EXPERIMENTAL AND CLINICAL TRANSPLANTATION

The shortage of available donor lungs is a continuing clinical problem. Lobar lung transplant and the extension of donor lung criteria may expand the pool of donor lungs. We here report a case of lobar lung transplant from a marginal deceased donor with bronchiectasis and fibrosis at the left upper lobe and a history of treated pulmonary tuberculosis. Our experience with this case suggests that a lobar lung transplant can be considered not only for size mismatches but also for use of locally damaged lungs. In addition, lungs from a donor who received treatment for pulmonary tuberculosis may be feasible for transplant with chemoprophylaxis for latent tuberculosis infection. Our current case indicates one possible option to overcome the persistent shortage of available donor lungs.

Key words : Chemoprevention, Donor selection tissue, Latent tuberculosis, Lobectomy, Organ procurement

Lung transplant is the definitive treatment for end-stage lung diseases, including pulmonary vascular disorders that show inadequate clinical responses to medical therapies.¹ The shortage of available donor lungs continues to be a problem, and the pretransplant mortality rates remain unacceptably high.² Because only 20% of multiorgan donors yield lungs that are suitable for transplant,² several strategies such as lobar lung transplant and extending the donor lung criteria have been proposed, to increase the usability of donor lungs.³ In this context, we report a case of successful lobar lung transplant from a marginal deceased donor with bronchiectasis and fibrosis at left upper lobe and a history of treated pulmonary tuberculosis.

A 48-year-old woman with blood type O (height, 154 cm; body weight, 58 kg; body surface area, 1.58 m²; and estimated vital capacity, 2.75 L) had been diagnosed with idiopathic pulmonary arterial hypertension 6 years previous to examination. The initial diagnostic tests included right heart catheterization (mean pulmonary arterial pressure, 60 mm Hg; and pulmonary capillary wedge pressure, 8 mm Hg) and revealed no other identifiable causes of her pulmonary hypertension, which supported the diagnosis. She had been treated with macitentan, treprostinil, and sildenafil but had steadily deteriorated. She was therefore listed for a lung transplant, but because of her blood type, short stature, and the priority given by the lung allocation system to patients who receive mechanical ventilation or extracorporeal membrane oxygenation,⁴ no donor lungs had become available to her for 2 years. Meanwhile, her dyspnea had worsened to World Health Organization functional class IV and her 6-minute walking distance had decreased to 150 m. On a follow-up examination of her right heart catheterization, the cardiac index had decreased to 1.52 L/min/m² with mixed venous oxygen saturation of 52%. These findings suggested that this patient was at a high risk of death, with an estimated 1-year mortality risk >10%, and she urgently required a lung transplant.¹

Lungs from a deceased donor with blood type O (height, 170 cm; body weight, 63 kg; body surface area, 1.72 m²; and estimated vital capacity, 4.38 L) became available after 2 years of waiting. However, in addition to size mismatch, these donor lungs had a marginal status with a lung donor score of 8 (ie, donor age, 51 years, 1 point; smoking history, <20 pack-years, 0 points; chest radiography, opacity >1 lobe, 3 points; secretions, moderate, 2 points; and ratio of partial pressure of arterial oxygen/fraction of inspired oxygen, 433, 2 points).⁵ Moreover, the donor had a medical history of treated pulmonary tuberculosis, which had caused bronchiectasis and fibrosis at left upper lobe (Figure 1). Although no microorganisms, including Mycobacterium tuberculosis, were identified from the donor’s respiratory specimens, 3 transplant centers with higher priority patients had refused to accept these lungs.

An institutional multidisciplinary lung transplant committee that included cardiothoracic surgeons, pulmonologists, intensivists, infectious disease specialists, and radiologists was convened to discuss whether a lung transplant could be performed in this patient. After careful deliberation, which took account of the pretransplant wait time and mortality risk, infection risk, size mismatch, and surgical technique-related issues, the committee decided that a lobar lung transplant could proceed. For this procedure, the affected left upper lobe is removed via a lobectomy, and the right whole lung and the left lower lobe are transplanted. The patient was informed and agreed to the procedure.

On the day of transplant, experienced cardio-thoracic surgeons went to the donor’s hospital and evaluated the lungs before procurement in the operation room. Fortunately, only focal adhesion and fibrosis were evident around the bronchiectasis at the left upper lobe, and the lungs were otherwise acceptable for transplant. The lungs were successfully procured without complications and were transferred to the recipient’s hospital. A sequential double-lung transplant was then performed with a clamshell incision. First, the right whole lung was anastomosed in the order of bronchus, pulmonary vein, and pulmonary artery. Meanwhile, the lobectomy for the left upper lobe was performed on a back table in the operation room, and the left lower lobe was anastomosed sequentially. Central venoarterial extracorporeal membrane oxygenation was used for hemodynamic support during the operation, from which the patient was successfully weaned immediately after the transplant. The total operation time was 471 minutes, including 241 minutes of cold ischemia time and 65 minutes of warm ischemia time.

Postoperative management was conducted at a medical intensive care unit. To prevent the possible transmission of M tuberculosis, a chemoprophylaxis for latent tuberculosis infection (LTBI) was commenced with isoniazid for 9 months. No hepatotoxicity was reported in subsequent laboratory tests. Otherwise, the perioperative medication regimens, including immunosuppressants and antibiotics, were similar to those previously reported.⁶ There was no evidence of primary graft dysfunction in the first 72 hours postsurgery, and the patient was successfully extubated on postoperative day 6. Because the patient’s pretransplant status had severely deteriorated (ie, to a World Health Organization functional class IV), she required postoperative rehabilitation in the medical intensive care unit and was transferred to the general ward on day 26. The echocardiography performed on the following day showed improved right ventricular function and reduced pulmonary hypertension (Figure 2). At 6 months posttransplant, she is still alive without infection such as active pulmonary tuberculosis.

We detail a rare strategy to perform a successful lobar lung transplant with a marginal organ. The donor in this case was deceased and had bronchiectasis and fibrosis at left upper lobe and also had a history of treated pulmonary tuberculosis. Since the first lobar lung transplant from a deceased donor was reported by Bisson and colleagues in 1994,⁷ the benefits of this procedure have been well-described.⁸ However, most previous reports of this technique have focused on the resolution of severe size mismatches, particularly in recipients with short stature or small chest cavities.⁸ On the other hand, there have been few studies that have highlighted the benefits and usability of donor lungs with some damage. Our experience indicates that locally damaged donor lungs with a marginal status can still be transplanted if the affected lobe is removed by lobectomy.

Another important issue highlighted by our current case is that we can perform lung transplant from a donor with a history of pulmonary tuberculosis. Although several previous reports have suggested the possibility of donor-derived transmission of M tuberculosis,⁹ there is no concrete evidence that lungs from donors with adequately treated pulmonary tuberculosis would increase the risk of active disease after transplant. Moreover, lungs from donors with LTBI but without active disease are generally accepted for transplant.⁹ The outcomes in our present patient indicate that lungs from a donor with prior pulmonary tuberculosis who had been adequately treated can feasibly be transplanted if the recipient undergoes an immediate posttransplant chemoprophylaxis regimen for LTBI.

We commenced chemoprophylaxis for LTBI in our current patient immediately after transplant with a 300-mg daily dose of isoniazid for 9 months. An alternative shorter regimen, such as a 4-month course of rifampicin monotherapy or a 12-week course of isoniazid and rifapentine, could also be considered but would be limited by the severe drug interactions that can occur between rifamycins and immunosuppressive agents.¹⁰ Furthermore, contrary to the traditional belief that isoniazid is frequently associated with hepatotoxicity,^11,12 recent studies have found that the risk for hepatotoxicity is low with these LTBI drugs, even in patients awaiting liver transplant.^13,14 Hence, we commenced isoniazid monotherapy for transplant recipients who require chemoprophylaxis for LTBI.

We report a case of lobar lung transplant from a marginal deceased donor with bronchiectasis and fibrosis at left upper lobe and a history of treated pulmonary tuberculosis. Our experience with this case suggests that lobar lung transplant may be considered not only for size mismatches but also to allow the use of locally affected or damaged donor lungs. Moreover, our present case has shown that lungs from donors with adequately treated pulmonary tuberculosis can potentially be used for transplant in conjunction with chemoprophylaxis for LTBI. We believe that this approach will significantly expand the pool of donor lungs, which is critically low at present in almost all settings. Future investigations are required to further evaluate the safety and outcomes of lung transplant from donors with treated pulmonary tuberculosis.

Volume: 19 Issue: 3 March 2021

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