, LC and WL drafted the manuscript, LC and WL reviewed the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the science and technology 2025 major project of Ningbo for their funding and support. We are grateful for their guidance and resources throughout the project.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1. \u0026nbsp; Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin 2021, 71(1)\u003cstrong\u003e:\u003c/strong\u003e 7-33.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;2. \u0026nbsp; Blumenthal GM, Karuri SW, Zhang H, et al. 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LUNG CANCER 2001, 32(1)\u003cstrong\u003e:\u003c/strong\u003e 19-25.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eTable 1.\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;Clinical characteristics and final diagnosis of included patients\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\n \u003ctable style=\"width: 4.0e+2pt;border-collapse: collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eCharacteristic\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eEnrolled patients (n= 301)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003eAge (mean\u0026plusmn; SDs)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e64\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e64.3\u0026plusmn; 10.85\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eSex\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eMale (n, %)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e213\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e70.8%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eFemale (n, %)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e88\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e29.2%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eSmoking condition (n, %)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eSmoker\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e171\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e56.8%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:24.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003ePack-years (mean\u0026plusmn; SDs)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e25 (25.28\u0026plusmn; 31.33)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eNonsmoker\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e130\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e43.2%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eMalignancy\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e199\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e66.1%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eAtypical hyperplasia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Squamous cell carcinomas\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e58\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Adenocarcinoma\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e81\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Small cell carcinoma\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Carcinosarcoma\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e27\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eHistological classification failed\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eBenign lung disease\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e100\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e33.2%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:12.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003ePulmonary nodules\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Granulomatous\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Chronic mucosal inflammation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e91\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eInfectious disease\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e2\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;'\u003e0.7%\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 205.55pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Fungal infection\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 196.75pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eTable 2.\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;Comparison of\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003ethe\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003ediagnostic rate between\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;the\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;WLB group and AFB\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eguide for cancerous and precancerous lesions\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.1e+2pt;border-collapse: collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;color:black;'\u003eStatistics\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eWLB\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eFluorescence-guided biopsy\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;border-width: 1pt medium;border-style: solid none;border-color: windowtext currentcolor;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;color:black;'\u003eP\u003c/span\u003e\u003c/em\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;color:black;'\u003e\u0026nbsp;value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eTrue positive (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e90\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e120\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;border: medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:24.0pt;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eFalse positive (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e31\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:24.0pt;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eFalse negative (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e109\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e79\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:24.0pt;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eTrue negative (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e71\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e102\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:24.0pt;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eSensitivity (95% CI)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e45.2% (38.2-52.4%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e60.3% (53.1-67.1%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0.0026*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eSpecificity (95% CI)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e69.6% (59.6-78.1%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e100% (95.5-100%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;height: 24.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003ePositive likelihood ratio\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;height: 24.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e1.48(1.06-2.07)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;height: 24.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eInfinity\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;height: 24.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;height: 28.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eNegative likelihood ratio\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;height: 28.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0.78 (0.68-0.90)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;height: 28.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0.40 (0.33-0.47)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;height: 28.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003ePositive predictive value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e74.3% (65.5-81.7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e100% (96.1-100%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003eNegative predictive value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.6pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e39.4% (32.3-47.0%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e56.3% (48.8-63.6%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53.55pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor windowtext;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family: \"Arial\",sans-serif;color:black;'\u003e0.0013*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003eCI, confidence interval; *\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05;\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003elikelihood\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;ratios were calculated by\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003ethe\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;font-family:\"Arial\",sans-serif;'\u003econventional estimation method.\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"AFB, Mucous, Early diagnosis, Lung cancer","lastPublishedDoi":"10.21203/rs.3.rs-3038489/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3038489/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Bronchoscopy is currently the most commontechnique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a retrospective studyin a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3% (95% confidence interval [CI]: 53.1%-67.1%), which was higher than that of patients with WLB alone (45.2%, 95% CI: 38.2-52.4%) (\u003cem\u003eP\u003c/em\u003e= 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100%, 95% CI: 95.5-100% \u003cem\u003eversus\u003c/em\u003e 69.6%, 95% CI: 59.6-78.1%), positive predictive value (100%, 95% CI: 96.1-100% \u003cem\u003eversus \u003c/em\u003e74.3%, 95% CI: 65.5-81.7%) and negative predictive value (56.3%, 95% CI: 48.8-63.6% \u003cem\u003eversus\u003c/em\u003e39.4%, 95% CI: 32.3-47.0%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.\u003c/p\u003e","manuscriptTitle":"Utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2024-01-04 20:34:25","doi":"10.21203/rs.3.rs-3038489/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2023-06-26 18:25:45","doi":"10.21203/rs.3.rs-3038489/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"909ea466-0de4-419e-a87d-b9cf3d796056","owner":[],"postedDate":"January 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-12T11:59:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-04 20:34:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-3038489","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3038489","identity":"rs-3038489","version":["v2"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}