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Right arrow Lung - transplantation

Ann Thorac Surg 2002;74:1934-1941
© 2002 The Society of Thoracic Surgeons

Original article: general thoracic

Endobronchial metallic stent placement for airway complications after lung transplantation

Longitudinal results

Karen E.A. Burns, MDa, Philip D. Orons, DOb, James H. Dauber, MDa, Wayne F. Grgurich, BSa, Larry W. Stitt, MSc, Sujatha Raghu, MDa, Aldo T. Iacono, MDa*

a Division of Pulmonary Transplantation, and Pulmonary, Critical Care Medicine, Division of , University of Pittsburgh Medical Center–Presbyterian Hospital, Pittsburgh, Pennsylvania, USA
b Division of Vascular and Interventional Radiology, University of Pittsburgh Medical Center–Presbyterian Hospital, Pittsburgh, Pennsylvania, USA
c Department of Epidemiology and Biostatistics, The University of Western Ontario, London, Ontario, Canada

Accepted for publication July 12, 2002.

* Address reprint requests to Dr Iacono, Division of Pulmonary, Allergy and Critical Care Medicine, Pulmonary Transplantation, A-714-2 Scaife Hall, 3550 Terrace St, Pittsburgh PA 15261 USA.
e-mail: iaconoat{at}msx.upmc.edu


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: In lung transplant recipients, bronchial stenosis (SB) and bronchomalacia (MB) result in obstructive airway disease and allograft dysfunction due to pulmonary infection. We hypothesized that endobronchial metallic stent placement for SB and MB would result in long-term improvement in respiratory function and rates of pulmonary infection.

METHODS: We studied symptomatic lung transplant recipients with bronchoscopic evidence of proximal airway complications (SB or MB) and a synchronous decline in forced expiratory volume in 1 second (FEV1) of at least 10% in the 6-month period before intervention. Stent placement was the primary intervention for SB and all focal MB lesions and for recurrent or refractory SB lesions failing a single initial attempt at balloon dilation. FEV1 and rates of pulmonary infection were assessed in the 12-month interval before and after stent placement. Spirometric evaluation was performed at 3-month intervals and compared with spirometry at the time of stent placement. The rates of pulmonary infection, determined by the number of antibiotics prescribed, was determined before and after endobronchial correction.

RESULTS: Thirty recipients underwent a total of 75 procedures (50 stent insertions and 25 balloon dilations). FEV1 improved significantly after stent placement compared with base line (1.29 ± 0.43 L) as follows: 3 months, 1.45 ± 0.50 L, p = 0.014; 6 months, 1.59 ± 0.57 L, p = 0.002; 12 months 1.59 ± 0.53 L, p = 0.006. The infection rate decreased from the 12-month period preceding stent insertion to the corresponding period after stent insertion (6.97/100 days ± 6.33 versus 5.74/100 days ± 7.76, p = 0.018). Recurrent SB occurred in 17.3%. No life-threatening complications occurred after stent placement and no deaths were attributed to stent malfunction or malposition.

CONCLUSIONS: In lung transplant recipients with SB and MB, maintenance of airway patency by stent placement is safe and resulted in improvements in lung function and reduced pulmonary infection rates for up to 1 year after their insertion.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
The therapeutic benefit of pulmonary transplantation is limited by poor long-term outcomes. Airway complications are reported to occur in 7% to 14% of lung transplant recipients and are characterized by either fixed anatomic obstruction due to the formation of exuberant fibrotic tissue (bronchial stenosis [SB]) or dynamic obstruction on exhalation (bronchomalacia [MB]) [1–3]. Airway complications manifest with marked decrements in pulmonary function and morbidity due to the occurrence of postobstructive infections in immunocompromised hosts [4–6]. Treatment options to alleviate bronchial narrowing include silicone stents, expandable metallic stents, balloon dilatation, laser debridement, and operative revision [7].

With recent advances in metallic stents, it is technically feasible to attain and maintain airway patency in both mainstem bronchi and in lobar bronchi where significant MB and SB may occur after lung transplantation. We present our results using endobronchial metallic stents to palliate airway complications. To assess the long-term efficacy of endobronchial correction with permanent metallic stent insertion, we focused on change in longitudinal spirometry and infection rates as the primary outcome measures. Previous studies have demonstrated short-term benefit after stent insertion. However, short-term benefits may be negated by the presence of an endobronchial foreign body or recurrent formation of granulation tissue leading to late reductions in pulmonary function and increased rates of infection. The long-term consequences of endobronchial metallic stent insertion for the palliation of airways complications in lung transplant recipients were determined. We hypothesized that longitudinal spirometric indices would improve after metallic stent insertion for SB and would be sustained for 1 year; improvement in lung function would be evident after stent insertion for the correction of MB; and infection rates per 100 patient-days of survival would decrease significantly from the 12-month period before intervention to the 12-month period after correction.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
Definition and patient population
Between February 1996 and April 1999, lung transplant recipients with bronchial obstruction necessitating stent insertion to attain luminal patency and a concurrent decline in FEV1 of at least 10% were analyzed. All cases were identified at the time of surveillance bronchoscopy performed under conscious sedation. Bronchial stenosis was defined by the presence of stricture formation or granulation tissue resulting in compromise of at least 50% of the luminal diameter, whereas significant MB was defined as dynamic occlusion of at least 50% of the lumen diameter on expiration. Once identified by bronchoscopic assessment, helical computed tomography (CT) with three-dimensional reconstruction was obtained to measure the diameter and length of the diseased endobronchial segment.

Techniques for endobronchial correction
All procedures were performed as a collaborative effort between the Departments of Pulmonary Transplantation and Interventional Radiology using flexible fiberoptic bronchoscopy and fluoroscopic-guided transcatheter techniques under either general anesthesia or conscious sedation. Procedures in the Department of Radiology were performed under general anesthesia, necessitating placement of a No. 8 endotracheal tube so as to admit a 4.9-mm bronchoscope; the remaining procedures were performed in the bronchoscopy suite using conscious sedation, topical endobronchial anesthesia and supplemental oxygen. In the former setting, a 9F introducer sheath (Boston Scientific, Natick, MA) was placed extending into the endotracheal tube, using a standard Y adapter to permit entry of a balloon or stent without risk of leakage of anesthetic gases. Digital bronchography was performed using a hand-injection of 6 to 8 mL nonionic contrast media (Optiray 320, Ioversol 68%, Mallinckrodt Inc, St. Louis, MO) through a 5F multi-sidehole straight catheter. Digital subtraction acquisition at 6 frames per second was performed on a Siemens Multistar angiography unit (Siemens, Germany). Access to lobar bronchi was achieved using standard catheter and guidewire techniques, frequently using hydrophilic, steerable guidewires (Boston Scientific). Measurement of bronchial dimensions obtained by helical CT scans was confirmed by bronchography.

Procedures in the bronchoscopy suite were performed under conscious sedation with topical anesthesia and supplemental oxygen. After bronchoscopic localization of the involved areas, a 180-cm guidewire (Super stiff, Boston Scientific) was advanced through the lesion under direct bronchoscopic guidance through the channel of the bronchoscope. The bronchoscope was subsequently retracted while maintaining access to the lesion with a guidewire to facilitate the transoral passage of balloon catheters or stents. Before removal of the bronchoscope, a combination of bronchoscopic and fluoroscopic visualization was used to identify and mark the site of pathology using radiopaque metallic markers affixed to the anterior chest wall.

Balloon dilation was performed using high-pressure angioplasty balloons (Marshall, Blue Max, Boston Scientific) inflated for 20 to 30 seconds. Balloon-expandable (Palmaz, Johnson and Johnson, Warren, NJ) and self-expanding stents (Wallstent, Schneider, Minneapolis, MN or Symphony, Boston Scientific) were used. Self-expanding stents were positioned by feeding a delivery system comprised of a 7F catheter over a 0.035'' guidewire so as to center the radiopaque stent markers and catheter positioning markers within the malacic or stenotic segment. As the sheath was retracted, the distal radiopaque deployment marker moved proximally and the stent was deployed. Alignment of the distal and proximal radiopaque markers confirmed stent deployment.

Patient follow-up
Patients received azathioprine, prednisone and either tacrolimus or cyclosporine as maintenance immunosuppressive therapy. Episodes of acute rejection were treated with pulse solumedrol while episodes of refractory rejection were treated with antithymocyte globulin. All patients underwent surveillance bronchoscopy, with bronchoalveolar lavage and transbronchial biopsy performed at 2- to 3-month intervals during the first year after transplantation and after endobronchial correction and at 4- and 6-month intervals in the second, third, and subsequent posttransplant years. Tests of pulmonary function were performed routinely at 2- to 3-month intervals. Pulmonary function data were collected for the 3- and 6-month periods before the intervention, at the time of endobronchial intervention, and at 3, 6, and 12 months after the intervention. For inclusion in the study, spirometry must have been completed within 35 days for the 3-month interval data and within 45-days for 1-year data. Surveillance transbronchial biopsies documented all episodes of acute rejection (grade A1–A4) and episodes of clinically significant (at least grade A2a) rejection. The number of acute rejection events per 100 patient-days in the 1-year period before and after intervention was determined through a lung transplant registry database. A manual chart review was performed to determine the number of antibiotic prescriptions issued per 100 patient-days before and after endobronchial correction.

Informed consent was obtained before all endobronchial interventions. Patients were evaluated for immediate technical success defined as restoration of a normal or near normal bronchial lumen with less than 10% residual narrowing. Complications of endobronchial dilatation were recorded and evaluated. This protocol was reviewed and approved by the Institutional Review Board.

Statistical analysis
Serial tests of pulmonary function were examined pre and postintervention to assess for immediate benefit and serially over a 12-month period to evaluate for longitudinal changes compared with the time of intervention by t tests using pairwise comparisons. A repeated-measures analysis of variance (ANOVA) was conducted on all serial spirometric measures. Further, a multivariate ANOVA was conducted to ascertain whether base line immunosuppressive therapy or the addition of mycophenolate mofetil (MMF) or aerosolized cyclosporine for recurrent rejection contributed significantly to the observed improvements in serial longitudinal FEV1 measurements from base line. Subgroup analyses were conducted to assess the benefit of the intervention based on the underlying lesion (MB versus stricture), transplant type (single versus double) and by the presence or absence of bronchiolitis obliterans (OB) at the time of initial intervention. Rates of infection per 100 patient-days pre and postintervention were tabulated and compared using the Student’s paired t test. The denominator, representing the 1-year time interval, was tabulated and averaged per 100 patient-days for each patient.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
Between February 1996 and May 1999, 30 of 431 (6.9%) transplants at risk, with telescoping anastomoses, developed significant airway complications. Initial lesions included 13 patients with SB, presenting an average of 559 ± 853 days posttransplant (median 182.5 days, range 46 to 2463 days), and 17 patients with MB, presenting an average of 1514 ± 1126 days posttransplant (median 1482 days, range 83 to 3027 days). The mean age was 39.2 ± 11.7 years at the time of transplantation (Table 1). Fifteen patients were analyzed as single-lung recipients and 15 patients were analyzed as double-lung recipients including 1 heart–lung transplant recipient. Two patients presented with synchronous lesions, 1 with SB and MB and another with bilateral MB lesions, and were analyzed as SB and MB, respectively. Ten patients had OB at the time of their first intervention, whereas 20 had no histopathologic evidence of OB. Base line immunosuppressive therapy consisted of tacrolimus in 19 patients and cyclosporine in 11 patients. Fifteen patients were treated with MMF before stent insertion and in 4 individuals MMF was added after endobronchial intervention. Treatment with aerosolized cyclosporine pre-dated stent insertion in 5 patients and followed insertion in 9 patients.


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  		Table 1. Demographic and Intervention Data

 
A total of 75 procedures were performed on 73 occasions in 30 lung transplant recipients including 25 balloon dilations and 50 stent insertions (32 Palmaz stents, 10 Wallstents, and 8 Symphony stents) for 39 episodes of SB and 23 episodes of MB including 13 stent revisions (7 stent-within-a-stent, 4 balloon dilations, 2 replacements) (Table 2). Sixty-three procedures were performed in the radiology department under general anesthesia, 11 procedures were performed in the bronchoscopy suite, and one procedure, a stent removal, was performed in the operating room. Procedures were performed at 36 mainstem bronchi and 39 lobar airways, including the bronchus intermedius and left upper lobe. All 30 patients underwent stent insertion for either SB or MB. Six patients presenting with SB who were initially treated with balloon dilation subsequently required stent insertion for refractory stricture formation. Of the 25 balloon dilations, 6 were performed as a primary intervention for SB, 18 were performed to modify in situ stents (10 Palmaz, 6 Wallstents, 2 Symphony stents) and one procedure was performed for a new focus of SB. Eleven (36.7%) of 30 patients required only one intervention to achieve patency whereas 19 (63.3%) of 30 patients required more than one procedure (range 2 to 12) to maintain patency.


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  		Table 2. Endobronchial Interventions Performed Including Number and Rationale for Each Intervention

 
Longitudinal spirometric indices
When tests of pulmonary function were compared immediately before and an average of 43.4 days ± 39.0 postintervention, neither the FEV1 nor the forced vital capacity increased significantly from immediately before intervention to postintervention (1.35 ± 0.45 L to 1.43 ± 0.52 L, p = 0.219 and 2.35 ± 0.84 L versus 2.36 ± 0.81 L, p = 0.228). Review of longitudinal spirometry for all patients revealed a 21% decline in the mean change in FEV1 from 6 months before intervention (1.56 ± 0.28 L, p = 0.012) to the time of intervention (1.29 ± 0.43 L) and a 15% decline from the mean FEV1 (1.48 ± 0.30 L, p = 0.061) at 3 months before intervention. After initial stent insertion and efforts to ensure luminal patency, a 12% increase in mean change in FEV1 was apparent at 3-months (1.45 ± 0.31 L, p = 0.014) after correction. This increased further to a 23% improvement in mean FEV1 at 6 months after intervention (1.59 ± 0.34 L, p = 0.002), which was sustained at 23% (1.59 ± 0.30 L, p = 0.006) at 1 year postcorrection (Fig 1). For patients with MB, statistically significant changes in mean FEV1 pre- and postintervention compared with the time of the first intervention were apparent at 6 months preintervention, and at 3 and 12 months postintervention. The percent change in mean FEV1 compared with intervention FEV1 (1.24 ± 0.51 L) was 15% at 3 months (1.42 ± 0.55 L, p = 0.006), 15% at 6 months (1.43 ± 0.64 L, p = 0.117) and 24% at 12 months (1.54 ± 0.64 L, p = 0.011) after correction. Whereas for those with SB, statistically significant changes in mean FEV1 were apparent only at 6 months postintervention and not sustained at 12 months. The percent change in mean FEV1 compared with intervention FEV1 for those with SB compared with intervention values (1.36 ± 0.29 L) was 10% at 3 months (1.50 ± 0.45 L, p = 0.290), 34% at 6 months (1.82 ± 0.38 L, p = 0.006), and 21% at 12 months (1.65 ± 0.42 L, p = 0.128) postintervention (Fig 2).



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  		Fig 1. Mean serial longitudinal forced expiratory volume in 1 second (FEV1) preendobronchial and postendobronchial metallic stent placement over time, where t = 0 months is the time of the first endobronchial intervention (n = 30).

 


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  		Fig 2. Change in mean forced expiratory volume in 1 second (FEV1) compared with the time of intervention for bronchial stenosis (shaded bars) and bronchomalacia (open bars). *p < 0.05.

 
Subgroup analysis revealed a strong trend toward sustained improvement with endobronchial correction in single-lung transplant recipients with statistically significant improvements in FEV1, compared with the time of intervention (1.23 ± 0.28 L), at 3 months (1.49 ± 0.29 L, p = 0.010), 6 months (1.60 ± 0.36 L, p = 0.024) and 12 months (1.61 ± 0.31 L, p = 0.011) postintervention compared with double-lung recipients at intervention (1.36 ± 0.55 L) at 3 months (1.42 ± 0.64 L, p = 0.341), 6 months (1.59 ± 0.72 L, p = 0.052), and at 12 months (1.57 ± 0.69 L, p = 0.246) postcorrection. Double-lung recipients did not differ significantly from single-lung transplant recipients with respect to the number of episodes of acute cellular rejection (ACR) before and after stent insertion, in the prevalence of OB at the time of intervention or in the development of recurrent stricture or the need for subsequent procedures. Patients without OB at the time of intervention similarly demonstrated statistically significant improvements in FEV1, compared with intervention values (1.25 ± 0.35 L), at 3 months (1.41 ± 0.42 L, p = 0.045) and 6 months (1.57 ± 0.46 L, p = 0.008)m with nearly significant values at 12 months (1.50 ± 0.44 L, p = 0.073) after the correction. Those with OB also demonstrated improvements in FEV1 compared with base line (1.37 ± 0.57 L) that, although not statistically significant at 3 and 6 months (1.56 ± 0.68 L, p = 0.058 and 1.64 ± 0.82 L, p = 0.095, respectively), revealed a trend toward significance and became significant at 1 year (1.82 ± 0.71 L, p = 0.003) after correction (Table 3).


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  		Table 3. Serial FEV1 Data

 
Changes in forced vital capacity compared with the time of intervention (2.20 ± 0.80 L) demonstrated statistically significant declines from 6 months (2.38 ± 0.73 L, p = 0.037) and 3 months (2.45 ± 0.98 L, p = 0.052) before intervention and significant improvement at 6 months (2.49 ± 0.86 L, p = 0.035) after correction with no apparent differences between the subgroups. Changes in FEF 25 to 75 paralleled changes in FEV1, revealing statistically significant improvements at 3 months (1.09 ± 0.73 L, p = 0.023), 6 months (1.15 ± 0.78 L, p = 0.010) and 12 months (1.16 ± 0.84 L, p = 0.038) after intervention compared with base line (0.82 ± 0.47 L) and more favorable responses in single-lung recipients, those with MB and those without OB (data not shown).

Infection and rejection rates
The number of prescriptions issued per 100 patient-days decreased significantly from 6.97 ± 6.33 preintervention to 5.74 ± 7.76 postintervention (p = 0.018). Similarly, the number or courses of antibiotics per 100 patient-days of survival decreased significantly from 3.75 ± 3.21 to 3.24 ± 4.86 (p = 0.010). The total number of episodes of acute rejection (grade A1–A4) also decreased significantly from 1.48 ± 1.53 episodes per 100 patient-days preintervention to 0.61 ± 0.72 episodes per 100 patient-days postintervention (p = 0.0004). Further, the number of episodes of clinically significant rejection (at least grade A2a) decreased significantly from 0.83 ± 1.03 to 0.36 ± 0.56 episodes per 100 patient-days after insertion (p = 0.008) (Table 4).


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  		Table 4. Secondary Outcome Data

 
Complications and survival
The overall complication rate was 17.3% (13/75) of all procedures performed involving 26% (13/50) of the stent insertions and occurring in 33% (10/30) of the patients. Complications were considered minor in 13% (10/75) and significant in 4.0% (3/75). Complications included one spontaneous stent fracture, two iatrogenically damaged stents (one at the time of bronchoscopy and one by a suction catheter at the time of a later endotracheal intubation), seven episodes of collapse (six partial, one complete in a double-lung transplant recipient), and three episodes of lobar obstruction due to occlusion of the left lower lobe orifice with stenting of the left mainstem bronchus and the right middle and lower lobe orifices with a stent in the bronchus intermedius. Complications occurred with five SB lesions and eight MB lesions at nine mainstem bronchi and four lobar bronchi. No life-threatening complications occurred during or immediately after stent placement and no deaths were directly attributed to stent malfunction or malposition. At the 12-month follow-up, 22 patients were alive and 8 patients were dead. Causes of death included pulmonary embolism in 1 patient, chronic respiratory failure in 4 patients and infection in 3 patients. The latter included 2 cases of extrapulmonary sepsis and 1 case of Aspergillus pneumonia and fungemia.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Therapeutic options for the correction of airways complications include balloon dilation, laser photocoagulation, silicone or expandable metallic stents, and operative revision. Although laser photocoagulation may successfully treat small segments of granulation tissue resulting in intraluminal obstruction, this technique is ineffective for luminal compromise related to MB or circumferential scarring. Endobronchial correction of airway complications by laser and balloon dilatation, while permitting immediate relief of symptoms, is often besieged by recurrence, necessitating more definitive palliation with endobronchial stent placement. Silicone stents have fallen out of favor due to their narrow internal lumen to external lumen diameter ratio, tendency to migrate, and interference with mucociliary clearance, which may predispose patients to the development of inspissated secretions and infection [8]. In addition, silicone stents are confined to endobronchial placement in mainstem bronchi and consequently when inserted into the right mainstem bronchus may obstruct the right upper lobe orifice. Conversely, wire stents have a more favorable internal to external diameter profile and are technically easier to insert [4]. Metallic stents frequently become epithelialized into the bronchial wall limiting the possibility of migration and allowing for optimal pulmonary hygiene [9]. Wire stents may be categorized as balloon-expandable or self-expanding. Balloon-expandable stents include Palmaz stents while self-expanding stents include Wallstents (Schneider Inc), Symphony nitinol stents (Boston Scientific, Natick, MA), and Gianturco stents (Cook Inc, Hertfordshire, United Kingdom). Resistance to compressive forces or "collar strength" is a common attribute of both stent types whereas only self-expanding stents possess radial expansile forces, which permit self-recovery after deformation. Conversely, whereas balloon-expandable stents collapse readily and may therefore be removed through a rigid bronchoscope, self-expanding stents have angulated struts that permit better stent-to-wall opposition but hinder efforts at their subsequent removal.

This retrospective cohort study provides novel information on longitudinal outcomes in lung allograft recipients in whom airway complications, including SB and MB, develop in the posttransplant period. We have demonstrated that SB is an early event occurring after a median of 182.5 days posttransplant with most cases (10/13, 77%) occurring during the first transplant year and the rest (3/13, 23%) occurring later. Conversely, MB is a late event that developed after a median of 1482 days posttransplant with 12/17 cases (71%) occurring after the first year posttransplant. We also demonstrated that longitudinal spirometry declines, on average, by 21% in the 6-month period before presentation and did not improve immediately postintervention. However, bronchoscopy performed at the time of the intervention demonstrated 41 (56.2%) of 73 BAL specimens with concomitant lower respiratory tract infection as defined by at least 104 cfu/mL. Predominant organisms included Pseudomonas aeruginosa (18/41), Aspergillus species (9/41), Candida albicans (6/41), and gram-negative bacilli (9/41). In addition, transbronchial biopsies revealed concomitant episodes of synchronous acute rejection (grade A1 to A4) in 21 (28.8%) of 73 procedures, and 6 (8.2%) of 73 procedures were clinically significant (A2–A4). After correction there was an improvement in FEV1 of 23% that was apparent at 6 months and maintained for at least 1 year. Further, select subgroups including single-lung recipients, patients with MB as their presenting lesion, and patients without evidence of OB at the time of first intervention benefited to a greater degree. The single-lung recipient with compromised ventilation, due to either SB or MB, appears to be particularly vulnerable. A multivariate ANOVA revealed that neither base line immunosuppressive therapy nor the addition of MMF or aerosolized cyclosporine contributed significantly to the observed improvements in serial, longitudinal FEV1 from base line.

Attaining and maintaining luminal patency with a foreign body did not result in increased infectious episodes but rather a decrease in infection rates. We postulate that incorporation of the stent into the wall of the bronchus improved both luminal patency and mucociliary clearance and consequently manifested with fewer treated intercurrent infections in this "at-risk" immunocompromised population. Interestingly, a decrease in rejection rates was also noted in the 12-month period after metallic stent insertion. Possible explanations for this observation include less cytokine activation due to enhanced pulmonary toilette with decreased neutrophil activation and inflammation and the tendency for rejection episodes to diminish in frequency over the posttransplant course.

The procedures performed were necessary to preserve allograft ventilation and to facilitate mucociliary clearance. The major adverse complication rate was acceptable. Most complications were minor and identified at surveillance bronchoscopy. The latter were managed with insertion of a stent within a preexisting stent in 7 patients, balloon dilation in 4 (including three episodes of partial collapse and one fracture), and laser modification in 4 patients to facilitate ventilation to a lobar bronchus. Two stents required removal, one in the operating theater and one with a snare in the bronchoscopy suite. No life-threatening events occurred during or immediately after stent placement and no deaths were attributed to stent malfunction or malposition.

Higgins and colleagues [10] previously reported their experience using predominantly Gianturco metal stents in 14 patients who developed SB after lung and heart–lung transplantation, noting that 6 patients required multiple stent placements to achieve airway patency. Concurrent infection was present in 12 patients with Aspergillus fumigatus isolated in 6 patients, Pseudomonas aeruginosa isolated in 6 patients, Staphylococcus aureus in 2 patients, and Klebsiella pneumoniae in 1 patient. The mean increase in FEV1 was 117% in 10 patients after stent insertion [10]. In our study, 19 (63.3%) of 30 patients required multiple procedures to maintain luminal patency compared with 6 (42.9%) of 14 patients in their study. Recurrent stricture formation at the same location was the predominant reason for multiple interventions in our study with new foci of stenosis in a different anatomic region being the second most common reason. Restenosis appears to be related to the unrestrained proliferation of myofibroblasts, rather than a reaction to the foreign body itself, as no patient with MB who required stent insertion developed a stricture at the same location. We also documented the prevalence of infection, at the time of presentation, to be 56.2% compared with 85.7% by Higgins and coworkers [10], with a similar spectrum of organisms. Further, we noted the prevalence of rejection at the time of presentation with airway complications to be 28.8%.

Kshettry and colleagues [3] noted complications occurring in 16.9% of single-lung anastomoses compared with 12.0% in double-lung recipients. Initial management of stenotic lesions included attempts at balloon dilation. Those patients failing serial attempts with balloon dilatation underwent metallic stent placement, laser recanalization, or silicone stent placement. Eight patients had nine stents (two Palmaz, five Gianturco, and two Wallstents) positioned for SB and MB with a statistically significant change in mean FEV1 after insertion [3]. Their incidence of anastomotic complications was higher than our rate of 6.9% using telescoping anastomoses. The authors, however, acknowledged a decrease in the complication rate with telescoping the anastomosis compared with omental wrapping. Our data support that initial balloon dilatation for SB was ineffective in achieving sustained luminal patency. In our study, all 6 patients initially treated with attempted balloon dilatation required subsequent stent placement.

Susanto and coworkers [1] subsequently reported their experience in 9.3% of anastomoses at risk involving 11 episodes of SB and 5 episodes of MB and including 4 concurrent presentations. Balloon dilation was successful as the sole intervention in 3 patients with SB, whereas 7 others required a total of 11 Palmaz stents. Six patients had pre- and poststent placement spirometry revealing a mean percent change in FEV1 of 43% ± 44%, whereas 1 patient with chronic rejection was noted to have worsening of spirometry after stent placement. Their complications were similar in type and frequency to those in our study and included two episodes of partial dehiscence of the stent from the bronchial wall, two episodes of lobar occlusion, three episodes of stent migration, and one case of longitudinal stent collapse [1].

More recently, Lonchyna and coworkers [11] published their experience with 28 stents at 24 sites of SB and MB in 18 patients, representing 15.9% of airways at risk. Four patients required multiple interventions with fewer interventions required for the Wallstent compared with the Palmaz stent (1.28 versus 5.22). In our study, complications were more frequent with Palmaz stents (36.7%) than with the Wallstent (10%) or the Symphony stent (12.5%). We postulate that this difference is attributable to their mechanical design, short length, and inability to resist deformation with coughing. Lonchyna and colleagues [11] also noted a significant change in mean FEV1 from a preintervention mean of 1.19 ± 0.64 L to 2.06 ± 0.70 L at an undisclosed time interval after insertion [11]. In the setting of concomitant infection and rejection, we did not witness an immediate improvement in spirometric indices until after the inflammatory process resolved. In our study, 11 (36.7%) of 30 patients required only one intervention to achieve patency whereas 19 (63.3%) of 30 patients required more than one procedure (range 2 to 12) to maintain patency. The requirement for reintervention was dominated by the development of restenosis in patients with fibrous stricture formation and the requirement for stent modification due to a mechanical complication. Orons and associated [12] have previously demonstrated in a cohort of 25 lung transplant recipients treated predominantly with Palmaz stents that the 6-month patency rate for fibrous stricture formation was 29% compared with 71% in those treated for MB. The fibrous stricture formation was attributed predominantly to recurrence and MB attributed to mechanical failure of the Palmaz stent [12].

Possible confounding factors in the interpretation of the data include the fact that this was analysis retrospective and therefore was possibly subject to ascertainment bias. Spirometric indices, however, were selected according to strict predefined criteria based on time relative to presentation. In the event that two tests of pulmonary function were available, the lower value was chosen so as to bias against the predefined hypothesis. An additional possible confounding effect is the tendency toward regression toward the mean, in that if the intervention occurred at a time point when a measurement was unusually low, then subsequent observations after the intervention will tend to be closer to the average value independent of the effect of the intervention. To address this concern, in addition to the standard repeated-measures ANOVA, a further paired t test analysis, including all sequential tests of pulmonary function in the University of Pittsburgh Lung Transplant Registry for the study patients, was performed. When comparisons were made for short time periods before and after stent placement (± 10 days and ± 30 days), significant improvements in the mean change in FEV1 of 0.165 L (95% CI 0.05, 0.28) and 0.139 L (95% CI 0.06, 0.19), respectively, were noted. Improvements in spirometry may have been due to a high level of bronchoscopic surveillance and meticulous attendance to the maintenance of airway patency. Concurrent interventions were assessed by means of a multivariate ANOVA analysis and found not to have an effect. Due to the practice of performing surveillance bronchoscopy at our institution, lavage and transbronchial biopsy data were available for all patients to assess the effect of stent placement on longitudinal infection and rejection rates. We cannot exclude the possible presence of survivor bias in our analysis of longitudinal spirometric indices as 4 of 8 deaths were secondary to chronic rejection. Our death rate of 8 (26.7%) of 30 patients occurring on average 44.4 months posttransplant (median 28.4 months, range 8.3 to 106.2 months) is comparable with the International Society for Heart and Lung Transplantation registry data. This suggests that when meticulous attention is paid to ensuring luminal patency, this patient population is not at higher risk of premature death compared with transplant recipients without endobronchial complications. We conclude that in lung transplant recipients with SB and MB, maintenance of airway patency by stent placement is safe and resulted in improvements in lung function and reduced pulmonary infection rates for up to 1 year after their insertion.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
The authors wish to express their gratitude to M. Kurs-Lasky, MS, and H. Rockette, PhD, in the Department of Biostatistics for their contributions to the statistical analysis of the data.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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