Published ahead of print on February 12, 2004, doi:10.1164/rccm.200312-1784OC
© 2004 American Thoracic Society doi: 10.1164/rccm.200312-1784OC
Stenting at the Flow-limiting Segment in Tracheobronchial Stenosis due to Lung CancerDepartment of Pulmonary Medicine, Hiroshima City Hospital; Department of Internal Medicine, Fukushima Co-op Hospital; Department of Pulmonary Medicine, Hiroshima Prefectural Hospital; and Department of Surgery, Hiroshima National Hospital, Hiroshima City, Hiroshima, Japan Correspondence and requests for reprints should be addressed to Teruomi Miyazawa, M.D., Ph.D., Department of Pulmonary Medicine, Hiroshima City Hospital, 7-33 Naka-Ku, Moto-machi, Hiroshima, Japan 730-8518. E-mail: miyazawt{at}carrot.ocn.ne.jp
Airway stenting at the wave-speed flow-limiting segment (the choke point) is assessed. We determined prospectively the precise location of the choke point using the flow–volume curve, endobronchial ultrasonography, ultrathin bronchoscopy, and three-dimensional computed tomography scan before and after stenting in 64 patients with extrincic compression due to lung cancer. We noted distinct flow–volume curve patterns specific to the type of stenosis. The tracheal stenosis group indicated fixed narrowing patterns with an expiratory plateau, bronchial stenosis group dynamic collapse patterns with an expiratory flow deterioration (choking), carinal stenosis group combined fixed and dynamic patterns, and extensive stenosis group complex patterns containing elements of all the former. After stenting, almost full-function patterns with significant improvement in PEF were observed in all groups (p < 0.01, p < 0.05, p < 0.001, p < 0.01, respectively). In patients with extensive stenosis, implantation of additional stents was required when the choke points were observed to have migrated to the areas of malacia with cartilage destruction by the tumor. Secondary stenting at migrated choke points resulted in a significant improvement in PEF over the initial stenting (p < 0.01). Stenting at the choke point improved expiratory flow limitation by increasing the cross-sectional area, supporting the weakened airway wall and relieving dyspnea.
Key Words: choke point • expiratory flow limitation • dynamic airway collapse • flow–volume curve More than 50% of patients with advanced stage lung cancer have stenoses of the central airways (1). In patients with symptoms, interventional pulmonology (2) is considered as a method of maintaining airway patency. Intraluminal tumors can be resected endoscopically by means such as laser photoresection or argon plasma coagulation (3). However, if airway stenoses are predominantly due to extrinsic compression by the tumor or metastatic lymph nodes, airway stenting should be considered (4–9). In our previous studies (7–9), stenting proved an effective procedure. However, some patients received no relief from dyspnea after stenting. We observed in these patients that the placement of the stent caused the area of greatest compression to shift to a weaker segment of the airway. Therefore we postulated that stenting might change the location of the flow-limiting segment (the choke point). Flow limitation during forced expiration is affected by the relationship between transmural pressure (Ptm) and cross-sectional area (A) of the airway. The wave speed is dependent on the stiffness of the airway wall, i.e., dPtm/dA and on the cross-sectional airway itself (10, 11). The flow–volume curve manifested specific configuration details related to the location of the choke point. Analysis of the flow–volume curve could be used in defining the nature of the stenosis (12–15). Whereas the digestive tract (16) and airway are similar tubular organs, only the airway has cartilage that strongly supports the lumen. According to the wave-speed theory (10, 11), we considered that the location of the choke point might have a close relationship to the presence of the cartilage. In our previous studies (17–19), endobronchial ultrasonography images revealed the layered structure of the cartilage of the tracheobronchial wall. Imaging using new technologies such as endobronchial ultrasonography, ultrathin bronchoscopy, and three-dimensional computed tomography (CT) scan might show collapsible segments and choke points in the airway. The aim of our study was to determine optimal positioning of the stent and its impact on pulmonary function. This study was designed to characterize the choke point, its location and migrations by flow–volume curve (12–15), endobronchial ultrasonography (17–20), ultrathin bronchoscopy (21), and three-dimensional CT scan (22–26), which can aid in the planning of bronchoscopic intervention.
Selection of Patients Between October 1998 and October 2003, we performed a prospective study, which was approved by the Ethics Committee. Written informed consent was obtained from all patients. To study the pure functional effect of stenting, we excluded patients with endoluminal tumors. We selected 64 patients who met all the following criteria: patients with World Health Organization dyspnea Grade III–IV, stage IIIB/IV inoperable lung cancer without further treatment options, central airway stenosis due to extrinsic compression, and residual stenosis of more than 50% after balloon dilatation. A randomized study of stenting using a no treatment arm or an unsuccessful treatment arm as a control group could not be selected due to the terminal nature of the patient's disease. Thus, a before and after study was done to obtain accurate information on tumor sites by dividing patients into four groups: tracheal stenosis, carinal stenosis, bronchial, and extensive stenosis from the trachea, carina, extending to the bronchi due to tumor and/or mediastinal lymphadenopathy.
Flow–Volume Curve, Endobronchial Ultrasonography, Ultrathin Bronchoscopy, and Three-dimensional CT Scan before and after Stenting
Statistical Analysis
Characteristics of the Patients In these 64 patients with inoperable lung cancer, histopathologically, there were 38 patients with adenocarcinoma, 18 with squamous cell carcinoma, and 8 with recurrence of small cell carcinoma after chemotherapy and/or radiotherapy. Groups were matched for sex, age, type of lung cancer, and previous treatment (Table 1) . A total of 64 Dumon stents including 36 Y stents and 28 uncovered Ultraflex stents were placed. Dumon stents including Y stents were used alone in just one session in patients with tracheal, carinal, and bronchial stenosis. Dumon Y stents and uncovered Ultraflex stents were used in combination in a second session in patients with extensive stenosis.
Analysis of the Flow-Volume Curve Configurations before and after Stenting All groups showed distinct flow–volume curve patterns particular to their type of stenosis. This study demonstrated tracheal stenosis indicated fixed narrowing patterns with an expiratory plateau, bronchial stenosis dynamic collapse patterns with an expiratory choking (an initial transient peak flow followed by acute flow deterioration and consecutive low flow), carinal stenosis combined fixed and dynamic patterns (descending expiratory limb with a plateau and choking), and extensive stenosis complex patterns containing elements of all the former. After stenting, each group exhibited a return to a near normal flow–volume curve configuration. In patients with extensive stenosis, the patterns of the flow–volume curve showed a stepwise improvement over the initial stenting after secondary stenting (Figure 1) .
Physiologic Parameters of Spirometry and Flow–Volume Curve before and after Stenting We show measured values obtained by spirometry and flow–volume curve in all groups in Table 2 . Significant improvement of FVC after stenting was observed in tracheal and bronchial stenosis groups (p < 0.05, p < 0.01, respectively). Significant improvement of FEV1 after stenting was observed in tracheal, carinal, bronchial, and extensive stenosis groups (p < 0.001, p < 0.001, p < 0.01, p < 0.01, respectively). Significant improvement of PEF after stenting was seen in all groups (p < 0.01, p < 0.001, p < 0.05, p < 0.01, respectively).
In the extensive stenosis group, a stepwise procedure was required after the initial intervention. Significant improvement in FEV1, PEF, and  max50% (maximal flow at 50% FEV) was seen after secondary stenting compared with the results of the initial stenting (p < 0.01, p < 0.01, p < 0.01, respectively).
Endobronchial Ultrasonography, Ultrathin Bronchoscopy, and Three-dimensional CT Scan before and after Stenting
Dyspnea Grades before and after Stenting We observed a shift in dyspnea to Grade 0 or I in all patients after stenting. The dyspnea grades (World Health Organization Index) improved significantly in tracheal, carinal, bronchial, and extensive stenosis groups (p < 0.001, p < 0.001, p < 0.001, and p < 0.01, respectively). In the extensive stenosis group, we observed a stepwise improvement after secondary stenting. A comparison of secondary stenting with initial stenting showed significant difference (p < 0.01) (Table 3) .
Survival after Stenting and Causes of Death The tracheal stenosis, carinal stenosis, and bronchial stenosis groups were similar, but the extensive stenosis group showed significantly shorter survival times after stenting (p < 0.01) (Figure 3) . Median survival times after stenting in the groups were as follows: tracheal stenosis group, 5.9 ± 5.0; carinal stenosis group, 5.6 ± 2.6; bronchial stenosis group, 5.5 ± 3.0; and extensive stenosis group, 3.0 ± 1.0 months. The causes of death were as follows: 39 patients died of cachexia, 15 patients died of respiratory infections, 6 patients died of respiratory failure, 3 patients died of cardiac failure, and 1 patient died of massive hemoptysis. None of the patients died of suffocation. Death could not be directly attributed to stent-related complications such as retained secretions (31%), tumor growth (28%), granulation tissue formation (22%), and stent migration (8%). Within the four groups there were no significant differences in stent-related complications. The complications we observed were all easily managed, and the patient's quality of life was not impaired in any major way.
This study indicates that correct positioning of the stent at the exact location of the choke point provides the greatest functional benefit to patients with extrincic compression due to lung cancer. The choke point occurs originally where the cross-sectional area of the airway is the narrowest. After stenting, migration of the choke point to a nonstented segment of the weakened airway results in its subsequent collapse. Secondary stenting at the site of migrated choke points, after initial stenting, results in significant functional improvement in patients with extensive stenosis from the trachea to the bronchi. On the basis of wave-speed concepts of maximal expiratory flow limitation, stenting at the choke point improved expiratory flow limitation by increasing the cross-sectional area, supporting the weakened airway wall and relieving dyspnea.
We succeeded in localizing the site of the choke point and defining the nature of the stenosis, i.e., whether due to fixed narrowing by tumor compression or to dynamic collapse by weakened cartilages. We noted distinct flow–volume patterns specific to the type of stenosis. A marked reduction of the expiratory flow with a plateau typically seen in a fixed narrowing indicated that the choke point disappears at higher lung volume levels. Constant flow represented by a plateau was seen on the expiratory curve in the effort-dependent portion near total lung capacity. It was caused by an increased airway resistance at the site of compression due to tumor, so that
Theoretical and experimental studies in both mechanical models and animals have been conducted and have predicted possible clinical uses of the choke point (11–14). Pedersen and Ingram (12) demonstrated the various effects of central airway changes produced in a two-compartment mechanical model of the lungs simulating both the trachea and bronchi. They observed the phenomenon of flow limitation as follows: when the trachea is partially obstructed at the site of the central choke point, the flow–volume curve shows a decrease in maximum flow volume over a plateau. When both bronchi are partially obstructed, choking occurs in airways showing decreasing Moreover, they reported that when a collapsing trachea is supported by a rigid tube, no choke point appears in the trachea but migrates to the bronchus. Postinterventional analysis of the flow–volume curve demonstrated that a plateau indicated that the choke point was being located in the trachea, but when the choke point migrates to the peripheral bronchi after the procedure, there is a disappearance of the plateau. In this study, we also found that the choke point migrated during the procedure of stenting. In some patients, even though the stent was accurately placed at the choke point, there was still choking present in flow–volume curve and implantation of additional stents was required when the choke points were observed to have migrated to the areas of malacia with cartilage destruction by the tumor. Whereas several patients in previous studies (7, 8) had suffered from continuing dyspnea after the procedure, which was evaluated by changes in the dyspnea grade, the postprocedure of the present study revealed that no patient suffered from persisting dyspnea greater than or equal to World Health Organization dyspnea Grade II. We demonstrated stepwise functional improvements after secondary stenting and relief of dyspnea in patients with extensive stenosis. However, the extensive stenosis group showed a significantly shorter survival time after stenting than other groups. Although stents provide only palliative treatment for relief of dyspnea, they can restore much of a patient's quality of life (28). The limitations of this study were due in part to underlying chronic obstructive pulmonary disease. The location of the choke point in patients with chronic obstructive pulmonary disease may be more peripheral than in other subjects. In patients with chronic obstructive pulmonary disease, MEF showed marked reduction in flow–volume curve, and superimposed lesions may be physiologically camouflaged (29). Whereas the flow–volume curve is actually useful in localizing the site of the choke point in the airway, new technologies such as endobronchial ultrasonography, ultrathin bronchoscopy, and three-dimensional CT scan demonstrate the choke point during forced expiration. Endobronchial ultrasonography revealed specific details of the cartilage destruction, enabling a diagnosis of malacia to be made in real time. An ultrathin bronchoscope was able to pass the collapsing segment and allowed assessment of the choke point directly. Three-dimensional CT images were obtained at end-expiration and provided an accurate, noninvasive method of assessing airway stenosis. In this study scanning was performed using single-detector helical CT; however, recent advances in CT imaging such as multidetector scanners should improve the overview of the airway, eliminating errors due to artifacts caused by motion, etc. The fast speed of CT scanning now permits dynamic assessment of the central airways (24–26). We are convinced that our procedure is a change in interventional practice as the combined use of endobronchial ultrasonography, ultrathin bronchoscope providing real-time imagery, with the adjunct of flow–volume analysis, plus three-dimensional CT imagery provide a new method of correctly positioning stents and effecting positive results in patients. These procedures are now standard at our institution due to the relative ease and short time required, resulting in maximum quality of life to patients with malignant airway stenosis. Many recent studies (30–35) have shown improved expiratory flow limitation after placement of metallic stents or silicone stents in benign or malignant stenosis. In this study, we used mainly the Dumon stent, which is made of silicone. The Dumon Y stent appears to be particularly good for stenosis involving the carina. We selected uncovered Ultraflex nitinol stents as the additional stents used because of their resistance to dynamic compression. Furthermore, this stent can be implanted without occluding the side bronchus. To our knowledge, this is the first clinical study to investigate the management of airway stenosis focusing on the choke point as the primary site for the accurate placement of stents in humans. We believe that the results of our study of choke point in humans closely follows the physiologic models predicted by the wave-speed theory of expiratory flow limitation. This clinical study might provide useful information on the significance of the choke point for the planning of interventional pulmonology. We consider this study has provided insight, eliminating or simplifying many procedures used in the bronchoscopic treatment of emergency conditions.
The authors thank Prof. N. Ohya and Dr. J. Huang of the Internal Medicine of Kanazawa Medical University for invaluable comments on this manuscript. The authors also thank Prof. J. Patrick Barron of the International Communications Center of Tokyo Medical University and Mr. Michael Taylor of the Department of Integrated Arts and Sciences of Hiroshima University for critical reading of the manuscript.
Supported in part by a Grant-in-Aid for Cancer Research (12-01) from the Ministry of Health, Labor, and Welfare. Conflict of Interest Statement: T.M. has no declared conflict of interest; Y.M. has no declared conflict of interest; Y.I. has no declared conflict of interest; A.I. has no declared conflict of interest; K.K. has no declared conflict of interest; H.S. has no declared conflict of interest; M.D. has no declared conflict of interest; N.K. has no declared conflict of interest. Received in original form November 24, 2003; accepted in final form February 9, 2004
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ABSTRACT
METHODS
2 test. All results were presented as the mean ± SD. All tests of significance were two-sided, and p values of less than 0.05 were considered to indicate statistically significant differences. 
