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Bronchoscopic Management of Patients With Symptomatic Airway Stenosis and Prognostic Factors for Survival
Bronchoscopic Management of Patients With Symptomatic Airway Stenosis and Prognostic Factors for Survival Lawrence Okiror, MBChB, Li Jiang, MBChB, Nicola Oswald, MBChB, Andrea Bille, MD, Pala Rajesh, FRCS (CTh), Ehab Bishay, FRCS (CTh), Richard Steyn, FRCS (CTh), Babu Naidu, FRCS (CTh), and Maninder Kalkat, FRCS (CTh) Department of Thoracic Surgery, Birmingham Heartlands Hospital, Birmingham, United Kingdom; and Department of Thoracic Surgery, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
Background. Interventional bronchoscopy is effective in the management of patients with symptomatic airway obstruction for both malignant and benign conditions. The main aim of this study is to report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction and identify prognostic factors for survival. Methods. This is a retrospective observational study of patients undergoing emergency interventional bronchoscopy over a 4-year period. Survival times were analyzed separately for patients with benign and malignant airway obstruction by the Kaplan-Meier method. Results. Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) patients were female. Seventy-two cases (43%) had airway obstruction due to malignant disease. There were 3 in-hospital deaths (2.7%). Median survival of the study population was 5.6 months (range, 0 to 51)
with a median follow-up of 7.3 months (range, 0 to 51). Median survival for patients with malignant airway obstruction was 3.5 months (range, 0 to 21), and 9.8 months (range, 0.1 to 51) for those with benign disease. Airway intervention facilitated palliative chemotherapy in 32 patients (44%) of those with malignant airway obstruction. At multivariate analysis in patients with malignant airway obstruction, presence of stridor (hazard ratio 1.919, 95% confidence interval: 1.082 to 3.404, p [ 0.026) and not receiving postprocedure chemotherapy (hazard ratio 2.05, 95% confidence interval: 1.156 to 3.636, p [ 0.014) were independent prognostic factors for death. Conclusions. Emergency interventional bronchoscopy for airway obstruction is safe, relieved symptoms, and facilitated palliative chemotherapy, which improved survival.
T
Malignant airway obstruction (MAO) is most commonly caused by lung or esophageal cancers [1]. Many of these patients have advanced cancer for which surgical resection is not indicated. In these patients, rigid bronchoscopy enables diagnosis, stabilization of the obstructed airway, and endoluminal management of the airway obstruction. Prompt intervention can be lifesaving for patients with critical airway obstruction, provide immediate palliation of obstructive symptoms, and facilitate further palliative treatment such as chemotherapy and radiotherapy [2, 3]. Interventional procedures to relieve airway obstruction include mechanical coring out of tumor, debridement, stenting, dilation, and disobliteration of stenotic material with laser, argon plasma, cautery, or cryotherapy. Despite the potential benefit of palliation of distressing airway obstruction, there is still a great deal of nihilism in the management of these patients, especially those with malignant obstruction because of perceived poor outcomes. There are very limited data in the literature on prognostic factors for patients undergoing procedures to alleviate airway obstruction. The aim of this study is to
racheobronchial stenosis is a debilitating and often life-threatening disorder. Patients usually present with stridor, exertional shortness of breath, and failure to clear secretions owing to airway obstruction. Stridor usually occurs when stenosis is down to less than 25% of luminal diameter. Surgical segmental airway resection is the definitive treatment of choice for patients with airway obstruction caused by benign disease if they are fit enough to tolerate the procedure. Patients with primary airway tumors are also best treated with surgical resection. Tracheobronchial resection is technically challenging, and patients have to be fit enough to tolerate major surgery to be considered for operation. Some patients will benefit from dilation before corrective airway surgery, and that is an important adjunct to the management of airway obstruction.
Accepted for publication Jan 27, 2015. Address correspondence to Dr Kalkat, Department of Thoracic Surgery, 1st Floor Stratford House, Birmingham Heartlands Hospital, Bordesley Green, Birmingham B9 5SS, United Kingdom; e-mail: maninder.kalkat@ heartofengland.nhs.uk.
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.061
2
OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction, with emphasis on postprocedure overall survival, and to identify prognostic factors for survival.
Material and Methods This is a retrospective observational study of a consecutive series of patients who underwent interventional bronchoscopy over a 4-year period between June 2009 and July 2013. All patients had symptoms of airway stenosis with computed tomography scan evidence of significant (> 50%) airway stenosis. Patients were excluded if they did not have any procedures aimed at relieving the airway stenosis during bronchoscopy. Patient data were obtained from a prospective departmental database. Institutional Review Board approval for this study was sought from the Heart of England NHS Foundation Trust and waived on the basis of it being a retrospective review with prior patient consent obtained for research.
Patients All patients had severe symptomatic airway stenosis. All procedures were done under general anesthesia with rigid and fiberoptic bronchoscopy. Biopsy specimens were taken during the procedure in patients with no prior diagnosis who had any visible endoluminal lesions. Rigid bronchoscopy was performed with adult standard 8.5mm rigid bronchoscopes unless patients had a narrow trachea, in which case the appropriately sized bronchoscope was used. The airway was visualized directly through the scope or by video assistance. Jet ventilation was then commenced through the ventilator channel on the bronchoscope after the airway was adequately suctioned. The airway was fully assessed, including the area distal to the stenosis whenever possible. If biopsies were required, these specimens were taken and sent for appropriate investigations. The appropriate interventional procedure was performed to relieve the obstruction and stabilize the airway. Procedures performed involved debridement or coring out of the endoluminal lesion, balloon dilation, serial mechanical dilation with tapering, variously sized dilators, laser disobliteration, or airway stenting. In some cases, more than one of these procedures was performed. After completing the procedure, patients were extubated in the operating room whenever this was possible. Patients with MAO were referred for appropriate treatment (eg, chemotherapy or radiotherapy). Data on overall survival and prognostic factors were analyzed separately for patients with benign airway obstruction (BAO) and patients with MAO.
Statistical Analysis Continuous data are reported as median and range, and categorical data are reported as count and percentage. Survival was measured from the date of surgery. Survival and prognostic factors were analyzed by the Kaplan-Meier method. Univariate analysis of data was performed using c2 test, log rank test, Fisher’s
Ann Thorac Surg 2015;-:-–-
exact test, unpaired t test, and analysis of variance, where appropriate. Factors that significantly affected survival in univariate analysis (at p < 0.10) were tested for their independent role in multivariate analysis using the Cox proportional hazards model. The stepwise backward procedure based on the likelihood ratio was used to assess the significance of covariates included in the model. Hazard ratios and 95% confidence intervals were calculated. A p value less than 0.05 was considered statistically significant. All analyses were conducted using the SPSS software package, version 18 (SPSS, Chicago, IL).
Results Patient Characteristics Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) were female. One hundred and three patients (61%) were less than 65 years old at the time of airway intervention. Baseline characteristics of the study population are summarized in Table 1. Seventy-two cases (42.9%) had MAO and 96 cases (57.1%) had BAO. The majority of patients with BAO had dilation procedures whereas patients with MAO mostly had airway stenting and laser disobliteration of tumor (Table 2). There were more male patients with MAO compared with BAO patients. Patients with MAO were also older compared with BAO patients (Table 2).
Operative Procedures, Outcomes, and Hospital Stay Interventions consisted of airway stenting in 45 cases (27%), dilation alone in 83 cases (49%) dilation and stenting in 5 cases (3%), laser disobliteration in 26 cases (15%), and laser with stenting in 3 cases (2%). Median length of hospital stay was 1 day (range, 0 to 132). The distribution of procedures done for patients with benign and malignant obstruction is summarized in Table 2. Airway stenting was achieved with self-expanding, covered silicone stents in 40 cases, Y-shaped covered stents in 2 cases, and covered silicone, nonexpanding stents in 3 cases. More than one stent was used in 14 cases. For purposes of analysis of prognostic factors for survival, procedures were categorized into three groups, namely, dilation, stenting, and other bronchoscopic interventions (laser obliteration, debridement, coring out of lesion). There were 3 inhospital deaths (2.7%). Ninety-nine patients were still alive at the time of censoring (March 2014) with a median follow-up of 17.7 months (range, 6.4 to 58). Overall survival of the study population is shown in Figure 1. At 1 year, 59.4% of patients were alive, and at 2 years, 57.5% of patients were alive.
Comparison of Survival of Patients With BAO and MAO Patients with MAO had a median overall survival of 3.7 months (range, 0 to 28), with 1-year survival of 26.1% and
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Table 1. Baseline Characteristics of Study Population (n ¼ 168) Characteristics Age, years, median (range) Sex Male Female Chest disease Asthma Chronic obstructive pulmonary disease Wegener’s granulomatosis Postlung transplant Posttracheal resection stenosis Posttracheostomy stenosis Posttracheal intubation stenosis Sarcoidosis Tracheomalacia Idiopathic tracheal stenosis Esophageal cancer Lung cancer Thyroid cancer Other chest cancera Obstructive symptoms Stridor Dysphagia Location of airway stenosis Laryngeal Subglottic Other tracheal Right main bronchus Left main bronchus Bronchus intermedius Distal airway
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OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
Table 2. Distribution of Procedures and Outcomes by Type of Pathology Causing Airway Stenosis
n (%) 63 (20–86) 77 (46) 91 (54) 6 12 6 18 7 22 12 3 2 4 3 50 4 5
(4) (7) (4) (11) (4) (13) (7) (2) (1) (2) (2) (30) (2) (3)
72 (43) 8 (5) 6 36 62 28 24 9 3
(4) (21) (37) (17) (14) (5) (2)
Lymphoma (n ¼ 1), metastatic breast cancer (n ¼ 1), metastatic colon cancer (n ¼ 1), tracheal (n ¼ 1), vocal cord (n ¼ 1).
a
Variable Age, years Male Length of stay, days Stent Dilation Laser Dead at follow-upa a
Benign (n ¼ 96) 53 31 1 12 78 8 15
(20–83) (32) (0–25) (13) (81) (8) (16)
Malignant (n ¼ 72) 66 46 1 33 5 28 54
(43–85) (64) (0–11) (46) (7) (39) (75)
Median follow-up 17.7 months.
Values are median (range) or n (%).
(p ¼ 0.3); age less than or more than 65 years (p ¼ 0.7); dysphagia (p ¼ 0.64); Eastern Cooperative Oncology Group performance status (p ¼ 0.9); diagnosis of lung cancer versus other type of cancer (p ¼ 0.6); and site of airway stenosis (p ¼ 0.13). None of these factors reached a predetermined level of significance of p less than 0.1. The following were significant prognostic factors for survival at univariate analysis: stridor (p ¼ 0.046; Fig 4); procedure, namely, other bronchoscopic intervention versus stenting versus dilation (p ¼ 0.01; Fig 5); and no chemotherapy received after bronchoscopy (p ¼ 0.014). Patients without stridor had a median survival of 6.1 months (95% confidence interval [CI]: 0.92 to 11.28) with 1- and 2-year survival rates of 35.5% and 31%, respectively. This compared with a median survival of 2.4 months (95% CI: 0.84 to 3.96) with 1- and 2-year survival rates of 12.5% and 0% for patients with stridor. Patients who only had other bronchoscopic intervention had a median survival of 8.6 months (95% CI: 2.5 to 14.66) with 1- and 2-year survival rates of 37.4% and 33.2%, respectively. Patients who had airway stenting had a median survival of 2.2 months (95% CI: 0.8 to 3.5) and 1- and
2-year survival of 21.7%. Patients with BAO had a median survival of 16.4 months (range, 0 to 58) with a 1-year and 2-year survival rate of 84% (p < 0.00001; Fig 2). A subgroup analysis of patients with MAO was performed comparing outcomes of patients who had palliative chemotherapy with patients who did not. After intervention to relieve their airway obstruction, 32 patients (44%) with MAO went on to have palliative chemotherapy. These patients had a median survival of 6.2 months (range, 0 to 28) compared with a median survival of 2.5 months (range, 0 to 27.7) for patients who did not have palliative chemotherapy (Fig 3). One-year and 2-year survival rates of patients who had palliative chemotherapy were 35.5% and 31.1%, respectively, and 18.4% and 13.8% for patients not fit for chemotherapy.
Prognostic Factors and Survival MALIGNANT AIRWAY OBSTRUCTION. In patients with MAO (n ¼ 72), the following factors were assessed for prognostic significance for survival at univariate analysis: sex
Fig 1. Kaplan-Meier curve showing overall survival of the study population.
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OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
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Fig 2. Kaplan-Meier curve showing overall survival of patients by pathologic cause of airway stenosis: benign stenosis (solid line) or malignant stenosis (dashed line).
Fig 4. Kaplan-Meier curve showing overall survival of patients with stridor (dashed line) compared with patients without stridor (solid line).
2-year survival rates of 12.1% and 8%, respectively. Patients undergoing dilation had a median survival of 5 months (95% CI: 2.1 to 11.12) and 1- and 2-year survival rates of 50%, respectively. At multivariate analysis, the following factors were independent prognostic factors for death: stridor (hazard ratio 1.919, 95% CI: 1.082 to 3.404, p ¼ 0.026); and not receiving chemotherapy after bronchoscopic intervention (hazard ratio 2.05, 95% CI: 1.156 to 3.636, p ¼ 0.014). BENIGN AIRWAY OBSTRUCTION. For patients with BAO (n ¼ 96), the following factors were assessed for prognostic significance for survival at univariate analysis and were found not to reach a significance level of less than 0.1: age
less than or greater than 65 years (p ¼ 0.7); stridor (p ¼ 0.1); Eastern Cooperative Oncology Group performance status (p ¼ 0.12); and site of airway stenosis (p ¼ 0.1). The following factors were significant prognostic factors for survival at univariate analysis: sex (p ¼ 0.016); and procedure (p ¼ 0.0008; Fig 6). One-year and 2-year survival rates were 90.7% for female patients and 69.5% for male patients. Patients who only had other bronchoscopic intervention had a 1- and 2-year survival rate of 76.9%, patients undergoing stenting procedure, 37.5%, and patients undergoing dilation, 90.6%. At the multivariate analysis, there were no independent prognostic factors for survival.
Fig 3. Kaplan-Meier curve showing overall survival of patient with malignant airway obstruction by additional treatment received after the procedure: patients not receiving chemotherapy (solid line) and patients receiving chemotherapy (dashed line).
Fig 5. Kaplan-Meier curve comparing overall survival of patients with malignant airway obstruction by bronchoscopic procedure: other bronchoscopic procedure (solid line), stenting (dashed line), or dilation (dotted line).
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Fig 6. Kaplan-Meier curve comparing overall survival of patients with benign airway obstruction by bronchoscopic procedure: other bronchoscopic procedure (solid line), stenting (dashed line), or dilation (dotted line).
Comment Our results show that timely interventional bronchoscopy is safe and effective in palliating obstructive symptoms in patients with airway stenosis. In patients with MAO, interventional bronchoscopy facilitated chemotherapy treatment, which may have had an impact on their overall survival. Central airway stenosis is debilitating and potentially life-threatening. Undue manipulation of stenosed central airways can cause an uncontrolled situation of complete obstruction from bleeding or mucosal swelling. The identification of significant airway stenosis by bronchoscopy in a symptomatic patient requires a quick decision as to the appropriate course of management. For these patients, any airway intervention is best performed by rigid bronchoscopy under general anesthesia. A rigid bronchoscope enables maintenance of airway patency and introduction of a coagulation device to attend to any troublesome bleeding [4, 5]. The majority of patients in this study were less than 65 years old, which probably reflects that more interventions were for patients with BAO, who tend to be younger [6]. As would be expected, patients with BAO mostly had repeated dilation procedures to relieve their airway stenosis, whereas patients with MAO were more likely to be treated with airway stenting and laser disobliteration of tumor. Most patients were in hospital for a day, and postprocedure inhospital mortality was low. A large number of patients died within 30 days of their procedure, however, especially in the group with MAO (Fig 2). That is consistent with other published large series and reflects the poor prognosis associated with what is usually advanced malignant disease [7, 8]. These low inhospital mortality figures show that interventional bronchoscopy, in experienced hands, is
OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
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safe and should be undertaken for symptomatic relief of airway stenosis. Although survival for many patients—especially those with MAO—is limited to a few months, their quality of life is significantly improved by relief of obstructive symptoms of stridor and shortness of breath. As symptomatic relief is almost instant after the procedure and hospital stay is short, we believe interventional bronchoscopy should be undertaken in these patients. We also demonstrate in this study that a significant number of patients with MAO proceeded to have palliative chemotherapy treatment for their underlying cancer diagnosis. As all patients had severe symptomatic airway stenosis, they would not have received any treatment before securing their airway with endobronchial procedures. These patients had a significantly better overall survival compared with patients who did not receive palliative chemotherapy. Postprocedure chemotherapy was an independent prognostic factor for survival in patients with MAO in this study. Reports of prognostic factors for survival for patients with MAO are very limited in the literature. In their study, Song and colleagues [3] reported postprocedure additional treatment (chemotherapy, radiotherapy, or both) was an independent prognostic factor for survival in patients with MAO. Radiotherapy after stent insertion for MAO was associated with a better median survival for those patients compared with patients not receiving radiotherapy in the study by Evans and associates [9]. We did not find any studies in the literature specifically reporting postprocedure chemotherapy after airway intervention with which to compare our results. The choice of procedure for relief of obstructive symptoms was determined by the underlying pathology. Although there are no standardized guidelines from randomized trials for selection of procedure, algorithms such as that proposed by Wood and associates [1] are a helpful guide. Herth and colleagues [10] have reported their results of a prospective, randomized trial of five different endoscopic techniques in patients with MAO. They reported a combination of argon plasma coagulation and tumor debridement to be the superior technique for recanalizing the airway [10]. The data from this study are limited as it is only an abstract. Patients were reassessed bronchoscopically 6 weeks after the procedure and survival reported at 6 weeks. Clearly, it is difficult to draw conclusions from this trial without more details of method of assessment of airway patency. Although the survival rate was different for the various endoscopic procedures performed in our study, that is more likely to reflect the underlying disease process as opposed to the interventional procedure. The main limitation of this study is that it involves a heterogeneous group of patients with both malignant and benign airway obstruction with a diverse etiology. Even among patients with MAO alone, the underlying cancer diagnosis was varied, and only limited conclusions can be drawn owing to lack of uniformity. In addition, the retrospective design inherently introduces selection bias. Nonetheless, we believe this study provides important
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information on the safety and prognostic factors for patients with symptomatic airway stenosis undergoing bronchoscopic intervention.
References 1. Wood DE. Management of malignant tracheobronchial obstruction. Surg Clin North Am 2002;82:621–42. 2. Stephens KE, Wood DE. Bronchoscopic management of central airway obstruction. J Thorac Cardiovasc Surg 2000;119:289–96. 3. Song JU, Park HY, Kim H, et al. Prognostic factors for bronchoscopic intervention in advanced lung or esophageal cancer patients with malignant airway obstruction. Ann Thorac Med 2013;8:86–92. 4. Freitag L, Darwiche K. Endoscopic treatment of tracheal stenosis. Thorac Surg Clin 2014;24:27–40.
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5. Dutau H, Vandemoortele T, Breen DP. Rigid bronchoscopy. Clin Chest Med 2013;34:427–35. 6. Stoelben E, Koryllos A, Beckers F, Ludwig C. Benign stenosis of the trachea. Thorac Surg Clin 2014;24:59–65. 7. Chhajed PN, Somandin S, Baty F, et al. Therapeutic bronchoscopy for malignant airway stenosis: choice of modality and survival. J Cancer Res Ther 2010;6:204–9. 8. Breitenbucher A, Chhajed PN, Brutsche MH, Mordasini C, Schilter D, Tamm M. Long-term follow-up and survival after Ultraflex stent insertion in the management of complex malignant airway stenosis. Respiration 2008;75:443–9. 9. Evans A, Rehmani S, Moghaddas HS, et al. Radiation therapy is an effective adjuvant modality following airway stenting for malignant airway obstruction. Chest 2014;145(Suppl):347A. 10. Herth FJ, Eberhardt R, Becker HD, Ernst A. Relief of malignant airway obstruction: prospective and randomized comparison of five different endoscopic techniques. Chest 2005;128:209S.
Background. Interventional bronchoscopy is effective in the management of patients with symptomatic airway obstruction for both malignant and benign conditions. The main aim of this study is to report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction and identify prognostic factors for survival. Methods. This is a retrospective observational study of patients undergoing emergency interventional bronchoscopy over a 4-year period. Survival times were analyzed separately for patients with benign and malignant airway obstruction by the Kaplan-Meier method. Results. Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) patients were female. Seventy-two cases (43%) had airway obstruction due to malignant disease. There were 3 in-hospital deaths (2.7%). Median survival of the study population was 5.6 months (range, 0 to 51)
with a median follow-up of 7.3 months (range, 0 to 51). Median survival for patients with malignant airway obstruction was 3.5 months (range, 0 to 21), and 9.8 months (range, 0.1 to 51) for those with benign disease. Airway intervention facilitated palliative chemotherapy in 32 patients (44%) of those with malignant airway obstruction. At multivariate analysis in patients with malignant airway obstruction, presence of stridor (hazard ratio 1.919, 95% confidence interval: 1.082 to 3.404, p [ 0.026) and not receiving postprocedure chemotherapy (hazard ratio 2.05, 95% confidence interval: 1.156 to 3.636, p [ 0.014) were independent prognostic factors for death. Conclusions. Emergency interventional bronchoscopy for airway obstruction is safe, relieved symptoms, and facilitated palliative chemotherapy, which improved survival.
T
Malignant airway obstruction (MAO) is most commonly caused by lung or esophageal cancers [1]. Many of these patients have advanced cancer for which surgical resection is not indicated. In these patients, rigid bronchoscopy enables diagnosis, stabilization of the obstructed airway, and endoluminal management of the airway obstruction. Prompt intervention can be lifesaving for patients with critical airway obstruction, provide immediate palliation of obstructive symptoms, and facilitate further palliative treatment such as chemotherapy and radiotherapy [2, 3]. Interventional procedures to relieve airway obstruction include mechanical coring out of tumor, debridement, stenting, dilation, and disobliteration of stenotic material with laser, argon plasma, cautery, or cryotherapy. Despite the potential benefit of palliation of distressing airway obstruction, there is still a great deal of nihilism in the management of these patients, especially those with malignant obstruction because of perceived poor outcomes. There are very limited data in the literature on prognostic factors for patients undergoing procedures to alleviate airway obstruction. The aim of this study is to
racheobronchial stenosis is a debilitating and often life-threatening disorder. Patients usually present with stridor, exertional shortness of breath, and failure to clear secretions owing to airway obstruction. Stridor usually occurs when stenosis is down to less than 25% of luminal diameter. Surgical segmental airway resection is the definitive treatment of choice for patients with airway obstruction caused by benign disease if they are fit enough to tolerate the procedure. Patients with primary airway tumors are also best treated with surgical resection. Tracheobronchial resection is technically challenging, and patients have to be fit enough to tolerate major surgery to be considered for operation. Some patients will benefit from dilation before corrective airway surgery, and that is an important adjunct to the management of airway obstruction.
Accepted for publication Jan 27, 2015. Address correspondence to Dr Kalkat, Department of Thoracic Surgery, 1st Floor Stratford House, Birmingham Heartlands Hospital, Bordesley Green, Birmingham B9 5SS, United Kingdom; e-mail: maninder.kalkat@ heartofengland.nhs.uk.
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.061
2
OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction, with emphasis on postprocedure overall survival, and to identify prognostic factors for survival.
Material and Methods This is a retrospective observational study of a consecutive series of patients who underwent interventional bronchoscopy over a 4-year period between June 2009 and July 2013. All patients had symptoms of airway stenosis with computed tomography scan evidence of significant (> 50%) airway stenosis. Patients were excluded if they did not have any procedures aimed at relieving the airway stenosis during bronchoscopy. Patient data were obtained from a prospective departmental database. Institutional Review Board approval for this study was sought from the Heart of England NHS Foundation Trust and waived on the basis of it being a retrospective review with prior patient consent obtained for research.
Patients All patients had severe symptomatic airway stenosis. All procedures were done under general anesthesia with rigid and fiberoptic bronchoscopy. Biopsy specimens were taken during the procedure in patients with no prior diagnosis who had any visible endoluminal lesions. Rigid bronchoscopy was performed with adult standard 8.5mm rigid bronchoscopes unless patients had a narrow trachea, in which case the appropriately sized bronchoscope was used. The airway was visualized directly through the scope or by video assistance. Jet ventilation was then commenced through the ventilator channel on the bronchoscope after the airway was adequately suctioned. The airway was fully assessed, including the area distal to the stenosis whenever possible. If biopsies were required, these specimens were taken and sent for appropriate investigations. The appropriate interventional procedure was performed to relieve the obstruction and stabilize the airway. Procedures performed involved debridement or coring out of the endoluminal lesion, balloon dilation, serial mechanical dilation with tapering, variously sized dilators, laser disobliteration, or airway stenting. In some cases, more than one of these procedures was performed. After completing the procedure, patients were extubated in the operating room whenever this was possible. Patients with MAO were referred for appropriate treatment (eg, chemotherapy or radiotherapy). Data on overall survival and prognostic factors were analyzed separately for patients with benign airway obstruction (BAO) and patients with MAO.
Statistical Analysis Continuous data are reported as median and range, and categorical data are reported as count and percentage. Survival was measured from the date of surgery. Survival and prognostic factors were analyzed by the Kaplan-Meier method. Univariate analysis of data was performed using c2 test, log rank test, Fisher’s
Ann Thorac Surg 2015;-:-–-
exact test, unpaired t test, and analysis of variance, where appropriate. Factors that significantly affected survival in univariate analysis (at p < 0.10) were tested for their independent role in multivariate analysis using the Cox proportional hazards model. The stepwise backward procedure based on the likelihood ratio was used to assess the significance of covariates included in the model. Hazard ratios and 95% confidence intervals were calculated. A p value less than 0.05 was considered statistically significant. All analyses were conducted using the SPSS software package, version 18 (SPSS, Chicago, IL).
Results Patient Characteristics Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) were female. One hundred and three patients (61%) were less than 65 years old at the time of airway intervention. Baseline characteristics of the study population are summarized in Table 1. Seventy-two cases (42.9%) had MAO and 96 cases (57.1%) had BAO. The majority of patients with BAO had dilation procedures whereas patients with MAO mostly had airway stenting and laser disobliteration of tumor (Table 2). There were more male patients with MAO compared with BAO patients. Patients with MAO were also older compared with BAO patients (Table 2).
Operative Procedures, Outcomes, and Hospital Stay Interventions consisted of airway stenting in 45 cases (27%), dilation alone in 83 cases (49%) dilation and stenting in 5 cases (3%), laser disobliteration in 26 cases (15%), and laser with stenting in 3 cases (2%). Median length of hospital stay was 1 day (range, 0 to 132). The distribution of procedures done for patients with benign and malignant obstruction is summarized in Table 2. Airway stenting was achieved with self-expanding, covered silicone stents in 40 cases, Y-shaped covered stents in 2 cases, and covered silicone, nonexpanding stents in 3 cases. More than one stent was used in 14 cases. For purposes of analysis of prognostic factors for survival, procedures were categorized into three groups, namely, dilation, stenting, and other bronchoscopic interventions (laser obliteration, debridement, coring out of lesion). There were 3 inhospital deaths (2.7%). Ninety-nine patients were still alive at the time of censoring (March 2014) with a median follow-up of 17.7 months (range, 6.4 to 58). Overall survival of the study population is shown in Figure 1. At 1 year, 59.4% of patients were alive, and at 2 years, 57.5% of patients were alive.
Comparison of Survival of Patients With BAO and MAO Patients with MAO had a median overall survival of 3.7 months (range, 0 to 28), with 1-year survival of 26.1% and
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Table 1. Baseline Characteristics of Study Population (n ¼ 168) Characteristics Age, years, median (range) Sex Male Female Chest disease Asthma Chronic obstructive pulmonary disease Wegener’s granulomatosis Postlung transplant Posttracheal resection stenosis Posttracheostomy stenosis Posttracheal intubation stenosis Sarcoidosis Tracheomalacia Idiopathic tracheal stenosis Esophageal cancer Lung cancer Thyroid cancer Other chest cancera Obstructive symptoms Stridor Dysphagia Location of airway stenosis Laryngeal Subglottic Other tracheal Right main bronchus Left main bronchus Bronchus intermedius Distal airway
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OKIROR ET AL EMERGENCY BRONCHOSCOPY FOR AIRWAY OBSTRUCTION
Table 2. Distribution of Procedures and Outcomes by Type of Pathology Causing Airway Stenosis
n (%) 63 (20–86) 77 (46) 91 (54) 6 12 6 18 7 22 12 3 2 4 3 50 4 5
(4) (7) (4) (11) (4) (13) (7) (2) (1) (2) (2) (30) (2) (3)
72 (43) 8 (5) 6 36 62 28 24 9 3
(4) (21) (37) (17) (14) (5) (2)
Lymphoma (n ¼ 1), metastatic breast cancer (n ¼ 1), metastatic colon cancer (n ¼ 1), tracheal (n ¼ 1), vocal cord (n ¼ 1).
a
Variable Age, years Male Length of stay, days Stent Dilation Laser Dead at follow-upa a
Benign (n ¼ 96) 53 31 1 12 78 8 15
(20–83) (32) (0–25) (13) (81) (8) (16)
Malignant (n ¼ 72) 66 46 1 33 5 28 54
(43–85) (64) (0–11) (46) (7) (39) (75)
Median follow-up 17.7 months.
Values are median (range) or n (%).
(p ¼ 0.3); age less than or more than 65 years (p ¼ 0.7); dysphagia (p ¼ 0.64); Eastern Cooperative Oncology Group performance status (p ¼ 0.9); diagnosis of lung cancer versus other type of cancer (p ¼ 0.6); and site of airway stenosis (p ¼ 0.13). None of these factors reached a predetermined level of significance of p less than 0.1. The following were significant prognostic factors for survival at univariate analysis: stridor (p ¼ 0.046; Fig 4); procedure, namely, other bronchoscopic intervention versus stenting versus dilation (p ¼ 0.01; Fig 5); and no chemotherapy received after bronchoscopy (p ¼ 0.014). Patients without stridor had a median survival of 6.1 months (95% confidence interval [CI]: 0.92 to 11.28) with 1- and 2-year survival rates of 35.5% and 31%, respectively. This compared with a median survival of 2.4 months (95% CI: 0.84 to 3.96) with 1- and 2-year survival rates of 12.5% and 0% for patients with stridor. Patients who only had other bronchoscopic intervention had a median survival of 8.6 months (95% CI: 2.5 to 14.66) with 1- and 2-year survival rates of 37.4% and 33.2%, respectively. Patients who had airway stenting had a median survival of 2.2 months (95% CI: 0.8 to 3.5) and 1- and
2-year survival of 21.7%. Patients with BAO had a median survival of 16.4 months (range, 0 to 58) with a 1-year and 2-year survival rate of 84% (p < 0.00001; Fig 2). A subgroup analysis of patients with MAO was performed comparing outcomes of patients who had palliative chemotherapy with patients who did not. After intervention to relieve their airway obstruction, 32 patients (44%) with MAO went on to have palliative chemotherapy. These patients had a median survival of 6.2 months (range, 0 to 28) compared with a median survival of 2.5 months (range, 0 to 27.7) for patients who did not have palliative chemotherapy (Fig 3). One-year and 2-year survival rates of patients who had palliative chemotherapy were 35.5% and 31.1%, respectively, and 18.4% and 13.8% for patients not fit for chemotherapy.
Prognostic Factors and Survival MALIGNANT AIRWAY OBSTRUCTION. In patients with MAO (n ¼ 72), the following factors were assessed for prognostic significance for survival at univariate analysis: sex
Fig 1. Kaplan-Meier curve showing overall survival of the study population.
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Fig 2. Kaplan-Meier curve showing overall survival of patients by pathologic cause of airway stenosis: benign stenosis (solid line) or malignant stenosis (dashed line).
Fig 4. Kaplan-Meier curve showing overall survival of patients with stridor (dashed line) compared with patients without stridor (solid line).
2-year survival rates of 12.1% and 8%, respectively. Patients undergoing dilation had a median survival of 5 months (95% CI: 2.1 to 11.12) and 1- and 2-year survival rates of 50%, respectively. At multivariate analysis, the following factors were independent prognostic factors for death: stridor (hazard ratio 1.919, 95% CI: 1.082 to 3.404, p ¼ 0.026); and not receiving chemotherapy after bronchoscopic intervention (hazard ratio 2.05, 95% CI: 1.156 to 3.636, p ¼ 0.014). BENIGN AIRWAY OBSTRUCTION. For patients with BAO (n ¼ 96), the following factors were assessed for prognostic significance for survival at univariate analysis and were found not to reach a significance level of less than 0.1: age
less than or greater than 65 years (p ¼ 0.7); stridor (p ¼ 0.1); Eastern Cooperative Oncology Group performance status (p ¼ 0.12); and site of airway stenosis (p ¼ 0.1). The following factors were significant prognostic factors for survival at univariate analysis: sex (p ¼ 0.016); and procedure (p ¼ 0.0008; Fig 6). One-year and 2-year survival rates were 90.7% for female patients and 69.5% for male patients. Patients who only had other bronchoscopic intervention had a 1- and 2-year survival rate of 76.9%, patients undergoing stenting procedure, 37.5%, and patients undergoing dilation, 90.6%. At the multivariate analysis, there were no independent prognostic factors for survival.
Fig 3. Kaplan-Meier curve showing overall survival of patient with malignant airway obstruction by additional treatment received after the procedure: patients not receiving chemotherapy (solid line) and patients receiving chemotherapy (dashed line).
Fig 5. Kaplan-Meier curve comparing overall survival of patients with malignant airway obstruction by bronchoscopic procedure: other bronchoscopic procedure (solid line), stenting (dashed line), or dilation (dotted line).
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Fig 6. Kaplan-Meier curve comparing overall survival of patients with benign airway obstruction by bronchoscopic procedure: other bronchoscopic procedure (solid line), stenting (dashed line), or dilation (dotted line).
Comment Our results show that timely interventional bronchoscopy is safe and effective in palliating obstructive symptoms in patients with airway stenosis. In patients with MAO, interventional bronchoscopy facilitated chemotherapy treatment, which may have had an impact on their overall survival. Central airway stenosis is debilitating and potentially life-threatening. Undue manipulation of stenosed central airways can cause an uncontrolled situation of complete obstruction from bleeding or mucosal swelling. The identification of significant airway stenosis by bronchoscopy in a symptomatic patient requires a quick decision as to the appropriate course of management. For these patients, any airway intervention is best performed by rigid bronchoscopy under general anesthesia. A rigid bronchoscope enables maintenance of airway patency and introduction of a coagulation device to attend to any troublesome bleeding [4, 5]. The majority of patients in this study were less than 65 years old, which probably reflects that more interventions were for patients with BAO, who tend to be younger [6]. As would be expected, patients with BAO mostly had repeated dilation procedures to relieve their airway stenosis, whereas patients with MAO were more likely to be treated with airway stenting and laser disobliteration of tumor. Most patients were in hospital for a day, and postprocedure inhospital mortality was low. A large number of patients died within 30 days of their procedure, however, especially in the group with MAO (Fig 2). That is consistent with other published large series and reflects the poor prognosis associated with what is usually advanced malignant disease [7, 8]. These low inhospital mortality figures show that interventional bronchoscopy, in experienced hands, is
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safe and should be undertaken for symptomatic relief of airway stenosis. Although survival for many patients—especially those with MAO—is limited to a few months, their quality of life is significantly improved by relief of obstructive symptoms of stridor and shortness of breath. As symptomatic relief is almost instant after the procedure and hospital stay is short, we believe interventional bronchoscopy should be undertaken in these patients. We also demonstrate in this study that a significant number of patients with MAO proceeded to have palliative chemotherapy treatment for their underlying cancer diagnosis. As all patients had severe symptomatic airway stenosis, they would not have received any treatment before securing their airway with endobronchial procedures. These patients had a significantly better overall survival compared with patients who did not receive palliative chemotherapy. Postprocedure chemotherapy was an independent prognostic factor for survival in patients with MAO in this study. Reports of prognostic factors for survival for patients with MAO are very limited in the literature. In their study, Song and colleagues [3] reported postprocedure additional treatment (chemotherapy, radiotherapy, or both) was an independent prognostic factor for survival in patients with MAO. Radiotherapy after stent insertion for MAO was associated with a better median survival for those patients compared with patients not receiving radiotherapy in the study by Evans and associates [9]. We did not find any studies in the literature specifically reporting postprocedure chemotherapy after airway intervention with which to compare our results. The choice of procedure for relief of obstructive symptoms was determined by the underlying pathology. Although there are no standardized guidelines from randomized trials for selection of procedure, algorithms such as that proposed by Wood and associates [1] are a helpful guide. Herth and colleagues [10] have reported their results of a prospective, randomized trial of five different endoscopic techniques in patients with MAO. They reported a combination of argon plasma coagulation and tumor debridement to be the superior technique for recanalizing the airway [10]. The data from this study are limited as it is only an abstract. Patients were reassessed bronchoscopically 6 weeks after the procedure and survival reported at 6 weeks. Clearly, it is difficult to draw conclusions from this trial without more details of method of assessment of airway patency. Although the survival rate was different for the various endoscopic procedures performed in our study, that is more likely to reflect the underlying disease process as opposed to the interventional procedure. The main limitation of this study is that it involves a heterogeneous group of patients with both malignant and benign airway obstruction with a diverse etiology. Even among patients with MAO alone, the underlying cancer diagnosis was varied, and only limited conclusions can be drawn owing to lack of uniformity. In addition, the retrospective design inherently introduces selection bias. Nonetheless, we believe this study provides important
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information on the safety and prognostic factors for patients with symptomatic airway stenosis undergoing bronchoscopic intervention.
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5. Dutau H, Vandemoortele T, Breen DP. Rigid bronchoscopy. Clin Chest Med 2013;34:427–35. 6. Stoelben E, Koryllos A, Beckers F, Ludwig C. Benign stenosis of the trachea. Thorac Surg Clin 2014;24:59–65. 7. Chhajed PN, Somandin S, Baty F, et al. Therapeutic bronchoscopy for malignant airway stenosis: choice of modality and survival. J Cancer Res Ther 2010;6:204–9. 8. Breitenbucher A, Chhajed PN, Brutsche MH, Mordasini C, Schilter D, Tamm M. Long-term follow-up and survival after Ultraflex stent insertion in the management of complex malignant airway stenosis. Respiration 2008;75:443–9. 9. Evans A, Rehmani S, Moghaddas HS, et al. Radiation therapy is an effective adjuvant modality following airway stenting for malignant airway obstruction. Chest 2014;145(Suppl):347A. 10. Herth FJ, Eberhardt R, Becker HD, Ernst A. Relief of malignant airway obstruction: prospective and randomized comparison of five different endoscopic techniques. Chest 2005;128:209S.