The Role of Bronchoscopy in the Assessment of Potential Lung Donors

Flexible bronchoscopy is an essential part of the evaluation of all potential lung donors.

Bronchoscopy can assess for evidence of lung injury, inflammation, aspiration, and infection. If bronchoscopy is normal, without anatomic abnormality, endobronchial lesions or secretions, acceptance of the organ for donation is appropriate. Only 33 percent of persons meeting criteria for brain death and being considered for donation will have a normal bronchoscopy. A normal bronchoscopy is not a requirement for accepting a potential lung donor; yet, the findings on flexible bronchoscopy can help differentiate donors acceptable for donation from donors that should be rejected.

Detailed Inspection of the Anatomy

An important finding during bronchoscopy is the presence of anatomic variations that influence the operative procedure and potential use of the organ. As an example, the author has encountered a potential donor in which the orifice for the RUL was located very proximally in relation to the carina making anastomosis difficult without sacrificing the RUL during the procedure. Decisions regarding specific anatomic variants and how they might impact the use of potential donor organs should be routinely discussed with the accepting transplant surgeon.

Obtaining Microbiologic Samples

Aspiration and pneumonia are common in potential donors, yet the presence of mucopurulent secretions among potential donors without clear clinical evidence of pneumonia and with a clear CXR is fairly common. Bronchoscopy can guide in the selection of organs in such cases. If extensive endobronchial inflammation is seen or if extensive secretions emanate from the distal segments that do not readily clear, the donor may have suffered a significant aspiration event and despite a clear CXR may be developing an infection that precludes accepting the lung for donation. Alternatively, if the endobronchial mucosa is normal in appearance and the secretions are easily suctioned clear during the examination, the potential donor lungs are likely appropriate for use. In this situation, bronchoscopy can also be used to obtain specimens to facilitate targeted antimicrobial therapy in the recipient during the immediate postoperative period. There is debate regarding the importance of a positive gram stain in the selection of donors for transplantation but prior studies have shown no correlation between a positive donor gram stain and subsequent postoperative pneumonia in the recipient.

Surveillance Bronchoscopy

Close surveillance of the allograft is the key to a successful transplant outcome. In many centers routine surveillance bronchoscopy at predetermined time intervals for the evaluation of acute rejection is a central component of this surveillance (Figure 14.1).

Figure 14.1 Sample schedule for routine surveillance bronchoscopy at a single lung transplant center. Surveillance bronchoscopy to assess anastomotic healing and to aid in pulmonary clearance is performed prior to extubation and at 1 week post-transplant. Routine surveillance bronchoscopy with transbronchial biopsy is performed at 1, 3, 6, and 12 months post-transplant.

Recent surveys of transplant programs across the United States and internationally, documented that over 50 percent of programs perform surveillance procedures. Transbronchial biopsy (TBBx) is the gold standard for the diagnosis of acute rejection with sensitivities in the range of 93 percent reported for acute rejection, however studies have shown a false negative rate of between 15 and 28 percent. Variation in yield may be related to technique as published reports have varied in their sampling methods from three pieces in one lobe to 17 pieces from both lungs. At most US centers only one lung is biopsied to avoid the risk of bilateral pneumothoraces (PTX). The decision regarding the number of biopsies is a balance between obtaining enough biopsies to achieve an adequate diagnostic yield without an unnecessarily high risk of complications. The consensus recommendation is that a specimen containing five pieces of alveolated lung parenchyma, each with a minimum of 100 alveoli and bronchioles is acceptable to minimize the risk of sampling error and false negative results and optimize yield.

Lung transplant recipients are at highest risk of acute rejection in the first 6–12 months following lung transplant. On the other hand, chronic rejection is rarely seen before six months. In addition, the presence of chronic rejection in biopsies does not correlate well with functional status and the diagnostic yield from flexible bronchoscopy in chronic rejection is much lower than with acute rejection. Therefore many lung transplant centers do not perform surveillance bronchoscopy with TBBx after the first year. The diagnosis and staging of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), are based on clinical criteria (FEV₁) and are defined as graft deterioration due to progressive airway disease for which there is no evidence of another superimposed process. Bronchoscopy does play an important role in excluding other treatable causes of graft dysfunction but cannot routinely confirm the diagnosis of chronic rejection.

The use of routine surveillance TBBx remains an area of debate among clinicians. Proponents underscore the frequency of unexpected findings during surveillance bronchoscopy seen in up to one quarter to one third of specimens during the first 400 days, which influence management. This is confirmed by a program that performed surveillance bronchoscopy among clinically healthy lung transplant recipients and found significant abnormalities in a large proportion of patients; 39 percent had some degree of acute rejection, 14 percent had evidence of CMV, 18 percent had nonspecific findings with only 24 percent being read as normal. Importantly, it has been demonstrated that asymptomatic mild acute rejection, when left untreated, can progress to symptomatic higher grade rejection, and that patients who experience multiple low grade rejection episodes in the first year of transplant may develop earlier onset chronic rejection, independent of whether they go on to develop higher grades of rejection, suggesting these patients may warrant more aggressive immunosuppression. Finally, the importance of follow-up bronchoscopy after a documented episode of rejection is highlighted, where persistent rejection was found in many cases that required further treatment.

In contrast, opponents of routine surveillance highlight the lack of data showing a significant difference in long term outcome, including mortality, among patients in whom surveillance bronchoscopy is performed, compared to patients in whom bronchoscopy is only performed when clinically indicated by symptoms or fall in lung function. In addition, opponents highlight the costs of repeated procedures and the associated risk of complications. No randomized controlled trials have examined this issue and the available data to guide this decision comes from retrospective, nonrandomized studies with their inherent limitations.

Diagnostic Bronchoscopy for Evaluation of Clinical Deterioration

Diagnostic bronchoscopy can provide valuable information in lung transplant recipients that present with new respiratory symptoms or a decline in functional status. Pulmonary infections in lung transplant patients can be difficult to diagnose. The presenting signs and symptoms are very similar between infectious and noninfectious complications of transplantation. DeVito Dabbs and colleagues found no significant differences in the severity or type of symptoms between patients that were diagnosed with infection vs. those found to have rejection. Bronchoscopy with BAL, and TBBx play a critical role in differentiating these two entities when interpretation of the biopsy is made in light of the entire clinical, microbiologic, and radiographic picture. Some reports highlight the role of cell counts and differentials counts in the management of lung transplant recipients but the routine use of this has not been adopted in all centers.

Infection represents a leading cause of death in the first year after transplant, with the rate of infection being higher among lung transplant patients compared with other solid organ transplants. The reasons for this increased risk of infection are several, but a primary reason is the required suppression of humoral and cell medicated immunity by immunosuppressant therapy. The dosing of immunosuppressant medications is highest during the first year secondary to a higher risk of rejection during this same period. Therefore, the balance of competing risks, infection and rejection, is more difficult in the first year (Figure 14.2).

Figure 14.2 Illustration of the pivotal role immunosuppressive therapy plays in the balance between the risk of rejection and risk of infection among lung transplant recipients. This balance is particularly difficult in the first year post-transplant.

Other changes in the innate defense of lung transplant patients play a role in the increased risk of infection. In the immediate postoperative period, lung transplant recipients have a blunted cough reflex due to postoperative pain and the denervation of the lung that occurs. This contributes to poor clearance of respiratory secretions and the potential for microaspiration, which is aggravated in many patients by postoperative gastroparesis. In addition, poor lymphatic drainage, impaired mucociliary clearance secondary to ischemic injury to the mucosa, and narrowing of the anastomosis with sloughing of devitalized cartilage can all impair pulmonary hygiene and secretion clearance, leading to the high incidence of bacterial infections after lung transplantation.

Secondary to inadequate secretion clearance, bronchoscopy is a valuable therapeutic tool in the postoperative period, discussed further (Therapeutic bronchoscopy). Of note the blunted cough reflex among lung transplant patients can have an advantage, reducing the amount of topical anesthesia needed within the airway. However, it is important to note that among patients with a single lung transplant, the cough reflex is intact in the native lung.

Bacterial infections occur most frequently, with 43–63 percent of infections following lung transplant secondary to bacterial pathogens. However viral (23–31 percent), fungal (10–14 percent), and other (4–10 percent) opportunistic pathogens including mycobacterial disease, Nocardia, Actinomyces, Legionella, and Listeria moncytogenes must be considered. Although, routine gram stain, and culture are essential components in the evaluation of a change in clinical status, other specimens should be tailored to risk factors and/or exposures known in a given patient. Aspergillus is commonly isolated during bronchoscopy among lung transplant patients but may be transient and associated with necrotic tissue found at the anastomotic site without true invasion. Pneumocystis carinii is a potential opportunist infection following lung transplantation but has been virtually eliminated by the routine use of prophylaxis. In the era before prophylaxis, infection was reported in up to 88 percent of heart and lung transplant recipients.

Even if bronchoscopy is performed, a pathogen is not always identified in the setting of clinical infection, secondary to initiating antibiotic treatment prior to the procedure. In addition, the sensitivity of bronchoscopy for diagnosing rejection is dependent on technique. In a study of bronchoscopy among patients with new respiratory symptoms utilizing TBBx, BAL, and protected specimen brush (PSB), only 17.5 percent of 114 diagnoses of bacterial infection were established using BAL. The diagnostic yield increased with the use of PSB.

Performing bronchoscopy in lung transplant patients is similar to that in non-transplant patients. Lung transplant recipients typically undergo multiple bronchoscopies during their post-transplant course and effective sedation is important to allow a safe and beneficial procedure and insure the patient is willing to undergo repeated procedures, it is important to note that patients with Cystic fibrosis, who make up a significant proportion of lung transplant patients, tend to require higher doses of sedative medication for the procedure. Propofol can be a useful alternative if adequate sedation cannot be achieved with usual doses of midazolam and fentanyl. A common observation among lung transplant patients is a suppressed cough reflex in the bronchial tree of their allograft, likely related to the denervation of the graft at the time of transplant, reducing the need for topical airway anesthesia. Similar to bronchoscopy performed in non-transplant patients, complications of TBBx in lung transplant recipients include pneumothorax (1–3 percent), pulmonary hemorrhage (10–15 percent), arrhythmia (2 percent), upper airway obstruction requiring intervention (10 percent), and cardiopulmonary arrest and death (0.01 percent). As with any procedure, the risk of not performing a diagnostic procedure and proceeding without additional information that may influence management must be weighed against the risk of the procedure.

The risk of bleeding has been reported to be higher in lung transplant recipients compared with that reported in other populations and appears to be independent of traditional bleeding risks, including coagulation parameters, platelet count, serum creatinine, or use of aspirin or immunosuppressive drugs. It is also not correlated with the presence of acute rejection, BOS, the number of biopsies taken or time since transplant. Improved bleeding rates among lung transplant patients has been shown after implementing a standardized protocol of (1) desmopressin for BUN >30, (2) avoidance of TBBx in patient with known pulmonary hypertension, and (3) withholding antiplatelet agents before the procedure. The contribution of each to the improved bleeding rates was not evaluated. Some programs, including ours, perform all procedures utilizing endotracheal intubation (without balloon deployed). This protocol can provide improved access to the airway during the procedure. In addition, it allows easy access to the airway for debridement when necessary in the early post-transplant period. Finally, lung transplant patients may be at a higher risk for desaturation during the procedure and performing the procedure following intubation can avoid upper airway obstruction, which is commonly implicated in desaturation events.

Visualization of the Anastomosis and Management of Airway Complications

Bronchoscopy is the gold standard in the diagnosis of airway complications and instrumental in their management. The most common anastomotic airway complications include; stenosis, bronchomalacia, granulation tissue, anastomotic dehiscence, bronchial fistulae (bronchomediastinal, bronchovascular, and bronchopleural), and anastomotic infections.

Airway complications are relatively common among lung transplant recipients and diagnosis of problems with the integrity of the anastomosis is critical in the management of lung transplant patients. Early studies suggested findings of airway complications in as many as 57 percent of patients. Changes in donor lung procurement, operative techniques, and postoperative management have lowered this risk, resulting in lower rates of airway complications reported in more recent reports (12–17 percent). The majority of airway complications involve the larger central airways and in particular the bronchial anastomosis. The bronchial artery circulation is lost during the harvest of the donor lung and limited bronchial artery revascularization from the recipient bronchial artery may take 3–4 weeks to occur after transplantation. During this time, the airway is dependent on retrograde low pressure flow from the poorly oxygenated blood available in the pulmonary artery and the risk of ischemia of the proximal donor bronchus (area just distal to the anastomosis in the recipient) is high. The majority of airways will suffer ischemic injury to the airway wall and display inflammation and erythema of some degree after transplantation. The severity of this process correlates with the risk of more serious airway complications. Several systems, such as the Courad, TEGLA, and MDS grading systems, have been proposed to standardize the reporting of airway complications. However, no universally accepted classification system has been adopted which contributes to the variable incidence rates of reported airway complications. In the immediate postoperative period bronchoscopy plays a role in monitoring the anastomosis and in helping with pulmonary hygiene and management of secretions. Early diagnosis of poor anastomotic healing can help in targeting a patient for close surveillance and determining the need for continued antimicrobial therapy secondary to airway infection. Changes in the innate defense in lung transplant patients discussed earlier, promote injury to the airway, which can lead to an increased risk of infection. In addition, poor lymphatic drainage in the transplanted lung dictates that patients are aggressively diuresed in the perioperative period; this can cause secretions to be thick and tenacious making mobilization difficult. Bronchoscopy, during this early period, can help clear blood clots, thick tenacious secretions, and necrotic tissue to help maintain a patent airway. In the majority of cases this can be completed with a flexible bronchoscope using forceps. Less commonly debridement in the OR using laser, cryotherapy, or a rigid bronchoscope may be necessary.

Airway Stenosis

Stenosis is a late complication felt to be secondary to healing of early anastomotic complications or the result of chronic rejection. Stenosis may cause secretion retention which may predispose to recurrent infections. Bronchoscopy can aid in the management of bronchial stenosis and may include mechanical dilation, bronchoscopic airway debridement, and ablative therapy using laser, cryotherapy, argon plasma coagulation (APC), brachytherapy, electrocautery, cryotherapy, and photodynamic therapy. Additional approaches that have been used in the treatment of benign airway stenosis include injection of small volumes of dexamethasone or a similar steroid, or mitomycin-C submucosally at the area of the stricture. Stenting may be required in cases of recurrent stenosis but mechanical dilation commonly requires serial procedures and most centers would utilize a multimodality approach and recommends dilation on at least two occasions prior to considering stent placement. Dilation allows for better evaluation of the extent of the stenosis and the airways distal to the narrowing. In addition if the stenosis is secondary to either infection or inflammation of the airway, serial dilations may allow improved airway function while the primary process (infection or rejection) is aggressively treated, which may improve the long term result and in many cases avoid stent placement. There is debate regarding the ideal stent for placement in stenotic airways. Silcone stents commonly require rigid bronchoscopy for placement. However they have several advantages including lower rates of granulation tissue, easy removal, ability to modify and customize (length and create customized holes for ventilation and secretion clearance). The disadvantage is that they are prone to problems with secretion clearance and plugging and migration. The advantage of self-expandable metallic stents is their ease of deployment using a flexible bronchoscope and flexibility, but they can also exacerbate the fibrosis and granulation response of the airway. They are also extremely difficult to remove once placed.

Segmental non-anastomotic bronchial stenosis or bronchomalacia (3 percent) can be seen in persons with infectious complications or in patients with multiple bouts of acute airway rejection. Treatment of the underlying infection or rejection is critical to managing these complications and may result in resolution of the stenosis. Alternatively mechanical balloon dilation and less commonly stent placement can be performed if the airway is proximal and large enough to allow successful placement.

Tracheobronchomalacia

Tracheobronchomalacia can occur in combination with bronchial stenosis or independently and is also commonly associated with cartilaginous injury due to perioperative ischemia, recurrent bronchial infection, and/or rejection. Inspiratory and expiratory CT scans can be diagnostic however direct visualization or the airway with flexible bronchoscopy is the gold standard for diagnosis to help guide decisions regarding management. While tracheobronchomalacia does not respond to balloon dilation, stent placement may improve airway patency. Silicone stents are preferred.

Granulation Tissue

Granulation tissue can form in response to prior injury or secondary to a foreign body reaction. The suture material can stimulate a granulation tissue response. If airway obstruction is present secondary to granulation tissue, several techniques for debridement are available including mechanical debridement using a forceps, cryotherapy, electrocautery, laser, and APC. Alternatively, local injection of corticosteroids has been used. The use of laser may cause thermal burns deep beneath the mucosal tissues and induce more scarring and granulation tissue formation or stenosis and should be used with caution. Recurrence is common and repeated therapy with a multimodality approach may be needed.

Anastomotic Dehiscence

Anastomotic dehiscence may be partial or complete. Complete dehiscence is very difficult to treat and associated with high mortality. Incomplete or partial dehiscence can be managed conservatively with frequent bronchoscopies to clear blood and necrotic tissue along with antibiotic therapy. In some cases temporary stenting, taking advantage of the propensity of metallic stents to cause granulation tissue, may stabilize the airway to allow healing. However stent placement should not be performed in the presence of an active infection. Endoscopic repair of an anastomotic dehiscence using injection of alpha-cyanoacrylate glue has also been reported. As surgical technique has improved, the incidence of dehiscence has been decreasing and this is a rare complication under current practice.