Advances in lung transplantation: 60 years on.

Lung transplantation is a well-established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all aspects of lung transplantation have evolved significantly and exponential growth in transplant volume. This has been particularly evident over the last decade with a substantial increase in lung transplant numbers as a result of innovations in donor utilization procurement, including the use donation after circulatory death and ex-vivo lung perfusion organs. Donor lungs have proved to be surprisingly robust, and therefore the donor pool is actually larger than previously thought. Parallel to this, lung transplant outcomes have continued to improve with improved acute management as well as microbiological and immunological insights and innovations. The management of lung transplant recipients continues to be complex and heavily dependent on a tertiary care multidisciplinary paradigm. Whilst long term outcomes continue to be limited by chronic lung allograft dysfunction improvements in diagnostics, mechanistic understanding and evolutions in treatment paradigms have all contributed to a median survival that in some centres approaches 10 years. As ongoing studies build on developing novel approaches to diagnosis and treatment of transplant complications and improvements in donor utilization more individuals will have the opportunity to benefit from lung transplantation. As has always been the case, early referral for transplant consideration is important to achieve best results.

Rescue Everolimus Post Lung Transplantation is Not Associated With an Increased Incidence of CLAD or CLAD-Related Mortality.

Everolimus (EVE) has been used as a calcineurin inhibitor (CNI) minimization/ elimination agent or to augment immunosuppression in lung transplant recipients (LTR) with CNI-induced nephrotoxicity or neurotoxicity. The long-term evidence for survival and progression to chronic lung allograft dysfunction (CLAD) is lacking. The primary aim was to compare survival outcomes of LTR starting EVE-based immunosuppression with those remaining on CNI-based regimens. The secondary outcomes being time to CLAD, incidence of CLAD and the emergence of obstructive (BOS) or restrictive (RAS) phenotypes. Single center retrospective study of 91 LTR starting EVE-based immunosuppression matched 1:1 with LTR remaining on CNI-based immunosuppression. On multivariate analysis, compared to those remaining on CNI-based immunosuppression, starting EVE was not associated with poorer survival [HR 1.04, 95% CI: 0.67-1.61, p = 0.853], or a statistically significant faster time to CLAD [HR 1.34, 95% CI: 0.87-2.04, p = 0.182]. There was no difference in the emergence of CLAD (EVE, [n = 57, 62.6%] vs. CNI-based [n = 52, 57.1%], p = 0.41), or the incidence of BOS (p = 0.60) or RAS (p = 0.16) between the two groups. Introduction of EVE-based immunosuppression does not increase the risk of death or accelerate the progression to CLAD compared to CNI-based immunosuppression.

Reproductive health after thoracic transplantation: An ISHLT expert consensus statement.

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.

Determining Clinical Thresholds for Donor HLA Eplet Compatibility to Predict Best Outcomes Following Lung Transplantation.

Currently, the assessment of immunological risk in lung transplantation (LTx) does not completely consider HLA compatibility at the molecular level. We have previously demonstrated the association of HLA eplets in predicting chronic lung allograft dysfunction following LTx; however, the associations between HLA eplet mismatch (epMM) loads and overall survival are unknown. Methods: In this retrospective, single-center study, 277 LTx donor-recipient pairs were high resolution HLA typed and analyzed for HLA epMMs using HLAMatchmaker (version 3.1). LTx pairs were also assessed for the presence of the previously described risk epitope mismatches DQ2-DQA1*05 and DQ7-DQA1*05. Results: HLA class I epMMs were not associated with deleterious outcomes; however, lower HLA class II (≤19), DQA1 (≤2), and combined HLA class I and II (≤29) epMM demonstrated an association with increased time to chronic lung allograft dysfunction and improved overall survival. The presence of a risk epitope mismatch was not associated with worse clinical outcomes. Conclusions: HLA epMM can risk-stratify LTx recipients and potentially guide donor-recipient matching and immunosuppression strategies.

Can we HALT obesity following lung transplant? A Dietitian- and Physiotherapy-directed pilot intervention.

INTRODUCTION: Unintentional weight gain, overweight and obesity following solid organ transplantation (SOT) are well-established and linked to morbidity and mortality risk factors. No interventional studies aimed at prevention have been undertaken among lung transplant (LTx) recipients. The combination of group education and telephone coaching is effective in the general population but is untested among SOT cohorts. METHODS: A non-randomized, interventional pilot study was conducted among new LTx recipients. The control group received standard care. In addition to standard care, the intervention involved four group education and four individual, telephone coaching sessions over 12-months. Data collection occurred at 2 weeks, 3- and 12 months post-LTx. Measurements included weight, BMI, fat mass (FM), fat mass index (FMI), fat-free mass (FFM), fat-free mass index (FFMI), waist circumference (WC), visceral adipose tissue (VAT), nutrition knowledge, diet, physical activity, lipid profile, HbA1C , FEV1 , six-minute walk distance and patient satisfaction. RESULTS: Fifteen LTx recipients were recruited into each group. One control participant died 120 days post-LTx, unrelated to the study. There were trends towards lower increases in weight (6.7±7.2 kg vs. 9.8±11.3 kg), BMI (9.6% of baseline vs. 13%), FM (19.7% vs. 40%), FMI, VAT (7.1% vs. 30.8%) and WC (5.5% vs. 9.5%), and greater increases in FFM and FFMI (all P > .05), among the intervention group by 12 months. The intervention was well-accepted by participants. CONCLUSION: This feasible intervention demonstrated non-significant, but clinically meaningful, favorable weight and body composition trends among LTx recipients over 12 months compared to standard care.

When immunosuppression and COVID-19 intersect: An exploratory qualitative study of young lung transplant recipient perceptions of daily life during a pandemic.

BACKGROUND: The COVID-19 pandemic poses an increased risk of infection, severe illness, hospitalization and mortality for young people who are immunosuppressed, including lung transplant (LTx) recipients. The aim of this study was to explore the intersection between immunosuppression and COVID-19, through the impacts of the pandemic upon the daily lives of young LTx recipients residing in the Australian state of Victoria. METHODS: An exploratory qualitative research study was undertaken via consumer engagement. A purposive sample of 11 LTx recipients, residing in Victoria, was recruited during the first year of the COVID-19 pandemic. Semi-structured interviews were conducted to gain insights into their daily life and healthcare experiences, including the impacts of the COVID-19 pandemic. Data were interpreted using thematic analysis. RESULTS: Four major themes were identified: (1) occupational deprivation due to the intersection of COVID-19 and lung transplant; (2) resilience and acceptance of restrictions; (3) infection control and vigilance about risk; and (4) care experiences of telehealth. CONCLUSIONS: Occupational deprivation emerged as a common theme, specifically in the context of loss of access to meaningful everyday activities of developmental significance. However, participants also commonly reflected upon their ability to flexibly adjust to changing socially regulated community and healthcare environments. A high degree of acceptance and compliance with public health orders was self-reported, may be indicative of this cohort's long-term experience of chronic illness and their understanding of the importance of minimizing infection risks. Youth-informed healthcare strategies were identified as keystone to engaging them in institutional change and program adaptation during a pandemic.

Airway cilia recovery post lung transplantation.

BACKGROUND: Normally functioning airway cilia is essential for efficient mucociliary clearance to protect the airway from various insults. Impaired clearance may lead to increased risk of infections and progressive lung damage. Significant morbidity in the immediate post lung transplantation period is associated with airway infection, which we hypothesize may be caused by impaired cilia function. METHODS: Airway cilia beating pattern (CBP) and frequency (CBF) were studied on brushing samples taken from above and below the transplant anastomosis of adult lung transplant recipients (n = 20) during routine bronchoscopies at 6, 12, and 26 weeks posttransplant. Bronchoaveolar Lavage (BAL) samples were also collected at each time points. RESULTS: At 6 weeks posttransplant (n = 16), CBP from the donated lung showed reduced beating amplitude with the overall CBF 2.28 Hz slower than the patients' native upper airway cilia (median ± SIQR: 5.36 ± 0.93 Hz vs. 7.64 ± 0.92 Hz, p value < .001). At 12 weeks (n = 16), donor lungs CBP showed recovery with the difference in CBF reduced to 0.74 Hz (6.36 ± 1.46 Hz vs. 7.10 ± 0.86 Hz, p value < .05). Impaired cilia function was not associated with positive BAL cultures. CONCLUSION: Reduced cilia function is evident in the first 12 weeks post lung transplant, with both CBP and CBF returning to levels of function indistinguishable to the patients' upper airway cilia beyond this time.

Abnormal one-year post-lung transplant spirometry is a significant predictor of increased mortality and chronic lung allograft dysfunction.

BACKGROUND: The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro12M), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients. METHODS: We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro12M as the mean of the 2 prebronchodilator FEV1 measurements 12-month post-transplant. Normal spirometry was defined as FEV1/FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro12M, survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro12M RESULTS: One hundred and eleven (51%) lung transplant recipients normalized their Spiro12M. Normal Spiro12M was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV1 increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro12M (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro12M. CONCLUSIONS: Abnormal Spiro12M is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care.

Outcomes Following ATG Therapy for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major factor limiting survival post lung transplantation (LTx) with limited effective therapeutic options. We report our 12-y experience of antithymocyte globulin (ATG) as second-line CLAD therapy. METHODS: Clinical and lung function data were collected on LTx patients receiving ATG. Rate of FEV1 decline (mL/d) was calculated before and after ATG. Partial response to ATG was defined by rate of FEV1 decline improving 20%. Complete response was defined by an absolute improvement or stability in baseline FEV1. RESULTS: Seventy-six patients received ATG for CLAD. Of these, 5 patients who had a clinical diagnosis of antibody-mediated rejection and were treated with plasmapheresis before or after ATG were excluded from analysis. Sixteen (23%) were complete responders, 29 (40%) were partial responders, and 26 (37%) did not respond. Those with CLAD stage 2 or 3 and younger age were more likely to respond. Partial responders had a 65% lower risk of death or retransplant (HR, 0.35; P = 0.003), whereas complete responders reduced their risk by 70% (HR, 0.30; P = 0.006). CONCLUSIONS: ATG appears to stabilize or attenuate lung function decline in CLAD, which may lead to improved retransplant-free survival. Although certain predictors of response have been identified in this large single-center review, these findings need to be confirmed by a multicenter randomized-controlled trial to determine predictors of response to ATG for CLAD.

Outcomes Following Extracorporeal Photopheresis for Chronic Lung Allograft Dysfunction Following Lung Transplantation: A Single-Center Experience.

INTRODUCTION: Survival following lung transplantation (LTx) is limited by the development of chronic lung allograft dysfunction (CLAD), for which there are few effective therapies and no standardized management. Several small studies have demonstrated the effectiveness of extracorporeal photopheresis (ECP) as a therapeutic option for CLAD. METHODS: A retrospective descriptive audit of 12 LTx recipients who received rescue ECP for CLAD over 5 years (2013-2018) at the Alfred Hospital, Melbourne, Australia, was completed. Nonresponders to ECP were defined as patients who experienced a 20% decrease in forced expiratory volume (FEV1) within 6 weeks of commencing therapy. RESULTS: Mean time since LTx was 849 days and mean time since diagnosis of CLAD was 131 days. Fifty-eight percent of patients were male (n = 7) and 67% responded to ECP therapy (n = 8). Among responders, the mean (95% confidence interval) decline in FEV1 pre-ECP was 9.0 mL/day (5-12 mL/day), compared to 1.4 mL/day (0-4 mL/day) post-ECP (P = .01). Among nonresponders, mean (95% confidence interval) decline in FEV1 was 7.2 mL/day (4-10 mL/day) pre-ECP and 5.0 mL/day (3-7 mL/day) post ECP (P = .2). Nonresponders were more likely to be female (P = .01) and neutropenic (P = .005). Patients with prior exposure to anti-thymocyte globulin had a lowered response to ECP. CONCLUSION: Rescue ECP arrested the decline of lung function in 67% of patients with CLAD. Sex, pre-ECP neutrophil count, and exposure to anti-thymocyte globulin may help determine response to ECP. Future clinical trials are needed to confirm this effect, help predict response to therapy, and ultimately guide the placement of ECP in the treatment algorithm for CLAD.

The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation.

Osteoporosis is prevalent among lung transplant candidates and is exacerbated post-transplant by immunosuppressive therapy. Low bone mineral density (BMD) is a well-recognized surrogate for fragility fracture risk, which is associated with significant morbidity and mortality. Intravenous zoledronic acid (ZA) effectively reduces BMD loss and prevents fractures in postmenopausal osteoporosis. Many groups, ours included, prophylactically treat lung transplant recipients (LTR) with bisphosphonates, but no documented consensus currently exists. Our protocol comprises ZA every 6-months from transplant wait-listing, with interval reassessment to guide ongoing treatment. We evaluate the impact of a dose of ZA within 6 months of transplantation on BMD and fracture occurrence. A retrospective analysis was performed on all adult LTR from April 2012 to October 2014, of which 60 met our inclusion criteria. LTR who received ZA within 6 months of transplantation (n = 37) were compared to those who did not (n = 23), and followed up for a minimum of three years. Outcome measures were BMD change at the lumbar spine and femur (primary), and fracture occurrence (secondary). LTR treated with ZA within 6 months of transplantation experienced a median BMD change of +8.11% at the lumbar spine and +1.39% at the femur, compared to -1.20% and -3.92%, respectively, in LTR who did not receive a ZA dose within 6 months of transplantation (p = 0.002 & p = 0.008 respectively). Our findings indicate that prophylactic ZA within 6 months of transplantation prevents BMD loss in LTR.

An update on chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) remains a significant challenge and the major determinant of morbidity and mortality post lung transplantation (LTx). The definition of CLAD has evolved significantly over the last ten years, reflecting better understanding of pathophysiology and different phenotypes. While there is an agreed consensus approach to CLAD, questions remain regarding the limitations of lung function parameters as well as the role of imaging and histopathology. Here we present a current snapshot of the definition of CLAD, its evolution and future directions.

Donor Lung Referrals for Lung Transplantation: A 'Behind The Scenes' View.

BACKGROUND: Australia's increasing organ donor rate has translated to increased lung donor referrals and subsequent lung transplantation (LTx). The LTx sector attempts to utilise as many organs as possible-but in reality, not all are used. This analysis aims to assess the utility and efficiency of donor lung referrals to the Alfred Hospital. METHODS: All Donatelife Australia donor lung referrals for the year 2017 were analysed retrospectively. RESULTS: From a total of 440 lung referrals, 220 were local from the state of Victoria (population 6.4 million) and 220 from the Rest-of-Australia (ROA). Sixty-eight per cent (68%) of Victorian and 48% of the ROA were via the donation after circulatory death (DCD) pathway. One hundred and two (102) LTx were performed: 32 represent 21% of 149 Victorian and 8% of 106 ROA DCD donors, 70 represent 54% of the Victorian and 24% of the ROA donation after brain death (DBD) donors. Eighty per cent (80%) of all donors aged <35 and 30% >35 years were used or potentially useable. Thirteen per cent (13%) of DCD and 44% of DBD donors aged >65 years were used. Logistical and resource considerations, around the retrieval of older DCD lungs, are a significant issue. At 11.1 LTx per-million-population the Alfred has one of the highest lung donor conversion and LTx activity rates in the world. CONCLUSION: The Australian donor lung pool could still be further extended by focussing effort and logistics on optimising DBD referrals. Additional resources (staff and transport), tighter referral criteria, and the use of extended warm ischaemic time donors could increase particularly DCD recovery rates.

Atrial Flutter and Fibrillation Following Lung Transplantation: Incidence, Associations and a Suggested Therapeutic Algorithm.

BACKGROUND: Atrial arrhythmias are relatively common following lung transplantation and confer considerable perioperative risk, specifically haemodynamic instability, pulmonary congestion, dyspnoea, and can mask other post-transplant complications such as infection or acute rejection. However, for most patients, arrhythmias are limited to the short-term perioperative period. METHODS: We present a retrospective case-control analysis of 200 lung transplant recipients and using multivariate regression analysis, document the present incidence, risk factors, and outcomes between the two groups. RESULTS: Twenty-five per cent (25%) of lung transplantation patients developed atrial flutter or fibrillation, most frequently at day 5-7 post lung transplantation, and more commonly present in older recipients and those with underlying chronic obstructive pulmonary disease (COPD), but not in those with previously noted structural heart disease, or in those undergoing single rather than double lung transplants. Atrial arrhythmias were associated with increased intensive care unit and overall length of stay, but were not associated with increased risk of in-hospital stroke, or mortality. Based on our experience, we propose a suggested management algorithm for pharmacological and mechanical rate/rhythm control strategies, for anticoagulation, and discuss the appropriate duration of treatment. CONCLUSIONS: Atrial arrhythmias are relatively common post lung transplantation. Carefully managed, the associated risk of perioperative morbidity and mortality can be mitigated. Further prospective studies are required to validate these strategies.

A donor PaO2/FiO2 < 300 mm Hg does not determine graft function or survival after lung transplantation.

BACKGROUND: A donor arterial PO2/FiO2 (P/F ratio) of less than the 300 threshold would frequently result in either exclusion of the donor or placement of the lungs on ex vivo lung perfusion (EVLP). The aim was to investigate the veracity of the P/F ratio threshold of 300 for donor lung acceptability. METHODS: In 93 brain dead lung donors, arterial blood gases were drawn in the intensive care unit (ICU) just before procurement and each of the 4 donor pulmonary veins in the operating room (OR). No donor lungs were rejected for transplantation based on the last ICU or OR P/F ratio, and EVLP was not used. The recipients were followed up 6 and 12 months following transplantation. RESULTS: There were 93 recipients of bilateral lung transplantation. An arterial P/F ratio of < 300 was largely driven by a low P/F ratio in the lower lobes. There were no differences between the recipients receiving donor lungs where the ICU P/F ratio was < 300 compared with ≥ 300 in the time to extubation, grade of primary graft dysfunction, pulmonary function at 6 and 12 months, and 12-month survival. CONCLUSIONS: From this study:(1) If a donor P/F threshold of 300 was adhered to, 36% would have been rejected, and (2) The donor P/F ratio threshold of 300 is excessively conservative and results in the wastage of donor lungs and the application of unnecessary EVLP.

Controlled donation after circulatory death (DCD) donors: A focus on the utilization of pediatric donors and outcomes after lung transplantation.

BACKGROUND: Access to timely suitably size-matched quality organs remains a challenge for pediatric (pLTx) and adult (aLTx) lung transplantation. The outcomes of donation after circulatory death (DCD) donor lungs from pediatric or adult donors are rarely reported. METHODS: This report describes the controlled DCD and pLTx activity (≤ age 18 years) and outcomes since 2006 when DCD LTx started at our center at the Alfred Hospital. RESULTS: Forty pLTx have been performed since 2006, 9 utilizing DCD and 31 donation after brain death (DBD) donors. A total of 22 pLTX have been conducted since 2012 (when DCD pLTx started); 9 DCD LTx (median age 15 years), including 4 pediatric DCD donors (mean age 8 years) and 5 adult (including 2 cutdown bilobar) DCD LTx donors (mean age 43 years). The other 13 pLTx utilized DBD donors - 8 pediatric (mean age 9 years) and 5 adult (including 2 cutdown bilobar) DBD LTx donors (mean age 44 years). One hundred percent survived 1 year, and 7 of 9 DCD pLTx (78%) are alive (median of 1,316 days), with one Chronic Lung Allograft Dysfunction (CLAD) death at 531 days and one renal failure death at 1,813 days. Three waiting list pediatric deaths occurred at 166 and 320 days. Since 2006, 77 pediatric donors have been used for LTx. Fifteen of these were DCD donors (median age 16 years), 11 of 15 have been used for aLTx (73%). Ten of 11 aLTx are alive at a median 1,992 days (91%) with 1 death at Day 2,444 from CLAD. CONCLUSIONS: Controlled DCD provide a significant and quality donor lung pool to increase LTx opportunities for pediatric patients (and adults) with terminal lung disease.

A Randomized Study of Quantiferon CMV-directed Versus Fixed-duration Valganciclovir Prophylaxis to Reduce Late CMV After Lung Transplantation.

BACKGROUND: We provide the results of the first interventional study of cytomegalovirus (CMV)-specific immune monitoring to direct the length of antiviral prophylaxis in lung transplantation (LTx). METHODS: Patients (n = 118) at risk of CMV infection were randomized 1:2 to either 5 months or variable length valganciclovir prophylaxis (5-11 mo post-LTx), as determined by the QuantiFERON (QFN)-CMV assay. Patients with a negative QFN-CMV assay (< 0.2 IU/mL) received prolonged valganciclovir prophylaxis. RESULTS: The primary endpoint that was the incidence of CMV infection in the lung allograft within 18 months of LTx was significantly reduced in the QFN-CMV directed arm (37% versus 58%, P = 0.03). Secondary endpoints that included blood viremia, acute rejection, and chronic lung allograft dysfunction did not differ between the 2 arms. Of the 80/118 patients who ceased antiviral prophylaxis at 5 months, the incidence of viremia (> 600 copies/mL) within the blood was significantly reduced in patients with a positive QFN-CMV assay compared with those without protective immunity (13% versus 67%, P = 0.0003), as was the incidence of severe viremia (> 10 000 copies/mL) (3% versus 50%, P < 0.001). Ceasing antiviral prophylaxis at 11 months in patients with a negative assay was associated with a 25% incidence of late CMV viremia. CONCLUSIONS: Cytomegalovirus immune monitoring allows an individualized approach to CMV prophylaxis and reduces late CMV infection within the lung allograft.

Cryptococcal infection in lung transplant recipients: A 5-year retrospective review at an Australian transplant center.

Cryptococcosis is a common invasive fungal infection (IFI) in solid organ transplant (SOT) recipients. Little is known about cryptococcosis in lung transplant (LTx) recipients despite having one of the highest risks of infection. The aim of this study was to describe demographic and clinical features of cryptococcal infection in LTx recipients. We performed a retrospective, observational study of cryptococcal infection in LTx recipients at The Alfred Hospital in Melbourne, Australia, from 2012 to 2017. A total of 11 cases were identified. Seven patients (64%) were male and the median age was 54.7 years (range 34-69 years). Diagnosis occurred at a median of 233 days (range 1-3650 days) post-transplant. Nine patients (82%) had isolated pulmonary infection of whom 7 (78%) were asymptomatic. All were treated with oral antifungal therapy and 1 required surgical resection of infected lung. Two patients (18%) had disseminated infection; 1 with pulmonary and central nervous system (CNS) infection and 1 with isolated CNS infection. Both patients presented with headache and brain imaging demonstrated cerebral edema, myelinosis, and leptomeningeal enhancement. One of these patients died. This study highlights the fact that cryptococcal infection should remain a consideration in asymptomatic LTx recipients, especially in the presence of non-specific nodules on chest imaging, and that the presence of headache in these patients requires urgent investigation for CNS infection.

Lung transplantation in Australia, 1986-2018: more than 30 years in the making.

Lung transplantation in Australia is 32 years old in 2018. From its early infancy in 1986, it continues to evolve and is internationally recognised as demonstrating world's best practices in organ donation, utilisation and transplantation procedures. Over the past decade, transplant numbers have increased substantially due to innovations in donor procurement, such as donation after circulatory death, the use of ex vivo lung perfusion, extended criteria and organ utilisation, with more than 200 lung transplants undertaken in Australia annually. Parallel to this, lung transplant outcomes have continued to improve. While the management of lung transplant recipients is heavily dependent on a tertiary care paradigm, this model is well developed and has been extremely successful, with Australian outcomes exceeding those of the International Society for Heart and Lung Transplantation Registry at all time points.