Diagnostic Yield Of Flexible Bronchoscopy Research Articles

The application of artificial intelligence for Rapid On-Site Evaluation during flexible bronchoscopy.

Rapid On-Site Evaluation (ROSE) during flexible bronchoscopy (FB) can improve the adequacy of biopsy specimens and diagnostic yield of lung cancer. However, the lack of cytopathologists has restricted the wide use of ROSE. To develop a ROSE artificial intelligence (AI) system using deep learning techniques to differentiate malignant from benign lesions based on ROSE cytological images, and evaluate the clinical performance of the ROSE AI system. 6357 ROSE cytological images from 721 patients who underwent transbronchial biopsy were collected from January to July 2023 at the Tangdu Hospital, Air Force Medical University. A ROSE AI system, composed of a deep convolutional neural network (DCNN), was developed to identify whether there were malignant cells in the ROSE cytological images. Internal testing, external testing, and human-machine competition were used to evaluate the performance of the system. The ROSE AI system identified images containing lung malignant cells with the accuracy of 92.97% and 90.26% on the internal testing dataset and external testing dataset respectively, and its performance was comparable to that of the experienced cytopathologist. The ROSE AI system also showed promising performance in diagnosing lung cancer based on ROSE cytological images, with accuracy of 89.61% and 87.59%, and sensitivity of 90.57% and 94.90% on the internal testing dataset and external testing dataset respectively. More specifically, the agreement between the ROSE AI system and the experienced cytopathologist in diagnosing common types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, demonstrated almost perfect consistency in both the internal testing dataset (κ) and the external testing dataset (κ). The ROSE AI system demonstrated feasibility and robustness in identifying specimen adequacy, showing potential enhancement in the diagnostic yield of FB. Nevertheless, additional enhancements, incorporating a more diverse range of training data and leveraging advanced AI models with increased capabilities, along with rigorous validation through extensive multi-center randomized control assays, are crucial to guarantee the seamless and effective integration of this technology into clinical practice.

Diagnostic Utility of Bronchoalveolar Lavage in Patients with Acute Leukemia under Broad-Spectrum Anti-Infective Treatment.

Simple SummaryInfections of bacterial, viral, or fungal origin pose a major threat to patients with acute leukemia. Empiric antibiotic and antifungal treatment is a commonly used approach in leukemia patients with febrile neutropenia. To investigate the utility of flexible bronchoscopy (FB) with bronchoalveolar lavage (BAL) in acute leukemia (AL) patients with pneumonia who were already treated with broad-spectrum antibiotics and antifungal agents, we investigated bronchoalveolar samples of 88 patients. Our results indicate that despite broad-spectrum anti-infective treatment, in approximately half of all patients, pathogens could still be isolated in bronchoalveolar samples. Nevertheless, the detection of pathogens does not lead to frequent changes in anti-infective treatments, with most changes performed in patients with herpes simplex and influenza virus detection, and these pathogens might also be detected in less invasive examinations. The need for FB with BAL in patients with AL who are already receiving broad-spectrum empiric anti-infective treatment should therefore be weighed carefully.Despite therapeutic advances in the prevention and treatment of febrile neutropenia, acute leukemia (AL) patients still have considerable febrile neutropenia-related mortality. However, the diagnostic yield of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) in acute leukemia patients is unclear. In this retrospective single-center study, we analyzed 88 BAL samples of patients with acute leukemia and pulmonary infiltrates in spite of treatment with broad-spectrum anti-infective agents. The aim was to investigate the impact of FB with BAL on detecting causative organisms, which would result in a change in treatment regimens. The median age was 59 years, and 86% had acute myeloid leukemia. In 47%, pathogens were detectable in BAL fluid (pathogen bacteria, viruses, and fungi in 2, 15, and 18%, respectively), with Aspergillus fumigatus detected most frequently. BAL-guided anti-infective therapy changes were performed in 15%. The detection of herpes simplex and influenza viruses were the main reasons for treatment changes. Despite broad-spectrum anti-infective treatment, in approximately half of all patients, pathogens could still be isolated in BAL samples. However, consecutive changes in anti-infective treatment were considerably less frequent, with most changes performed in patients with Herpes simplex virus and Influenza A detection. The need for FB with BAL in patients with AL receiving broad-spectrum empiric anti-infective treatment should therefore be weighed carefully.

Scoping the Problem

Scoping the Problem

Diagnostic yield of fiber optic bronchoscopy in alveolar and/or ground glass opacification in chest computed tomographic scan

Background and objectiveTransbronchial lung biopsy (TBLB) can be obtained using forceps and usually represents the centrilobular regions. Therefore, disorders that are centered around terminal and respiratory bronchioles or distributed along the lymphatic routes can be diagnosed. This study investigated the diagnostic yield of flexible bronchoscopy in patients with ground-glass opacity (GGO) or alveolar filling for histopathological diagnosis and found out its complications.Patients and methodsTwenty-six patients with predominant GGO or alveolar opacity in the chest computed tomographic (CT) scan were submitted for TBLB for histopathological confirmation. Patients with respiratory failure, heart failure, coagulopathy, or pathognomonic CT patterns were excluded. All patients were subjected to full history taking, chest CT scan, and TBLB with histopathological examination of the specimens.ResultsThe diagnostic yield of TBLB was 73.1%. Histopathological diagnoses included hypersensitivity pneumonitis (23.1%), sarcoidosis (19.2%), adenocarcinoma (11.5%), small cell lung cancer (7.7%), alveolar proteinosis (3.8%), alveolar hemorrhage (3.8%), organizing pneumonia (3.8%), and chronic nonspecific inflammation (26.9%). There was no significant correlation between age, sex, smoking, and histopathological diagnoses. Regarding the predominant CT finding, 15 (57.7%) patients had GGO, whereas 11 (42.3%) patients had alveolar filling with significant (P=0.008) positive correlation between the CT predominant pattern and histopathological diagnoses. There was a positive significant correlation between lymph node enlargement in CT and histopathological diagnosis (P=0.029). Complications from TBLB included the pneumothorax (15.4%) and bleeding (7.7%).ConclusionsTBLB seems to be a useful and safe procedure. It is of a high diagnostic value. Therefore, it could be considered a routine diagnostic procedure before thoracoscopic or open lung biopsy.

Safety and efficacy of diagnostic flexible bronchoscopy in very old patients with lung cancer

Although there is a remarkable increase in diagnostic flexible bronchoscopy (FB) in old patients, safety and efficacy of FB in very old patients remain to be elucidated. In this study, we aimed to evaluate the complications and diagnostic yield of FB in patients aged≥80years with lung cancer compared with those aged<80years. We retrospectively analysed the medical records of 668 consecutive patients, which included 89 patients aged≥80years (older group) and 579 patients aged<80years (younger group) who underwent bronchoscopy for the diagnosis or staging of lung cancer between April 2011 and March 2016. The median age of the patients was 82 and 69years in the older and younger groups, respectively. Performance status and Charlson comorbidity index were comparable between the study groups. Diagnostic yield in the older and younger groups was equivalent, and stage distribution in both the groups was similar. Sixty-one patients (68.5%) received anticancer treatment including surgery, radiation and chemotherapy with cytotoxic or molecular-targeted agents in the older group. There were no statistical differences in the occurrence of overall complications between the two groups. Safety and efficacy of FB in the diagnosis of lung cancer in very old patients are comparable with those of younger patients. Accurate diagnosis established by bronchoscopy leads to appropriate treatment decision in very old patients.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Increases the Yield of Transbronchial Lung Biopsy for the Evaluation of Peribronchial Lesions.

Background:Due to absence of visible endobronchial target, the diagnostic yield of flexible bronchoscopy for peribronchial lesions has been unsatisfactory. Convex probe endobronchial ultrasound (CP-EBUS) has allowed for performing real-time transbronchial needle aspiration (TBNA) of enlarged hilar and mediastinal lymph nodes and therefore could also be used as a means of diagnosing proximal peribronchial lesions.Methods:We retrospectively analyzed the results related to 72 patients who underwent CP-EBUS for peribronchial lesions without endobronchial involvement and adjacent to three-grade bronchi based on chest computed tomography (CT) scan. We recorded the images during EBUS as well as the diagnostic results of TBNA and conventional-transbronchial lung biopsy/brush (C-TBLB/b), and final diagnoses were based on pathologic analysis and follow-up.Results:In all cases, the mass was able to be identified using EBUS in 97.2% patients (70/72) who were performed with EBUS-TBNA + C-TBLB/b. Sixty-six patients had a final diagnosis, 80.0% patients (56/70) had malignancies, and 14.3% patients (10/70) had benign disease. In malignancies, the diagnostic yield of C-TBLB/b was 57.1% (32/56) and in EBUS-TBNA was 85.7% (48/56), whereas pathologic diagnosis reached 94.6% when EBUS-TBNA was combined with C-TBLB/b. C-TBLB/b + EBUS-TBNA also exhibited stronger potency of histolytic diagnosis for malignancies than either EBUS-TBNA or C-TBLB/b alone. Furthermore, there are data supporting the value of EBUS-TBNA for the diagnosis of benign lung disease.Conclusion:The combined endoscopic approach with EBUS-TBNA and C-TBLB/b is an accurate and effective method for the evaluation of peribronchial lesions, with better results than using each technique alone.

Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions.

BackgroundWe aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible.MethodsThis was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield.ResultsWe included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56–103.32; p<0.001 and OR, 4.91; 95% CI, 1.76–13.72; p=0.002).ConclusionThe presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.

Factors Related to Diagnostic Yield of Flexible Bronchoscopy Without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions

Factors Related to Diagnostic Yield of Flexible Bronchoscopy Without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions

Utility of Cell-Block of Bronchial Washings in Diagnosis of Lung Cancer- A Comparative Analysis with Conventional Smear Cytology.

Bronchoscopy is a safe & effective means of diagnosing bronchogenic carcinoma with a varying diagnostic yield of different bronchoscopic procedures. Cell-Block (CB) preparation of cytology specimen has been shown to increase the diagnostic yield further. To the authors' knowledge, the diagnostic value of CB as an adjunct to conventional smear cytology (CS) of bronchial washing specimens in the detection of bronchogenic carcinoma has not been well evaluated. The present study was aimed to evaluate the diagnostic utility of CB of bronchial washings when compared with CS. A total of 104 patients of suspected bronchogenic carcinoma were subjected to bronchoscopy as per British Thoracic Society (BTS) protocol. Bronchial biopsy, brushings and washings were collected. Smears were prepared immediately of bronchial washings and another aliquot was subjected to CB preparation and further processing by paraffin embedding and H&E staining. Out of 104 patients, 92 were diagnosed by bronchoscopy with a cumulative diagnostic yield of all sampling techniques being 88.46%. Yield of CB of bronchial washings (44.23%) was higher than Bronchial washings - conventional smears (36.53%). CB detected additional 8 cases of malignancy where corresponding bronchial washings-conventional smears were negative. Exclusive diagnosis by CB was obtained in 2 cases. Brushings and biopsy confirmed malignancy in 49.03% and 57.69% cases. CB of bronchial washings had a higher yield as compared to corresponding conventional smears. Increase in yield was also noted when CB of bronchial washings was combined with biopsy and compared to bronchial washings- conventional smears combined with biopsy. In limited resource settings, CB preparation is a simple method that increases diagnostic yield of flexible bronchoscopy, is cost effective & hence can be routinely used. The immunohistochemical and molecular studies are possible with CB only, which is a distinct advantage over conventional smears of bronchial washings.

Conventional transbronchial needle aspiration in community practice.

Conventional transbronchial needle aspiration (C-TBNA) provides an opportunity to diagnose mediastinal lesions and stage bronchogenic carcinoma in a minimally invasive fashion. The procedure is easy to learn and requires zero upfront cost. Any community pulmonologist can acquire and maintain the skills of C-TBNA without undergoing formal interventional pulmonary fellowship training. Besides being used for the diagnosis and staging of lung cancer, C-TBNA can be used in patients suspected to have benign conditions such as sarcoidosis and tuberculosis. It also contributes in improving the diagnostic yield of flexible bronchoscopy while dealing with endobronchial, submucosal, peribronchial, or peripheral lesions. C-TBNA may be the only diagnostic modality that can be performed in patients in whom mediastinoscopy is contraindicated due to a bleeding diathesis. The procedure is safe and has great potential to augment the welfare of patients with pulmonary ailments. The learning curve of the procedure is short and steep. Every community pulmonologist should be able to perform C-TBNA.

Electromagnetic navigation‐guided TBNA vs conventional TBNA in the diagnosis of mediastinal lymphadenopathy

Conventional transbronchial needle aspiration (C-TBNA) is a safe method for the diagnosis of hilar and mediastinal lymphadenopathy (MLN). However, diagnostic yield of this technique varies considerably. Electromagnetic navigation bronchoscopy (ENB) is a new technology to increase the diagnostic yield of flexible bronchoscopy for the peripheral lung lesions and MLN. The aim of this prospective study was to compare the diagnostic and sampling success of ENB-guided TBNA (ENB-TBNA) in comparison with C-TBNA while dealing with MLN. Consecutive patients with MLN were randomized into two groups - C-TBNA and ENB-TBNA - using a computer-based number shuffling system to avoid recruitment bias. Procedures were performed in usual fashion, published previously. Ninety-four cases (M/F: 45/49) with a total of 145 stations of MLN were enrolled in the study. In 44 patients, 81 stations were sampled by ENB-TBNA, and in 50 patients 64 stations by C-TBNA. The mean size of MLN in study subjects was 17.56 ± 6.25 mm. The sampling success was significantly higher in ENB-TBNA group (82.7%) compared with C-TBNA group (51.6%) (P < 0.005). Defined by histopathological result, the diagnostic yield in ENB-TBNA was 72.8%, and 42.2% with C-TBNA (P < 0.005). For subcarinal localization, sampling or diagnostic success was higher in ENB-TBNA than that of C-TBNA (P < 0.05). Based on the size of the MLN ≤15 mm or >15 mm, the sampling success of ENB-TBNA was also significantly higher than C-TBNA in both subgroups (P < 0.005 and P < 0.005, respectively). No serious complication was observed. In this study comparing ENB-TBNA and C-TBNA, the sampling and diagnostic success of ENB-TBNA was found to be superior while dealing with MLN, in all categories studied.

Teaching Conventional Transbronchial Needle Aspiration. A Continuum

Proponents of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) propose that in this era of EBUS-TBNA, training for conventional transbronchial needle aspiration (C-TBNA) should be abandoned. The authors of this editorial provide the opposing view. C-TBNA has a short and a steep learning curve and adds to the diagnostic yield of flexible bronchoscopy in a cost-effective fashion. Considering its simplicity, availability, affordability, safety, and several unique indications, C-TBNA continues to contribute to the welfare of patients worldwide. It should remain as an integral part of pulmonary fellowship training programs.

Rapid on-site evaluation and low registration error enhance the success of electromagnetic navigation bronchoscopy

BACKGROUND:Electromagnetic navigation bronchoscopy (EMN) is a novel technology which allows localizing peripheral lung lesions and mediastinal lymph nodes for sampling and thus increasing diagnostic yield of Flexible Bronchoscopy.OBJECTIVES:A prospective study was conducted to investigate the diagnostic yield of EMN with lower average fiducial target registration error (AFTRE) and rapid on-site evaluation (ROSE).METHODS:Consecutive patients with peripheral lung lesion (PL) or enlarged mediastinal lymph node (MLN) which could not be diagnosed by conventional techniques and/or if the patients were not suitable for such interventions were included. The navigation procedure was continued once registration error was reached below/equal to the absolute value of 5 mm. ROSE was performed by an expert cytopathologist.RESULTS:A total of 76 patients; 22 having only PLs, 41 having only MLNs, and 13 having both PLs and MLNs together were enrolled. Thirty-two of 35 PLs (91.4%) and 85 of 102 MLNs (83.3%) were successfully sampled. Overall diagnostic yield was 89.5%. PLs and MLNs were further grouped according to their size (PLs: <20 mm vs ≥20 mm, MLNs: <15 mm vs ≥15 mm). The sampling yield was independent of size for both PL and MLN (P = 1.00, P = 0.38). In diagnostic EMN cases, mean AFTRE was 4.33 ± 0.71 mm, whereas it was 5.16 ± 0.05 mm (P = 0.008) in nondiagnostics. The total duration of procedure was 36.17 ± 9.13 min. Pneumothorax was observed in three patients (3.9%).CONCLUSION:EMN with low AFTRE in combination with ROSE is a reliable method with high sampling and/or diagnostic rate in PLs and MLNs.

Diagnostic Yield of Flexible Bronchoscopy Without Fluoroscopic Guidance in Evaluating Peripheral Lung Lesions

Flexible bronchoscopy (FB) is frequently performed in patients with peripheral lung lesions. The aim of this study was to evaluate the diagnostic yield, factors affecting diagnostic yield, complications, and safety of FB without fluoroscopic guidance in patients with peripheral lung lesions. We retrospectively reviewed the medical records of all patients who underwent FB without fluoroscopic guidance for the diagnosis of peripheral lung lesions between 1999 and 2004. Ninety-three patients were enrolled. Among these, 38 lesions were malignant, 46 were benign, and 9 were indeterminate. The overall diagnostic rate was 65%, and the diagnostic sensitivities for malignant and benign lesions were 68% and 74%, respectively. The diagnostic yield was significantly higher for lesions >2 cm (70%) than for lesions ≤2 cm (11%; P <0.001). The diagnostic yield of transbronchial lung biopsy (46%) was higher than that of bronchial washing (29%; P=0.025) or brushing (29%; P=0.022). The yield of transbronchial lung biopsy for malignant disease (70%) was higher than that of benign disease (35%; P=0.003). Pneumothoraces and significant bleeding developed in 4.3% and 2.2% of patients, respectively. This study showed that FB sampling without fluoroscopic guidance was safe with a high rate of accuracy for the diagnosis of lung lesions not visible through a bronchoscope. When we performed a computed tomography scan and determined the exact location of the lesion before FB, the diagnostic yield of FB without fluoroscopic guidance was comparable with that reported earlier using fluoroscopy.

Use of flexible bronchoscopy for rapid diagnosis of suspected tubercular cases in rural India

Reaching a correct diagnosis is a challenge for physicians treating any of the 30% to 50% of pulmonary tuberculosis patients who have negative sputum cultures or who present with no sputum. Flexible bronchoscopy acquires special importance for these cases for whom empirical anti-tuberculosis therapy is the only option left. In our study we aimed to assess the diagnostic yield of flexible bronchoscopy in patients, suspected to have tuberculosis, whose sputum smears were negative. In our hospital-based cross-sectional study, 42 patients were enrolled by consecutive sampling. Flexible bronchoscopy and selective bronchial washings were done in all patients. Bronchoscopy lavage smears were positive for M. tuberculosis in 10 (23.8%) patients. Fifteen (35.7%) patients had positive culture. Flexible bronchoscopy has an important role in the diagnosis of patients suspected to have tuberculosis, whose sputum smears are negative or who can not produce sputum.

Bronchoscopic diagnosis of endoscopically visible lung malignancies: should cytological examinations be carried out routinely?

The aim of this study was to determine the diagnostic yield of flexible bronchoscopy in endoscopically visible malignancies and to evaluate whether cytological examination, including bronchial washings and brushings, increase the diagnostic yield compared with bronchial biopsy alone. We reviewed a series of bronchoscopies over a period of 7.5 years in which an endoscopically visible tumour was identified and which had a definite cytological or histological diagnosis of pulmonary malignancy obtained by bronchoscopy or any other examination. The criteria were met by 174 bronchoscopies. In 155 bronchoscopies all specimens including bronchial washings, brushings and biopsies were obtained; the overall diagnostic yield was 88%. This compared with a diagnostic yield of 77% for biopsies only (P < 0.001). The individual diagnostic yields for biopsies, brushings and washings were 77, 50 and 38%, respectively. The overall diagnostic yield of cytology was 61%, providing a diagnosis in 95 patients. Of 11 repeat bronchoscopies after an initial non-diagnostic bronchoscopy, 9 were diagnostic. The tumour detection rate with flexible bronchoscopy in endoscopically visible lung malignancies is high. Cytology-based sampling techniques by means of bronchial washings and brushings significantly increase the overall diagnostic yield compared with forceps biopsy only. Repeat bronchoscopies after an initial non-diagnostic bronchoscopy have a relatively high diagnostic yield and should therefore be considered in all patients with endoscopically visible tumour.

Bronchoscopic diagnosis of endoscopically visible lung malignancies: should cytologic examinations be performed routinely?

Aims: The aim of this study was to determine the diagnostic yield of flexible bronchoscopy in endoscopically visible malignancies and to evaluate whether cytological examination including bronchial washings and brushings increase the diagnostic yield compared with bronchial biopsy alone. Methods We reviewed a series of bronchoscopies over a period of 7.5 years in which an endoscopically visible tumour was identified and which had a definite cytological or histological diagnosis of pulmonary malignancy obtained by bronchoscopy or any other examination. Results The above criteria were met by 174 bronchoscopies. In 155 bronchoscopies all specimens including bronchial washings, brushings and biopsies were obtained, the overall diagnostic yield of which was 88%. This compared with a diagnostic yield of 77% for biopsies only (p<0.001). The individual diagnostic yields for biopsies, brushings and washings were 77%, 50% and 38%, respectively. The overall diagnostic yield of cytology was 61%, providing a diagnosis in 95 patients. Of 11 repeat bronchoscopies after an initial non-diagnostic bronchoscopy, 9 were diagnostic. Conclusions The tumour detection rate with flexible bronchoscopy in endoscopically visible lung malignancies is high. Cytology-based sampling techniques by means of bronchial washings and brushings significantly increase the overall diagnostic yield compared to forceps biopsy only. Repeat bronchoscopies after an initial non-diagnostic bronchoscopy have a relatively high diagnostic yield, and should therefore be considered in all patients with endoscopically visible tumour.

Electromagnetic Navigational Bronchoscopy: A Surgeon’s Perspective

Diagnostic yield of flexible bronchoscopy is often limited by the size and location of the lesion of interest. Novel technologies have evolved that can improve the accuracy and expand the applicability of flexible bronchoscopy in rendering a tissue diagnosis for pulmonary nodules. One recent technical advance uses electromagnetic guidance to improve the ability of the bronchoscopist to navigate within the lung parenchyma as well as to localize and biopsy mediastinal pathology. We have gained a preliminary experience with navigational bronchoscopy using electromagnetic guidance to successfully biopsy peripheral lung lesions, place fiducial catheters to aid stereotactic radiotherapy, and to biopsy mediastinal lymph nodes in the staging of lung cancer. Not only will navigational bronchoscopy lead to improvements in the diagnostic yield of standard flexible bronchoscopy, but we envision potential therapeutic modalities that can be used this system.

E08-03: Innovative bronchoscopic diagnostic techniques: electromagnetic navigation

E08-03: Innovative bronchoscopic diagnostic techniques: electromagnetic navigation

Multimodality Bronchoscopic Diagnosis of Peripheral Lung Lesions

Endobronchial ultrasound (EBUS) and electromagnetic navigation bronchoscopy (ENB) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions. However, the role of combining these modalities to overcome each individual technique's limitations and, consequently, to further increase the diagnostic yield remains untested. A prospective randomized controlled trial involving three diagnostic arms: EBUS only, ENB only, and a combined procedure. All procedures were performed via flexible bronchoscopy and transbronchial forceps biopsies were obtained without fluoroscopic guidance. In the combined group, after electromagnetic navigation, the ultrasound probe was passed through an extended working channel to visualize the lesion. Biopsies were taken if ultrasound visualization showed that the extended working channel was within the target. Primary outcome was diagnostic yield. The reference "gold standard" was a surgical biopsy if bronchoscopic biopsy did not reveal a definite histological diagnosis compatible with the clinical presentation. Secondary outcomes were yields by size, lobar distribution, and lesion pathology. Complication rates were also documented. Of the 120 patients recruited, 118 had a definitive histological diagnosis and were included in the final analysis. The diagnostic yield of the combined procedure (88%) was greater than EBUS (69%) or ENB alone (59%; p = 0.02). The combined procedure's yield was independent of lesion size or lobar distribution. The pneumothorax rates ranged from 5 to 8%, with no significant differences between the groups. Combined EBUS and ENB improves the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising safety.