Lung transplant anastomotic airway complications and bronchoscopic management

Introduction

Airway complications in the lung transplant recipient have been recognized since the first successful transplantation by Dr. James Hardy in 1963. Airway complications are a continual source of morbidity and mortality in this population with early incidence ranging from 60% to 80%. As the field grew and techniques surrounding transplantation improved, the incidence of airway complications reduced to approximately 2% to 18% (1-5).

Airway complications are known to arise in the early and late posttransplant period with the majority occurring in the first year of transplantation. Complications are varied in their presentation, location, and occurrence, and include regional ischemic necrosis, dehiscence, hypertrophic granulation tissue, fistula, tracheobronchomalacia and bronchial stenosis. The anastomosis is most susceptible to complications, with up to a third of patients experiencing a second airway complication within 2 years of their first (3).

Herein, we provide a comprehensive review of the risk factors, clinical manifestations, diagnostic classifications, and management strategies of lung transplant airway complications.

Anatomical considerations

Lung anatomy plays a central role in understanding the etiology of airway complications. The lung has a dual blood supply from the bronchial and pulmonary arteries, but the bronchial circulation is not routinely included during lung transplantation. Bronchial arteries arise from the descending thoracic aorta or the intercostal arteries and ultimately terminate in the submucosal plexus of the bronchial wall (6). The proximal mainstem bronchi are primarily supplied by the bronchial circulation, although a small contribution is derived from the pulmonary arterial system through retrograde collaterals. Consequently, the transplanted lung is wholly dependent on retrograde flow via the low pressure, poorly oxygenated pulmonary arterial circulation for bronchial and anastomotic healing. This process continues for 2 to 4 weeks posttransplant placing the anastomosis and distal airways at risk for ischemic injury until revascularization of the bronchial arteries occurs (7,8).

Reestablishing the bronchial circulation at the time of transplantation has been performed successfully using a technique called bronchial artery revascularization (BAR). The experience of two large transplant centers performing BAR was described in a series of 131 patients at Copenhagen and the Cleveland Clinic. The procedure had an overall success rate of 90% with normal airway healing observed in all patients undergoing BAR. The risk of bleeding is higher with BAR, but safety outcomes were similar between BAR and non-BAR groups (9). While these results are promising, BAR is not routinely performed across transplant centers, supporting the need for multicenter studies to establish the safety and efficacy of this procedure in preventing airway complications.

Risk factors

Multiple risk factors have been linked to airway complications after lung transplantation. A review of the most common risk factors including perioperative, donor and recipient and immunosuppressive medications is provided below.

Perioperative factors

The surgical technique employed in lung transplantation has long been known to influence the development of airway complications. Over the past several decades, the surgical approach to lung transplantation has markedly evolved from the original description of a tracheal anastomosis to that of an end-to-end bronchial anastomosis. The modern-day technique at most institutions is the creation of a direct end-to-end anastomosis as close to the secondary carina as possible. By minimizing the length of the donor bronchus, the anastomotic blood supply is better preserved, and wound healing is more effective (10). Additive techniques such as wrapping the anastomosis with a vascularized pedicle or omental flap may increase the time and difficulty of the procedure without reducing the incidence of airway complications (11). Telescoped anastomoses may be necessary in the event of a donor-recipient size mismatch, but in general should be avoided due to an increased risk for airway obstruction. The telescoped airway is significantly narrowed and may be secondarily compromised by infection with at least one group reporting airway complication rates as high as 32% using this technique (12).

Organ handling and preservation are additional techniques that influence graft perfusion and mucosal healing (13). Preservation solutions that combine low-potassium dextran with glucose and utilization of antegrade plus retrograde administration techniques have been shown to lengthen preservation times and reduce the risk of airway ischemia (14-17). Although donor ischemic time intuitively should impact postoperative airway complications, no study to date has found a direct correlation between the two (3). In fact, for patients undergoing bilateral lung transplantation, the second anastomosis is no more likely to develop an airway complication (18-20). Postoperatively, patients are at risk for primary graft dysfunction, a severe form of ischemia-reperfusion acute lung injury resulting in diffuse alveolar damage, increased vascular permeability and airway ischemia. These patients often require extended periods of mechanical ventilatory support and higher levels of positive end expiratory pressure (PEEP). Greater PEEP values can disrupt bronchial mucosal blood flow, impairing anastomotic healing. Early rejection episodes (within the first 3 months) have also been linked to airway complications due to perturbations in the bronchial microcirculation from increased pulmonary vascular resistance and reduced collateral pulmonary blood flow (13,21).

Infection and microbial colonization pre- and post-operatively can also significantly increase the risk for airway complications. Multiple bacterial and fungal organisms have been implicated (4,21). Aspergillus species, for example, have been shown to increase the risk for airway necrosis (22). As such, clinicians should have a low threshold for investigating and aggressively treating infections in the perioperative period.

Donor and recipient factors

Awori Hayanga and colleagues, in a large retrospective study using shared data from the United Network for Organ Sharing, identified male gender, advancing recipient age and pretransplant admission to the ICU as risk factors for airway complications (23). Van De Wauwer et al. in Belgium, also found that taller recipients and prolonged exposure (between 50 and 70 hours) of the donor to mechanical ventilation prior to organ procurement significantly increased the risk for airway complications (24). Factors such as body mass index, organ donor type (brain-dead versus donors after cardiac death), cytomegalovirus status, transplant indication and preoperative corticosteroid use have not demonstrated a consistent impact on the incidence of airway complications (13,21,22,25-28).

Immunosuppression

Immunosuppressant medications are of paramount importance to the survival of the lung allograft. The typical regimen includes a combination of a calcineurin inhibitor, an anti-metabolite, and corticosteroids. These medications increase susceptibility for infection, which if left untreated can increase the risk for airway complications. It has long been debated that steroid impair healing of the anastomosis (29); however, recent studies have shown that steroids in the perioperative period do not compromise airway healing (22,29,30).

Sirolimus has also been used in posttransplant immunosuppressive regimens. It acts by inhibiting the mammalian target of rapamycin and has powerful immunosuppressive and antiproliferative properties. Studies found that sirolimus use in the early posttransplant period was associated with an increased incidence of airway complications, which in some cases were fatal. Therefore, it is recommended that sirolimus be avoided for at least 90 days posttransplant pending complete airway healing (31,32).

Classification of airway complications

Multiple grading systems have been used to classify airway complications, but no single method has been widely adopted across transplant centers. An early grading schematic proposed by Couraud et al. assessed the anastomosis for ischemia and necrosis fifteen days posttransplant. The authors then used this information to subsequently predict anastomotic complications (33). The major limitations of this system included the subjective grading and the inability to capture the full spectrum of airway complications. Shennib and Massard later proposed a classification system that built on the work of Couraud, but included strictures and bronchomalacia in their evaluation (34).

Chhajed et al. many years later expanded the grading system for airway complications to include an assessment of the sutures and presence of granulation tissue. This system also described complications at or distal to the anastomosis including bronchial stenosis, malacia and dehiscence (35). Dutau et al. in 2013 published the macroscopic, diameter, suture (MDS) grading system, which described the airway abnormality and rated the severity of the complication (36).

A recently published ISHLT consensus statement proposes a universal grading system for adoption across lung transplant centers. This system has four pathophysiologic categories: (I) ischemia and necrosis, (II) dehiscence, (III) stenosis and (IV) malacia. Each category is then further subdivided into the location and extent or severity of the airway complication. The grading system should be applied at regular time intervals within 2–3 weeks of lung transplantation (37).

Airway necrosis and dehiscence

Varying degrees of airway ischemia and necrosis are common during the first few weeks post transplantation (Figure 1). These findings are thought to reflect the normal airway healing process during which the necrotic mucosa sloughs and healthy vascularized tissue emerges. Airway dehiscence is a rare, but feared complication with high morbidity and mortality that typically arises during the first 1–6 weeks posttransplant. Dehiscence presumably exists on a continuum of ischemic injury and necrosis, and may occur despite an uneventful surgery and postoperative course (38). Prolonged exposure to mechanical ventilation and fungal colonization are proposed risk factors for dehiscence (39).

Figure 1 Airway necrosis.

Diagnosing an airway dehiscence is challenging as the clinical presentation often mimics other complications arising during the early posttransplant period. Red flags that should alert the clinician to a possible dehiscence include a persistent pneumothorax or pneumomediastinum, difficulty weaning from mechanical ventilation and sepsis of unclear origin. Chest computed tomography (CT) is a highly sensitive and specific technique for identifying a dehiscence. CT findings include bronchial wall defects, luminal narrowing and peribronchial air around the anastomosis (40). Flexible bronchoscopy, however, remains the gold standard modality for diagnosis of anastomotic dehiscence (Figure 2). Bronchoscopic inspection of the anastomosis as part of a surveillance protocol or for clinical reasons may provide clues to an airway that could undergo dehiscence. Severe necrosis and loosening of sutures are findings that may suggest an anastomosis is at-risk of dehiscing (1,39).

Figure 2 Dehiscence.

Management of necrosis and dehiscence depends on the location and severity of the defect. If necrotic mucosal slough is observed without evidence of bronchial wall necrosis, then a conservative approach can be taken, including debulking of necrotic debris, aggressive treatment of infection and frequent follow-up bronchoscopies. More severe bronchial wall necrosis and frank dehiscence often require endoscopic or surgical intervention (2,41). Success with bronchoscopic topical therapies such as alpha-cyanoacrylate glue for dehiscence closure is limited to case reports (42). A more common approach involves using an oversized uncovered self-expanding metallic stent (SEMS) to overlap the defect. This technique takes advantage of the SEMS tendency to form granulation tissue at the stent site, which in this case, stimulates healing of the dehiscence. The stent is typically removed after a few weeks as epithelization occurs. If the defect is still present then another oversized uncovered stent can be placed until the dehiscence is sealed. Silicone stents should be avoided as they fail to promote epithelization, and the force required for their insertion risks extending the defect (43). If conservative measures fail then surgery may be considered, including reanastomosis and possibly retransplantation.

Close monitoring after successfully managing the dehiscence is critical as these patients remain at risk for future complications including bronchial stenosis and malacia.

Granulation tissue

Hypertrophic granulation tissue is thought to reflect a robust inflammatory response to airway injury leading to an overgrowth of tissue, similar to a keloidal scar. The reaction typically occurs at the anastomosis within the first several months posttransplant. Signs and symptoms are related to endoluminal obstruction including cough, dyspnea and difficulty clearing secretions. A drop in peak expiratory flows may be seen during spirometry. Like other airway complications, suspicion for this abnormality should be confirmed bronchoscopically (44).

Several techniques can be used to manage excessive granulation tissue in the airway. Mechanical debulking using flexible or rigid forceps is one option, especially for minor obstructions. The beveled edge of the rigid bronchoscope can also be used to core out the tissue, but requires additional skills. Cryotherapy is the preferred modality at our institution since granulation tissue is very cryosensitive. This technique has the additive effect of providing excellent hemostasis during tissue ablation. The safety profile of cryotherapy is superior to that of heat-based modalities, which carry an increased risk for airway fires, bronchial perforation, and gas emboli. Conversely, cryotherapy can be used safely in areas of high oxygen concentration including around stents without risk of ignition (2,45). Mitomycin-C applied topically using pledgets is an adjunctive technique that may prevent recurrence of granulation tissue through inhibition of fibroblast proliferation (46).

Fistula

Fistula formation is an uncommon complication in the lung transplant population. Fistulous connections may occur between the airway wall and the pleura, vascular space, or mediastinum. Clinical findings of a bronchopleural fistula include shortness of breath, subcutaneous emphysema, and pneumothorax with a persistent air leak. Closure of the fistula can be accomplished surgically or bronchoscopically. The preferred approach is akin to management of a dehiscence using an uncovered stent to seal the defect (2).

A bronchovascular fistula is a rare and often fatal complication. The typical location of the defect is between the anastomosis and the pulmonary artery. A sentinel bleed may precede the development of massive hemoptysis. Management options are limited to endovascular stenting, fistula repair and transplant pneumonectomy (47-49).

Tracheobronchomalacia (TBM)

TBM is a condition characterized by softening of the supportive cartilage of the tracheal and bronchial wall and reduced tone of myoelastic elements. This results in cartilage weakening and endoluminal narrowing of at least 50% during forced expiration. The incidence of airway malacia in the posttransplant population is unknown. Recurrent infection and ischemic injury are suspected predisposing factors, or in some cases, the condition may have been missed in the donor lung prior to transplant. The malacic segment may be at the level of, distal or proximal to the anastomosis (50,51).

Clinical manifestations of TBM are often indistinguishable from other chronic lung pathologies. Dyspnea, cough, and inability to clear secretions are the most commonly reported symptoms. A characteristic, seal-like barking cough may arise during expiratory collapse of the posterior membrane reverberating against the anterior wall. Additional patient complaints may include wheezing, stridor and recurrent infections.

Diagnostic studies routinely employed for TBM include dynamic CT imaging and bronchoscopy. Paired inspiratory-dynamic expiratory CT imaging involves scanning the patient at end inspiration and during forced expiration. The change in cross-sectional area and sagittal diameters of the airway between inspiration and expiration may reliably predict the presence of TBM (52). Dynamic flexible bronchoscopy, however, remains the gold standard modality for diagnosing this condition (Figure 3). This procedure enables real-time visualization of the airway dynamics, degree of collapse, cartilage integrity and classification of the type and extent of TBM. During dynamic bronchoscopy, the patient is lightly sedated, and instructed to perform various maneuvers, including deep inhalation, cough, and forceful exhalation. The exam is repeated at different locations in the tracheobronchial tree to assess the extent of airway malacia. Operators are then able to calculate the airway cross-sectional area, although inter- and intra-observer disagreement exists (50,53).

Figure 3 Bronchomalacia. BI, bronchus intermedius; RUL, right upper lobe.

Management of posttransplant TBM follows the same therapeutic principles applied to the non-transplant population. Airway irritants such as smoke and gastric acid should be eliminated or optimally controlled. Continuous positive airway pressure (CPAP) is a commonly used non-invasive modality that reduces airway resistance, improves expiratory flow, and facilitates secretion drainage by creating a pneumatic splint. Airway stents can restore endoluminal patency and provide symptomatic relief, but generally are used as part of a short-term therapeutic trial to assess a patient’s response to central airway stabilization. If a stent trial is successful then patients can be considered for surgery. Tracheobronchoplasty is a surgical option for patients with TBM that involves splinting the posterior membranous wall using a polypropylene mesh, preventing endoluminal invagination. Referral to a center with expertise in this operation is strongly recommended (54,55).

Bronchial stenosis

Bronchial stenosis is the most common airway complication after lung transplantation, with incidence rates ranging from 1.6% to 32% (12,56-58). The etiology of bronchial stenosis is likely multifactorial with inflammation, ischemia and infection cited as potential contributing factors (59). The site of stenosis is often divided into two types: central and distal. Central airway stenosis is located at or within 2 cm of the anastomotic suture line (Figure 4). Distal or non-anastomotic stenosis involves the lobar, segmental and subsegmental airways (1,37,60) (Figure 5). The most common non-anastomotic site of stenosis is the bronchus intermedius, which may result in complete stenosis or vanishing bronchus intermedius syndrome (VBIS) (Figure 6). VBIS is technically very difficult to manage conferring a mean survival of 25 months from the time of diagnosis (61,62).

Figure 4 Central anastomotic stenosis.

Figure 5 Distal lobar stenosis.

Figure 6 Complete stenosis of the bronchus intermedius.

Signs and symptoms of bronchial stenosis are usually non-specific. In many instances, the diagnosis is uncovered during routine imaging or surveillance bronchoscopy. Dyspnea, cough, wheezing and inability to clear secretions are the most common patient complaints. Spirometric findings may include diminution of peak expiratory flow and flattening of the flow-volume loop (63). Chest imaging can also be a useful adjunct for the diagnosis of bronchial stenosis. For example, a focal stricture or narrowing may be seen, or in the case of VBIS, complete collapse of the right middle and lower lobe. However, like other airway complications, bronchoscopy remains the gold standard modality for diagnosis (2,34,62).

The management of bronchial stenosis is often individualized and dependent on local expertise and available treatment options. An objective assessment of symptom burden (i.e., using dyspnea scores or pulmonary function testing) should be sought prior to and immediately after any intervention to document response. Therapeutic maneuvers that may be combined or used in isolation include endobronchial dilation, ablative modalities, and stenting. Balloon dilation is a common initial technique that may achieve durable results when performed alone. However, repeated dilations at regular intervals may be required to provide sustained symptomatic relief (35,64). Airway dilation can be achieved using an inflatable balloon or rigid bronchoscopy. While neither of these techniques has been shown superior to the other, the balloon has several distinct advantages. The balloon is translucent allowing the operator to visualize the airway during dilation, and then select the inflation pressure needed to optimally dilate while avoiding mucosal tearing. Inflatable balloons are also available in different sizes and lengths that fit through the working channel of a flexible bronchoscope. The ability to select and alternate between balloons is a faster and simpler option when compared to serially upsizing with a rigid bronchoscope for dilation. A noteworthy point with the balloon occlusion technique is ventilation will be interrupted. In contrast, the rigid bronchoscope has the advantage of providing collateral ventilation through its side ports. Additionally, if silicone stenting or debulking is anticipated during the same procedure then the rigid scope may be preferred (2,65).

Multiple ablative techniques can be used to treat bronchial stenosis including laser, cryotherapy, argon plasma coagulation and photodynamic therapy. The preferred modality at our institution is the electrocautery blade, which is used to make small incisions in the stenotic scar. Using this technique, the scar will preferentially tear in the previously incised areas during airway dilation. Mitomycin-C is sometimes applied topically after the procedure to prevent scar tissue formation.

Airway stenting is an option typically reserved for recurrent stenosis. Stenting in the transplant population must be carefully considered because of their immunocompromised status and higher risk for complications. If indicated and performed correctly, stenting can achieve excellent results. Silicone stents are preferred to SEMS for any benign stenosis, including those arising in the lung transplant recipient. Unlike SEMS, silicone stents can only be inserted through a rigid bronchoscope. The advantage of silicone when compared to SEMS is a lower incidence of granulation tissue formation, which makes removal easier, even if the stent has been present for a long time. Silicone can also be modified to a desired length and notched to prevent blockage of an airway orifice. Drawbacks of silicone stents include a higher risk for migration, mucous plugging, and halitosis. SEMS on the other hand offer the advantage of being deployable through a flexible bronchoscope. In addition, the internal to external diameter of the SEMS is more favorable and migration is less common. A challenging scenario arises when SEMS are left in place for extended periods and granulation tissue forms, making removal technically challenging. Additional complications include stent fracture, bacterial colonization, and restenosis (65-67) (Figure 7). The airway stents mentioned above are traditionally used in central airways to maintain patency, however many lung transplant patients have lobar and segmental bronchial stenosis. Recently, we published a case series at the Cleveland Clinic utilizing a polytetrafluoroethylene covered stainless steel balloon deployed stent (Atrium iCast stent) in lung transplant patients with lobar bronchial stenosis with exceptionally good outcomes (68) (Figure 8). These stents were found to be safe and improved symptoms as well as radiographic outcomes.

Figure 7 Stenosis of right bronchus intermedius, right middle lobe & right lower lobe with iCast stent placement.

Figure 8 Left upper lobe stenosis with iCast stent placement.

Conclusions

Despite advances in the field, airway complications after lung transplantation remain a consistent source of morbidity and mortality in this patient population. The management varies depending on the type of complication with no studies showing that one treatment modality is superior to another, underscoring the need to discuss these cases in a multidisciplinary setting. Further investigation is needed to define the optimal treatment algorithm for each of these complications. Referral to a center with expertise in managing airway complications is strongly recommended.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Jing Yu Chen and Michael Hsin) for the series “Highlights of the First International Symposium on Lung transplantation, Wuxi, China, 2019” published in Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-20-163/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-20-163/coif). The series “Highlights of the First International Symposium on Lung transplantation, Wuxi, China, 2019” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Santacruz JF, Mehta AC. Airway complications and management after lung transplantation: ischemia, dehiscence, and stenosis. Proc Am Thorac Soc 2009;6:79-93. [Crossref] [PubMed]
2. Frye L, Machuzak M. Airway Complications After Lung Transplantation. Clin Chest Med 2017;38:693-706. [Crossref] [PubMed]
3. Murthy SC, Blackstone EH, Gildea TR, et al. Impact of anastomotic airway complications after lung transplantation. Ann Thorac Surg 2007;84:401-9, 409.e1-4.
4. Yserbyt J, Dooms C, Vos R, et al. Anastomotic airway complications after lung transplantation: risk factors, treatment modalities and outcome-a single-centre experience. Eur J Cardiothorac Surg 2016;49:e1-8. [Crossref] [PubMed]
5. FitzSullivan E, Gries CJ, Phelan P, et al. Reduction in airway complications after lung transplantation with novel anastomotic technique. Ann Thorac Surg 2011;92:309-15. [Crossref] [PubMed]
6. Walker CM, Rosado-de-Christenson ML, Martínez-Jiménez S, et al. Bronchial arteries: anatomy, function, hypertrophy, and anomalies. Radiographics 2015;35:32-49. [Crossref] [PubMed]
7. Deffebach ME, Charan NB, Lakshminarayan S, et al. The bronchial circulation. Small, but a vital attribute of the lung. Am Rev Respir Dis 1987;135:463-81. [PubMed]
8. Siegelman SS, Hagstrom JW, Koerner SK, et al. Restoration of bronchial artery circulation after canine lung allotransplantation. J Thorac Cardiovasc Surg 1977;73:792-5. [Crossref] [PubMed]
9. Pettersson GB, Yun JJ, Nørgaard MA. Bronchial artery revascularization in lung transplantation: techniques, experience, and outcomes. Curr Opin Organ Transplant 2010;15:572-7. [Crossref] [PubMed]
10. van Berkel V, Guthrie TJ, Puri V, et al. Impact of anastomotic techniques on airway complications after lung transplant. Ann Thorac Surg 2011;92:316-20; discussion 320-1. [Crossref] [PubMed]
11. Khaghani A, Tadjkarimi S, al-Kattan K, et al. Wrapping the anastomosis with omentum or an internal mammary artery pedicle does not improve bronchial healing after single lung transplantation: results of a randomized clinical trial. J Heart Lung Transplant 1994;13:767-73. [PubMed]
12. Garfein ES, McGregor CC, Galantowicz ME, et al. Deleterious effects of telescoped bronchial anastomosis in single and bilateral lung transplantation. Ann Transplant 2000;5:5-11. [PubMed]
13. Ruttmann E, Ulmer H, Marchese M, et al. Evaluation of factors damaging the bronchial wall in lung transplantation. J Heart Lung Transplant 2005;24:275-81. [Crossref] [PubMed]
14. Keshavjee SH, Yamazaki F, Yokomise H, et al. The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation. J Thorac Cardiovasc Surg 1992;103:314-25. [Crossref] [PubMed]
15. Date H, Matsumura A, Manchester JK, et al. Evaluation of lung metabolism during successful twenty-four-hour canine lung preservation. J Thorac Cardiovasc Surg 1993;105:480-91. [Crossref] [PubMed]
16. Okada Y, Kondo T. Preservation solution for lung transplantation. Gen Thorac Cardiovasc Surg 2009;57:635-9. [Crossref] [PubMed]
17. Chen CZ, Gallagher RC, Ardery P, et al. Retrograde versus antegrade flush in canine left lung preservation for six hours. J Heart Lung Transplant 1996;15:395-403. [PubMed]
18. Patterson GA, Todd TR, Cooper JD, et al. Airway complications after double lung transplantation. Toronto Lung Transplant Group. J Thorac Cardiovasc Surg 1990;99:14-20; discussion 20-1. [Crossref] [PubMed]
19. Alvarez A, Algar J, Santos F, et al. Airway complications after lung transplantation: a review of 151 anastomoses. Eur J Cardiothorac Surg 2001;19:381-7. [Crossref] [PubMed]
20. Machuzak M, Santacruz JF, Gildea T, et al. Airway complications after lung transplantation. Thorac Surg Clin 2015;25:55-75. [Crossref] [PubMed]
21. Thistlethwaite PA, Yung G, Kemp A, et al. Airway stenoses after lung transplantation: incidence, management, and outcome. J Thorac Cardiovasc Surg 2008;136:1569-75. [Crossref] [PubMed]
22. Moreno P, Alvarez A, Algar FJ, et al. Incidence, management and clinical outcomes of patients with airway complications following lung transplantation. Eur J Cardiothorac Surg 2008;34:1198-205. [Crossref] [PubMed]
23. Awori Hayanga JW, Aboagye JK, Shigemura N, et al. Airway complications after lung transplantation: Contemporary survival and outcomes. J Heart Lung Transplant 2016;35:1206-11. [Crossref] [PubMed]
24. Van De Wauwer C, Van Raemdonck D, Verleden GM, et al. Risk factors for airway complications within the first year after lung transplantation. Eur J Cardiothorac Surg 2007;31:703-10. [Crossref] [PubMed]
25. Weder W, Inci I, Korom S, et al. Airway complications after lung transplantation: risk factors, prevention and outcome. Eur J Cardiothorac Surg 2009;35:293-8; discussion 298. [Crossref] [PubMed]
26. Mason DP, Brown CR, Murthy SC, et al. Growing single-center experience with lung transplantation using donation after cardiac death. Ann Thorac Surg 2012;94:406-11; discussion 411-2. [Crossref] [PubMed]
27. De Oliveira NC, Osaki S, Maloney JD, et al. Lung transplantation with donation after cardiac death donors: long-term follow-up in a single center. J Thorac Cardiovasc Surg 2010;139:1306-15. [Crossref] [PubMed]
28. Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 1986;314:1140-5. [Crossref] [PubMed]
29. Miller JD, DeHoyos A. An evaluation of the role of omentopexy and of early perioperative corticosteroid administration in clinical lung transplantation. The University of Toronto and Washington University Lung Transplant Programs. J Thorac Cardiovasc Surg 1993;105:247-52. [Crossref] [PubMed]
30. Park SJ, Nguyen DQ, Savik K, et al. Pre-transplant corticosteroid use and outcome in lung transplantation. J Heart Lung Transplant 2001;20:304-9. [Crossref] [PubMed]
31. King-Biggs MB, Dunitz JM, Park SJ, et al. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation 2003;75:1437-43. [Crossref] [PubMed]
32. Groetzner J, Kur F, Spelsberg F, et al. Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression. J Heart Lung Transplant 2004;23:632-8. [Crossref] [PubMed]
33. Couraud L, Nashef SA, Nicolini P, et al. Classification of airway anastomotic healing. Eur J Cardiothorac Surg 1992;6:496-7. [Crossref] [PubMed]
34. Shennib H, Massard G. Airway complications in lung transplantation. Ann Thorac Surg 1994;57:506-11. [Crossref] [PubMed]
35. Chhajed PN, Malouf MA, Tamm M, et al. Interventional bronchoscopy for the management of airway complications following lung transplantation. Chest 2001;120:1894-9. [Crossref] [PubMed]
36. Dutau H, Vandemoortele T, Laroumagne S, et al. A new endoscopic standardized grading system for macroscopic central airway complications following lung transplantation: the MDS classification. Eur J Cardiothorac Surg 2014;45:e33-8. [Crossref] [PubMed]
37. Crespo MM, McCarthy DP, Hopkins PM, et al. ISHLT Consensus Statement on adult and pediatric airway complications after lung transplantation: Definitions, grading system, and therapeutics. J Heart Lung Transplant 2018;37:548-63. [Crossref] [PubMed]
38. Usuda K, Gildea TR, Pandya C, et al. Bronchial Dehiscence. J Bronchol Interv Pulmonol 2005;12:164.
39. Ernst A, Herth FJ. Principles and Practice of Interventional Pulmonology. In: Machuzak MS. Management of Posttransplant Disorders. New York: Springer Science & Business, 2013:463-75.
40. Herman SJ, Weisbrod GL, Weisbrod L, et al. Chest radiographic findings after bilateral lung transplantation. AJR Am J Roentgenol 1989;153:1181-5. [Crossref] [PubMed]
41. Maloney JD, Weigel TL, Love RB. Endoscopic repair of bronchial dehiscence after lung transplantation. Ann Thorac Surg 2001;72:2109-11. [Crossref] [PubMed]
42. Chang CC, Hsu HH, Kuo SW, et al. Bronchoscopic gluing for post-lung-transplant bronchopleural fistula. Eur J Cardiothorac Surg 2007;31:328-30. [Crossref] [PubMed]
43. Mughal MM, Gildea TR, Murthy S, et al. Short-term deployment of self-expanding metallic stents facilitates healing of bronchial dehiscence. Am J Respir Crit Care Med 2005;172:768-71. [Crossref] [PubMed]
44. Kshettry VR, Kroshus TJ, Hertz MI, et al. Early and late airway complications after lung transplantation: incidence and management. Ann Thorac Surg 1997;63:1576-83. [Crossref] [PubMed]
45. Maiwand MO, Zehr KJ, Dyke CM, et al. The role of cryotherapy for airway complications after lung and heart-lung transplantation. Eur J Cardiothorac Surg 1997;12:549-54. [Crossref] [PubMed]
46. Penafiel A, Lee P, Hsu A, et al. Topical mitomycin-C for obstructing endobronchial granuloma. Ann Thorac Surg 2006;82:e22-3. [Crossref] [PubMed]
47. Samano MN, Saka JA, Caramori ML, et al. Fatal bronchovascular fistula after a single lung transplantation: a case report. Clinics (Sao Paulo) 2009;64:1031-3. [Crossref] [PubMed]
48. Sourrouille I, Mordant P, Karsenti A, et al. Successful surgical treatment of a posttransplantation bronchovascular fistula involving the pulmonary vein. Ann Thorac Surg 2011;92:1891-3. [Crossref] [PubMed]
49. Knight J, Elwing JM, Milstone A. Bronchovascular fistula formation: a rare airway complication after lung transplantation. J Heart Lung Transplant 2008;27:1179-85. [Crossref] [PubMed]
50. Murgu SD, Colt HG. Tracheobronchomalacia and excessive dynamic airway collapse. Respirology 2006;11:388-406. [Crossref] [PubMed]
51. Mahajan AK, Folch E, Khandhar SJ, et al. The Diagnosis and Management of Airway Complications Following Lung Transplantation. Chest 2017;152:627-38. [Crossref] [PubMed]
52. Aquino SL, Shepard JA, Ginns LC, et al. Acquired tracheomalacia: detection by expiratory CT scan. J Comput Assist Tomogr 2001;25:394-9. [Crossref] [PubMed]
53. Majid A, Gaurav K, Sanchez JM, et al. Evaluation of tracheobronchomalacia by dynamic flexible bronchoscopy. A pilot study. Ann Am Thorac Soc 2014;11:951-5. [Crossref] [PubMed]
54. Ernst A, Majid A, Feller-Kopman D, et al. Airway stabilization with silicone stents for treating adult tracheobronchomalacia: a prospective observational study. Chest 2007;132:609-16. [Crossref] [PubMed]
55. Buitrago DH, Wilson JL, Parikh M, et al. Current concepts in severe adult tracheobronchomalacia: evaluation and treatment. J Thorac Dis 2017;9:E57-66. [Crossref] [PubMed]
56. Herrera JM, McNeil KD, Higgins RS, et al. Airway complications after lung transplantation: treatment and long-term outcome. Ann Thorac Surg 2001;71:989-93; discussion 993-4. [Crossref] [PubMed]
57. Wilson IC, Hasan A, Healey M, et al. Healing of the bronchus in pulmonary transplantation. Eur J Cardiothorac Surg 1996;10:521-6; discussion 526-7. [Crossref] [PubMed]
58. Marulli G, Loy M, Rizzardi G, et al. Surgical treatment of posttransplant bronchial stenoses: case reports. Transplant Proc 2007;39:1973-5. [Crossref] [PubMed]
59. Yousem SA, Dauber JH, Griffith BP. Bronchial cartilage alterations in lung transplantation. Chest 1990;98:1121-4. [Crossref] [PubMed]
60. Hasegawa T, Iacono AT, Orons PD, et al. Segmental nonanastomotic bronchial stenosis after lung transplantation. Ann Thorac Surg 2000;69:1020-4. [Crossref] [PubMed]
61. Souilamas R, Wermert D, Guillemain R, et al. Uncommon combined treatment of nonanastomotic bronchial stenosis after lung transplantation. J Bronchol Interv Pulmonol 2008;15:54.
62. Shah SS, Karnak D, Minai O, et al. Symptomatic Narrowing or Atresia of Bronchus Intermedius Following Lung Transplantation Vanishing Bronchus Intermedius Syndrome (VBIS). Chest 2006;130:236S. [Crossref]
63. Anzueto A, Levine SM, Tillis WP, et al. Use of the flow-volume loop in the diagnosis of bronchial stenosis after single lung transplantation. Chest 1994;105:934-6. [Crossref] [PubMed]
64. De Gracia J, Culebras M, Alvarez A, et al. Bronchoscopic balloon dilatation in the management of bronchial stenosis following lung transplantation. Respir Med 2007;101:27-33. [Crossref] [PubMed]
65. Dutau H, Cavailles A, Sakr L, et al. A retrospective study of silicone stent placement for management of anastomotic airway complications in lung transplant recipients: short- and long-term outcomes. J Heart Lung Transplant 2010;29:658-64. [Crossref] [PubMed]
66. Gottlieb J, Fuehner T, Dierich M, et al. Are metallic stents really safe? A long-term analysis in lung transplant recipients. Eur Respir J 2009;34:1417-22. [Crossref] [PubMed]
67. Kapoor BS, May B, Panu N, et al. Endobronchial stent placement for the management of airway complications after lung transplantation. J Vasc Interv Radiol 2007;18:629-32. [Crossref] [PubMed]
68. Sethi S, Gildea TR, Almeida FA, et al. Clinical Success Stenting Distal Bronchi for "Lobar Salvage" in Bronchial Stenosis. J Bronchology Interv Pulmonol 2018;25:9-16. [Crossref] [PubMed]