Over the past decade, notable changes have occurred in the epidemiology and prevention of lung cancer due to shifts in smoking habits, major progress in understanding the genetic basis of lung cancer, the crucial role of the immune system in controlling lung cancer, and the growing variety of treatment options available. The 5-year survival rate of patients with lung cancer has exhibited an increase from 15.6% in 2011 to 19.4% in 2019. However, despite these advancements, lung cancer remains a leading cause of cancer-related mortality. In 2018, ~2.09 million new cases, constituting 11.6% of the total cancer cases, and 1.76 million deaths, accounting for 18.4% of the total cancer-related deaths, were attributed to lung cancer. This confirms its status as the leading cause of cancer-related mortality among males. Furthermore, it is the third most common type of cancer and the second leading cause of cancer-related mortality among females (1,2). Low-dose computed tomography (CT) is standard practice for lung cancer screening. This specific screening method achieves a selectivity of 85% and a specificity of 99% compared to the absence of screening. However, the overall false-positive rate can be as high as 81%. This substantial rate necessitated supplementary imaging or diagnostic procedures to validate the findings (3).

Bronchial washing is a clinical procedure used to collect cellular samples from the airways that are linked to the lungs. It is frequently used to identify infections and detect potential cancerous or pre-cancerous cellular changes. This method involves using a bronchoscope, a flexible and narrow instrument equipped with a light and a lens for visual guidance, to maneuver through the nasal or oral cavity, and into the lungs. By contrast, forceps biopsy involves the use of a specialized instrument to extract a small tissue sample from the tumor for further investigation (4-6). There is empirical evidence to indicate that the application of both diagnostic techniques, in conjunction, can result in a diagnostic yield exceeding 90% in patients with observable lung cancers during endoscopy. Consequently, it has been demonstrated that the utilization of both techniques in combination outperforms the diagnostic accuracy of either technique used in isolation (7). Among the diagnostic procedures conducted through bronchoscopy, forceps biopsy stands out for enhancing the diagnostic yield by almost 95%. By contrast, the diagnostic yield associated with bronchial washing for lung cancers featuring visibly observable tumors during endoscopy ranges widely from 45 to 85%. Generally, it falls below that achieved by forceps biopsy (8). The necessity of coupling bronchial washing with forceps biopsy has been a topic of debate. Specifically, certain investigations have reported a substantial increase in diagnostic yield by incorporating bronchial washing alongside forceps biopsy. Conversely, other studies have found no significant improvement in the overall diagnostic yield by employing bronchial washing in conjunction with forceps biopsy (9).

The majority of bronchoscopists collect washing samples in a seemingly arbitrary sequence by their personal preferences. In theory, it is conceivable that the diagnostic yield of bronchial washing could be elevated following forceps biopsy or brushing, as these techniques may prompt the shedding of additional malignant cells from the tumor into the washing samples. In addition to the ongoing debate surrounding the utility of bronchial washing, various other elements of this methodology, such as the ideal quantity of saline to be administered and the appropriate timing of the procedure in relation to biopsy or brushing, have yet to be definitively established (10). The present study aimed to compare the diagnostic yield of bronchial washing conducted before and after forceps biopsy in patients presenting with visible lung tumors during an endoscopy.

The present study included 50 patients with an average age of 72.1 years (±10.3) ranging from 52 to 93 years. The males comprised 36 (72%) of the patients. As regards the smoking status, 9 (18%) patients had 0-1 pack years, 4 (8%) patients had 1-20 pack years, 21 (42%) patients had 20-40 pack years, and 16 patients (32%) had >40 pack years. In terms of their occupation, 29 (58%) were retired. As regards their medical history, 10 (20%) of the patients had hypertension (HTN). The most frequent chief complaint was chronic cough in 28 (56%) patients (Table I).

The chest X-ray revealed abnormal findings in 38 (76%) patients. As regards the size of their masses, the CT scan results indicated that 14 (28%) were between 5 and 7 cm, and only 1 patient (2%) had a mass located in the right main bronchus. Morphological analysis of the lesions revealed that 40 (80%) were tumorous (Table II). The pre-biopsy bronchial wash (pre-BW) was positive in 21 patients (42%), while the post-biopsy bronchial wash (post-BW) was positive in 23 patients (46%). Of note, four pre-BW positive results turned negative post-BW, and six pre-BW negative results turned positive post-BW. This change was statistically significant (P-value <0.001; Table III). The biopsy results revealed that 22 (44%) of the cases were squamous cell carcinoma (Fig. 1), 18 (36%) were adenocarcinoma (Fig. 2), 8 (16%) were small cell lung carcinoma (Fig. 3), 1 (2%) was acinar cell carcinoma and 1 (2%) was non-malignant. However, the comparison of the morphological and histopathological findings of the endobronchial lesions with the corresponding pre-BW and post-BW results did not reveal any significant differences (P-value >0.05; Table IV).

The effectiveness of using bronchial washing as a diagnostic tool for visually detectable lung cancers during endoscopy is a subject of debate. Certain individuals argue against its use, citing cost and time constraints without notable improvements in diagnostic yield (12,13). On the other hand, others disagree, and present evidence of an improved diagnostic accuracy compared to relying solely on forceps biopsy, suggesting that it may even be cost-effective (14,15). Forceps biopsy, brushing and bronchial washing through flexible bronchoscopy are commonly used to make the cytological or histological diagnosis. Combining these procedures can achieve a diagnostic yield as high as 85 to 94% in patients with endoscopically visible lung cancers. The critics argue for further evidence to support its inclusion in diagnostic protocols, particularly when combined with other sampling methods (5,16,17).

Smoking represents a prominent risk factor in the development of lung cancer, with the duration and intensity of smoking contributing to an elevated likelihood of developing this condition. Carcinogenic substances found in cigarette smoke have the potential to harm the epithelial cells of the lungs, consequently fostering tumor growth. It is worth highlighting that lung cancer can also manifest in individuals who have never smoked or have been extensively exposed to secondhand smoke. Regrettably, there is a paucity of research pertaining to the impact of smoking on forceps biopsy and bronchial wash outcomes in patients presenting with visually detectable lung tumors (18). The findings of the present study indicated that the majority of patients were elderly males, revealing varying levels of smoking exposure within the group. Furthermore, the majority of the patients had other medical comorbidities and exhibited abnormal findings on a chest radiography, while CT scans revealed that almost half of the patients had masses >5 cm. These characteristic distributions offer valuable insight into factors influencing the surgical candidacy and post-operative outcomes of this population. A related study by Stanzel (19), performed in 2013, recommended selecting the area with the most prominent abnormality observed on chest radiographs or CT scans as the preferred site for bronchial washing in patients exhibiting substantial radiographic heterogeneity or localized lesions due to inflammatory infiltrates malignant growths, or other causes. Some researchers advocate performing bronchial washing at two or three different sites to enhance sample representation (19).

Several studies have investigated the impact of lung tumors located in the lower lobes on patient outcomes. The findings have indicated that lower lobe cancer is associated with higher overall mortality rates of patients with lung cancer, potentially due to lower rates of beneficial epidermal growth factor receptor mutations. The location of these tumors in the lower lungs may, therefore, contribute to poorer prognoses, particularly in cases of endobronchial lesions (20,21). The present study reported that the right side exhibited a slightly higher overall involvement, although it should be noted that almost half of the lesions were predominantly located in the lower lobes of the lungs, which, as aforementioned earlier, can be a negative prognostic factor for this patient group. Less frequent involvement was observed in the right middle lobe and right main bronchus. The histopathological examination further identified squamous cell carcinoma as the most prevalent subtype, which can be explained by the higher rate of squamous cell carcinoma amongst smokers compared to non-smokers (22), which is in accordance with the current cohort of patients with the vast majority being smokers, followed by adenocarcinoma, and small cell lung carcinoma. Furthermore, the study by Biciuşcă et al (23) reported that the majority of endobronchial lesions exhibited infiltrative morphology. However, tumorous patterns, as well as less common characteristics, such as necrosis, submucosal involvement and fungating features, were also observed (23). In contrast to these findings, the present study demonstrated that the predominant morphology of endobronchial lesions was tumorous, accounting for 80% of the cases, followed by an infiltrative pattern. Uncommon morphologies, including tumorous necrosis, submucosal features and a fungating appearance, were also detected, suggesting a diverse range of growth presentations and heterogeneity in the morphological characteristics and providing valuable insights into the histological characteristics within the analyzed cohort. Considering this diversity, it is necessary to further examine the mechanisms through which specific growth presentations can affect diagnostic evaluations and treatment planning approaches to optimize patient outcomes.

A previous study reported a diagnostic yield of 52-77% for bronchial brushing in endoscopically visible tumors, which was not significantly superior to the yield achieved with biopsy alone. The efficacy of brushing may depend on the order in which it is performed relative to the biopsy, although this aspect has yet to be extensively studied (24). However, the study by Lim et al (10), examining the optimal washing sequence before or after the biopsy on 166 patients, found no significant difference in the diagnostic yield between the two sequences. The study by Rao et al (4) demonstrated that bronchial wash cytology had a low sensitivity in detecting pulmonary lesions. However, it can still provide value for patients with contraindications for biopsy. In situations where biopsy is not feasible, morphometry can be a useful adjunct to cytomorphology (4). Notably, Hou et al (24), in a study on 362 patients, revealed that pre-biopsy brushings outperformed post-biopsy brushings in diagnosing exophytic tumors; the enhanced diagnostic efficacy through pre-biopsy brushings is elucidated in the following manner: Prior to the biopsy procedure, exophytic tumors are readily visualized and amenable to sampling due to their distinctive nodular or focal mass appearance. Conversely, post-biopsy, the occurrence of bleeding introduces contamination to the already confined area designated for brushing, thereby complicating the identification and sampling of pertinent tissue (20). This is in contrast to the findings of the study by Chaudhary et al (25) on the sequencing of bronchial washing and biopsy. Chaudhary et al (25) suggested that post-biopsy washing yielded higher diagnostic rates. They clarified their findings by proposing that the biopsy procedure released tumor cells, thereby enabling a greater collection of these cells during the washing process (25). In the study by Lee et al (16) involving 207 patients with a definitive cytological or histological diagnosis of lung cancer, it was determined that the sequence of performing bronchial washing, whether before or after forceps biopsy, did not affect the diagnostic yield of bronchial washing. However, bronchial washing significantly increased the overall diagnostic yield of bronchoscopy in patients with lung cancer (16).

In their study on 75 patients, Fernández-Villar et al (26) found that bronchial washing fluid was positive in 40 patients (53.3%) when the washing was performed before brushing and forceps biopsy. When the washing was performed after these procedures, it was positive in 43 patients (57.3%) (P=0.6) (26). However, Raymond et al (27) found no significant differences in diagnostic yield for central tumors regardless of the timing of wash fluid collection. However, they observed differences for tumors not visible on endoscopy: Positive results were found in 25% of wash fluids collected before other sampling procedures compared to 45% for samples collected afterward (27).

In another study involving 54 patients, Yigla et al (28) found that washing was positive for malignancy in 33% of cases before brushing and biopsy, compared to 48% when performed afterward. However, this difference was not statistically significant (28). Additionally, van der Drift et al (29) reported a diagnostic yield of 72% from aspirated wash fluids collected before biopsy and brushing and 74% after these procedures in a series of 137 patients with endoscopically visible tumors (P=0.85).

Unlike these studies, the present study demonstrated a significant change in the results pre-BW and post-BW. Of note, four pre-BW positive results became negative post-BW, while six pre-BW negative results became positive post-BW (P-value <0.001; Table III). Despite this change, the overall positive results included 23 (46%) patients. In addition, the comparison of the morphological and histopathological findings of endobronchial lesions with the corresponding pre-BW and post-BW results did not reveal any significant differences.

The present study is limited by its small sample size, and it should be noted that the findings may only partially represent the broader population. Additionally, the present study was a single-center experience, which may limit the generalizability of the findings.

Further studies using larger sample sizes or meta-analyses, are required to evaluate the effectiveness of this strategy and optimize the diagnostic methods by exploring sample collection sequences or integrating multiple techniques. Understanding these findings may help tailor flexible bronchoscopy protocols to maximize diagnostic accuracy and improve clinical decision-making. Additionally, the specifics of bronchoscopic procedures could affect their diagnostic yield.

Of note, a limitation of the present study is that the details of the histopathological and immunohistochemical analyses could not be retrieved, as these analyses were conducted at an external center. In conclusion, bronchial washing pre- and post-BW may affect the yield of diagnostic outcomes for endoscopically visible lung tumors. However, additional research, such as studies using larger sample sizes or meta-analyses, are warranted to fully determine the efficacy of this approach.