Airway complications after lung transplantation

INTRODUCTION — During lung transplantation, the airway anastomosis is typically performed between the bronchus of the donor lung and that of the recipient. The airway anastomosis has traditionally been the most vulnerable site for operative complications of lung transplantation. Airway anastomotic complications include focal infection, bronchial necrosis and dehiscence, excess granulation tissue, tracheobronchomalacia, stenosis, and fistula formation.

The pathogenesis, diagnosis, treatment, and prevention of airway anastomotic complications of lung transplantation will be reviewed here. Other airway complications, such as bacterial and viral tracheobronchitis and bronchiolitis obliterans, and noninfectious problems related to lung transplantation are discussed separately. (See "Bacterial infections following lung transplantation" and "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome" and "Noninfectious complications following lung transplantation".)

TYPES AND DEFINITION — Anastomotic airway complications after lung transplantation include those that typically develop within the first month of surgery (eg, necrosis or dehiscence) and those that develop later (eg, excess granulation tissue, bronchomalacia, airway stenosis, anastomotic infection, bronchopleural fistula, bronchomediastinal fistula, or bronchovascular fistula) (table 1 and figure 1) [1].

Limited mucosal necrosis and sloughing at the anastomotic site are commonly observed during bronchoscopy in the first two to three weeks after transplant. These mild mucosal changes are not usually considered an "airway complication," if satisfactory healing occurs without intervention. Complications are considered significant when they necessitate an intervention such as debridement, dilatation, or stent placement.

Several classification systems for lung transplant airway complications have been proposed, though none have been universally adopted [1-3]. The International Society for Heart and Lung Transplantation (ISHLT) has proposed a grading system that includes the location and extent of lung transplant airway complications including ischemia and necrosis, dehiscence, stenosis, and malacia (table 2) [2]. The older Santacruz and Mehta classification system included six categories of post-transplant airway complications [1].

INCIDENCE AND IMPACT — Reported incidences of airway anastomotic complications range from 2 to 33 percent, although most centers have rates in the range of 7 to 18 percent [1,4,5]. In one large meta-analysis (35 studies, over 50,000 transplants), the pooled incidence of airway complications was 12.5 percent (95% CI 9.5-16 percent) [6]. Airway stenosis was the most common individual complication with an incidence of 8.4 percent; airway dehiscence occurred in 2.3 percent of transplants. Airway complications were reported four times more frequently at anastomotic sites than in other locations.

Airway complications after lung transplant lead to increased costs, greater morbidity, and decreased quality of life. Impact on survival has varied in small case series, but two large metanalyses demonstrate significantly decreased one- and five-year survival [6,7]. (See 'Prognosis' below.)

PATHOGENESIS AND RISK FACTORS

●Pathogenesis – Impairment of blood flow is believed to be the principal cause of most airway complications following lung transplant. During the lung recovery procedure, the normal bronchial blood supply is interrupted, leaving the bronchial vessels at the anastomotic site dependent on retrograde filling from the pulmonary artery circulation through communications in the submucosal plexus [1,8,9]. Revascularization of the donor bronchus typically takes two to four weeks and during this time period the airway is particularly vulnerable to ischemic insult.

The surgical anastomotic technique may be a factor in the development of airway complications. Excessive length of the donor bronchus contributes to airway complications [10], and current surgical techniques involve minimizing the length of the donor bronchus to within one to two cartilaginous rings of the take-off of the upper lobe bronchus.

The original technique of using an omentopexy (surrounding the anastomosis with a piece of omentum) was associated with a high rate of dehiscence [11]. Subsequent techniques have used a simple buttressing of the anastomosis with peribronchial tissues, which has decreased the rate of dehiscence [12,13].

An aspect of the anastomotic technique that remains controversial is telescoping the anastomosis by preferentially intussuscepting the recipient bronchus into that of the donor [1,4]. This technique may reduce early dehiscence, but may lead to increased rates of bronchial stenosis months later [1,14,15]. The use of an end-to-end anastomotic technique is generally preferred, while the telescoping anastomotic technique is reserved for situations where there is a size discrepancy between the donor and recipient bronchi [1,4,16].

●Risk factors — Several factors are associated with an increased risk of anastomotic airway complications.

•Severe primary graft dysfunction [17]

•Acute rejection within the first post-transplant year [6,18]

•Pre and postoperative pulmonary infection [1,6,19]

•Prolonged mechanical ventilation [20]

•Colonization with Aspergillus fumigatus [19]

•Preoperative Burkholderia cepacia infection [15]

•Use of sirolimus prior to complete anastomotic healing [1]

•Donor-recipient height mismatch [4]

Use of glucocorticoids to treat acute cellular rejection has not been associated with an increased risk of airway complications following lung transplantation [21].

AIRWAY SURVEILLANCE — Surveillance bronchoscopy is generally performed at regular intervals over the first six months after lung transplantation to assess for acute rejection, infection, and airway complications. If airway complications are identified, repeat bronchoscopy to inspect for appropriate healing of the airway or for management of the airway complication may be warranted [15,22]. Bronchoscopy is also performed when symptoms or imaging suggest possible anastomotic complications.

SPECIFIC COMPLICATIONS — The clinical presentation of the airway anastomotic complications varies, depending on the specific complication. Most of the post-transplant bronchial complications can be treated successfully with non-surgical interventions, as described below.

Bronchial stenosis — Bronchial stenosis in lung transplant patients can be classified as central airway stenosis (CAS), which is located at or within 2 cm of the anastomosis (picture 1) and distal airway stenosis (DAS), which involves the airways distal to the anastomosis and/or the lobar bronchi (picture 2). These two types of stenoses can exist separately or they can coexist [2]. (See 'Distal airway stenosis' below.)

With a reported incidence ranging from 4 to 24 percent, bronchial stenosis is the most common airway complication following lung transplantation. Bronchial stenosis typically occurs within the first two to nine months, but has been reported to occur over a year after transplantation [13]. Bronchial ischemia, early rejection, and severe primary graft dysfunction are risk factors for developing this complication [17].

Clinical features — Bronchial stenosis can be asymptomatic and diagnosed as an incidental finding during surveillance bronchoscopy, or it may present with dyspnea, wheezing, stridor, deteriorating pulmonary function tests, or postobstructive pneumonia. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Diagnostic evaluation — The diagnosis of CAS and DAS is based upon bronchoscopic visualization. Computed tomography (CT), performed with multiplanar reconstruction of the bronchial tree or virtual bronchoscopy, is typically done to provide additional information regarding the exact location and length of the bronchial or anastomotic stenosis (image 1) [23]. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)

Spirometry with flow-volume curves is used to assess the severity of airflow limitation. However, interpretation of spirometric results may be difficult in the setting of single lung transplantation for chronic obstructive pulmonary disease (COPD) as airflow obstruction may reflect the diseased native lung. Inspiratory and expiratory flow-volume curves help to distinguish between airflow obstruction caused by bronchial stenosis and that caused by bronchomalacia or bronchiolitis obliterans syndrome. Bronchial stenosis typically results in a pattern of fixed airflow limitation during both inspiration and expiration, while bronchomalacia has variable obstruction worse on expiration than inspiration (figure 2). (See "Physiologic changes following lung transplantation", section on 'Spirometry' and "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome", section on 'Diagnosis' and "Flow-volume loops", section on 'Mainstem bronchial obstruction' and "Flow-volume loops", section on 'Variable intrathoracic obstruction'.)

Initial management — Mild, asymptomatic bronchial stenosis (less than 50 percent of the bronchial diameter) can be managed conservatively with observation [24]. As Aspergillus fumigatus infection has been strongly associated with the development of airway complications, assessment for this infection and appropriate treatment are essential. For more severe, symptomatic bronchial stenosis (usually greater than 50 percent of bronchial diameter), bronchoscopic dilation is the initial and preferred treatment [24,25]. These choices are described further in the following paragraphs.

●Endobronchial dilation – Endobronchial dilation is usually accomplished with a rigid or a flexible bronchoscope using balloon dilation [15,24,26-28]. In a series of 41 patients with moderate to severe bronchial stenosis after lung transplant, 18 patients were managed successfully with balloon dilation alone, while 23 patients received a stent because of balloon dilation failure or recurrence of stenosis [29]. In a prospective study of lung transplant patients with significant anastomotic stenosis, airway stents were avoided in 50 percent by using balloon dilation as the initial treatment method [27]. Repeat dilations can be performed if the stenosis recurs.

For web-like bronchial stenoses, an electrocautery knife or Neodymium-yttrium-aluminum-garnet (Nd:YAG) laser may be used to create controlled radial incisions at the site of the stenosis prior to balloon dilation to more effectively expand the airway. Injection of glucocorticoids at the sites of the radial incisions may also be used to help prevent restenosis [3,30]. (See "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)".)

●Other therapies – Topical application of mitomycin (also known as mitomycin-C) has been used to prevent restenosis, but is less well-studied [31,32]. Case series have also described the successful use of high-dose brachytherapy to manage airway stenosis after lung transplantation, although this remains experimental [3,33]. Hyperbaric oxygen therapy in patients with extensive airway necrosis at one month after lung transplantation did not reduce the severity of central airway stenosis or stenting [34]. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)

Management of refractory stenosis — Measures for stenosis that is refractory to balloon bronchoplasty include placement of an endobronchial stent, sleeve resection of the stenotic area, lobectomy, and retransplantation [35,36].

●Endobronchial stents – The placement of endobronchial stents is reserved for cases of severe and refractory stenosis, as stents are associated with a high incidence of complications such as mucus impaction, granulation tissue formation, dislodgement, and migration [15,22,26,37,38]. (See "Airway stents" and "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)".)

Stent placement is often performed under general anesthesia, using rigid bronchoscopy, and may be combined with a dilation procedure to enable placement of the largest stent possible. Silicone stents are generally preferred over metallic stents as they can be custom made to conform to the patient's unique anatomy, are more easily repositioned and removed, are less expensive, and have adequate firmness to resist external compression (picture 3) [39,40]. In a series of 27 patients who received 32 silicone stents, symptoms were relieved in all patients and pulmonary function improved [40]. Stents needed repositioning or removal in eight patients, and one patient had a serious complication leading to hemorrhage and pneumonectomy. After a median of six months, 22 of 25 stents were removed with persistent airway patency. Drawbacks to silicone stents include risk of migration, impaired secretion clearance, and granulation tissue formation. (See "Airway stents", section on 'Silicone stents'.)

Regular surveillance bronchoscopy of silicone stents every four to six weeks is prudent; no consensus has emerged regarding the duration that silicone stents should remain in the airway [3].

Self-expanding metallic stents (SEMS) have been shown to provide immediate dyspnea relief after placement, but they are associated with a complication rate of over 50 percent, including infection, migration, and granulation tissue formation [41]. Removal of these stents can be extremely difficult and may cause significant bleeding as well as airway or vascular perforation. Given difficulties with removal, clinical practice favors changing the metallic stent to a silicone stent approximately four to six weeks after initial placement [3]. (See "Airway stents", section on 'Uncovered metal stents'.)

Case reports using biodegradable stents, lobar stents, and three-dimensional, computer-assisted customized airway stents exist, though larger prospective studies are needed to validate their safety and efficacy [42-44].

●Surgical intervention – When attempts at dilation and stenting fail, surgical strategies include sleeve resection, lobe resection, and also retransplantation [3,24,36,45]. This situation is rare, so data on surgical outcomes are lacking. (See "Lung transplantation: Procedure and postoperative management", section on 'Retransplantation'.)

Distal airway stenosis — DAS most commonly affects the bronchus intermedius, causing what is known as vanishing bronchus intermedius syndrome (VBIS), and has been reported to occur in approximately 3 percent of lung transplants [2]. DAS usually occurs between two to six months after transplant [46]. Ischemic injury is believed to be the inciting factor, as ischemic changes in this area are often visible on post-transplant bronchoscopy. However, acute cellular rejection may also contribute.

Similar to CAS, the diagnosis of DAS is typically made by flexible bronchoscopy (see 'Diagnostic evaluation' above). Right middle and lower lobe collapse may be visible on chest radiography. A chest CT scan can be helpful to delineate the length of the obstruction.

Limited data exist to guide the management of DAS. The therapeutic approach is often similar to that of CAS, although the management of DAS may present a greater challenge for bronchial stent placement due to the location of the adjacent lobar airways and tapering of the distal airway (see 'Initial management' above). A small case series called into the question the utility of airway stents in this patient population [47]. DAS is associated with a high mortality rate [2,48].

Anastomotic infection — The bronchial anastomotic site is prone to infection by both bacterial and fungal organisms. This predisposition is probably related to immunosuppression, poor vascular supply, and impaired clearance of secretions (image 2) [1]. Pseudomonas and Staphylococcus aureus are the most common bacterial infections [3]. Aspergillus colonizes the airways of approximately 20 percent of lung transplant recipients in the immediate postoperative period and may become invasive in 3 to 6 percent [49,50]. Less common airway infections include Candida, Zygomycetes (mucormycosis), Scedosporium apiospermum, and Scedosporium prolificans [51,52]. The latter two can colonize suture material and infect the anastomosis [53]. (See "Fungal infections following lung transplantation", section on 'Other fungal infections'.)

Patients are often asymptomatic when anastomotic infection is detected at the time of surveillance bronchoscopy, although some patients have fever, cough, wheezing, and/or hemoptysis. Findings include airway erythema, pseudomembranes, ulcerations, and positive cultures of secretions. The diagnosis of invasive Aspergillus infection is based on the combination of endoscopic appearance and confirmation by histopathologic evidence of invasive Aspergillus and/or fungal culture. (See "Fungal infections following lung transplantation", section on 'Tracheobronchial aspergillosis'.)

Anastomotic infections appear to predispose to airway complications such as dehiscence, bronchomalacia, bronchial stenosis, and fistula formation. In one series, isolation of Aspergillus from respiratory secretions in the first 30 postoperative days was highly associated with subsequent bronchial complications [19].

Treatment of anastomotic infection includes bronchoscopic debridement of any devitalized tissue and specific antimicrobial therapy based on culture results. Aspergillus fumigatus infection is treated with a combination of systemic voriconazole and inhaled amphotericin. (See "Fungal infections following lung transplantation", section on 'Tracheobronchial aspergillosis'.)

Granulation tissue — Development of hyperplastic granulation tissue usually occurs within a few months of surgery (picture 4) [1]. The initial granulation reaction is thought to be caused by perioperative ischemia and repair. Infection, predominantly with Aspergillus, may exacerbate the growth of granulation tissue. (See "Fungal infections following lung transplantation", section on 'Tracheobronchial aspergillosis' and 'Anastomotic infection' above.)

Hyperplastic granulation tissue may be asymptomatic and detected on surveillance bronchoscopy or may result in dyspnea, cough, or postobstructive pneumonia [1]. Airflow limitation may be noted on spirometry in severe cases.

Continued observation is reasonable if the amount of granulation tissue does not narrow the airway substantially and symptoms are minimal. However, when granulation tissue narrows the airway by 25 percent or more, the patient is symptomatic, and/or spirometry shows worsening airflow obstruction, the obstructing granulation tissue may be removed by bronchoscopy, using one or more of the following techniques: flexible or rigid forceps, cryotherapy or cryodebridement, Nd:YAG laser, argon plasma coagulation, and electrocautery [3,24]. (See "Bronchoscopic cryotechniques in adults" and "Bronchoscopic laser in the management of airway disease in adults".)

Bronchial necrosis and dehiscence — Bronchial necrosis and dehiscence range from mild, focal mucosal sloughing to extensive bronchial wall necrosis that extends more than 2 cm from the anastomosis and may be associated with partial or complete separation of the anastomosis (table 1 and picture 5 and table 2) [1,3]. Most patients have some degree of anastomotic site ischemic injury and necrosis in the days following transplantation. Dehiscence is believed to be the result of extreme airway necrosis. When anastomotic dehiscence occurs, it is usually within one to five weeks after transplantation [54].

The reported incidence of dehiscence ranges from 1 to 10 percent, but severe dehiscence is less than 2 percent [2].

Clinical features — Mild bronchial necrosis is asymptomatic. More severe necrosis and bronchial dehiscence may present with dyspnea, difficulty weaning from the ventilator, pneumomediastinum, subcutaneous emphysema, pneumothorax, persistent air leak, and sepsis. Focal infection and peribronchial abscess may also occur. Aspergillus anastomotic infection may lead to bronchial dehiscence, bronchopleural fistulae, abscesses, or dissemination [55]. (See 'Fistulae' below.)

Chest radiography is insensitive for detecting dehiscence; however, CT scanning can often identify dehiscence on the basis of bronchial wall defects and irregularities, mediastinal and subcutaneous air or fluid collections, pneumothorax, or poor allograft aeration [1,23].

Diagnosis — The diagnosis of bronchial necrosis and dehiscence requires bronchoscopic visualization, although CT scan features may provide an initial indication [2]. At the time of bronchoscopy, the degree of necrosis, presence of unraveled sutures, and evidence of focal infection (including Aspergillus) are assessed. Cultures of airway secretions are obtained, if indicated.

Management — Management of bronchial necrosis and dehiscence depends on the severity of necrosis and the presence of any associated complications.

●If the necrosis involves the mucosa, but not the bronchial wall, and no air leak is detected, conservative management with antibiotic treatment and frequent surveillance bronchoscopies to assess for evolution of the necrosis and new endobronchial infections may suffice [1]. Treatment of Aspergillus airway infection requires early initiation of antifungal therapy [55].

●For clinically significant bronchial anastomotic dehiscence, some experts, including us, suggest placement of an uncovered self-expanding metallic stent, which appears to facilitate healing by stimulating neoepithelialization [3,54,56-58]. These stents are usually removed after healing of the area of dehiscence, which is usually about four to six weeks after placement [1,3].

Silicone stents have been successful in the management of bronchial dehiscence, although they are often avoided in this setting as they do not promote neoepithelialization, and the force required for placement may enlarge the defect [58]. (See "Airway stents", section on 'Uncovered metal stents'.)

●For patients with partial dehiscence, primary repair using application of fibrin glue or alpha-cyanoacrylate glue has been described in case reports, generally followed by placement of an uncovered metallic stent [54,59].

●Failure of the above measures and complete dehiscence are associated with high morbidity and mortality. Open surgical repair for reanastomosis, pneumonectomy, or retransplantation may be considered based on factors such as the operability of the patient, anticipated response to pneumonectomy, and availability of a new lung for retransplantation [60,61].

Fistula formation between the bronchial anastomotic site and the pleura, mediastinum, or a vascular structure is a potential consequence of bronchial anastomotic necrosis. (See 'Fistulae' below.)

Bronchomalacia — Bronchomalacia refers to weakness of the bronchial walls leading to an accentuation of the normal airway narrowing on expiration. A diagnostic criterion of greater than 50 percent decrease in the luminal diameter on exhalation has been widely used [62,63]. Though the incidence of bronchomalacia in lung transplant patients is not well documented, single-center studies have described an incidence of approximately 1 to 4 percent (picture 6) [64]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation".)

In the lung transplant population, bronchomalacia can be classified as perianastomotic (localized to 1 cm proximal or distal to the bronchial anastomosis) or diffuse.

Donor organ ischemia is presumed to be a primary cause of cartilaginous damage, leading to weakness and collapsibility of the bronchial wall. Preoperative and postoperative pulmonary infections are also postulated to predispose to the development of malacia. The mechanism underlying generalized bronchomalacia in lung transplant recipients is also not well understood, though it has been associated with the presence of bronchiolitis obliterans [65].

Clinical features — Anastomotic malacia often occurs within four months of transplant. Both generalized and anastomotic malacia often present with symptoms similar to nontransplant patients with tracheobronchomalacia and include cough, wheezing, dyspnea, sputum production, and recurrent respiratory infections [3]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Clinical manifestations'.)

Diagnostic evaluation — While the diagnosis of bronchomalacia may be suspected on the basis of clinical features and spirometric flow-volume loops showing variable obstruction worse on expiration (figure 1), the “gold standard” for diagnosis is bronchoscopy with dynamic visualization of the airway during expiration. While there is no universally accepted protocol for diagnosing bronchomalacia on flexible bronchoscopy, a structured approach may be useful to assess the location and degree of dynamic collapse [66]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Diagnostic criteria'.)

Multidetector CT imaging with inspiratory and expiratory images may be useful in the diagnosis [63]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Dynamic airway CT'.)

Management — Management of bronchomalacia in transplant patients is similar to that of the nontransplant-related malacia. The decision to treat depends on the severity of symptoms and the extent of airway collapse [2]. If infection or rejection is present, specific treatment may provide symptomatic relief. (See "Tracheomalacia in adults: Treatment and prognosis".)

●Asymptomatic patients – Asymptomatic patients may not require treatment but should be monitored for worsening.

●Symptomatic patients with moderate collapse – Patients with moderate airway collapse and functional impairment may benefit from one or more of the following: airway clearance techniques (eg, oscillatory device [flutter valve] or percussion vest), maintenance of airway hydration with saline nebulizer treatments, mucolytics, and noninvasive ventilation (NIV) [3]. Titration of NIV pressure during flexible bronchoscopy has been described [2]. NIV can be used at night and intermittently during the day, as needed. (See "Tracheomalacia in adults: Treatment and prognosis", section on 'Symptomatic patients'.)

●Severe stenosis – If significant symptoms and functional impairment persist despite conservative medical management, endobronchial stent placement may improve symptoms by establishing and maintaining patency of the malacic airway segment. In a small series, stenting of airways for management of bronchomalacia was shown to result in significant improvements in pulmonary function tests [22]. Both metal and silicone stents have been evaluated in lung transplant patients. As in nontransplant patients with bronchomalacia, silicone stents are generally preferred, as they are more easily repositioned and removed than metal stents [1,41]. If the location of the malacia and shape of the airway does not allow silicone stent to be placed in a proper position, a self-expanding metallic stent may be used. (See "Tracheomalacia in adults: Treatment and prognosis", section on 'Stent trial'.)

Surgical interventions including resection of the involved airway and retransplantation are additional options but are rarely performed.

Fistulae — Bronchopleural, bronchomediastinal, and bronchovascular fistulae have all been described in lung transplant recipients [1]. These complications are rare, usually occur after prolonged or profound ischemia of the anastomosis, and are associated with a high morbidity [3,67].

Clinical features — Signs of a bronchopleural fistula include a new or worsening pneumothorax, subcutaneous emphysema, respiratory distress, and hypotension [1,68,69]. Bronchomediastinal fistulae typically present with signs of mediastinal infection, such as fever, bacteremia, or a mediastinal abscess [1].

A chest CT scan will usually identify pleural or mediastinal air and can be useful in guiding aspiration or drainage of mediastinal fluid collections.

Bronchovascular fistulae may connect the bronchus with the pulmonary artery, pulmonary vein, aorta, or left atrium [1,70,71]. Patients may present with sepsis, hemoptysis, or air embolism. Risk factors for this complication include Aspergillus infection of the anastomotic site and the presence of a bronchial stent [1].

Diagnosis and management — The diagnosis of fistulae is typically made by a combination of clinical features, CT scan, and direct visualization during bronchoscopy. The optimal management approach to bronchopleural, bronchomediastinal, and bronchovascular fistulae is not known, as these complications are rare. The following suggested approach is largely based on expert opinion and a few case reports.

●Bronchopleural fistulae – Bronchopleural fistulae (BPF) are treated acutely with drainage of any pleural air or empyema fluid and initiation of antibiotic therapy [1]. Ventilator management of patients who have a BPF is discussed separately. (See "Management of persistent air leaks in patients on mechanical ventilation".)

For patients who have a small BPF (eg, 3 to 5 mm diameter) or are not candidates for surgical closure, endoscopic closure using fibrin glue may be effective [1,68,69,72].

Endoscopic glue closure is usually not effective for larger fistulae; these may require placement of a covered metallic stent or surgical flap closure and reinforcement, if the patient is able to tolerate a thoracotomy [72]. (See 'Management' above.)

●Bronchomediastinal fistulae – Treatment of bronchomediastinal fistulae generally includes antimicrobial therapy and percutaneous drainage of any mediastinal fluid collections [1]. Depending on the extent of the mediastinal infection and the clinical stability of the patient, surgical debridement of the mediastinum may be indicated. Antimicrobial therapy should be broad initially and then narrowed when the sensitivities of the infecting organism are known. (See "Postoperative mediastinitis after cardiac surgery", section on 'Treatment'.)

●Bronchovascular fistulae – Bronchovascular fistulae have a high mortality rate, due to their abrupt presentation with massive hemoptysis [1]. Successful management with lobectomy and pneumonectomy has been reported in individual cases [73,74].

PROGNOSIS — While several smaller series have not shown an impact of airway complications on survival, two large meta-analyses have shown a significant increase in mortality in this group [6,7,67,75]. A retrospective review of 16,156 lung transplant recipients, of whom 233 had airway complications, survival rates were significantly reduced in patients with airway complications (54.6 versus 84.4 percent at one year and 33.2 versus 54.2 percent at five years.) [7]. In a large meta-analysis that included 2669 patients with airway complications, the one-year mortality was 23.6 percent and the five-year mortality was 66 percent [6]. Airway complication is NOT a risk factor for the development of chronic rejection [15].

PREVENTION — Attention to lung preservation, meticulous surgical technique and measures to prevent ischemia-reperfusion injury and acute rejection are important steps to prevent post-transplant airway complications. With careful management, the rate of major airway complications (dehiscence or stenosis requiring stenting) is usually less than 5 percent [76].

Bronchial anastomotic technique — Direct bronchial revascularization had been proposed by some centers in an effort to lower the incidence of airway complications [77,78]; however, there is no strong evidence to support this approach and it is not widely performed.

Prophylactic antibiotics — Most lung transplantation programs use antifungal prophylaxis starting within 24 hours of transplantation, as Aspergillus airway infection is associated with an increased risk of airway complications [19,79]. The optimal duration of antifungal prophylaxis is not known [1].

Delaying use of sirolimus — Sirolimus, a rapamycin derivative used to suppress transplant rejection, is associated with a markedly increased risk of airway complications when used in the first 90 days following lung transplantation. Most experts suggest delaying initiation of sirolimus until after the anastomosis is completely healed [1]. (See "Induction immunosuppression following lung transplantation".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lung transplantation".)

SUMMARY AND RECOMMENDATIONS

●The airway anastomosis is a vulnerable site for operative complications following lung transplantation due to interruption of the bronchial artery blood supply in the transplantation process. Complications include focal infection, bronchial necrosis and dehiscence, excess granulation tissue, tracheobronchomalacia, stenosis, and fistula formation. (See 'Introduction' above.)

●Bronchial stenosis may be asymptomatic and diagnosed during surveillance bronchoscopy, or it may present with dyspnea, wheezing, stridor, deteriorating pulmonary function tests, or postobstructive pneumonia. (See 'Bronchial stenosis' above.)

●For patients with symptomatic anastomotic bronchial stenosis, a stepwise approach is used, starting with initial balloon dilation, which can be performed via flexible or rigid bronchoscopy. For a web-like stenosis, using an electrocautery knife or Neodymium-yttrium-aluminum-garnet (Nd:YAG) laser to create controlled radial incisions can facilitate balloon dilation. Temporary stent placement is reserved for refractory stenosis, due to the relatively high complication rate associated with stents. (See 'Bronchial stenosis' above and "Airway stents".)

●Anastomotic site infections are usually asymptomatic and diagnosed at the time of surveillance bronchoscopy. Pseudomonas and Staphylococcus aureus are the most common bacterial infections; Aspergillus infection is less common, but can lead to severe sequelae. (See 'Anastomotic infection' above and "Fungal infections following lung transplantation", section on 'Tracheobronchial aspergillosis'.)

●Bronchial necrosis and dehiscence range from mild, focal mucosal sloughing to extensive bronchial wall necrosis, which may be associated with partial or complete separation of the anastomosis. (See 'Bronchial necrosis and dehiscence' above.)

●The management of bronchial necrosis and dehiscence depends on the severity of necrosis and the presence of associated complications. For most patients with bronchial necrosis, we suggest antimicrobial therapy as guided by culture results (Grade 2C). In the absence of dehiscence, most patients respond to conservative management with antimicrobial therapy, maintenance of full expansion of the transplanted lung(s), and continued surveillance. For patients with anastomotic dehiscence, limited data support placement of an uncovered metallic stent, with or without application of fibrin or cyanoacrylate glue. (See 'Management' above.)

●Complete dehiscence of the anastomosis is associated with high morbidity and mortality. Open surgical repair for reanastomosis, pneumonectomy, or retransplantation may be considered based on factors such as the operability of the patient, anticipated response to pneumonectomy, and availability of a new lung for retransplantation. (See 'Management' above.)

●Hyperplastic granulation tissue, which typically develops within a few months of transplantation, can cause airway narrowing. Symptomatic patients may have dyspnea, cough, or postobstructive pneumonia. When the granulation tissue narrows the airway by 25 percent or more, we suggest debridement via flexible or rigid bronchoscopy (Grade 2C). Forceps, cryotherapy, or laser may be used to clear the granulation tissue. (See 'Granulation tissue' above.)

●Bronchomalacia is defined as a 50 percent or greater narrowing of the airway lumen during expiration, confirmed bronchoscopically. Therapy is based on the severity of symptoms and degree of airway narrowing. Asymptomatic airway collapse generally does not require treatment. For mild-to-moderate degrees of airway collapse (eg, 50 to 75 percent) associated with symptoms, supportive care with airway clearance techniques and noninvasive ventilation, as needed, is usually sufficient. If significant symptoms and functional impairment persist despite conservative medical management, placement of a temporary endobronchial stent, usually silicone, may alleviate symptoms. Surgical interventions including resection of the involved airway and retransplantation are rarely performed. (See 'Bronchomalacia' above.)

●Bronchopleural, bronchomediastinal, and bronchovascular fistulae are rare complications of lung transplantation. Treatment of bronchopleural fistulae includes acute drainage of pleural air or empyema fluid and antibiotic therapy, as fistulae are highly associated with anastomotic infection. Treatment of bronchomediastinal fistulae includes percutaneous drainage of any mediastinal abscess collection and antibiotic therapy. A variety of methods have been tried to close the bronchial orifice of fistulae including surgery, application of fibrin glue, and placement of a covered metallic stent. (See 'Fistulae' above.)

ACKNOWLEDGMENTS — The editorial staff at UpToDate acknowledge Marcelo Cypel, MD, MSc, FRCSC, Tom Waddell, MD, MSc, PhD, FRCS, FACS, and Shaf Keshavjee, MD, MSc, FRCSC, FACS, who contributed to earlier versions of this topic review.