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Objectives The nailfold videocapillaroscopy (NVC) has been known to assist with interstitial lung disease (ILD) classification. However, evidence on its diagnostic efficacy is limited, particularly in some connective tissue disease-related interstitial lung diseases (CTD-ILD), and in interstitial pneumonia with autoimmune features (IPAF). This study aimed to address this limitation by conducting a meta-analysis on the efficacy of the NVC in ILD subgroups of CTD-ILD, IPAF and idiopathic pulmonary fibrosis (IPF). Methods MEDLINE, EMBASE, CENTRAL were screened from inception to December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that report prevalence of nailfold abnormalities (NVC+) in CTD-ILD, IPAF and IPF cohorts were included. Data were presented as prevalence ratio (PR) with 95% CI using a random-effects model. Quality of evidence was assessed using GRADE criteria. Results Twenty-one studies were eligible. Prevalence of NVC+ was highest in CTD-ILD; PR (95 CI%) 80.4% (74.3%, 85.3%), followed by IPAF; 27.4% (10.9%, 53.7%), and IPF; 13.8% (5.7%, 29.9%). Late scleroderma pattern was the most prevalent nailfold pattern; 40.4% (28.1%, 54.1%) in our CTD-ILD cohort. Quality of evidence was low for CTD-ILD, IPAF and IPF cohorts, moderate for the late scleroderma pattern cohort. Conclusion NVC can increase the diagnostic accuracy of ILD when used in a multi-disciplinary setting, and appears to have greatest utility in CTD-ILD, followed by IPAF and IPF. The Late Scleroderma Pattern was the most frequent nailfold capillary pattern in SSc-ILD. Future research will allow for greater understanding of the prognostic value of the NVC in ILD.

Background and objective: The increasing awareness of the prevalence and chronic nature of the COVID-19 disease burden requires a better understanding of effective interventions in large scale clinical trials. Telerehabilitation is effective in other chronic disease groups and the aim of this study was to assess the feasibility of a specific, group-based telerehabilitation exercise intervention for Long-COVID. Methods People with Long-COVID symptoms, defined as persistent dyspnoea, fatigue or chest pain, at least 110 days post COVID-19 diagnosis and who had not undertaken exercise training three months prior to randomisation into the trial were included. Participants were randomised to receive a twice-weekly supervised group telerehabilitation program for ten weeks or continue with usual care. Feasibility outcomes included recruitment rate, adherence, completion rate, adverse events and technological issues. Exploratory clinical outcomes including exercise capacity, fatigue and health-related quality of life were also assessed. Results 21 participants with mean age 53 ± 14 yrs, 17 of whom were not hospitalised, were recruited 365 ± 67 days after diagnosis of COVID-19. The recruitment rate was 39% of possible participants. Nine (82%) of the intervention group completed the follow-up assessments. The telerehabilitation participants completed 18 ± 2 sessions, with 100% completing 16 sessions or more. There were no adverse events and two technological problems reported for the intervention group. Conclusion Supervised group telerehabilitation appears to be feasible and safe for people with Long-COVID. A future study is required to examine the efficacy and generalizability of the supervised group-based telerehabilitation exercise intervention. Trial registration: Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12621000031864)

Global attention is gradually turning to focus on the problem of prolonged illness following acute coronavirus disease 2019 (COVID-19), commonly termed ‘Long COVID’ or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Whilst an increasing number of reports now recognise this condition, accurate characterisation of its prevalence, clinical features and natural history is complicated by choice of denominator population, lack of case definition and marked self-selection bias. Nevertheless, a picture is emerging of a syndrome characterised predominantly by fatigue, dyspnoea, chest tightness, and ‘brain fog’ present in around 10–30% of individuals at 2–3 months post-acute infection and affecting both those with initial severe illness and those in whom acute infection was mild [1–3].

Aim: Single (SLTx) and double lung transplantation (DLTx) are therapeutic options for end-stage interstitial lung disease (ILD). The aim of this study is to describe oscillometry indices in stable SLTx compared to DLTx recipients. Methods: Oscillometry & spirometry were performed on all stable LTx recipients at 2 Australian centres from 2020-2021 using TremoFlo C-100 to obtain resistance (R5, R5-19), reactance (X5) and reactance area (Ax). Subjects with baseline, acute or chronic lung allograft dysfunction were excluded. SLTx for ILD (SLTx-ILD) recipients were compared with DLTx for ILD (DLTx-ILD) and were matched by age and gender. Results: 17 SLTx-ILD were included and compared with 10 matched stable DLTx-ILD. Baseline demographics of SLTx-ILD [88% males; mean age 64 (SD 5)] and DLTx-ILD [90% males; mean age 63 (SD 6)] were similar. Median X5 (-1.86 vs -1.14, p=0.02) and Ax (12.60 vs 5.57, p=0.04) differed significantly between SLTx-ILD and DLTx-ILD recipients, but resistance (R5, R5-19) measurements did not. Conclusion: SLTx for ILD is characterised by significantly worse X5 and Ax (increased elastance) as compared to DLTx for ILD. The abnormal reactance, in addition to insignificant differences in resistance measurements between SLTx and DLTx, may be due to the fibrotic contralateral native lung. However, contribution from other factors such as differences in lung size matching needs to be assessed. Longitudinal oscillometry studies are required to ascertain whether abnormal reactance – when assessed against patients9 baseline measurements – can be indicative of earlier progressive lung graft dysfunction and a worse prognosis in SLTx, as compared to using traditional methods.

Despite continued surgical advancements in the field of cardiothoracic transplantation, post-operative complications remain a burden for the patient and the multidisciplinary team. Lesser known complications including swallowing disorders (dysphagia) and voice disorders (dysphonia) are now being reported. Such disorders are known to be associated with increased morbidity and mortality in other medical populations, however their etiology amongst the heart and lung transplant populations has received little attention in the literature. This paper explores the potential mechanisms of oropharyngeal dysphagia and dysphonia following transplantation and discusses optimal modalities of diagnostic evaluation and management. A greater understanding of the implications of swallowing and laryngeal dysfunction in the heart and lung transplant populations is important to expedite early diagnosis and management in order to optimise patient outcomes, minimise allograft injury and improve quality of life.

There is increasing evidence that the spectrum of human polyomavirus 2 (JCV) CNS disease includes novel syndromes other than progressive multifocal leukoencephalopathy (PML), the appreciation of which is increasingly important in the context of MS therapies and immunodeficiency states. Our objective is to describe unusual presentations of JCV infection to heighten clinician awareness. We describe three case reports of various PML presentations. Firstly a 56-year-old HIV positive male with decades of viral suppression and normal immune function presented with 1 month of non-specific headache that spontaneously resolved despite an MRI showing a new area of PML and CSF being JC DNA + . He had had two similar episodes in 2013 and 2014 with MRI scans consistent with PML, CSF, JCV, and PCR positivity once and brain biopsy-positive twice. Another 61-year-old male presented with subacute binocular vision loss and was found to have newly diagnosed HIV and JCV DNA detected in CSF. MRI brain only demonstrated symmetrical chiasmo-hypothalamic enhancement. There has been some improvement with combination antiretroviral therapy and corticosteroids for immune reconstitution inflammatory syndrome (IRIS). Thirdly, a 65-year-old male presented with subacute progressive confusion and behavioural disturbance, one year post-bilateral lung transplantation. MRI brain demonstrated no evidence of PML but CSF on three occasions demonstrated a progressively increasing JCV DNA load. Despite reduction in his immunosuppression, the patient developed profound encephalopathy without localising features leading to death two months later. These cases emphasise the atypical presentations of JCV: chronic relapsing, unusual symmetrical visual pathway disease, and non-localising encephalopathy without MRI evidence of PML.

Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.

Background Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols. Aim To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation. Methods We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min). Results Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes. Conclusion There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

Purpose Baseline and chronic lung allograft dysfunction (BLAD & CLAD) are leading causes of reduced patient survival. Airway oscillometry characterises the lung's mechanical properties with greater sensitivity than spirometry. This study aims to characterise BLAD and CLAD with airway oscillometry. Methods Oscillometry was performed on all bilateral lung transplant (LTx) recipients at 2 Australian centres between Jan-Oct 2020 with the TremoFlo C-100 device to obtain resistance (R5, R19-5), reactance (X5), and reactance area (Ax). Patients with acute lung allograft dysfunction were excluded. CLAD was diagnosed/staged using spirometry as per ISHLT 2019 Consensus Criteria. BLAD was defined as failure to ever achieve >80%-pred FEV1 and FVC. Multivariate logistic regression measured the association between oscillometry risk of CLAD. Results A total of 179 LTx recipients [47% males; median age 54 (IQR 25); duration post-LTx 5 years (IQR 7)] were recruited. 112/179 (63%) patients had no CLAD and of these 27 (24%) patients had BLAD. There was a significant difference in median X5 (-1.64 vs -1.20, p Conclusion BLAD is characterised by abnormal reactance (X5 & Ax), yet resistive airway properties (R5 & R5-19) are similar to patients without BLAD. The association between oscillometry parameters and CLAD demonstrates that oscillometry provides complimentary information about lung dysfunction after transplant. Longitudinal studies are required to determine whether oscillometry has a role in earlier detection of CLAD.

Purpose Whilst the United States, Germany and the Netherlands use the Lung Allocation Score for donor-recipient matching, there currently exists no similar scoring system in Australia. Our objective was to develop a lung allocation algorithm to be used at a thoracic transplantation centre in Sydney, Australia. Methods A review of the current literature and survival analyses of data from lung transplant activity at this centre from 1 January 2015 to 31 December 2019 was performed to determine the prognostic variables to be included in our algorithm. The algorithm was developed using Microsoft Excel, then prospectively validated over a 10-week period in which the transplant clinicians were surveyed on the algorithm's choice of recipient. It was further validated retrospectively by comparing the patients put forward for crossmatch by the algorithm with the clinician's selection for all lung transplants performed between 1 January and 22 June 2020. Results Patient parameters were stratified into suitability, urgency and risk categories (Table 1). Each of these parameters are scored from -100 to a maximum of 500 points, then weighted from 0 to 1. The resultant priority list ranks patients based on total score.The algorithm was trialled a total of 39 times. Almost twice as many patients were put forward for crossmatch by the algorithm than selected by the clinician. However, 3.3% of patients put forward by the clinician fell outside of the algorithm's selection criteria. In all trials, the final recipient chosen by the clinician was within the algorithm's top 5 candidates. Conclusion A working lung allocation algorithm that is able to streamline the allocation process and assist transplant clinicians in allocating lungs to recipients in an equitable, transparent and reproducible manner was developed. Further adjustments and validation may be required before implementation at this centre.

Purpose The effect of matching donor and lung transplant (LTx) recipient lung volumes on LTx outcomes is unknown. The Forced Oscillation Technique (FOT) is a simple measure of the mechanical properties of the respiratory system. We have recently developed novel measures of airway closure using FOT. This study aims to assess the effect of matching donor and recipient lung volumes on respiratory system mechanics using FOT. Methods A multi-centre (Alfred Hospital, Melbourne and St Vincent's Hospital, Sydney) prospective study of (n=19) subjects (63% male, age 56 ±13yrs) at one time point 3-6 months post bilateral LTx were divided into two groups: G1 - Recipient measured pre-LTx total lung capacity (rTLC) predicted dTLC, n=10. All subjects underwent pulmonary function testing including, spirometry, plethysmography and FOT (Tremoflo 2000, Thorasys, Canada). Results In G1, respiratory system elastance (stiffness=AX5) positively correlated with difference between dTLC and rTLC (p Conclusion Novel measurements of respiratory mechanics from FOT demonstrate both oversizing and under-sizing donor TLC can alter recipient respiratory mechanics post-LTx. Longitudinal studies are underway to correlate these effects with the incidence and extent of baseline or chronic lung allograft dysfunction (BLAD & CLAD).

Purpose Low baseline diffusing capacity (DLCO), at 1-year after lung transplant, is associated with an increased risk of graft loss. DLCO is the product of 2 measurements; the gas transfer factor (KCO) and the accessible alveolar volume (VA). Our aim was to understand the relative contributions of baseline KCO and VA on survival after lung transplant. Methods A retrospective cohort analysis was conducted of all bilateral lung transplant recipients between 1998 and 2018, with DLCO measured at 1 year after transplant. Low baseline VA was defined as 80%-pred. Patients were divided into 4 groups: Normal VA-Normal KCO, Normal VA-Low KCO, Low VA-Normal KCO, Low VA-Low KCO. Multivariate logistic regression and Cox proportional hazard models were used for statistical analysis. Results 708 patients underwent double lung transplant during the study period. 258 patients had DLCO measured at 1-year post transplant. The mean recipient age was 44.0 (SD 15.5) with 50% males. The median time to measurement of DLCO was 378 days. The median (IQR) VA %-pred was 82 (21), %-Pred KCO 74 (19) and %-Pred FEV1 84 (29). Donor age was significantly associated with low KCO OR 1.06 (95%CI 1.03-1.08), p Conclusion Donor age, ILD and transplant era were associated with baseline KCO and VA. Low baseline VA was a greater risk for future graft loss than low KCO. There may be benefit in the incorporation of baseline VA and KCO at 1-year post transplant to identify patients with an increased risk of graft loss.

Purpose Respiratory Syncytial Virus (RSV) infection after lung transplantation (LTx) has been associated with acute and chronic allograft dysfunction. A previous study at our center demonstrated an IV loading regimen followed by oral therapy was an effective and cost-efficient treatment for RSV infection after LTx. This study evaluates efficacy, safety, and cost-efficiency of an entirely oral ribavirin regimen for treatment of RSV infection after LTx. Methods We performed a single center retrospective analysis of 49 consecutive LTx recipients from Aug-2016 to Aug-2019. RSV was diagnosed by PCR from nasopharyngeal swab or bronchoalveolar lavage fluid. Patients were followed for 3 months post RSV treatment. Data collected included longitudinal spirometry, hemoglobin and drug cost. Results Forty-nine patients (mean age 47±15, male:female ratio 25:24), presented with 52 episodes of clinically symptomatic RSV. Complete spirometry data was available for 33 episodes. Mean FEV1 fell from baseline 2.33±0.69 to 2.06±0.71 (p Conclusion An exclusively oral regimen of loading and maintenance dose ribavirin for treatment of RSV post LTx appears to be effective and well-tolerated. Furthermore, it carries a significant cost saving and completely avoids hospital admission in 69% of patient episodes.

Purpose Chronic lung allograft dysfunction (CLAD) is a major contributor to reduced survival after lung transplantation. Specific HLA-DQ risk epitope mismatches (REM) predict the development of de novo DQ donor specific antibodies (dn-DSA). We hypothesise that the presence of DQ REM would be associated with an increased risk of CLAD. Methods A retrospective cohort analysis was conducted of all bilateral lung recipients at a single centre between Jan-2014 and Jan-2019. DQ REM was defined as donor-recipient mismatch at DQA1*05-DQB1*02 (DQ2) and/or DQA1*05-DQB1*03:01 (DQ7). De novo REM DSA (DQ2 and/or DQ7) were defined as MFI >1000 on surveillance Luminex testing. Multivariate Cox proportional hazards models were used for time-to-event analyses. Results Complete molecular typing was available on 241/248 (97.2%). 156 (64.7%) recipients had no DQ REM, 37 (15.4%) had a DQ7 REM, 42 (17.4%) had a DQ2 and 6 (2.5%) had both. The median follow-up time was 3.2 years. A significantly higher proportion of recipients with DQ REM developed dn-REM-DSA compared to those without, 38/86 (44.7%) vs 0/156 (0%) p Conclusion DQ REM status alone was not significantly associated with an increased risk of CLAD within the follow-up period. Patients with DQ REM who developed dn-REM-DSA, however, had a shorter time to CLAD. Avoidance of DQ REM at allocation represents a strategy to reduce dn-REM-DSA and the risk of CLAD in this subgroup. Transplantation across DQ REM still may be an acceptable risk for urgent recipients.

Community acquired respiratory infections (CARV) are associated with severe acute illness and potentially long term sequelae in lung transplant patients. CARV triggers innate and adaptive immune responses that may amplify lung allograft injury and lead to chronic lung allograft disease.

Purpose BMI outside of the range 16-30 kg/m2 is considered a relative contraindication to lung transplantation. We hypothesised that patients transplanted outside of this target range would have poorer graft survival compared to recipients within this range. Methods A single center retrospective analysis was performed of all first bilateral lung transplant (BLTx) recipients with available pre-transplant BMI data, between January 2000-October 2018. Graft survival was defined as time to death or re-transplantation. Kaplan-Meier curves were generated for recipients with a pre-transplant BMI > 30, and those with a BMI Results 671 patients underwent a first BLTx during the study period. 585 patients had a BMI at the time of transplant within the range of 16-30kg/m2. 52 patients had a BMI>30, and 34 had a BMI 30 groups there was a significant difference in native lung disease (ILD 21% vs 42%, p 30 and 3434 days for BMI 30 compared to BMI 16-30 (p=0.04) [figure 1A]. There was no significant difference in survival between patients with BMI Conclusion Patients with a pre-transplant BMI>30 had significantly shorter survival than those with target range BMI. Younger patients with BMI 30 should remain a relative contra-indication to lung transplantation but BMI

Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients.Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors.The incidence of PTLD was 7.59% in heart-lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (1 year post-transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p0.001) and serum albumin30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p0.001). Five-year overall survival was 29%.This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation.

Respiratory syncytial virus (RSV) causes serious respiratory tract infections in lung transplant (LTx) recipients, is associated with development of bronchiolitis obliterans syndrome, and has no proven effective therapy. We evaluated the efficacy, safety, and cost-effectiveness of oral ribavirin for the treatment of RSV infection after LTx.Between December 2011 and May 2014, 52 LTx recipients developed 56 episodes of symptomatic RSV infection, which was diagnosed by positive RSV polymerase chain reaction on nasopharyngeal swabs. An intravenous (IV) loading dose of ribavirin (33 mg/kg) was given in 52 of 56 episodes; an equivalent oral loading dose was given in 2 episodes. Oral ribavirin (20 mg/kg/day) was given by day 2 in 53 of 56 episodes. Median duration of therapy was 8 days (range 6-31 days).Mean forced expiratory volume in 1 sec decreased from 2.38 ± 0.78 liters to 2.07 ± 0.85 liters (p0.001) at presentation, recovered to 2.26 ± 0.82 liters at cessation of ribavirin, and was maintained at 2.31 ± 0.81 liters within 3 months. New-onset bronchiolitis obliterans syndrome developed in 1 of 38 patients (2.6%) at 3 months. Anemia worsened in 23 episodes, and de novo anemia developed in 5 episodes. Mean hemoglobin decreased from 118 ± 16 g/liter to 113 ± 21 g/liter (p = 0.015). There were 4 late deaths. Compared with IV therapy, mean drug cost saving was US $6,035 per episode, and mean inpatient bed days was reduced by 6.7 days (p0.001).To our knowledge, we report the largest series of LTx recipients treated with oral ribavirin for RSV. Oral ribavirin appears to be an effective, well-tolerated alternative to IV or inhaled ribavirin; provides considerable cost savings and reduces length of hospital stay. Potential long-term benefits in preventing development of chronic lung allograft dysfunction are yet to be determined.

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.

© 2015 The Authors. Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population.

Lung ultrasound has been suggested as an alternative to routine chest radiography (CXR) to screen for pneumothorax after transbronchial lung biopsy. In post-lung transplant patients, who may have altered anatomy and pleural adhesions, the validity of lung ultrasound to screen for postbiopsy pneumothoraces has not been investigated.Lung ultrasound using an ultraportable handheld device was performed in a standardized manner 2-hour after biopsy in post-lung transplant patients. Ultrasound assessment was then compared with CXR performed immediately after lung ultrasound.In total, 165 patients were enrolled in the study. Eight pneumothoraces were diagnosed by image intensifier or CXR before lung ultrasound. There were 8 pneumothoraces diagnosed on CXR 2-hour postbiopsy. Lung ultrasound had a sensitivity of 75% and specificity of 93%. Positive predictive value was 35% and negative predictive value was 99%. The mean number of biopsies taken in patients with and without a pneuomothorax on CXR was 10.6 (±3.1) and 10.9 (±2.1), respectively (P=0.79). The overall pneumothorax rate was 9.7%.Lung ultrasound is a valid tool in excluding penumothoraces after lung biopsy. Ultrasound scans with features of a pneumothorax or patients with symptoms should still undergo CXR. The high false positive rate may be due to small pneumothoraces being seen or the presence of pleural adhesions and altered lung anatomy in post-lung transplant patients.

Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols.To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation.We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min).Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes.There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

Background Epidermal growth factor receptor (EGFR) mutation positivity in primary non-small-cell lung cancer (NSCLC) may confer increased sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy with improved progression-free survival over EGFR wild-type tumours. Some mutation subtypes may not confer such TKI sensitivity. The incidence of rare and compound subtypes in the Australian lung cancer population is not fully defined. Aims The aim of the study was to audit the incidence of EGFR mutation in serial cases of primary non-squamous NSCLC presenting to two multidisciplinary team meetings in metropolitan Sydney for incidence, type of mutation and phenotypic association with mutation positivity. Methods Serially presenting cases of primary non-squamous NSCLC were tested for EGFR mutation. The cases presented to either of two multidisciplinary team meetings in metropolitan Sydney and were referred for EGFR mutation testing on the basis of non-squamous NSCLC histopathology. Samples from the two sites were analysed for EGFR mutation at one of three different laboratories, each using a slightly different assay. Data on phenotypic characteristics, smoking history and clinicopathological features of the tumour were collected. Results There is a relatively high incidence of EGFR mutation in non-squamous NSCLC in a series of patients drawn from two metropolitan multidisciplinary team meetings in Sydney at a rate of 23.8%. A high proportion of rare and compound EGFR mutations were identified (6/32 mutation positive cases, 18.8%). Conclusions The incidence of EGFR mutation may be higher in Australian populations than in other populations of predominantly European origin. Rare and compound EGFR mutations may occur and may have implications for treatment that differ from classically activating mutations.

e20563 Background: Lung cancer (LC) is common with a dismal prognosis. Although treatment with immunotherapy (IO) has improved survival outcomes, these therapies remain expensive. Even using biomarker selection, response rates still fall short of 50%. The majority of immune cell profiling done previously uses samples taken from early stage patients focusing on a single immune cell subtype. Here we use single cell RNA sequencing (scRNA-seq) and Cellular Indexing of Transcriptome and Epitopes by sequencing (CITE-seq) to characterise the innate and adaptive immune cell activation state and assess the response to exposure to IO in vitro from patients with advanced LC. Methods: Patients with locally advanced or metastatic LC having an Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) have biopsies collected for analysis. Cells are grown in culture +/- nivolumab for 48 hours. scRNA-seq and CITE-seq is conducted using established protocols. Transcriptomic and proteomic data on the innate and adaptive immune cell subsets assess markers of immune activation and/or suppression and the changes after nivolumab are quantified. Results are correlated with clinical outcomes. Results: In a locally advanced/metastatic population, EBUS-TBNA biopsies yield highly cellular samples with a heterogeneous population of immune cells able to be cultured +/- IO using novel, inclusive techniques. Transcriptomic clustering reveals distinct sub-populations within the T-cell, B-cell and innate immune cell compartments. Within these clusters, CITE-seq shows protein expression on individual cells can determine states of exhaustion, cytolytic ability, migratory potential and innate immune activation. Conclusions: Single cell genomics is feasible and informative in patients with advanced LC. This work will form the basis of a functional, real-time assay to assess individualised responses to IO therapy that has the potential to predict IO response.

Purpose Early and intermediate lung transplant outcomes for DCD are equivalent to donation-after-brainstem-death. Our aim is to describe long-term graft survival for lung transplant recipients since the implementation of DCD. Methods A retrospective cohort analysis was conducted of all bilateral lung transplant patients at a single center between Nov-2007 and Sep-2018. The method of donation was collected for all recipients in additional to baseline surgical co-variates. The mechanism of death in DCD donation were categorised into cerebrovascular event, hypoxic injury and trauma. Graft survival was defined as the time to death or retransplantation. For survival analysis, Kaplan-Meier curves were generated for the donation type and compared using the Log Rank test. Results 485 patients underwent bilateral lung transplant during the study period. 98 patients received a DCD donor and 387 patients received a DBD donor. There were no significant differences between the groups in recipient age, donor age, pre-explantation donor PaO2, % CMV mismatch, recipient BMI or length of hospital stay for transplant admission. There were no significant differences in the proportions of native lung disease, except for a greater number of patients with pulmonary hypertension in the DCD group (9.2 vs 1.6%, p Conclusion There was no significant difference in the long-term graft survival benefit gained from bilateral lung transplantation depending on the mode of donation (DCD vs DBD). Our experience confirms that DCD donation is a viable mode of donation which serves to increase recipient access to transplantation with no apparent decrease in long-term post-transplant survival.

Purpose Chronic lung allograft dysfunction (CLAD) is the major determinant of mortality in lung transplant (LTX) recipients after 1 year. CLAD is strongly associated with de-novo HLA donor specific antibodies (DSA), but can present as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The term clinical antibody mediated rejection (AMR) is often used to refer to any patient with possible or probable AMR by ISHLT criteria, but this group may include more than one disease. Methods Hierarchical cluster analysis of LTX recipients treated for Clinical AMR 2008-18 at a single center, grouped by radiological opacities and change of FEV1/FVC. P-values adjusted for multi-comparisons (Bonferroni). Results Of 118 patients, by ISHLT criteria, none had definite AMR, 18% probable, 56% possible and 26% were unclassifiable. AMR grade was not correlated with specific clinical features, outcome or treatment response. Cluster analysis identified 3 clinical phenotypes: acute obstruction, restriction and indolent (O: R: I). Rates of possible and probable AMR were similar in each group. Clusters differed in the patterns of FEV1 (figure 1), FVC and ratio (p Conclusion The current criteria for AMR do not describe one disease. We identified 3 main phenotypes with distinct clinical features, outcomes and treatment responses. Clinically validated acute phenotypes are needed.

Rapid on-site evaluation (ROSE) of endobronchial ultrasound-guided transbronchial needle aspirates (EBUS-TBNA) has not been compared to final detailed cytological analysis in patients with suspected sarcoidosis. To assess the diagnostic accuracy of EBUS-TBNA with ROSE in patients with suspected sarcoidosis, a prospective two-centre study performed EBUS-TBNA with ROSE of cellular material followed by transbronchial lung biopsy (TBLB) and endobronchial biopsy (EBB). The diagnostic accuracy of EBUSTBNA with ROSE was compared to the final cytological assessment and to TBLB and EBB. Analysis confirmed 49 out of 60 cases of sarcoidosis. ROSE sensitivity was 87.8% (specificity 91%, positive predictive value 97.7%). ROSE slide interpretation in combination with the final fixed slide and cell block preparations had a sensitivity of 91.8% (specificity 100%, positive predictive value 100%). 67% of patients were confirmed as having sarcoidosis on TBLB and 29% on EBB. Interobserver agreement between cytotechnologists and pathologists was very good (κ=0.91, 95% CI 0.80-1.0 and κ=0.91, 95% CI 0.79-1.0, respectively). EBUS-TBNA with ROSE has high diagnostic accuracy and interobserver agreement and informs the bronchoscopist in theatre whether additional diagnostic procedures need to be undertaken. EBUS-TBNA with ROSE should therefore be considered as the first-line investigation of sarcoidosis. Copyright

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate and minimally invasive technique that has been shown to have excellent diagnostic yield in the investigation of mediastinal and hilar lymphadenopathy. There is, however, little evidence comparing this procedure to the traditional diagnostic approach of transbronchial lung (TBLB) and endobronchial (EB) biopsies combined with characteristic clinical and radiological features in sarcoidosis. Aim: To compare the diagnostic yield of EBUS-TBNA, TBLB and EB in patients with suspected sarcoidosis. Methods: Data from 40 consecutive patients with suspected sarcoidosis who underwent combined EBUS-TBNA with TBLB and EB biopsies were recorded. Results: A total of 37 patients was confirmed as sarcoidosis, and three had other diagnoses. There was no difference in diagnostic accuracy rates between EBUS-TBNA and TBLB for all stages of sarcoidosis (84% vs 78%, P= 0.77). Combined EBUS-TBNA and TBLB procedures yielded a diagnostic accuracy of 100%. There was a highly significant difference in diagnostic accuracy between EBUS-TBNA and EB in stage I (80% vs 27%) (P < 0.01) and stage II disease (86% vs 27%) (P < 0.01). Similarly, a highly significant difference in diagnostic accuracy was seen between TBLB and EB (P < 0.01). No adverse events occurred. Conclusion: Endobronchial ultrasound-guided transbronchial needle aspiration alone has a high diagnostic yield with a very low complication rate for patients with suspected sarcoidosis.

Primary laryngeal aspergillosis in immunocompetent patients is rare. We describe a case of a 59-year-old woman with laryngeal aspergillosis thought to be secondary to long-term inhaled fluticasone therapy. Laryngeal aspergillosis may be an underrecognized complication of inhaled corticosteroid therapy.

Objective: To describe the results of lung transplantation (LTx) in adolescents at a hospital for adults. Design and setting: Prospective cohort study set in an LTx unit at an adult tertiary referral hospital from 1991 to 2006. Patients: 37 consecutive adolescent lung transplant recipients including 13 males and 24 females (mean age, 16.7 ±2.0 [SD] years; range 12–19 years) who received heart–lung (six patients) or bilateral LTx (31 patients) for cystic fibrosis (29), congenital heart disease (four), acute respiratory failure (two), or another disorder (two). Two patients were transplanted after invasive ventilation, five after non-invasive ventilation and two after extracorporeal membrane oxygenation. Main outcome measures: Overall survival compared with an adult cohort; survival free of bronchiolitis obliterans syndrome (BOS); overall and BOS-free survival in those transplanted before and after January 2000. Results: Mean waiting time was 273 days (range, 5–964 days; median, 163 days), mean donor age was 28 years (range, 9–53 years). Median inpatient stay was 11 days (range, 7–94 days). Mean follow-up was 1540 ±1357 days (range, 35–5163 days). The 5-year survival rate for the 16 patients transplanted before January 2000 was 38%, versus 74% for the 21 transplanted since January 2000 (P = 0.05; Mantel–Cox). Overall, 18 of 35 evaluable patients developed BOS. Only BOS was associated with an increased mortality risk (P

Interstitial lung disease (ILD) is the major determinant of morbidity and mortality in the anti-synthetase syndrome (ASS). The therapeutic efficacy of corticosteroids for the ILD component is limited; hence, additional immunosuppressive and immunomodulatory therapies have been tried with a modicum of success in recent years. Tacrolimus, a calcineurin inhibitor, is one potential therapy. We describe four consecutive patients with ASS whom we treated with tacrolimus at a quaternary referral hospital in 2009–2013. All four patients had significant ILD, three had severe and progressive ILD, and two had been referred for consideration of lung transplantation. Tacrolimus use was associated with improvement in ILD in all four patients with a mean follow-up of 3 years. Our case series adds further evidence to support the use of tacrolimus as salvage therapy for severe respiratory failure due to ILD in ASS, which may be associated with a dramatic and enduring response.