Utilising organs from hepatitis C virus PCR-positive donors in Western Australia.

We transplanted six solid organs from three hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive donors during 2018-2023. Recipients were treated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir for 4-12 weeks, with all six achieving sustained virological response without significant adverse events. As occurs in other jurisdictions, solid organ transplants from HCR PCR-positive donors can be safely utilised in Australia.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy.

BACKGROUND: Current guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with cardiopulmonary comorbidities, despite limited available evidence to guide management. RESEARCH QUESTION: Do left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of patients with PAH? STUDY DESIGN AND METHODS: The Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial criteria was used to define the phenotype of patients with PAH with risk factors for LHD. Treatment strategy, functional outcome, long-term survival, and risk discrimination were compared with a reference PAH cohort using the Pulmonary Hypertension Society of Australia and New Zealand Registry. RESULTS: A total of 487 incident patients with PAH diagnosed between 2011 and 2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors, with 384 (78.9%) remaining as the reference group. Patients in the PAH with LHD risk factors group were older (66 ± 13 vs 58 ± 19 years; P < .001), had lower pulmonary vascular resistance (393 ± 266 vs 708 ± 391 dyn.s/cm5; P = .031), and had worse 6-min walk distance (286 ± 130 vs 327 ± 136 m; P = .005) at diagnosis. The PAH with LHD risk factors group was less likely to receive initial combination therapy (27% vs 44%; P = .02). Changes in 6-min walk distance at 12 months were similar in both groups (43 ± 77 m in the PAH with LHD risk factors group and 50 ± 90 m in the reference group; P = .50), including when stratified by initial treatment strategy (PAH with LHD risk factors group vs reference PAH group: monotherapy: 40 ± 81 vs 38 ± 95 m, P = .87; combination therapy: 53 ± 78 vs 64 ± 106 m, P = .511). Functional class improvements were also similar in both groups. REVEAL Registry 2.0 risk score effectively discriminated risk in both populations (C statistic = 0.756 for the PAH with LHD risk factors group and C statistic = 0.750 for the reference PAH group). There was no difference in survival between the two groups (log-rank test, P = .29). INTERPRETATION: In a real-world cohort, patients with PAH with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected patients with PAH with LHD risk factors who were treated with initial combination therapy derived similar functional response compared with the reference group. Further studies are needed to phenotype patients with PAH with cardiopulmonary comorbidities who may benefit from initial combination therapy.

Mycoplasma and Ureaplasma Donor-Derived Infection and Hyperammonemia Syndrome in 4 Solid Organ Transplant Recipients From a Single Donor.

Hyperammonemia syndrome (HS) is a life-threatening condition occurring in solid organ transplant patients, affecting primarily lung recipients, and is associated with Mycoplasma hominis and/or Ureaplasma spp infection. The organ donor was a young man who died of hypoxic brain injury and had urethral discharge antemortem. The donor and 4 solid organ transplant recipients had infection with M hominis and/or Ureaplasma spp. The lung and heart recipients both developed altered conscious state and HS associated with M hominis and Ureaplasma spp infections. Despite treatment with antibiotics and ammonia scavengers, both the lung and heart recipients died at day +102 and day +254, respectively. After diagnosis in the thoracic recipients, screening samples from the liver recipient and 1 kidney recipient were culture positive for M hominis with or without Ureaplasma spp. Neither the liver nor kidney recipients developed HS. Our case series demonstrates the unique finding of M hominis and Ureaplasma spp dissemination from an immunocompetent donor across 4 different organ recipients. Phylogenetic whole genome sequencing analysis demonstrated that M hominis samples from recipients and donor were closely related, suggesting donor-derived infection. Screening of lung donors and/or recipients for Mycoplasma and Ureaplasma spp is recommended, as well as prompt treatment with antimicrobials to prevent morbidity.

Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing.

BACKGROUND: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. METHODS: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). RESULTS: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). CONCLUSION: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted.

Chronic thromboembolic pulmonary hypertension in Australia and New Zealand: An analysis of the PHSANZ registry.

BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand. METHODS: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported. RESULTS: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients. CONCLUSION: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities.

A novel highly bio-available itraconazole formulation (SUBA®-Itraconazole) for anti-fungal prophylaxis in lung transplant recipients.

BACKGROUND: Antifungal prophylaxis remains a mainstay of lung transplantation, given invasive fungal infection is a common and serious complication after lung transplantation. Choice of systemic agent to prevent invasive fungal infection varies between centers and funding of agents remains challenging. Our center has recently changed from posaconazole to a highly bioavailable formulation of itraconazole (SUBA®-itraconazole) at substantially reduced cost, but safety and toxicity require further assessment. A retrospective study of lung transplant patients receiving systemic antifungal prophylaxis from December 2016 through December 2019 following change from posaconazole to itraconazole as standard practice. 150 patients with lung transplants were managed in this time period, with 88 (59%) receiving at least 1 mold-active triazole during the study period. 48 (58%) of these patients received SUBA®-itraconazole; 68 (82%) received posaconazole and 10 (12%) received voriconazole. The average cost per patient during the study period was significantly lower on SUBA®-itraconazole (mean $1548/patient/6 month course) than posaconazole (mean $16 921.35/patient/6 month course). Target trough concentrations for prophylaxis of itraconazole > 0.5 mg/L and posaconazole > 0.7 mg/L were achieved on empiric dosing in 49% and 68% respectively. Overall trough itraconazole (0.50 vs 1.12 mg/L, P < .001) and posaconazole (1.37 vs 2.10 mg/L P < .001) concentrations were significantly lower in patients with cystic fibrosis. Calcineurin inhibitor dose changes on introduction or cessation were similar for SUBA®-itraconazole and posaconazole. Breakthrough invasive fungal infection and toxicity were rare. SUBA®-itraconazole is well-tolerated, associated with rare breakthrough invasive fungal infection, and lower cost. Prospective studies following general introduction are required to determine long-term safety, tolerability, and efficacy.

Pulmonary arterial hypertension with below threshold pulmonary vascular resistance.

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25-30 mmHg), PAWP 13 mmHg (IQR 11-14 mmHg) and PVR 2.2 Wood units (IQR 1.9-2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280-416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7-96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32-101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and "borderline" PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

Pharmacological Treatment of Pulmonary Arterial Hypertension in Australia: Current Trends and Challenges.

BACKGROUND: Combination drug therapy for pulmonary arterial hypertension (PAH) is the international standard of care for most patients, however in Australia there are barriers to drug access. This study evaluates current treatment of PAH patients in Australia and the consistency of therapy with international guidelines. METHODS: Cross-sectional analysis of patients with Group 1 PAH enrolled in the Pulmonary Hypertension Society of Australia and New Zealand Registry (PHSANZ) at 31 December 2017. Drug treatment was classified as monotherapy or combination therapy and adequacy of treatment was determined by risk status assessment using the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculator. Predictors of monotherapy were assessed using a generalised linear model with Poisson distribution and logarithmic link function. RESULTS: 1,046 patients met the criteria for analysis. Treatment was classified as monotherapy in 536 (51%) and combination therapy in 510 (49%) cases. Based on REVEAL 2.0, 184 (34%) patients on monotherapy failed to meet low-risk criteria and should be considered inadequately treated. Independent predictors of monotherapy included age greater than 60 years (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.09-1.38; p=0.001), prevalent enrolment in the registry (RR 1.21 [95%CI 1.08-1.36]; p=0.001) and comorbid systemic hypertension (RR 1.17 [95%CI 1.03-1.32]; p=0.014), while idiopathic/heritable/drug-induced PAH subtype (RR 0.85 [95%CI 0.76-0.96]; p=0.006), functional class IV (RR 0.50 [95%CI 0.29-0.86]; p=0.012), increased right ventricular systolic pressure (RR 0.99 [95%CI 0.99-1.00]; p<0.001) and increased pulmonary vascular resistance (RR 0.96 [95%CI 0.95-0.98]; p<0.001) were less likely to be associated with monotherapy. CONCLUSIONS: Most Australian PAH patients are treated with monotherapy and a significant proportion remain at risk of poor outcomes. This is below the standard of care recommended by international guidelines and at risk patients should be escalated to combination therapy.

Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.

BACKGROUND AND OBJECTIVE: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. METHODS: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. RESULTS: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. CONCLUSION: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.

Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium.

BACKGROUND: Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO), and its clinical correlate bronchiolitis obliterans syndrome (BOS). This study compared gene and cellular characteristics of injury and repair in large (LAEC) and small (SAEC) airway epithelial cells of transplant patients. METHODS: Subjects were recruited at the time of routine bronchoscopy posttransplantation and included patients with and without BOS. Airway epithelial cells were obtained from bronchial and bronchiolar brushing performed under radiological guidance from these patients. In addition, bronchial brushings were also obtained from healthy control subjects comprising of adolescents admitted for elective surgery for nonrespiratory-related conditions. Primary cultures were established, monolayers wounded, and repair assessed (±) azithromycin (1 µg/mL). In addition, proliferative capacity as well as markers of injury and dysregulated repair were also assessed. RESULTS: SAEC had a significantly dysregulated repair process postinjury, despite having a higher proliferative capacity than large airway epithelial cells. Addition of azithromycin significantly induced repair in these cells; however, full restitution was not achieved. Expression of several genes associated with epithelial barrier repair (matrix metalloproteinase 7, matrix metalloproteinase 3, the integrins ß6 and ß8, and ß-catenin) were significantly different in epithelial cells obtained from patients with BOS compared to transplant patients without BOS and controls, suggesting an intrinsic defect. CONCLUSIONS: Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with BOS, particularly with SAEC. We also show that azithromycin partially mitigates this pathology.

Retrospective Validation of the REVEAL 2.0 Risk Score With the Australian and New Zealand Pulmonary Hypertension Registry Cohort.

BACKGROUND: Pulmonary arterial hypertension (PAH) prognosis has improved with targeted therapies; however, the long-term outlook remains poor. Objective multiparametric risk assessment is recommended to identify patients at risk of early morbidity and mortality, and for optimization of treatment. The US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk score is a new model proposed for the follow-up of patients with PAH but has not been externally validated. METHODS: The REVEAL 2.0 risk score was applied to a mixed prevalent and incident cohort of patients with PAH (n = 1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier survival was estimated for each REVEAL 2.0 risk score strata and for a simplified three-category (low, intermediate, and high risk) model. Sensitivity analysis was performed on an incident-only cohort. RESULTS: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ Registry cohort, with a C statistic of 0.74 (both for full eight-tier and three-category models). When applied to incident cases only, the C statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12- and 60-month survival estimates (all risk category comparisons P < .001). Although the full eight-tier REVEAL 2.0 model separated patients at low, intermediate, and high risk, survival estimates overlapped within some of the intermediate- and high-risk strata. CONCLUSIONS: The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of patients with PAH at follow-up. The simplified three-category model may be preferred for clinical use and for future comparison with other prognostic models.

Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients.

BACKGROUND AND OBJECTIVE: Human rhinovirus (RV) is a common upper and lower respiratory pathogen in lung allograft recipients causing respiratory tract exacerbation and contributing towards allograft dysfunction and long-term lung decline. In this study, we tested the hypothesis that RV could infect both the small and large airways, resulting in significant inflammation. METHODS: Matched large and small airway epithelial cells (AEC) were obtained from five lung allograft recipients. Primary cultures were established, and monolayers were infected with RV1b over time with varying viral titre. Cell viability, receptor expression, viral copy number, apoptotic induction and inflammatory cytokine production were also assessed at each region. Finally, the effect of azithromycin on viral replication, induction of apoptosis and inflammation was investigated. RESULTS: RV infection caused significant cytotoxicity in both large AEC (LAEC) and small AEC (SAEC), and induced a similar apoptotic response in both regions. There was a significant increase in receptor expression in the LAEC only post viral infection. Viral replication was elevated in both LAEC and SAEC, but was not significantly different. Prophylactic treatment of azithromycin reduced viral replication and dampened the production of inflammatory cytokines post-infection. CONCLUSION: Our data illustrate that RV infection is capable of infecting upper and lower AEC, driving cell death and inflammation. Prophylactic treatment with azithromycin was found to mitigate some of the detrimental responses. Findings provide further support for the prophylactic prescription of azithromycin to minimize the impact of RV infection.

Epidemiology of invasive fungal infections in lung transplant recipients in Western Australia.

BACKGROUND: Invasive fungal infections (IFI) are common after lung transplantation with reported incidence of 8.1% to 16% at 12 months post-transplant, and 3-month all-cause mortality after IFI of 21.7%. METHODS: We performed a retrospective study of IFI and fungal colonization in lung transplants (LTs) from November 2004 to February 2017. RESULTS: 137 LTs were followed for a median 4.1 years (IQR 2.1-6.2 years). In addition to nebulized amphotericin for the transplant admission to all LTs, systemic mold-active azole was given to 80/130 (61.5%) LTs in the first 6 months post-transplant, 57/121 (47.1%) in the period 6-12 months after transplant, and 93/124 (75%) in the period more than 12 months post-transplant. Mold airways colonization was found in 81 (59.1%) LTs before and 110 (80.3%) LTs after transplantation. There were 13 IFIs for an overall incidence of 2.1 per 100 person-years, occurring at a median 583 days (IQR 182-1110 days) post-transplant, a cumulative incidence of 3.8% at 1 year, 7.6% at 3 years and 10.1% at 5 years post-transplant. All-cause 3-month mortality after IFI was 7.7%. Aspergillus species followed by Scedosporium apiospermum and Cryptococcus species were the commonest fungi causing IFI. CONCLUSIONS: In our cohort the rate of IFI was comparatively low, likely because of comprehensive early antifungal use and preemptive therapy at any time after transplant. Prospective studies of fungal colonization late after LT are required to determine the risks and benefits of watchful waiting compared to preemptive therapy.

Cytomegalovirus viremia in lung transplantation during and after prophylaxis.

BACKGROUND: Lung transplantation has a high risk of cytomegalovirus (CMV) viremia and disease. METHODS: Valganciclovir was planned for 6 months in CMV recipient seropositive (R+) lung transplants (LTs) and given long-term in D+R- LTs. CMV viremia was monitored regularly during and after prophylaxis in all patients. RESULTS: Of 137 LTs, 22 were D+R-, 49 D+R+, 43 D-R+, and 23 D-R-, with median follow up 4.1 years (IQR 2.1-6.2 years). CMV viremia at any time occurred in 44.5% of LTs. CMV viral load >103  c/mL was uncommon (9/77 episodes). CMV viremia occurred at median 665 days (IQR 271-1411 days), in 5.1% LTs <6 months, 20.3% LTs 6-12 months, and 35.8% LTs >12 months. CMV disease occurred in 6 (4.4%) LTs at an overall rate of 1.0 episode per 100 person-years: two of these cases were organ-specific disease, four were CMV syndrome. One case of ganciclovir-resistant CMV was diagnosed. D+R+ and D+R- LTs had higher viremia rates than the D-R+ group. No viremia occurred in D-R- LTs. CMV viremia was not associated with age, gender, type of LT, indication for LT, acute rejection, bronchiolitis obliterans syndrome, or mortality. CONCLUSIONS: Prophylaxis for 6 months in D+R+ and D-R+, and past 12 months in D+R- LTs, with long-term monitoring in all patients using a sensitive assay, and reinstitution of valganciclovir for low-level viremia was effective at markedly reducing the incidence of CMV disease. CMV D-R- LTs do not need routine CMV monitoring.

Safe and effective exercise training for patients with pulmonary arterial hypertension: putting current evidence into clinical practice.

INTRODUCTION: While there have been significant advances in the medical treatment of pulmonary arterial hypertension (PAH), life expectancy, and quality of life remain reduced in this disease. Strenuous exercise may be hazardous for PAH patients; however, several relatively small trials have confirmed that exercise training programs can be used safely and effectively as adjunctive treatment for selected patients. The use of exercise training is now recommended in consensus international PAH treatment algorithms; however, there is no published guideline detailing how this intervention should be carried out. Areas covered: This review describes the evidence available and evaluates its applicability to 'real life' clinical practice. The limitations of current evidence are acknowledged, and we discuss how the existing data can be applied to management of PAH patients in Australia, New Zealand, and countries with similar healthcare systems. Recommendations for PAH exercise training are proposed including patient selection, program structure and duration, training modalities, training intensity, supervision, monitoring, safety precautions, and outcome assessments. Expert commentary: It is recognized that knowledge gaps remain and further research is required into physiological mechanisms associated with improved exercise capacity, optimal outpatient exercise regimen, durability of benefit, and whether there is any disease-modifying effect or impact on long-term prognosis.

Analysis of the QuantiFERON-CMV assay, CMV viraemia and antiviral treatment following solid organ transplantation in Western Australia.

Prevention of cytomegalovirus (CMV) infection remains an important aspect of improving long term outcomes of solid organ transplantation and currently relies on prophylactic antiviral medication and early detection of viraemia or disease. Uptake of diagnostic tools to personalise assessment of CMV immunity and guide interpretation of viral testing remains low. We assessed the QuantiFERON-CMV assay in 54 Western Australian recipients of renal, heart, lung or liver allografts to determine the relationship between CMV-specific immunity, viraemia and disease following cessation of antiviral prophylaxis. We carried out an initial validation study which demonstrated that the QuantiFERON-CMV assay is highly precise and strongly correlated with CMV-specific antibodies in 30 healthy blood donors (sensitivity 82%, specificity 95%). In the solid organ transplant recipients we examined, the prevalence of asymptomatic CMV viraemia was high at 61% but only two patients ultimately developed CMV disease, both of whom had negative QuantiFERON-CMV responses, indicating lack of CMV T-cell immunity. The vast majority (94%) of patients who had spontaneous resolution or stability of asymptomatic CMV viraemia without any antiviral treatment had positive QuantiFERON-CMV responses. Positive QuantiFERON-CMV responses at cessation of antiviral prophylaxis were significantly associated with pre-transplant CMV seropositivity and the development of asymptomatic viraemia post-transplantation. Overall, 27% of patients were recommenced on antiviral therapy because of asymptomatic CMV viraemia. Patients with non-reactive QuantiFERON-CMV responses had earlier onset, higher level CMV viraemia compared to those with positive QuantiFERON-CMV responses, although the difference did not reach statistical significance. QuantiFERON-CMV results may contribute to decision making in concert with the serological risk profile, net state of immunosuppression and CMV viral load.

Lung transplant: the Western Australian experience.

BACKGROUND: The Western Australian lung transplant programme commenced in 2004 to serve the growing demand of patients with end-stage lung disease. AIM: This report summarises our 11-year experience in lung transplantation. METHODS: Data on 115 consecutive patients and their respective donors transplanted between 2004 and 2015 were collected. The Kaplan-Meier method was used to estimate survival. Cox regression was used to analyse the impact of donor and recipient characteristics on survival. RESULTS: A total of 88 bilateral, 22 single-lung and 5 heart-lung transplants were performed in Western Australia during the first 11 years of the lung transplant programme. The most common indications for transplantation were interstitial lung disease (30.4%), cystic fibrosis (27.8%) and chronic obstructive pulmonary disease (excluding alpha-1 antitrypsin deficiency) (22.6%). Median recipient age was 50 years. Overall survival rates were 96% at 3 months, 93% at 1 year, 84% at 3 years and 70% at 5 years. Older age and higher BMI negatively impacted survival. Chronic lung allograft dysfunction was the leading cause of late mortality. CONCLUSION: Lung transplantation is a treatment option in end-stage lung disease, with annual transplant rates in Western Australia continuing to rise. Our patients enjoy survival rates that compare favourably against international standards.

Sjögren Syndrome With Associated Lymphocytic Interstitial Pneumonia Successfully Treated With Tacrolimus and Abatacept as an Alternative to Rituximab.

Interstitial lung disease (ILD) is a significant complication of Sjögren syndrome (SS) associated with increased morbidity and mortality. The mainstay of treatment remains corticosteroid administration, with or without additional immunosuppressive therapies. Preliminary studies in SS have shown benefit in glandular and serologic parameters following treatment with the CTLA4 immunoglobulin fusion protein abatacept. Topical tacrolimus has been effective for ocular symptoms in SS, but systemic therapy has not been reported. We describe the first case, to our knowledge, of the successful use of a combination of systemic tacrolimus and abatacept in severe refractory SS and related ILD.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand.

BACKGROUND: Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. METHODS: Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. RESULTS: Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality.