A multi‐centre retrospective review of the bronchoscopic management of upper tracheal stenosis: an Australian perspective

Abstract

Background

Upper tracheal stenosis (UTS) is a rare process with multiple causes and variable approaches to treatment. Australian data on management patterns are lacking and patient resources reflecting local practices are scarce.

Aims

To describe the management strategies of UTS over 12 years among three teaching hospitals in New South Wales, Australia. A secondary aim is to formulate an evidence‐based patient information sheet for this condition and its management.

Methods

Retrospective descriptive case series. Demographic, procedural and spirometric data were obtained from the medical records of patients undergoing bronchoscopy for UTS between March 2012 and February 2024.

Results

A total of 31 patients (81% female) underwent 120 procedures (median: 3; interquartile range: 1–5) with a median procedure interval of 134 days. The interventions included 82 balloon dilatations, 37 steroid injections, 54 radial incisions (28 endoscopic scissors, 26 laser) and seven stent insertions. Following serial procedures, there were improvements in mean maximum forced expiratory flow (FEF_max) by 1.62 L/s (95% CI: 1.05–2.15, P < 0.001) and FEF_max percent predicted by 27% (95% CI: 18–36, P < 0.001). The mean FEV₁ improved by 0.36 L (95% CI: 0.15–0.54, P = 0.002) and 14% predicted. There was a documented improvement in symptoms in 80% of therapeutic procedures. Complications were infrequent and higher in procedures involving stents. Based on these findings, a patient information sheet has been developed.

Conclusions

Patients with UTS undergo several bronchoscopies that result in improvements in symptoms and function with relatively low rates of complications.

Introduction

Laryngotracheal stenosis denotes a heterogenous group of disorders resulting in airway narrowing that can occur in the supraglottis, glottis, subglottis and trachea. Supraglottic and glottic stenosis are areas of pathology managed principally by otorhinolaryngologists and will not be addressed further in this study. Subglottic stenosis describes the pathological narrowing of the larynx between the glottis (vocal cords) superiorly and the inferior margin of the cricoid cartilage inferiorly. Beneath the subglottis is the trachea, a 10‐ to 12‐centimetre‐long cylindrical organ, which contains approximately 16 to 22 cartilage rings anteriorly, with the longitudinal trachealis muscle comprising its posterior wall. Depending on the vertical length of a stenosis, it can often affect both the subglottis and/or trachea, with longer stenoses generally causing more severe impairment in spirometric indices and attributable symptoms. ¹ Strictly for the purposes of this study, the phrase ‘upper tracheal stenosis’ (UTS) will be used to describe stenoses of both the subglottis and the upper third of the trachea, as patients with these lesions tend to undergo common treatment pathways. Of note, patients with idiopathic subglottic stenosis (iSGS) comprise the largest group within our UTS cohort.

UTS is a rare condition, given estimates of 0.5 cases per 100 000 for post‐endotracheal intubation laryngotracheal stenosis, and a population incidence estimate of iSGS of approximately 0.2 to 0.25 per 100 000 population. ¹ , ² The aetiology of UTS varies and includes post‐intubation, post‐tracheostomy, autoimmune conditions, malignancy, infection, human papillomavirus tracheal papillomatosis, infiltrative processes and inhalational airway injuries. iSGS is an important subset of this condition, usually characterised by a web‐like circumferential stenosis and comprises a significant proportion of cases, with a female predominance. It is important to note that the management strategy for UTS is highly individualised to each patient due to the different aetiologies, precise anatomical location, severity and extent, symptoms, local expertise and patient constitution.

The optimal management of UTS remains debated and varied, with no standardised treatment algorithm. Clinical trials are hindered by the rareness of the condition, the wide variety of therapeutic options and the frequent need for several interventional techniques per procedure, making comparison of strategies difficult. Once symptomatic, intervention is generally required, with serial therapeutic bronchoscopic interventions typically used as first‐line therapy. Surgical management is reserved for patients with disease refractory to bronchoscopic management, with high reported complication rates (18%–25%), a procedural mortality rate of ~1% and a frequent need for repeat surgical procedures. ³ , ⁴

Given the uncommon nature of the condition, a median time from symptom onset to diagnosis of 36 months, its heterogenous pathology and the common need for serial procedures, patients are often faced with significant uncertainty around their disease course and treatment outcomes. ⁵ Therefore, the objectives of this study are to describe the bronchoscopic management of UTS in an Australian setting and to subsequently use these data to formulate a patient information sheet to assist patients with decision making and consent.

Methods

This retrospective descriptive case series investigated the bronchoscopic management of non‐malignant UTS in patients managed by three interventional pulmonologists in three teaching hospitals in New South Wales, Australia – Macquarie University Hospital, Liverpool Hospital and Concord Repatriation General Hospital between March 2012 and February 2024. Approval was obtained by the relevant ethics committees (Macquarie University Hospital: 520241677957874, Liverpool Hospital and Concord Repatriation General Hospital: 2023/ETHO1308). Participants with non‐malignant UTS confirmed via bronchoscopy were identified from each centre's prospectively collected bronchoscopy database. Medical records were accessed to obtain demographic data including age at diagnosis, sex, comorbidities, smoking status, aetiology of stenosis, the number and timing of procedures and specific interventions performed the complications of these procedures and documented symptomatic benefit. In addition, spirometric indices including pre‐ and post‐intervention forced expiratory volume in 1 second (FEV₁, L) and maximum forced expiratory flow (FEF_max, L/s) were collected.

The FEF_max, which is interchangeable with the peak expiratory flow (PEF), was collected as it has been shown to be the most sensitive and specific conventional spirometric measure of central airway stenosis and can predict the need for surgical intervention. ⁶ Both the FEF_max and FEV₁ preceding the first therapeutic intervention were compared with the FEF_max and FEV₁ performed after the most recent procedure. Values preceding diagnostic procedures where no therapeutic intervention was performed were only used if a more recent pre‐intervention value was not present. A sub‐analysis of spirometric indices in the iSGS subgroup, the commonest cause of UTS, was also performed. In addition, non‐bronchoscopic therapies to treat the underlying aetiology during the period of bronchoscopic intervention were also noted. For all patients, symptomatic improvement was noted if documented by a clinician following intervention. If a significant complication occurred after intervention and a change in symptoms was not documented during follow‐up, this was classified as a worsening of symptoms. We used R version 4.4.1 for statistical analysis, where linear mixed‐effects models were used to separately compare FEF_max and FEV₁ between procedures. Statistical inference was performed with 95% parametric bootstrap confidence intervals and P values, where a P value <0.05 was considered statistically significant. If diagnostic plots did not demonstrate that model assumptions were met, P values were not used.

Results

Patient characteristics

A total of 31 participants underwent bronchoscopy for UTS during the 12‐year period, with women comprising 81% (n = 25) and a mean age 55 years (Table 1). A total of 77% (n = 24) of participants were non‐smokers. In 42% of cases, the aetiology of the UTS was iSGS (n = 14). Other notable aetiologies included post‐tracheostomy (n = 6), post‐intubation (n = 3), post‐radiotherapy (n = 3) and vasculitis (n = 3). The mean baseline FEV₁ was 1.98 L ($\pm$0.75 L), with an FEV₁ percent predicted of 79% ($\pm$22%). The mean baseline FEF_max was 3.4 L/s ($\pm$1.4 L/s) corresponding to 52% ($\pm$21%) predicted. Common comorbidities included chronic obstructive pulmonary disease, diabetes, gastro‐oesophageal reflux disease, ischaemic heart disease and obstructive sleep apnoea. A total of 17% of patients did not have any relevant comorbidities.

Table 1.

Patient characteristics

Patient characteristics	n (%) or mean ($\mathit{\pm }$SD)
Total patients	31
Men	6 (19)
Women	25 (81)
Age at diagnosis (years)
Mean$\mathit{\pm }$SD	54.87$\pm$14.85
Range	17–83
Smoking status at diagnosis
Non‐smoker	24 (77)
Current smoker	3 (10)
Former smoker	4 (13)
Aetiology of stenosis
Idiopathic	14 (42)
Post‐tracheostomy	6 (18)
Post‐intubation	3 (9)
Post‐radiotherapy	3 (9)
Vasculitis	3 (9)
Other	4 (12)
Baseline spirometry
FEV1 (L)	1.98 ($\pm$0.75)
FEV1 (% predicted)	79 ($\pm$22)
FEFmax (L/s)	3.4 ($\pm$1.4)
FEFmax (% predicted)	52 ($\pm$21)
Comorbidities
Chronic obstructive pulmonary disease	4 (8)
Diabetes	4 (8)
Ischaemic heart disease	4 (8)
Obstructive sleep apnoea	4 (8)
Other cardiovascular disease	3 (6)
Vasculitis	3 (6)
Asthma	2 (4)
Other	10 (21)
None relevant	8 (17)

FEV₁, forced expiratory volume in 1 second; FEF_max, maximum forced expiratory flow; SD, standard deviation.

Procedure characteristics

The 31 patients underwent a total of 120 procedures, for a median of three procedures (interquartile range (IQR): 1–5) per patient (Table 2). There was no difference between the median number of procedures between the iSGS group (median, 3 (range, 1 to 16)) and those with the other aetiologies (median, 3 (range, 1–9)). A total of 105 (87%) of these procedures involved therapeutic interventions, with the remaining procedures being diagnostic. One patient underwent 16 procedures, and another underwent 12. The median time between each procedure was 134 days (IQR: 28–334 days). The timing of these interventions was determined by patient symptom recurrence, except for two patients who during their care both trialled regular monthly bronchoscopies, over a 3‐ and 5‐month period respectively. For all patients with at least two procedures, the median time between the first and second procedure (n = 22) was 47.5 days, between the second and third procedure (n = 19) was 215 days and between the third and fourth procedure (n = 12) was 350 days.

Table 2.

Procedure characteristics

Procedure characteristics	n (%) or mean$\mathit{\pm }$SD
Total number of procedures	120
Therapeutic	105 (88)
Diagnostic	15 (12)
Number of procedures per patient
Mean$\mathit{\pm }$SD	3.87$\pm 3.54$
Median	3
Range	1–16
Procedure interval (days)
Mean$\mathit{\pm }$SD	259$\pm$326
Median	134
Location of therapeutic procedures
Concord Repatriation General Hospital	14 (12)
Liverpool Hospital	41 (34)
Macquarie University Hospital	65 (54)

SD, standard deviation.

Interventions commonly performed during these procedures included dilatations, local corticosteroid injections, radial incisions and stent insertions. Dilatations were the most common intervention performed (n = 82), with the majority of these being radial expansion balloon catheter dilatations. Fifteen of these dilatations were performed using rigid tracheoscopes. Paclitaxel‐coated balloon catheters were used a total of five times. One patient underwent a single procedure involving dilatation using a rigid Groningen dilating tracheoscope.

Local corticosteroid injections were the second most common intervention (n = 37). The corticosteroid of choice was triamcinolone 80 mg due to its long‐acting nature with minimal systemic effects. This was given either transcutaneous/translaryngeal via the cricothyroid membrane with bronchoscopic visualisation or directly injected via a transbronchial needle aspiration needle. Endoscopic radial incisions were also frequently performed (n = 28) and were usually followed by balloon dilatation. Holmium laser was used to make radial incisions in 26 procedures. In total, seven tracheobronchial stents were inserted. Five of these were silicon stents (including one hourglass stent) and two were covered metal stents.

Infrequently used interventions included the use of a carbon dioxide cryoprobe, argon plasma coagulation (APC), intralesional cidofovir, a laryngeal debrider and a rigid diathermy hook. Cryoprobe was used in a total of five procedures. In four of these procedures, the cryoprobe was used for debulking, with three of these procedures being performed on one patient with recurrent papillomatosis. Endotracheal cryobiopsies were performed in one procedure. APC was used in addition to cryoprobe in two procedures for the patient with recurrent papillomatosis. This patient also had three procedures where 375 mg of cidofovir was injected directly into the papillomata, and the same patient also underwent a procedure involving a laryngeal debrider. One procedure involved the use of a rigid diathermy hook.

While dilatation alone was the most common procedure (n = 23), most procedures involved at least two interventions (Fig. 1). Dilatation coupled with endoscopic scissor radial incision was common (n = 14), and these were also frequently performed in combination with triamcinolone injections (n = 12). Other commonly used combinations included dilatation with laser radial incision with (n = 9) or without (n = 10) local triamcinolone injections.

Figure 1.

Frequency of intervention combinations.

Spirometry and symptoms

Overall, the mean FEF_max increased by 1.62 L/s (95% CI: 1.05–2.15; P < 0.001) from a baseline of 3.38 L/s to an FEF_max of 5.00 L/s per patient following serial procedures (Table 3). This correlated to a significant improvement in the FEF_max percent predicted, which increased by 27% (95% CI: 18–36; P < 0.001) from a baseline of 52% to a FEF_max percent predicted of 79%. Similarly, the mean FEV₁ increased by 0.36 L (95% CI: 0.18–0.54; P = 0.002) per patient following serial procedures, which equated to a non‐significant 14% increase in the FEV₁ percent predicted. Within the subgroup of patients with iSGS, the mean improvement in FEF_max after serial procedures did not reach significance but increased by 1.07 L/s (95% CI: 0.03–2.24; P = 0.091) per patient following serial procedures. The FEF_max percent predicted did increase significantly by 20% (95% CI: 3.2–37; P = 0.034) and all interventions for this subgroup resulted in a trend towards improvement in all spirometric parameters.

Table 3.

Changes in spirometry after serial interventions in patients with UTS

	Result	95% CI	P value
All procedures
FEV1 (L)	0.36	0.18–0.59	0.002
FEV1 (% predicted)	14.06	N/A	N/A
FEFmax (L/s)	1.62	1.07–2.16	<0.001
FEFmax (% predicted)	26.74	17.91–35.07	<0.001
First procedure only
FEV1 (L)	0.25	0.01–0.51	0.065
FEV1 (% predicted)	9.76	1.29–17.62	0.039
FEFmax (L/s)	1.49	0.64–2.18	0.003
FEFmax (% predicted)	23.32	N/A	N/A
iSGS (n = 14)
FEV1 (L)	0.43	−0.24 to 1.05	0.184
FEV1 (% predicted)	16.3	N/A	N/A
FEFma x (L/s)	1.07	0.03–2.24	0.091
FEFm ax (% predicted)	19.73	3.18–37.08	0.034

CI, confidence interval; FEV₁, forced expiratory volume in 1 second, FEF_max, maximum forced expiratory flow; iSGS, idiopathic subglottic stenosis; N/A, not available; UTS, upper tracheal stenosis.

Given the most common aetiologies were iSGS and post‐intubation and post‐radiotherapy stenosis, there were minimal instances of non‐bronchoscopic therapies used during the period of bronchoscopic intervention. One patient with tracheal stenosis due to papillomatosis received radiotherapy following the course of his serial bronchoscopic procedures with complete eradication of the human papillomavirus and subsequent resolution of the stenosis. One patient was noted to have received prednisone and methotrexate for treatment of vasculitis at the time of their only therapeutic bronchoscopic procedure; however, spirometric measurements were measured within 2 weeks of the procedure. Another patient with vasculitis received regular concurrent rituximab infusions during the course of her serial bronchoscopies. A third patient with vasculitis, another with stenosis as a sequela of tuberculosis infection and another patient with rheumatoid arthritis‐associated subglottic stenosis either had diagnostic procedures only or did not receive any concurrent therapies during the course of their serial bronchoscopies.

Overall, there was a documented improvement in symptoms in 80% of therapeutic procedures (n = 84). Following 15% of interventions, either symptoms had not improved or a change in symptoms was not documented. In six therapeutic procedures (6%) where a complication occurred, a worsening of symptoms was documented.

Complications

In total, 14 complications occurred from 120 procedures, for an overall complication rate of 11.6%. The complication rate was higher in the 20 procedures involving stents, where a complication occurred in 25% of cases, compared with a complication rate of 9% in procedures that did not involve stents (n = 100). Significant complications included a post‐operative admission to the emergency department for laryngeal oedema that required oral steroids and a period of observation, an admission to the intensive care unit for anaesthetic‐related hypoventilation requiring non‐invasive ventilation and two instances of partial airway obstruction requiring emergency procedures — both complications occurred following UTS dilatations using the rigid bronchoscope. In total, there were seven repeat procedures owing to a complication, six of which were in the first week, with one occurring 73 days post‐procedure due to stent migration. Four of these seven were in procedures involving stents.

Discussion

UTS is a rare heterogenous condition with a variable clinical course. Serial bronchoscopic intervention is the cornerstone of therapy for patients with this condition. To date, this is the largest retrospective study to describe the management of UTS by interventional pulmonologists in Australia. In this study, serial bronchoscopic intervention generally led to statistically significant improvements in spirometry, as well as an improvement in patient symptoms. Complications were infrequent but occurred at the expected rate for this condition and were more common in patients for whom tracheal stents were inserted. These data have been used to formulate a patient information sheet to assist patients with the provision of informed consent when undergoing treatment for UTS.

The female predominance, mean age of 55 years and the most common cause of UTS being due to iSGS (42%) are in keeping with the pre‐existing literature for this condition. ¹ , ² , ⁷ The median number of procedures per patient was comparable to previously published data. ⁸ Noting a median procedural interval of 134 days, the mean procedural interval of 259 days was slightly more frequent than the mean interval of 12.6 months in a systematic review of bronchoscopic interventions for iSGS. ⁸ This difference may be attributed to closer follow‐up timeframes, the inclusion of non‐idiopathic cases and the two patients who trialled regular monthly bronchoscopies, over a 3‐ and 5‐month period respectively.

Radial expansion balloon dilatation was the most common intervention performed in this series, often in combination with radial mucosal incisions as a ‘mucosal sparing technique’. ⁹ , ¹⁰ , ¹¹ This was preferred to dilatations with the barrels of rigid tracheoscopes given the risk of increased recurrence from mucosal trauma. ¹² Furthermore, one proceduralist stopped using rigid tracheoscopes for dilatation after use of the technique led to two instances of partial airway obstruction due to mucosal sloughing 2 days following the procedure requiring emergency bronchoscopy and debridement. Paclitaxel‐coated balloon dilatations have been performed for vascular, urological and oesophageal stenoses, with some retrospective data in benign central airway obstruction. ¹³ A prospective trial, OXYGEN‐1 (Prospective Trial of Paclitaxel‐Coated Pulmonary Balloon for the Treatment of Benign Airway Obstruction), is currently underway (clinical trial NCT05895305). Similarly, single topical application of mitomycin C has been shown to inhibit fibroblast proliferation and has previously been used for laryngotracheal stenosis. However, this antineoplastic agent may theoretically increase the risk of laryngeal cancer ¹⁴ , ¹⁵ and mitomycin C was not used in this case series.

A cryoprobe was used in five procedures without significant adverse events. A 2023 systematic review of cryotherapy for large airway stenoses found that the use of cryotherapy or cryospray with or without the addition of balloon dilatation improved patient symptoms in 89% of symptomatic patients, with two patients experiencing minor complications and one death unrelated to the intervention. ¹⁶

Stents are often used when there is loss of structural integrity of the airway or in cases where less invasive endoscopic measures have been unsuccessful, and it is well described that their use comes with a high risk of stent‐related complications including migration and impaired sputum clearance. For this reason, where possible, stents are generally avoided in non‐malignant conditions. ¹⁷ Silicon stents were predominantly used by our proceduralists given the risk of excessive granulation tissue formation from metallic stents, ¹⁷ and due to their ability to be removed easily when required. The variability in intervention combinations between procedures was in keeping with the variable combinations within the literature, and, as of yet, no ideal combination has been identified. ⁸

While spirometry has been shown to aid in the diagnosis of UTS, scarce data exist on the spirometric changes post‐intervention. A 2023 systematic review of spirometry in patients undergoing balloon dilatation for laryngotracheal stenosis found that PEF was the most reported spirometric parameter for assessing and determining laryngotracheal stenosis, with post‐operative changes in PEF between 1.16 and 2.3 L/s per procedure. ¹⁸ This measurement is easy to perform in the office or home environment using peak flow meters, which are inexpensive and readily available, making them an ideal monitoring tool.

Our overall complication rate of 11.6% for treatments related to UTS is similar to the reported complication rate, with stent complications comprising a significant proportion. ⁸ Despite this, none required a tracheotomy or open surgery for failed treatment (despite opinions frequently being sought from otolaryngology), compared with a mean rate of 7% and 11% of patients respectively in one published cohort of iSGS. ⁸ This may be due to the nature of the referral pathways within the involved centres, which are directed to interventional pulmonologists rather than surgeons.

This study is limited by its retrospective nature and the small sample size due to the rarity of the condition. Missing spirometric data limited the analysis of spirometric changes per procedure. This also prevented the use of calculating the expiratory disproportion index expressed as the ratio of the PEF over the FEV₁ multiplied by 100, which has been shown to be the most reliable parameter for diagnosing UTS, and can be used to monitor the condition. ¹⁹ An additional limitation of this study is the grouping of UTS, which can have variable aetiologies and bronchoscopic morphologies into one cohort. The effect of bronchoscopic interventions on spirometry may have been influenced by non‐bronchoscopic therapies, as one patient also received prednisone and methotrexate and another patient received rituximab for treatment of their vasculitis around the time of their therapeutic bronchoscopic procedures; however, neither of these would be expected to result in an immediate spirometry benefit.

Furthermore, only binary data of post‐operative symptomatic improvement could be obtained. Symptoms can be better assessed with quantitative scales such as the Dyspnoea Index or Vocal Hoarseness Index. ²⁰ , ²¹ More recently, scores from the novel Subglottic Stenosis 6 (SGS‐6) questionnaire have been shown to predict the need for intervention and should be used to monitor patients with iSGS in combination with spirometry. ²² This is advantageous as it is inexpensive and can be used in remote settings.

This analysis of retrospective data has also identified the need to improve data collection methods, with the involved centres in this study moving towards the use of electronic data capture software, such as REDCap databases. ²³ The data gathered from this study have been used to create a patient information sheet that provides significant insight into the patient experience for this rare disease (Appendix S1), and has also identified methods to improve the assessment and management of this rare condition in an Australian context. Future directions include the need to establish higher levels of evidence for specific interventions or intervention combinations and forming management guidelines to assist clinicians who encounter this condition in their practice.

Conclusion

UTS is a rare condition that creates challenges for both clinicians and patients. Patients can expect serial bronchoscopic procedures involving multiple different modalities that improve symptoms and pulmonary function with infrequent complications. As the field of interventional pulmonology continues to expand both in Australia and globally, it is important to document the management and outcomes of this rare and often challenging condition for both clinicians and patients.

Supporting information

Appendix S1. Subglottic stenosis patient information sheet.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.