Utility of the Stanford Integrated Psychosocial Assessment for Transplant in predicting outcomes before and after lung transplantation.

BACKGROUND: Optimizing donor use and achieving maximal survival following lung transplantation (LTx) require a pretransplant assessment that identifies clinical, physiological, and psychosocial patient factors associated with both poor and optimal post-LTx survival. We examined the utility of a psychosocial tool, the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT), to identify patient suitability for LTx, as well as its association with clinical outcomes before and after LTx. METHODS: This was a retrospective single-center study analyzing LTx assessment clinical variables (age, gender, diagnosis, functional capacity, nutrition, renal function), with a particular focus on the utility of the SIPAT score, to predict patient suitability for LTx. The same variables were analyzed against LTx waitlist mortality, as well as post-LTx survival. RESULTS: Over an 8-year period dating from December 2012, 914 patients (male 54.4%, mean age 55.2 years) underwent LTx assessment. Patients declined for LTx (n = 152, 16.6%) were older and had reduced functional capacity, nutritional markers, and renal function but had a higher SIPAT score. Once listed for LTx, a higher SIPAT score was not associated with waitlist mortality or reduced post-LTx survival. CONCLUSIONS: The SIPAT tool measures psychosocial suitability for transplantation that can be incorporated into a standardized assessment of LTx suitability. While patients with higher SIPAT score were more likely to be declined for LTx, the SIPAT score did not predict outcome in transplanted patients. A subgroup of patients with high SIPAT scores were successfully transplanted, suggesting that unfavorable psychosocial variables are potentially modifiable with a well-resourced multidisciplinary LTx team.

Clinical outcomes following cessation of parenteral immunoglobulin therapy following lung transplantation.

Broad use of parenteral immunoglobulin (IgG) therapy in lung transplant (LTx) patients occurs without robust clinical evidence or guidelines. Main indications include secondary hypogammaglobulinemia, antibody-mediated rejection (AMR), and treatment or prevention of graft rejection where the use of conventional immunosuppressive therapies is contraindicated. As part of routine auditing of IgG use in our LTx service, we assessed for adverse clinical outcomes related to IgG therapy cessation between November 2017 and February 2022. Of 220 LTx recipients receiving IgG therapy at our center during this period (approximately 20% of our total LTx cohort), 48 patients ceased therapy. No adverse outcomes were experienced in 83.3% patients. About 10.4% recommenced therapy for the same indication within 6 months with no longer term sequelae. One AMR patient developed progressive Chronic lung allograft dysfunction and died within 12 months, where therapy cessation was patient-initiated and associated with general noncompliance. These data provide reassurance that physician-directed cessation of IgG therapy is safe when based on sound clinical information and part of a robust clinical auditing process.

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.

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.

Artificial stone-associated silicosis: clinical-pathological-radiological correlates of disease.

Occupational lung disease secondary to inhalation of silica particles is variable and potentially life-threatening. As the artificial stone industry has grown over the last two decades, the development of silicosis has been seen to accelerate and behave differently to chronic silicosis. In this case report, we present two patients who underwent lung transplantation for silicosis at the Alfred Hospital, both with predominantly artificial stone masonry exposure. We have identified the presence of both fibrotic/nodular silicosis and conspicuous alveolar proteinosis within the same lung parenchyma of both patients. We then demonstrate the radiological and histopathological correlates of disease; the first time this has been shown clearly in the literature.

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.

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.

Donation after Brain Death versus Donation after Circulatory Death: Lung Donor Management Issues.

Lung transplantation (LTx) has traditionally been limited by a lack of suitable donor lungs. With the recognition that lungs are more robust than initially thought, the size of the donor pool of available lungs has increased dramatically in the past decade. Donation after brain death (DBD) and donation after circulatory death (DCD) lungs, both ideal and extended are now routinely utilized. DBD lungs can be damaged. There are important differences in the public's understanding, legal and consent processes, intensive care unit strategies, lung pathophysiology, logistics, and potential-to-actual donor conversion rates between DBD and DCD. Notwithstanding, the short- and long-term outcomes of LTx from any of these DBD versus DCD donor scenarios are now similar, robust, and continue to improve. Large audits suggest there remains a large untapped pool of DCD (but not DBD) lungs that may yet further dramatically increase lung transplant numbers. Donor scoring systems that might predict the donor conversion rates and lung quality, the role of ex vivo lung perfusion as an assessment and lung resuscitation tool, as well as the potential of donor lung quality biomarkers all have immense promise for the clinical field.

Characteristics of patients who progress from bridging to long-term oxygen therapy.

BACKGROUND: Patients with persistent hypoxia following an acute hospital admission may be discharged with 'bridging' domiciliary oxygen as per criteria defined by the Thoracic Society of Australia and New Zealand. The need for continuous long-term oxygen therapy (LTOT) is then reassessed at a clinic review 1-2 months later. AIM: To describe the characteristics of patients discharged from an acute hospital admission with continuous short-term oxygen therapy (STOT), and subsequently to investigate for differences between subjects who proceeded to qualify for continuous LTOT versus those who were able to cease STOT at review. METHODS: This is a retrospective cohort study involving all subjects discharged from Alfred Health between 2011 and 2015 inclusive with bridging domiciliary oxygen. Multiple biochemical, physiological and demographic characteristics were collated and analysed. RESULTS: Of all patients prescribed continuous STOT at time of discharge, 47.3% qualified for LTOT at outpatient review. This cohort had a significantly lower PaO2 measurement at time of discharge, compared with those who no longer qualified. CONCLUSION: PaO2 at time of discharge provides a signal with the potential to identify who will require continuous LTOT following an acute hospital admission. Additionally, this study highlights the need to re-evaluate patients' oxygen requirements during a period of clinical stability.

How can we improve the quality of transplantable lungs?

INTRODUCTION: Optimization of lungs for organ donation is becoming increasingly important as donation rates stagnate despite growing waiting lists. Improving procurement and utilization of donated lungs has the ability to reduce mortality and time on the lung transplantation (LTx) waiting list. Additionally, assessment and optimization of donor lungs can reduce both early and late post-LTx morbidity and mortality, as well as reduce overall costs and resource utility. Areas covered: Strategies that we will discuss in detail include intensive care management practices, such as targeted ventilation protocols and therapeutic bronchoscopy, as well as the ever expanding possibilities within the arena of ex vivo lung perfusion (EVLP). Expert commentary: Donor lung quality is currently optimized both in vivo prior to organ procurement, and also via EVLP circuits. Despite good evidence demonstrating the utility of both approaches, data remain elusive as to whether EVLP is beneficial for all donor lungs prior to implantation, or instead as a tool by which we can evaluate and recondition sub-optimal donor lungs.

Clinical impact of the interstitial lung disease multidisciplinary service.

BACKGROUND AND OBJECTIVE: Multidisciplinary discussions (MDDs) have been shown to improve diagnostic accuracy in interstitial lung disease (ILD) diagnosis. However, their clinical impact on patient care has never been clearly demonstrated. We describe the effect that an ILD multidisciplinary service has upon the diagnosis and management of patients with suspected ILD. METHODS: Patients at two specialized centres with suspected ILD underwent ILD multidisciplinary team review (ILD-MDT) (standard ILD clinic visit and diagnostic review at ILD-MDD). We compared changes in ILD diagnosis and management at referral to those following the ILD-MDT. RESULTS: Ninety patients, 60% males (54/90), aged 67.3 years (SD = 11.4) were reviewed for suspected ILD. Overall, the ILD-MDT resulted in a change in specific ILD diagnosis in 48/90 (53%) patients. Of the 27 patients referred with a diagnosis of idiopathic pulmonary fibrosis (IPF), the diagnosis was changed at MDD in 10 patients. In contrast, seven patients had their diagnosis changed to IPF. There was also a significant reduction in 'unclassifiable' diseases and disease behaviour classifications provided additional information beyond ILD diagnosis. CONCLUSION: Dedicated tertiary ILD-MDT service has an important clinical impact on the care of the ILD patient, with frequent changes in ILD diagnosis and subsequent management. Further research to investigate long-term clinical outcomes of ILD-MDT is required.

Evaluating the interstitial lung disease multidisciplinary meeting: a survey of expert centres.

BACKGROUND: Multidisciplinary meetings (MDM) are the current "gold standard" in interstitial lung disease (ILD) diagnosis and comprise inter-disciplinary discussion of multiple forms of information to provide diagnostic and management outputs. Although bias could be potentially inserted at any step in the discussion process, to date there has been no consensus regarding the appropriate constitution and governance of MDM. We sought to determine the features of ILD MDMs based within ILD centres of excellence around the world. METHODS: An internet based questionnaire was sent to twelve expert centres in Europe, North America, and Australia seeking information regarding the structure and governance of their MDM. Data was analysed for consistent themes and points of contrast. RESULTS: Responses were received from 10 out of 12 centres. Similarities were demonstrated with regards to contributing attendees, meeting frequency and case numbers reviewed. Significant heterogeneity in attendee speciality group type, quantity and method of data presentation, approach to diagnosis formulation and documentation, and information provision was apparent. CONCLUSIONS: The constitution of ILD MDMs differs considerably between expert centres. Such differences may result in discordant outcomes, and emphasise the need for further evidence regarding the appropriate constitution and governance of ILD MDMs.