Gait-speed and oxygen flow during six-minute walk test predicts mortality in patients with advanced lung disease.

The six-minute walk test (6MWT) is a useful tool to predict outcomes in patients with advanced lung diseases. Greater distance walked has been shown to have more favorable prognostic value compared to other recorded variables.  We reviewed the medical records of 164 patients with advanced lung disease who underwent lung transplant evaluation. Results of the 6MWT (distance walked, oxygen required, and mean gait speed) were recorded and analyzed with respect to mortality. 6MWT mean oxygen (O2) flow via nasal cannula was 3.5 ± 3.7 L/min. The distance walked in meters (m) and % predicted were inversely associated with mortality, OR: 0.995 (0.992-0.998) and 0.970 (0.950-0.990), respectively. Patients who walked < 200 meters (OR: 2.1 (1.1-4.0)) or < 45% of predicted, OR: 2.7 (1.2-5.7) had higher mortality. O2 flow during the test had a direct association with mortality (OR: 1.1 (1.0-1.2). In multivariate analysis, O2 flow > 3.5 L/min remained predictive of mortality, OR: 1.1 (1.0-1.2). Mean gait speed was higher in patient who lived compared with patients who died (mean 0.83 ± 0.35 m/mim vs mean 0.69 ± 0.33 m/min, respectively, p= 0.03). Gait speed was a predictor of survival, OR 3.4 (1.1, 10.6). O2 flow during the 6MWT was an independent predictor of mortality in patients with advanced lung disease. The patients that required more than 3.5 L/m of O2 had a higher mortality. Faster gait speed during the 6MWT was also associated with better survival.

Bacterial meningitis as a cause of death in lung transplant donors: Early outcomes in recipients.

BACKGROUND: Lung transplant remains an established treatment for end-stage lung disease, but limited organ availability remains a major barrier and contributor to waitlist mortality.1 Only 20% of available organs are considered suitable for lung transplantation (Am J Transplant, 16, 2016 and 141; Thorac Surg Clin, 25, 2015 and 35). Successful lung transplantation has been reported from donors infected with bacterial or fungal organisms, but there is a paucity of evidence regarding the use of donors with bacterial meningitis (Transplant Proc, 32, 2000 and 75; Transplantation, 64, 1997 and 365; Ann Thorac Surg, 86, 2008 and 1554). METHOD: The Cleveland Clinic lung transplant database was retrospectively reviewed for patients between January 1998 and December 2014. Post-transplantation outcomes collected included graft dysfunction, infectious complications, and survival. RESULTS: The recipients were identified as having lungs from donors with bacterial meningitis. All recipients remained free of infectious organisms responsible for bacterial meningitis related in the donor. Severe primary graft dysfunction (PGD) was not seen in these recipients. CONCLUSION: In our study, lung transplantation from increased risk donors with bacterial meningitis was not associated with an increased risk of early infectious complications in recipients. Donors with bacterial meningitis should be considered for lung donation and may expand the donor pool safely.

Pulmonary hypertension before first and second lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. METHODS: We included consecutive adult (16-yr-old or older) patients who underwent lung re-transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. RESULTS: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re-transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re-transplantation (p = 0.91). Pre-capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re-transplantation. PH before re-transplantation did not predict survival or development of BOS after re-transplantation. CONCLUSIONS: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re-transplantation.

Discrepancies between clinical and autopsy diagnoses in lung transplant recipients.

We sought to investigate the role of autopsy diagnoses in lung transplantation by comparing the clinically derived cause of death with autopsy deduced cause of death in a cohort of lung transplant recipients. We retrospectively reviewed all consecutive autopsy findings on lung transplant recipients transplanted between March 1994 and March 2007. We reviewed medical records and our lung transplant database to determine the clinical diagnosis of cause of death based on the clinical assessment and discharge summary at the time of death. Our study showed that 21% of the autopsies performed on lung transplant recipients at our institution revealed findings unsuspected at the time of death. Myocardial infarction, pulmonary embolism, high grade acute cellular rejection and infections were the most frequently missed diagnoses. The autopsy remains a useful tool in confirming diagnostic accuracy in lung transplant recipients.

Spontaneous pneumothorax in a single lung transplant recipient-a blessing in disguise: A case report.

BACKGROUND: End-stage chronic obstructive pulmonary disease (COPD) is one of the common lung diseases referred for lung transplantation. According to the international society of heart and lung transplantation, 30% of all lung transplantations are carried out for COPD alone. When compared to bilateral lung transplant, single-lung transplant (SLT) has similar short-term and medium-term results for COPD. For patients with severe upper lobe predominant emphysema, lung volume reduction surgery is an excellent alternative which results in improvement in functional status and long-term mortality. In 2018, endobronchial valves were approved by the Food and Drug Administration for severe upper lobe predominant emphysema as they demonstrated improvement in lung function, exercise capacity, and quality of life. However, the role of endobronchial valves in native lung emphysema in SLT patients has not been studied. CASE SUMMARY: We describe an unusual case of severe emphysema who underwent a successful SLT 15 years ago and had gradual worsening of lung function suggestive of chronic lung allograft dysfunction. However, her lung function improved significantly after a spontaneous pneumothorax of the native lung resulting in auto-deflation of large bullae. CONCLUSION: This case highlights the clinical significance of native lung hyperinflation in single lung transplant recipient and how spontaneous decompression due to pneumothorax led to clinical improvement in our patient.

Lung Transplant for Patient With Idiopathic Pneumonia Syndrome.

Idiopathic pneumonia syndrome (IPS) is a serious complication after hematopoietic stem cell transplantation. Despite the high mortality rate with medical management, there have been no reported cases of lung transplants for patients with IPS. We report a case involving a 44-year-old woman who developed IPS 5 months after hematopoietic stem cell transplantation for myelodysplastic syndrome. Despite aggressive medical management, the patient required intubation and was administered extracorporeal membrane oxygenation while awaiting recovery. However, her condition continued to deteriorate, and she subsequently underwent a double lung transplant with uneventful recovery. With the high mortality of medically managed IPS, lung transplant could prove to be lifesaving.

A Novel Diagnostic Algorithm for Heparin-Induced Thrombocytopenia in a Retrospective Cohort of Lung Transplant Recipients.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia and potential for thromboembolism. Lung transplant recipients are at risk of developing HIT due to heparin exposure peritransplant. We describe the incidence and impact of HIT in lung transplant recipient index hospital length of stay and survival. DESIGN: A retrospective cohort was obtained from electronic medical records which were queried for all recipients treated with bivalirudin (institutional treatment of choice for HIT) between January 1, 2005, and February 16, 2017 (N = 1171). Patients who developed HIT >30 days after transplant or after their index transplant admission were excluded. A diagnostic algorithm was used retrospectively to determine clinical HIT with an intermediate or high pretest clinical suspicion ("4T" score ≥4) and either (1) positive anti-heparin-platelet-factor 4 (HPF4) assay and a positive functional platelet assay or (2) a positive HPF4 assay only, in patients who did not undergo cardiopulmonary bypass. RESULTS: Among all lung transplant recipients, 2.1% were found to develop HIT in the peritransplant period (N = 25, mean = 88%) with a mean lung allocation score of 50.8 and an incidence of venous thromboembolism of 72%, most upper extremity in location. When matched with historical controls, patients with HIT had a longer overall index hospital length of stay of 43 days (P = .008). There was no difference in short- or long-term survival posttransplant. CONCLUSION: Vigilance for the development of HIT in lung transplant recipients is necessary to prevent further morbidity from thromboembolic events. In our cohort, HIT increased hospital length of stay but did not appear to affect recipient survival.

Pleural mesothelial cell transformation into myofibroblasts and haptotactic migration in response to TGF-beta1 in vitro.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis noted in the pulmonary parenchyma. Pleural mesothelial cells (PMC) are metabolically dynamic cells that cover the lung and chest wall as a monolayer and are in intimate proximity to the underlying lung parenchyma. The precise role of PMC in the pathogenesis of pulmonary parenchymal fibrosis remains to be identified. Transforming growth factor (TGF)-beta1, a cytokine known for its capacity to induce proliferative and transformative changes in lung cells, is found in significantly higher quantities in the lungs of patients with IPF. High levels of TGF-beta1 in the subpleural milieu may play a key role in the transition of normal PMC to myofibroblasts. Here we demonstrate that PMC activated by TGF-beta1 undergo epithelial-mesenchymal transition (EMT) and respond with haptotactic migration to a gradient of TGF-beta1 and that the transition of PMC to myofibroblasts is dependent on smad-2 signaling. The EMT of PMC was marked by upregulation of alpha-smooth muscle actin (alpha-SMA), fibroblast specific protein-1 (FSP-1), and collagen type I expression. Cytokeratin-8 and E-cadherin expression decreased whereas vimentin remained unchanged over time in transforming PMC. Knockdown of smad-2 gene by silencing small interfering RNA significantly suppressed the transition of PMC to myofibroblasts and significantly inhibited the PMC haptotaxis. We conclude that PMC undergo EMT when exposed to TGF-beta1, involving smad-2 signaling, and PMC may be a possible source of myofibroblasts in IPF.

Obliterative bronchiolitis in lung allografts removed at retransplant for intractable airway problems.

BACKGROUND AND OBJECTIVE: The role of large airway ischaemia, with resultant airway narrowing, in the development of post-lung transplant bronchiolitis obliterans has not been defined. A determination of clinical bronchiolitis obliterans syndrome (BOS), which is defined as a decline in FEV(1) from a stable post-transplant baseline, is difficult in the setting of airway complications. The aim of this study was to assess the evidence for histological bronchiolitis obliterans in lung allografts removed during retransplantation for severe recurrent airway narrowing. METHODS: Case records and histological findings in allograft lungs removed at retransplantation were retrospectively reviewed. RESULTS: Five lung transplant recipients, who had undergone retransplantation because of severe recalcitrant airway stenosis, were identified. In each case, explant allograft lung pathology revealed evidence of bronchiolitis obliterans. CONCLUSIONS: There is a possible link between airway ischaemia, large airway stenosis and the development of bronchiolitis obliterans, which is the most common cause of death in lung transplant recipients after the first year. These findings may provide an impetus for evaluation of the role of bronchial artery revascularization techniques in the prevention of bronchiolitis obliterans.

Patterns of Recurrence and Overall Survival in Incidental Lung Cancer in Explanted Lungs.

BACKGROUND: Recurrence and overall survival for incidental lung cancer in explanted lungs vary between different series. Recurrence patterns are also not well described. The primary objective of this study is to study the recurrence patterns and time to recurrence for various stages of lung cancer in lung transplant recipients. METHODS: A retrospective review of our institutional database was performed to identify patients who had incidental lung cancer found in transplant pneumonectomy specimens from 1990 to 2017. Demographic, radiographic, and perioperative clinical variables were collected. Time to recurrence, overall survival, and recurrence patterns were recorded. Freedom from recurrence and overall survival were estimated by using Kaplan-Meier analysis. RESULTS: Thirty-one patients had unexpected malignancy and 29 patients (1.6%) had primary lung carcinoma in the explanted lung. Indication for transplantation was chronic obstructive pulmonary disease in 15 patients (48%) and interstitial lung disease for 16 patients (52%). Preoperative imaging showed indeterminate nodules in 10 patients (32%). Pathologic review showed stage I disease in 15 patients (54%), stage II disease in 10 patients (35%), and stage III disease in 2 patients (7%). Recurrence was noted in 8 patients (28%). Most patients had nodal disease (25%) or systemic recurrence (75%). All recurrences occurred within 2 years of the transplantation. For patients with stage I and II disease, freedom from recurrence at 1, 3, and 5 years was 91%, 55%, and 55%, respectively. Overall survival at 1, 3, and 5 years was 78%, 18%, and 14%, respectively. CONCLUSIONS: Most recurrences occur within 2 years after transplantation and are the cause of death in these patients. Patients with nodal disease tend to have higher recurrence rates. Multidisciplinary review of abnormal radiographic findings before transplantation and close follow-up may allow for detection of undiagnosed cancers.

Post-transplant lymphoproliferative disorder of the bladder in a lung transplant recipient.

Post-transplant lymphoproliferative disorder (PTLD) occurs in ~5% of solid organ and hematopoietic stem cell transplant recipients. We report a unique presentation of PTLD in the bladder of a lung transplant recipient. Our patient was a 62-year-old female who received a bilateral lung transplant for chronic obstructive pulmonary disease. She presented with fever, left-sided flank pain and foul-smelling urine consistent with urosepsis. An abdominal and pelvic computerized tomography revealed an irregular and nodular bladder wall thickening suspicious for urothelial neoplasm. Cystoscopy revealed multiple bladder masses and biopsy demonstrated non-Hodgkin lymphoma consistent with PTLD. She was treated with a reduction in immunosuppression followed by chemotherapy and achieved remission. PTLD in the lung transplant recipients has been described in the gut, respiratory tract, skin, liver and kidney but not in the bladder. This case highlights the need for maintaining a high clinical vigilance even when transplant recipients present with seemingly benign clinical complaints.

Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation.

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation.

Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation.

New Nodule-Newer Etiology.

AIM: To evaluate frequency and temporal relationship between pulmonary nodules (PNs) and transbronchial biopsy (TBBx) among lung transplant recipients (LTR). METHODS: We retrospectively reviewed 100 records of LTR who underwent flexible bronchoscopy (FB) with TBBx, looking for the appearance of peripheral pulmonary nodule (PPN). If these patients had chest radiographs within 50 d of FB, they were included in the study. Data was compared with 30 procedures performed among non-transplant patients. Information on patient's demographics, antirejection medications, anticoagulation, indication and type of lung transplantation, timing of the FB and the appearance and disappearance of the nodules and its characteristics were gathered. RESULTS: Nineteen new PN were found in 13 procedures performed on LTR and none among non-transplant patients. Nodules were detected between 4-47 d from the procedure and disappeared within 84 d after appearance without intervention. CONCLUSION: FB in LTR is associated with development of new, transient PPN at the site of TBBx in 13% of procedures. We hypothesize that these nodules are related to local hematoma and impaired lymphatic drainage. Close observation is a reasonable management approach.

Characteristics and outcomes of patients with lung transplantation requiring admission to the medical ICU.

BACKGROUND: There are few data on characteristics and outcomes among patients with lung transplantation (LT) requiring admission to the medical ICU (MICU) beyond the perioperative period. METHODS: We interrogated the registry database of all admissions to the MICU at Cleveland Clinic (a 53-bed closed unit) to identify patients with history of LT done > 30 days ago (n = 101; mean age, 55.4 ± 12.6 years; 53 men, 48 women). We collected data regarding demographics, history of bronchiolitis obliterans syndrome, preadmission FEV1, clinical and laboratory variables at admission, MICU course, length of stay, hospital survival, and 6-month survival. RESULTS: The most common indication for MICU admission was acute respiratory failure (n = 51, 50.5%). Infections were most frequently responsible for respiratory failure, whereas acute rejection (cellular or humoral) was less likely (16%). Nearly one-fourth of the patients required hemodialysis (24.1%), and more than one-half required invasive mechanical ventilation (53.5%). Despite excellent hospital survival (88 of 101), 6-month survival was modest (56.4%). APACHE (Acute Physiology and Chronic Health Evaluation) III score at admission and single LT were independent predictors of hospital survival but did not predict outcome at 6 months. Functional status at discharge was the only independent predictor of 6-month survival (adjusted OR, 5.1; 95% CI, 1.1-22.7; P = .035). CONCLUSIONS: Acute rejection is an infrequent cause of decompensation among patients with LT requiring MICU admission. For patients admitted to the MICU, 6-month survival is modest. Functional status at the time of discharge is an independent predictor of survival at 6 months.

Treatment of airway complications following lung transplantation.

OBJECTIVE: To describe our experience in airway complications following lung transplant and to suggest a management algorithm, using different tools from the Interventional Pulmonology armamentarium. METHOD: Retrospective chart review of all airway complications following lung transplant from January 1999 to July 2007. RESULTS: During that period 223 patients underwent lung transplantation, with a total of 345 anastomoses in the airway. Seventy anastomoses (20.23%) had complications requiring endoscopic treatment. The total number of endoscopic interventions were 631 in 52 patients. Thirty three patients had a combination of bronchial stenosis and bronchomalacia. Eighteen patients had bronchial stenosis only and 1 patient had dehiscence of the anastomosis. Balloon dilation was most commonly transiently effective and ultimately 47 patients required stent placement. The most common complication associated with the use of stent was granulation tissue formation, seen in 57.3% of patients. After stent placement, the forced expiratory volume in 1(st) second (FEV(1)) improved significantly. CONCLUSION: Airway complications after lung transplant are frequent. Balloon dilation was effective only in a few patients with bronchial stenosis, although the majority ultimately needed a stent. Airway repermeabilization after stent placement improved FEV(1). Based on our experience, we propose a management algorithm for airway complications after lung transplant.

Invasive fungal infections in lung transplant recipients not receiving routine systemic antifungal prophylaxis: 12-year experience at a university lung transplant center.

STUDY OBJECTIVE: To determine the rate of invasive fungal infection among the lung transplant population at a center that does not provide routine systemic antifungal prophylaxis, and to compare that rate with rates currently reported in the literature. DESIGN: Retrospective medical record review. SETTING: University-affiliated lung transplant center. PATIENTS: Two hundred forty-two adults without cystic fibrosis who underwent lung transplantation between March 1, 1994, and June 30, 2006. MEASUREMENTS AND MAIN RESULTS: Patients were followed by the adult lung transplant service. Twenty-three cases of invasive fungal infections were identified in 22 patients, resulting in a 9.1% overall invasive fungal infection rate in our study population. Aspergillus infections were the most common type of fungal infection identified, occurring in 11 (47.8%) of the 23 cases, with an overall rate of 4.5% (11/242 patients). Invasive fungal infections in lung transplant recipients have been reported in the literature at a rate 15-35%, with rates of Aspergillus infections reported as 3-15%. CONCLUSION: Despite the absence of routine systemic antifungal prophylaxis, the overall invasive fungal infection rate and the Aspergillus infection rate in these lung transplant recipients do not appear to be higher than the rates reported in the literature.

Prevalence of pulmonary hypertension in end-stage cystic fibrosis and correlation with survival.

BACKGROUND: Limited information is available about the prevalence of pulmonary hypertension diagnosed by right heart catheterization (RHC) in patients with cystic fibrosis being evaluated for lung transplantation. It is unclear whether there are factors that can predict the presence of pulmonary hypertension and whether the presence of pulmonary hypertension influences patient outcomes. METHODS: The study included 57 unique and consecutive adult patients (33 women) with cystic fibrosis who underwent lung transplant evaluation at the University of Florida. RESULTS: The average age at evaluation was 31.8 +/- 10 years. All patients were in New York Heart Association class III. The median (interquartile range) of mean pulmonary artery pressure (PAP) was 26 (24-30) mm Hg. Thirty-six patients (63.2%) had pulmonary hypertension (mean PAP >or= 25 mm Hg) and had a significantly higher degree of hypoxemia and oxygen requirements. Echocardiography evidenced limitations for the diagnosis of pulmonary hypertension. The 5-year mortality rate was similar in patients with or without pulmonary hypertension; however, it was higher in 7 patients identified by cluster analysis and in patients with a left ventricular ejection fraction < 55%. CONCLUSIONS: More than half of our patients with cystic fibrosis and advanced lung disease have elevation of PAP, usually of mild degree. A lower left ventricular ejection fraction, but not the presence of pulmonary hypertension, was associated with worse outcomes.

Clinical experience with a new removable tracheobronchial stent in the management of airway complications after lung transplantation.

BACKGROUND: Airway complications are among the most challenging problems after lung transplantation. This article describes the use of a new tracheobronchial stent that can be placed and removed easily by flexible bronchoscopy. METHODS: A retrospective review was done of 24 consecutive patients requiring tracheobronchial stent placement after lung transplantation. A new self-expanding hybrid nitinol stent was used, and changes in airway diameter and spirometry were assessed. Stent related complications were recorded. RESULTS: Between February 2007 and April 2008, 24 patients underwent stent placement, and 49 stents were placed for 36 anastomoses at risk. Indications included bronchial stenosis in 12, bronchomalacia in 12, bronchial stenosis plus bronchomalacia in 20, and partial bronchial dehiscence in 5. Adjunctive procedures included electrocautery in 1, balloon dilatation in 7, and electrocautery plus balloon dilatation in 4. The average degree of stenosis decreased from 80% to 20%. After stent placement, the average increase was 0.28 liters in forced vital capacity and 0.44 liters in forced expiratory volume in 1 second. Complications included granulation tissue formation in 10 stents, migration in 9, thick mucus formation in 2, and fracture in 3. CONCLUSION: Airway complications in lung transplant patients were effectively palliated. Our complication rate with this new stent is comparable with other airway stents. This stent has the advantage of easy removability during flexible bronchoscopy if complications from the stent outweigh the benefits of palliation.