A. Kapasi

Emergence of Aspergillus calidoustus infection in the era of posttransplantation azole prophylaxis.

Background Universal antifungal prophylaxis with azoles is commonly used after lung transplantation. We noted an increase in isolates of Aspergillus calidoustus in our transplant population and hypothesized that increasing azole use (universal prophylaxis since 2008) may be promoting this infection. Methods Clinical and microbiologic data for A. calidoustus cases from 2008 to 2011 were extracted from chart review. For lung transplant patients, a case-control study was performed to determine risk factors, and incidence rates were calculated. Results From 2008 to 2011, we identified seven organ transplant recipients and one hematopoietic stem-cell transplant patient with positive A. calidoustus culture results in bronchoalveolar lavage at a median of 13 months after transplantation (interquartile range, 4–39 months). Chest computed tomographic scan was consistent with fungal infection in six of eight patients, and the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria classified these as “probable” invasive aspergillosis. In the case-control study, there were no differences in immunosuppression, number of respiratory samples taken, length of intensive care unit stay, or rejection rates. Of controls, 33.3% received third-generation azole prophylaxis compared with 83.3% of cases (P=0.13). However, median duration of exposure was greater in cases than in controls (3 vs. 0 months, P=0.045). Fungal minimum inhibitory concentration for voriconazole was 4 µg/mL or greater for six of eight cases. Incidence rates in lung transplants showed an increase of A. calidoustus (0/1000 vs. 11.3/1000 patient-years in 2006–2007 and 2008–2011, respectively; P=0.018), whereas Aspergillus fumigatus cases decreased (73.9/1000 vs. 49.0/1000 patient-years, P=0.0066). Conclusions Pulmonary A. calidoustus seems to be an emerging pathogen mainly in lung transplants. We suggest that third-generation azole use reduced the incidence of A. fumigatus, but the incidence of A. calidoustus, an azole-resistant fungus, was increased.

Outcomes of Lung Transplantation in Recipients with Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV‐positive, compared to 443 HCV‐negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1‐, 3‐, and 5‐year survival were similar in HCV RNA–positive versus ‐negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long‐term follow‐up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon‐free HCV therapies this should not be a barrier to LuTx.

The use of patient-reported outcomes becomes standard practice in the routine clinical care of lung–heart transplant patients

Objective: To assess the use of patient-reported outcome (PROs) measures in the routine clinical care of lung–heart transplant patients. We assessed whether the addition of PROs in routine clinical care affected the duration of the consultation and patient’s and clinician’s views. Method: Consecutive lung–heart transplant patients visiting the outpatient clinic, University of Alberta Hospital, completed the Chronic Respiratory Questionnaire (CRQ) and the Health Utilities Index (HUI) on touchscreen computers. Information on the patient’s responses was made available to the members of the transplant team prior to the encounter with the patient. The duration of clinical encounters was noted. At the end of every visit, clinicians completed a questionnaire on the usefulness of having PRO information available. After 6 months patients completed a survey of their experiences. Results: The final patient sample consisted of 172 patients with a mean (SD) age of 52 (13.3) years old; 47% were female; 68% were organ recipients and 32% candidates. The transplant team, comprising four pulmunologists, two nurses, and one pharmacist had an average of 9 years of practical experience in pulmunology. The mean duration of patient–clinician encounters in minutes was 15.15 (4.52). Ninety-eight percent of patients indicated that they would be happy to complete the CRQ and HUI at every clinic visit. Ninety-one percent of the assessments completed by clinicians showed complete satisfaction with the use of PROs in routine practice. Further, the clinicians developed guidelines for the use of PRO information in clinical practice. Conclusions: The incorporation of PRO measures in the routine clinical care of lung–heart transplant patients resulted in a reduction of the duration of patient–clinician encounters. The experience was well accepted by patients and clinicians. We conclude that the routine use of PROs in lung–heart transplant patients has become standard practice.

Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study.

PURPOSE Acute kidney injury (AKI) is a common occurrence after lung transplantation (LTx). Whether transient AKI or early recovery is associated with improved outcome is uncertain. Our aim was to describe the incidence, factors, and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS We performed a retrospective cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. Our primary outcome transient AKI was defined as return of serum creatinine below Kidney Disease-Improving Global Outcome AKI stage I within 7days after LTx. Secondary outcomes included occurrence of postoperative complications, mortality, and long-term kidney function. RESULTS Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%) within the first week after LTx. Of these, transient AKI (or early recovery) occurred in 157 (51.3%). Transient AKI was associated with fewer complications including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%; P<.001), decreased duration of mechanical ventilation (median [interquartile range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%, P=.01) compared with persistent AKI. Factors independently associated with persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95% confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67; P=.01), longer duration of mechanical ventilation (per hour [log transformed]; OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29; P<.001). Persistent AKI was associated with higher adjusted hazard of death (hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44 [0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS Transient AKI after LTx is associated with fewer complications and improved survival. Among survivors, persistent AKI portends an increased risk for long-term chronic kidney disease.

Case Report of Vertebral Osteomyelitis and Mycotic Abdominal Aortic Aneurysm Caused by Scedosporium apiospermum in a Lung Transplant Patient With Cystic Fibrosis

Cystic fibrosis patients are frequently plagued by infections, often with unusual or hardy organisms. Their infections are only complicated by transplantation. In this report, we review the case of a young woman who had a double lung transplant secondary to cystic fibrosis who developed a lumbar osteomyelitis/discitis several years after transplantation. After treatment, she went on to develop a mycotic abdominal aortic aneurysm. The patient underwent thoracic and abdominal aortic replacement, and histopathology revealed Scedosporium apiospermum infection. The patient recovered well from surgery and was discharged home on long-term antifungal therapy. This represents the first reported case of S apiospermum mycotic aneurysm in a lung transplant patient, and possibly the largest number and longest duration of S apiospermum infections reported in a single patient.

Long-term outcome of lung transplantation in previous intravenous drug users with talc lung granulomatosis.

Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.

Lung Transplantation from Hepatitis C Viremic Donors to Uninfected Recipients

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Mechanical Circulatory Support as a Bridge to Lung Transplantation: A Single Canadian Institution Review

Background Lung transplant (LTx) waitlists continue to grow internationally. Consequently, more patients are progressing to require mechanical circulatory support (MCS) as a bridge to transplantation (BTT). MCS strategies include interventional lung assist (iLA) and venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO). We review our series of patients bridged with MCS while listed for LTx. Methods All consecutive patients, listed for LTx requiring MCS as a BTT at the University of Alberta from 2004 to 2015, were included. Patient demographics and outcomes were compared for the 3 groups (iLA, VV-ECMO, and VA-ECMO). Results Of the 24 patients supported with MCS devices, 17 were successfully transplanted and 7 died waiting. In total, 25% (n = 6) were bridged with VA-ECMO, 54% (n = 13) with VV-ECMO, and 21% (n = 5) with iLA. Overall, 71% of patients were bridged successfully to LTx. The 1-year survival posttransplantation was 88%. Conclusion We have demonstrated the feasibility of utilizing the MCS modalities of VA-ECMO, VV-ECMO, and most recently iLA, as a BTT. MCS is a viable strategy for BTT, offering improved survival outcomes for decompensating adult patients awaiting LTx, resulting in excellent survival posttransplantation.

A Case Report of Living-donor Lobar Lung Transplantation for Scleroderma-associated Usual Interstitial Pneumonia: Eight Years and Counting

INTRODUCTION Scleroderma-associated interstitial lung disease is a life-limiting complication of scleroderma, often requiring lung transplantation. Living-donor lobar lung transplantation (LDLLT) is a viable alternative to deceased-donor lung transplantation in specialized centers under select circumstances. CLINICAL CASE A 47-year-old female underwent LDLLT after nine years of symptomatic scleroderma-associated usual interstitial pneumonia and three years awaiting deceased-donor lung transplantation. Her manifestations of scleroderma included mild sclerodactyly, periungual erythema, Raynauds phenomenon, and gastroesophageal reflux, with positive antinuclear autoantibodies. Several years post-transplantation, manometry revealed feeble lower esophageal sphincteric pressure with ineffective esophageal motility. Bronchiolitis obliterans syndrome developed 64 months post-transplantation without evidence of aspiration or reflux on transbronchial biopsy. Currently, she has normal renal function and good allograft function [FEV1 1.52 L (73% predicted) and FVC 2.50 L (99% predicted)]. RELEVANCE This is the second reported case of LDLLT in scleroderma, and the first reporting long-term pulmonary, renal, and esophageal function post-transplantation.

Baseline lung allograft dysfunction is associated with impaired survival after double-lung transplantation

BACKGROUND The prognostic value of defining normal vs abnormal baseline post-transplant lung function (or baseline lung allograft dysfunction [BLAD]) has not been studied using standardized reference values of percent predicted of the population. Our aim was to assess the association between BLAD and survival in double-lung transplant recipients and assess for potential pre-transplant donor and recipient risk factors for BLAD. METHODS We conducted a retrospective cohort study of double-lung transplant recipients in our program during the period 2004 to 2009. We defined normal baseline function as both forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥80% predicted on at least 2 consecutive tests ≥3 weeks apart; we defined BLAD as failure to meet these criteria. We used a Cox regression model to assess the association between BLAD and survival. We used logistic regression to assess potential pre-transplant donor and recipient factors associated with BLAD. RESULTS Of 178 patients double-lung transplant recipients eligible for study, 75 (42%) met the criteria for BLAD. BLAD was associated with impaired survival (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.41 to 3.54]) via Cox regression compared to patients with normal baseline, and lower baseline was associated with greater risk of death in a dose-dependent fashion. Pre-transplant factors associated with BLAD included interstitial lung disease (ILD) as an indication for transplant (odds ratio [OR] 2.66, 95% CI 1.17 to 6.15) and heavy donor smoking history (OR 3.07, 95% CI 1.17 to 8.43). CONCLUSIONS BLAD is dynamic risk state associated with impaired survival after double-lung transplantation, and should be considered when physiologically phenotyping patients.