In this study, we classified bronchus subtypes on CT into six types in 1,372 patients with PPLs who underwent EBUS-GS to clarify the differences in their characteristics and investigated the factors associated with successful rEBUS detection and diagnosis. The results of multivariable logistic regression analysis demonstrated that penetrating bronchus type Ic directly impacted the diagnostic yield without affecting the rEBUS visualization yield in CT-BS group I. These findings indicate that in addition to previously reported factors such as lesion size, distance from the hilum, and visibility on chest X-ray [7–10, 13–15, 20], the presence of type Ic is a key novel factor for determining the indication for bronchoscopy in the diagnosis of PPLs.
In previous studies, CT-BS group I cases have been classified into one to three types, as shown in Fig. 1. Tsuboi types I and II correspond to bronchus types Ia and Ib in this study, respectively [18, 19]. Unlike type Ia, type Ib is characterized by the presence of intratumoral air bronchograms, comprising a high frequency of lepidic tumor growth [28]. An air-containing bronchus that predominantly penetrates into PPLs without narrowing of the lumen is classified as our proposed type Ic. Type Ic is also characterized by a size < 30 mm and ground-glass nodules accounting for > 70% each.
The overall diagnosis yield for CT-BS group I in our study was 75.9%, comparable to a meta-analysis [24]. Similar to this study which used EBUS-GS, a previous study reported that bronchus types Ia and Ib had good diagnostic outcomes using ENB, with no difference between types [16]. However, in type Ic, as represented by ground-glass nodules, the bronchus penetrated into the tumor without mucosal invasion [25], making it challenging to obtain sufficient samples for diagnosis relative to the other types, despite confirmation of “within” images by rEBUS. Accordingly, for the diagnosis of type Ic lesions, the use of sampling devices that can obtain larger tissue samples beyond the peripheral bronchial wall is recommended, such as large forceps with a large GS that were predominantly used in this study [8, 29]. In this regard, cryoprobes permitting deep biopsies of the entire circumference may be a preferable solution, although bleeding is a greater concern for this approach than for forceps biopsy [13]. Cryobiopsy is reportedly useful in cases for which it is difficult to obtain tissue by forceps biopsy due to air space dilation within the tumor [30]. An intratumoral dilated bronchus of this type is referred to as open-bronchus sign, which is directly connected to the central airway and does not act as a tamponade against bleeding. This type has been identified as a significant risk factor for TTNA-related hemoptysis [31]. Continued discussion is needed to resolve the dilemma often faced by pulmonologists in deciding between TTNA or bronchoscopy while balancing the risk of complications and diagnostic performance.
CT-BS group II has been classified into two or four types in the literature. Despite minor differences in classification, Tsuboi type III, CT-BS 1 reported by Tokoro et al., type B reported by Minezawa et al. and CT signs type 2 reported by Shinagawa et al. correspond to bronchus type IIa in this study [10, 18–21]. This type is typically classified as positive CT-BS [10, 16, 21, 22, 32], while studies focusing on negative CT-BS are considered negative [33, 34], with a diagnostic yield ranging from 37.9–74.1%. Among CT-BS group II types, type IIa has a higher rEBUS visualization yield [20, 33] although it contains many “adjacent to” images with comparable diagnostic performance relative to other types [35] or intermediate to CT-BS group I [20, 21]. Moreover, similar to other types, the diagnostic advantage of TBNA over forceps biopsy supports classification of type IIa as negative CT-BS.
Type IIb consists of the most peripherally located lesions in CT-BS group II. As the responsible bronchus is not traceable on CT, the pulmonary artery leading to the lesion is traced instead, corresponding to CT signs types 3 and 4, termed “CT-artery sign” and Tsuboi type IV [10]. This “follow the vessel approach” is considered useful in ENB and CT-guided ultrathin bronchoscopy which can reach such peripheral areas [36]. However, in this study, the fluoroscopy-guided EBUS-GS method did not exhibit any difference in rEBUS visualization and diagnostic yields between types IIb and IIc, in which neither bronchus nor artery led to the lesion.
Based on the results of this study, it would be appropriate to classify positive and negative CT-BS into two categories: CT-BS group I and II. When further subdividing the groups, CT-BS group I can be classified into types Ia/Ib and Ic, and CT-BS group II into types IIa and IIb/IIc.
We highlighted some values of CT-BS subclassification in peripheral diagnosis using the EBUS-GS method. Subdividing CT-BS allows for more accurate prediction of rEBUS findings [20]. In addition, this study revealed that the diagnostic yield of “within” images by rEBUS, a strong predictor for successful diagnosis, differs according to bronchus type. These findings will guide pulmonologists in determining the appropriate sampling devices, such as selecting the GS kit (large or small), adding TBNA, or switching to methods other than EBUS-GS. This should consider not only diagnostic performance, but also cost and the amount of tissue samples required for molecular analysis in advanced lung cancer [37].
This study had several limitations. First, this was a retrospective study at a single center. Diagnostic outcomes may vary by technique, institution, and proportion of malignant disease. Moreover, bronchus type classification may vary by reviewer and CT imaging conditions. Further, the interobserver agreement regarding CT-BS reported by Minezawa et al. [20] was moderate (Fleiss's κ: 0.559) in 109 PPLs without CT-BS, as described by Hong et al. [33]. Second, the study may have been subject to selection bias. Although this study was conducted using a relatively large cohort with an average diagnostic yield, some cases were excluded due to CT imaging conditions and inadequate follow-up. Therefore, the results of this study may not be generalizable and warrant external validation in prospective, multicenter cohort studies. Finally, the clinical significance of subdividing bronchus types belonging to negative CT-BS in EBUS-GS, which is highly dependent on the presence of CT-BS, was limited. This should be verified using newer guided bronchoscopic techniques such as bronchoscopic transparenchymal nodule access, which is considered to be less dependent on the presence of CT-BS [34]. In addition, lesion visibility on chest X-ray, which affords a potential alternative to fluoroscopic visibility, was also a key predictor of successful bronchoscopic diagnosis, regardless of CT-BS. Combinations of approaches such as virtual fluoroscopy, cone-beam CT, and augmented fluoroscopy as assistive guidance for lesions that are invisible on fluoroscopy may improve bronchoscopic diagnostic outcomes and further expand indications for bronchoscopy [11, 38].