Background Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. Methods COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and. values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. Findings Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66.1 years [SD 9.3]; forced vital capacity 83.7% [SD 14.2]; diffusing capacity for carbon monoxide 63.4% [SD 12.8]). TBLC (7.1 mm, SD 1.9) and SLB (46.5 mm, 14.9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70.8% (weighted. 0.70, 95% CI 0.55-0.86); diagnostic agreement at MDD was 76.9% (kappa 0.62, 0.47-0.78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. Interpretation High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

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.

Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicenter study investigating agreement between TBLC and SLB. ILD patients referred for lung biopsy after central screening underwent sequential TLBC and SLB, under one anesthetic. Blinded analysis of samples was conducted by 3 pathologists, individually and by consensus. At multidisciplinary discussion (MDD), deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiology data, in random non-consecutive order. Primary endpoints were agreement of TBLC and SLB for 1) “definite/probable usual interstitial pneumonia (UIP)”, “indeterminate for UIP” and “alternative diagnosis” histopathologic patterns; and for 2) MDD diagnoses. Concordance and kappa values were calculated. Results: 65 patients (30 males; age 66±9yrs; FVC 84±14%; DLCO 63±13%) were enrolled. TBLC (7.1±1.9mm) and SLB samples (47±15mm) were taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70.8%, weighted κ 0.70 (95%CI 0.55-0.86); agreement at MDD was 76.9%, κ 0.62 (95%CI 0.47-0.78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 94.9% were concordant with SLB diagnoses. In the 26 with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 to alternative high/definite MDD diagnoses. Conclusion: High agreement between TBLC and SLB for pathologic and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms.

A REVIEW OF ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION (EBUS--TBNA) USE AT MULTIPLE CENTRES AS DIAGNOSTIC GUIDE FOR SARCOIDOSIS SHU HAN EMILY LIU, VICKY CHANG, ALVIN ING, BENJAMIN NG, JOHNATHAN WILLIAMSON Respiratory Department, Wollongong Hospital, Wollongong, NSW, Australia, Respiratory Department, Sutherland Hospital, Caringbah, NSW, Australia, Respiratory Department, Macquarie University Hospital, Macquarie Park, NSW, Australia, Respiratory Department, Nepean Hospital, Penrith, NSW, Australia, and Respiratory Department, Liverpool Hospital, Liverpool, NSW, Australia