Nasal insertion overall satisfaction with EUS-b (NOSE): evaluating the feasibility of transnasal diagnostic EUS-b

INTRODUCTION
Esophageal endoscopic ultrasound using an endobronchial ultrasound (EBUS) bronchoscope (EUS‑b) has become an important tool in many bronchoscopy units. The procedure is generally performed through the mouth and there are currently no studies published evaluating the feasibility of transnasal EUS-b nor comparing it to the transoral approach. We aimed to evaluate the technical feasibility, patient comfort and safety of transnasal EUS-b.


MATERIAL AND METHODS
A single-centre prospective study enrolling patients undergoing diagnostic EUS-b was conducted. Nasal insertion was attempted in all cases. Procedure difficulty and perceived patient's comfort were reported by the bronchoscopists. Comfort, overall satisfaction and willingness to repeat the procedure were reported by the patients. Data regarding demographics, procedure details, patients' comfort and overall satisfaction, histological analysis and final diagnosis were collected and analysed.


RESULTS
A total of 119 patients were consecutively enrolled. Nasal insertion was successful in 87.4% and the mean duration of the procedure was 15.7 ± 4.9 minutes. No severe complications were reported. Procedure difficulty was usually graded as "simple" or "very simple" (71.4%). Mean values for bronchoscopists' assessment of patient comfort and patients' reported comfort were 4.2 and 4.1, respectively, on a 5-point scale. Only moderate correlation between these values was found (τb = 0.301, P = 0.001). Willingness to repeat transnasal EUS-b was very high (99.0%). Adequate samples were obtained in 88.5% of patients and overall diagnostic yield of EUS‑b needle aspiration was 85.9%.


CONCLUSIONS
EUS-b is an effective procedure that can be performed safely through the nasal cavity without significant discomfort for the patient.


Introduction
The emergence of endobronchial ultrasound (EBUS) and esophageal endoscopic ultrasound (EUS) was a critical development in thoracic oncology, enabling minimally invasive and accurate sampling of mediastinal lesions and staging of lung cancer through EBUS-guided needle aspiration (EBUS-NA) or EUS-guided needle aspiration (EUS-NA) [1,2].The combination of both procedures provides access to most lymph node stations in the mediastinum and many lung lesions adjacent to the mediastinal pleura, frequently obviating the need of invasive and expensive surgical procedures [3,4].Despite being similar in concept and image interpretation, these procedures use two very different devices and consequently require different skillsets and cannot usually be performed by the same operator, increasing costs and waiting time.Performing EUS using an EBUS bronchoscope (EUS-b) provides a solution to this problem and a pulmonologist proficient in EBUS is expected to expeditiously be able to perform it [5].
EUS-b was first reported in 2007 [6] and after the expanding evidence on its application for lung cancer staging [7,8] it swiftly became another tool in the hands of interventional pulmonologists in many bronchoscopy units.Along with becoming the standard of care for mediastinal staging of lung cancer [9,10], the combination of EBUS and EUS-b provides a higher yield for the diagnosis of mediastinal lymphadenopathies [11].
All previous reports have in common the use of the oral route for the insertion of the ultrasound bronchoscope.In a similar fashion, the few articles that provide a more indepth description of the procedure relate transoral intubation as the only route [12,13].
An exception to this were two recent publications by Christiansen et al. [14,15] that mention intubation being performed either via the mouth or the nasal cavity.Overall, the nasal route is generally viewed as a last resort in EUS-b [16], even though it has been favoured in conventional flexible bronchoscopy as it is associated with increased bronchoscope stability and manoeuvrability, reduced pharyngeal reflex, protection against biting damage and increased patient's willingness to return [17,18].This dogmatic stance is due to the limited bronchoscopic view and the perceived discomfort and nasopharyngeal trauma the nasal insertion could cause, as a result of the larger diameter and rigid nature of the distal end of the ultrasound bronchoscope.However, no studies evaluating the feasibility of transnasal EUS-b or comparing it to the transoral approach are published.The available evidence on the nasal route for the insertion of an ultrasound bronchoscope is mostly limited to a single centre's experience with transnasal EBUS [19,20], showing no difference in comfort or diagnostic yield compared to transoral EBUS.

Objectives
We performed this study to evaluate the technical feasibility and safety of EUS-b through the nasal route under conscious sedation with midazolam, how well tolerated it is by the patients and, ultimately, its diagnostic yield.

Study Design
We designed a single-centre, prospective study enrolling all patients with suspected malignant or benign disease undergoing diagnostic EUS-b at an oncological centre between November 2019 and January 2021.
The pulmonologist responsible for the procedure completed a short questionnaire regarding the difficulty of the exam (qualitative assessment, from very hard to very easy) and the perceived patient's comfort (on a 5-point scale).Patients were discharged according to the Aldrete-Kroulik scoring system and, at discharge, were asked to fill a questionnaire reporting their comfort during the exam, overall satisfaction with it (on a 5-point scale), as well as their willingness to undergo EUS-b in the future, if necessary.Data regarding demographics, procedure details, patients' comfort (perceived and reported) and overall satisfaction, histological analysis and final diagnosis were collected.Patients with normal or non-specific inflammatory ganglia were followed for at least 3 months and subsequent investigations recorded to exclude false negative results.

The EUS-b equipment and procedure
All patients underwent the procedure in supine position, under conscious sedation with midazolam and local anaesthesia with lidocaine, with the pulmonologist positioned at the head of the patient.A flexible ultrasound bronchoscope with 6.9 mm outer tip diameter (Olympus BF-UC180F, Olympus Corporation) and 21 or 22-gauge needles (Olympus ViziShot 2, Olympus Corporation) were used for all procedures.Nasal insertion was attempted in all cases according to the technique described in Figure 1.

Study endpoints
The primary endpoint of the study was the feasibility of transnasal EUS-b under conscious sedation.The secondary endpoint were patient comfort, safety and diagnostic yield of the procedure.

Statistical analysis
Data analysis was conducted using IBM SPSS Statistics 27 software.Regarding descriptive statistics, mean and standard deviation were used to characterise the distribution of continuous variables.Absolute frequencies and percentages were used to describe categorical variables.Kendall's τ correlation coefficient was used to evaluate concordance between reported and physician perceived patient's comfort.

Clinical characteristics
During the 15-month period, 119 patients were consecutively enrolled.Mean age was 64.4 ± 12.7 years and the patients were predominantly male (68.1%).Most patients were proposed for diagnostic EUS-b because of suspected oncological disease (Table 1).

Procedure details
Procedure details are listed in Table 1.Nasal insertion of the EBUS probe was successful in 87.4%, with the remaining 15 procedures concluded through the oral route.Mean duration of the transnasal procedure was 15.7 ± 4.9 minutes.Procedure difficulty was graded by the bronchoscopist as "simple" or "very simple" in 71.4% of cases.Frequently only one location was sampled (78.8%) and lymph node station 7 was the most sampled location.Only one immediate complication occurred with the patient presenting moderate epistaxis.No late complications were identified.Mean time after procedure until hospital discharge was 54.0 ± 18.9 minutes.
In the 15 cases the procedure was converted to transoral EUS-b, the reasons for nasal insertion failure were anatomical incompatibility (11), pain (3) and incoercible sneezing (1).No immediate or late complications were identified beside the reasons for failure.There were no significative differences regarding age (62.4 ± 14.2 vs 64.7 ± 12.6 years, P = 0.512) or sex (66.7% vs 68.3% male, P = 0.901) between this group and the patients in whom nasal insertion was successful.

Patient comfort and overall satisfaction
Regarding the 104 patients in whom the procedure was completed through the nasal route, mean values for bronchoscopists' assessment of patient comfort and patients' reported comfort were similar (4.2 and 4.1, respectively, on a 5-point scale).However, Kendall's τ correlation coefficient showed only moderate correlation between discomfort perceived by the bronchoscopists and reported by the patients (τb = 0.301, P = 0.001).Mean overall satisfaction with the procedure was 4.3 and patients' willingness to return for repeated EUS-b, if necessary, was very high (99.0%).

Sample adequacy and diagnostic yield
Adequate EUS-b-NA samples were obtained in 88.5% of patients who underwent transnasal EUS-b.In the remaining 12 cases, either the suspected lesion was not accessible by the procedure (5) or the specimens collected were not representative (7).
Overall diagnostic yield of EUS-b-NA was 85.9% (Table 2).Oncological disease was diagnosed in 50.5% of patients, most commonly lung adenocarcinoma and breast carcinoma.The collected tissue samples were usually suitable for molecular characterization of lung adenocarcinoma, allowing EGFR mutation analysis in 93.3% of cases and for ROS1 and ALK rearrangement analysis in 73.3%.In regard to PD-L1 expression, quantification was possible in 92.3% of non-small cell lung carcinomas.
Needle aspiration of the left adrenal gland was attempted in 2 patients, both yielding lung adenocarcinoma diagnosis with the tissue suitable for molecular characterization.

Discussion
In this paper, our data showed that transnasal diagnostic EUS-b is a feasible, safe and well tolerated procedure and reinforced its diagnostic sensitivity.
Transnasal EUS-b has been commonly employed in our hospital with the main perceived advantages of increased stability of the bronchoscope, reduced pharyngeal reflex, reduced discomfort from not using a bite block and diminished risk of equipment damage.These are essentially the same benefits expected from performing conventional flexible bronchoscopy through the nose [17].In our study, nasal insertion was successful in 87.4% of cases, documenting the feasibility of this route.This compares favourably to the 73.5 to 75.5% success rate reported by Beaudoin et al. [19,20] in EBUS (not EUS-b, thus limiting the comparison).
Besides the technical feasibility of inserting the ultrasound bronchoscope through the nose, we also intended to evaluate patient comfort.Patients' self-reported comfort during the procedure was high and conversion to the oral route due to nasal pain was necessary in only 3 patients.While there is no previously published evidence we can directly compare these results to, comfort appears to be in line with transoral EUS-b: using a 100mm visual analogue scale, Oki et al. [21] documented patients' reported comfort and Madan et al. [22] documented operator's perceived comfort as 10.0 ± 17.8mm and 21.9 ± 12.4mm, respectively.Incidentally, in our study there was only moderate concordance between the patient's reported discomfort and the bronchoscopist's perception of it, highlighting the inaccurate nature of the latter.
Regarding feasibility and patient comfort, it should also be noted that more recently developed ultrasound bronchoscopes (Fujifilm EB-530US, Fujifilm Corporation; Olympus BF-UC190F, Olympus Corporation) are thinner and have smaller rigid distal ends, making nasal insertion theoretically easier.
The diagnostic yield of transnasal EUS-b-NA was 85.9%, similar to the previously reported sensitivity of 74 to 95% [7,12,22,23].Despite being an oncological centre, a high prevalence of benign disease was noted in our study and could be explained by the fact that it is one of the few hospitals performing EBUS/EUS-b in the region and, therefore, patients with suspected benign disease are frequently referred from other hospitals to undergo the procedure.Regarding the yield, it is important to highlight that the left adrenal gland is still accessible by nasal insertion, despite the greater length the ultrasound bronchoscope needs to transverse.
Our study presents some limitations.The inexistence of a control group submitted to transoral EUS-b for comparison and the fact that it is a single centre study are the most evident and may partially limit our analysis.As the scope reaches the middle concha, the bronchoscope is turned 45º counterclockwise (1B).Then, the bronchoscope is gently introduced in order to go through the space between the middle and lower conchae and the nasal septum (1C; 1D).After passing the conchae, the bronchoscope is turned 135º clockwise to the usual position (1E) and forward angled to enter the oropharynx (1F)

Figure 1 .
Figure 1.Nasal insertion of the EBUS bronchoscope (right nasal cavity).After external inspection of the nasal cavity, the ultrasound bronchoscope is slowly introduced in the direction of the middle nasal concha, with the ultrasound transducer facing medially (1A).As the scope reaches the middle concha, the bronchoscope is turned 45º

Table 1 .
EUS-b procedure details