Safety and Feasibility of a Novel Externally Cooled Bronchoscopic Radiofrequency Ablation Catheter for Ablation of Peripheral Lung Tumours: A First-In-Human Dose Escalation Study.

BACKGROUND: Radiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode. OBJECTIVES: The objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC. METHODS: Patients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distribution/uniformity of ablation and efficacy of tumour ablation. RESULTS: RFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 = 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ). CONCLUSION: Bronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.

An Australian COVID-19 respiratory care unit experience.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a heterogeneous presentation ranging from severe pneumonitis to asymptomatic infection. International studies have demonstrated the utility of respiratory care units (RCUs) to facilitate the delivery of non-invasive ventilation techniques to patients with COVID-19 pneumonitis. AIMS: This study aims to describe the patient characteristics, flow and outcomes of admissions to the Royal Melbourne Hospital (RMH) COVID-19 RCU (CRCU) during its initial period of operation. METHODS: Single-centre retrospective cohort study, all patients admitted to CRCU between 17 September and 10 December 2021 were included in this study. Patient demographics, including comorbidities and limitations of medical treatment, were analysed. Admission source and discharge destination were reviewed. Length of stay was recorded. Finally, in-hospital and CRCU mortality were analysed. RESULTS: Ninety-seven patients, comprising 111 admissions, occurred during the study period with median age of 65 years (48% female). Most patients were admitted from and discharged to the ward. Twenty patients died in hospital (21%), with age, 4C score, comorbidity and presence of obstructive lung disease predicting mortality (area under the curve (AUC) 0.85, P < 0.001). Mortality was significantly higher in those over 65 years of age compared to those under 65 (P < 0.001), or those deemed not for intubation compared to those for intubation (P = 0.0019). CONCLUSIONS: This study demonstrates the feasibility of operating a CRCU within an Australian tertiary healthcare setting.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

BACKGROUND: Lung cancer is the most common cause of cancer-related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer-related mortality, however there has been increasing evidence supporting screening with low-dose computed tomography (LDCT).  OBJECTIVES: To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer-related mortality and to evaluate the possible harms of LDCT screening. SEARCH METHODS: We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021.  SELECTION CRITERIA: Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes.  DATA COLLECTION AND ANALYSIS: Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer-related mortality and harms of screening. We performed a meta-analysis, where appropriate, for all outcomes using a random-effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow-up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I2 statistic to investigate heterogeneity.  MAIN RESULTS: We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack-year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow-up was from 5 years to approximately 12 years.  None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta-analysis of trials assessing lung cancer-related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate-certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer-related mortality benefit compared to males with LDCT screening. There was also a reduction in all-cause mortality (including lung cancer-related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate-certainty evidence).  Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate-certainty evidence). However, analysis of 60-day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate-certainty evidence).  False-positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low-certainty evidence in the meta-analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI -0.00 to 0.36; 5 trials, 28,656 participants; low-certainty evidence). Four trials compared different aspects of health-related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) -0.43, 95% CI -0.59 to -0.27; 3 trials, 8153 participants; low-certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour.  AUTHORS' CONCLUSIONS: The current evidence supports a reduction in lung cancer-related mortality with the use of LDCT for lung cancer screening in high-risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non-smokers.

Sustaining the Australian respiratory workforce through the COVID-19 pandemic: a scoping literature review.

The outbreak of the COVID-19 pandemic in late 2019 and in 2020 presented challenges to healthcare workers (HCW) around the world that were unexpected and dramatic. The relentless progress of infection, starting in China and rapidly spreading to Europe, North America and elsewhere gave more remote countries, like Australia, time to prepare but also time for unease. HCW everywhere had to readjust and change their work practices to cope. Further waves of infection and transmission with newer variants pose challenges to HCW and health systems, even after mass vaccination. Respiratory medicine HCW found themselves at the frontline, developing critical care services to support intensive care units and grappling with unanticipated concerns about safety, risk and the need to retrain. Several studies have addressed the need for rapid changes in the healthcare workforce for COVID-19 and the impact of this preparation on HCW themselves. In this paper, we present a scoping review of the literature on preparing HCW for the pandemic, explore the Australian experience of building the respiratory workforce and propose evidence-based recommendations to sustain this workforce in an unprecedented high-risk environment.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.

Bronchoscopic Thermal Vapour Ablation for Localized Cancer Lesions of the Lung: A Clinical Feasibility Treat-and-Resect Study.

BACKGROUND: Bronchoscopic thermal vapour ablation (BTVA) is an established and approved modality for minimally invasive lung volume reduction in severe emphysema. Preclinical data suggest potential for BTVA in minimally invasive ablation of lung cancer lesions. OBJECTIVES: The objective of this study is to establish the safety, feasibility, and ablative efficacy of BTVA for minimally invasive ablation of lung cancers. METHODS: Single arm treat-and-resect clinical feasibility study of patients with biopsy-confirmed lung cancer. A novel BTVA for lung cancer (BTVA-C) system for minimally invasive treatment of peripheral pulmonary tumours was used to deliver 330 Cal thermal vapour energy via bronchoscopy to target lesion. Patients underwent planned lobectomy to complete oncologic care. Pre-surgical CT chest and post-resection histologic analysis were performed to evaluate ablative efficacy. RESULTS: Six patients underwent BTVA-C, and 5 progressed to planned lobectomy. Median procedure duration was 12 min. No major procedure-related complications occurred. All 5 resected lesions were part-solid lung adenocarcinomas with median solid component size 1.32±0.36 cm. Large uniform ablation zones were seen in 4 patients where thermal dose exceeded 3 Cal/mL, with complete/near-complete necrosis of target lesions seen in 2 patients. Tumour positioned within ablation zones demonstrated necrosis in >99% of cross-sectional area examined. CONCLUSION: BTVA of lung tumours is feasible and well tolerated, with preliminary evidence suggesting high potential for effective ablation of tumours. Thermal injury is well demarcated, and uniform tissue necrosis is observed within ablation zones receiving sufficient thermal dose per volume of lung. Treatment of smaller volumes and ensuring adequate thermal dose may be important for ablative efficacy.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

Pandemic printing: a novel 3D-printed swab for detecting SARS-CoV-2.

OBJECTIVES: To design and evaluate 3D-printed nasal swabs for collection of samples for SARS-CoV-2 testing. DESIGN: An iterative design process was employed. Laboratory evaluation included in vitro assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma-irradiated SARS-CoV-2. A prospective clinical study compared SARS-CoV-2 and human cellular material recovery by 3D-printed swabs and standard nasopharyngeal swabs. SETTING, PARTICIPANTS: Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID-19 screening clinic and two inpatients with laboratory-confirmed COVID-19. INTERVENTION: In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid-nasal sample from the other nostril was collected with the 3D-printed swab. RESULTS: In the laboratory evaluation, qualitative agreement with regard to SARS-CoV-2 detection in mock samples collected with 3D-printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D-printed swabs was complete. Qualitative agreement with regard to SARS-CoV-2 detection in three pairs of 3D-printed mid-nasal and standard swab samples from two inpatients with laboratory-confirmed SARS-CoV-2 was also complete. CONCLUSIONS: Using 3D-printed swabs to collect nasal samples for SARS-CoV-2 testing is feasible, acceptable to patients and health carers, and convenient.

Health impacts of bushfire smoke exposure in Australia.

Smoke exposure from bushfires, such as those experienced in Australia during 2019-2020, can reach levels up to 10 times those deemed hazardous. Short-term and extended exposure to high levels of air pollution can be associated with adverse health effects, although the most recent fires have brought into sharp focus that several important knowledge gaps remain. In this article, we briefly identify and discuss the existing Australian evidence base and make suggestions for future research.

Safe performance of diagnostic bronchoscopy/EBUS during the SARS-CoV-2 pandemic.

The SARS-CoV-2 pandemic is unprecedented in our professional lives and much effort and resources will be devoted to care of patients (and HCW) affected by this illness. We must also continue to aim for the same standard of care for our non-COVID respiratory patients, while minimizing risks of infection transmission to our colleagues. This commentary addresses the key paired issues of minimizing performance of diagnostic/staging bronchoscopy in patients with suspected/known lung cancer while maximizing the safety of the procedure with respect to HCW transmission of COVID-19.

Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens.

OBJECTIVES: PD-L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non-small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti-PD-1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD-L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. METHODS: Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD-L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. RESULTS: Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell-blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut-offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. CONCLUSIONS: PD-L1 IHC on cytology cell-block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD-L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.

Utility of Endobronchial Ultrasound in Assessment of Intrathoracic Lesions in Paediatric Patients.

INTRODUCTION: In adults, linear endobronchial ultrasound (EBUS) is the preferred modality to sample intrathoracic adenopathy and radial EBUS is a useful tool to biopsy peripheral pulmonary nodules. Utility in children is less well known. OBJECTIVES: The objective of this study was to review the EBUS experience of two specialist centres to better define the current role of EBUS in paediatric practice. METHODS: A retrospective record review of EBUS procedures undertaken in patients aged 0-17 years at the Royal Children's Hospital (Melbourne, Australia) and Thoraxklinik (Heidelberg, Germany) was performed. Data extracted included patient demographics, clinical presentation, bronchoscope (size and model), EBUS technique used, pathologic results, need for further invasive investigation, and complications. RESULTS: Between 2008 and 2017, ten EBUS procedures were performed (6 linear EBUS and 4 radial EBUS). No complications were reported. Linear EBUS was performed on subjects who were between 4 and 15 years old, with a 100% diagnostic yield. Radial EBUS was non-diagnostic in three cases of non-malignant disease. In one case, it was used successfully for imaging alone. CONCLUSION: Both linear and radial EBUS are safe and feasible in children. Diagnostic yield of linear EBUS was 100%. Radial EBUS did not demonstrate utility, likely reflecting the pathologies of underlying parenchymal masses in paediatric populations.

Models of care for non-invasive ventilation in the Acute COPD Comparison of three Tertiary hospitals (ACT3) study.

BACKGROUND AND OBJECTIVE: Non-invasive ventilation (NIV) improves clinical outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal model of care remains unknown. METHODS: We conducted a prospective observational non-inferiority study comparing three models of NIV care: general ward (Ward) (1:4 nurse to patient ratio, thrice weekly consultant ward round), a high dependency unit (HDU) (1:2 ratio, twice daily ward round) and an intensive care unit (ICU) (1:1 ratio, twice daily ward round) model in three similar teaching tertiary hospitals. Changes in arterial blood gases (ABG) and clinical outcomes were compared and corrected for differences in AECOPD severity (Blood urea > 9 mmol/L, Altered mental status (Glasgow coma scale (GCS) < 14), Pulse > 109 bpm, age > 65 (BAP-65)) and co-morbidities. An economic analysis was also undertaken. RESULTS: There was no significant difference in age (70 ± 10 years), forced expiratory volume in 1 s (FEV1 ) (0.84 ± 0.35 L), initial pH (7.29 ± 0.08), partial pressure of CO2 in arterial blood (PaCO2 ) (72 ± 22 mm Hg) or BAP-65 scores (2.9 ± 1.01) across the three models. The Ward achieved an increase in pH (0.12 ± 0.07) and a decrease in PaCO2 (12 ± 18 mm Hg) that was equivalent to HDU and ICU. However, the Ward treated more patients (38 vs 28 vs 15, P < 0.001), for a longer duration in the first 24 h (12.3 ± 4.8 vs 7.9 ± 4.1 vs 8.4 ± 5.3 h, P < 0.05) and was more cost-effective per treatment day ($AUD 1231 ± 382 vs 1745 ± 2673 vs 2386 ± 1120, P < 0.05) than HDU and ICU. ICU had a longer hospital stay (9 ± 11 vs 7 ± 7 vs 13 ± 28 days, P < 0.002) compared with the Ward and HDU. There was no significant difference in intubation rate or survival. CONCLUSION: In acute hypercapnic Chronic obstructive pulmonary disease (COPD) patients, the Ward model of NIV care achieved equivalent clinical outcomes, whilst being more cost-effective than HDU or ICU models.

CT-Fluoroscopic Guidance for Performance of Targeted Transbronchial Cryobiopsy: A Preliminary Report.

BACKGROUND: Bronchoscopic transbronchial cryobiopsy is increasingly used for the histological assessment of diffuse parenchymal lung disease. Diagnostic performance may be improved by more accurate targeting of biopsy to radiologic abnormalities, and complication rates may be reduced by avoiding biopsy of pleura or larger vessels. OBJECTIVES: To report the preliminary experience of using CT-fluoroscopic guidance for accurate targeting of bronchoscopic transbronchial cryobiopsy. METHODS: Bronchoscopic cryobiopsy was performed in a hybrid CT theatre. 3D CT images were acquired following positioning of the cryoprobe in a distal airway segment. Where cryoprobe position was observed to be too close to the chest wall/diaphragm pleura, or not within the region of interest within the lung parenchyma, re-positioning of probe was undertaken and repeat 3D images were acquired to confirm positioning prior to cryobiopsy. RESULTS: CT-fluoroscopic transbronchial cryobiopsy was successfully performed in 4 patients: 3 patients with interstitial lung infiltrates, and one with an enlarging left upper lobe mass. Images were reviewed following each acquisition to accurately assess the probe position within the lung parenchyma, and relative to other thoracic structures. Intra-procedural imaging was of sufficient quality to allow the accurate positioning of the cryoprobe tip with respect to both the parenchymal region of interest and pleural surfaces. No complications were experienced, and all procedures yielded diagnostic specimens. CONCLUSIONS: Our preliminary experience confirms the feasibility of performing transbronchial cryobiopsy under CT-fluoroscopic guidance. Accurate targeting of transbronchial cryobiopsy may be achieved using CT-fluoroscopic guidance. Positioning of the probe tip, both with respect to parenchymal region of interest and to pleural surfaces, can be established with high accuracy.

Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment.

Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.

Endoscopic ultrasound fine-needle aspiration by experienced pulmonologists: a cusum analysis.

Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.

Pulmonologist-performed transoesophageal sampling for lung cancer staging using an endobronchial ultrasound video-bronchoscope: an Australian experience.

BACKGROUND: Transoesophageal endobronchial ultrasound (EBUS) video-bronchoscope insertion provides pulmonologists access to conduct endoscopic fine-needle aspiration (EUS-B-FNA) of mediastinal lymph node (LN) lesions and also assist in lung cancer staging by sampling left adrenal gland (LAG) lesions. Limited literature has described additional diagnostic value whilst maintaining patient safety. To elicit whether combining endoscopic transoesophageal fine-needle aspiration using convex probe bronchoscope (EUS-B-FNA) and EBUS bronchoscopy enhances the diagnostic yield of mediastinal nodal staging in lung cancer, whilst maintaining safety. METHODS: All eligible patients with paraoesophageal lesions on thoracic computed tomography (CT) underwent pulmonologist-performed EUS-B-FNA at two tertiary centres and were included in this prospective observational cohort study. RESULTS: EUS-B-FNA sampling was performed at 69 mediastinal LN lesion sites, including 17 sites inaccessible to bronchoscopic sampling. Four LAG lesions were sampled via EUS-B-FNA. There were no complications. EBUS-TBNA was augmented by EUS-B-FNA because of accessibility of sampling lesions otherwise unamenable bronchoscopically, thereby increasing diagnostic utility. Diagnostic sensitivity of EUS-B-FNA for malignancy in mediastinal LN lesions was 88% (51 of 58). For mediastinal LN lesions not amenable to EBUS-TBNA, the sensitivity for diagnosis of malignancy via EUS-B-FNA was 88% (15 of 17). Diagnostic sensitivity of EUS-B-FNA for malignancy in LAG lesions was 50% (2 of 4). CONCLUSION: EUS-B-FNA is a precise and safe approach in the evaluation and staging of lung cancer when performed by a pulmonologist. It complements and increases the diagnostic utility of EBUS-TBNA by further coverage of mediastinal LN stations and access to LAG lesions.

Commencement of cardioselective beta-blockers during hospitalisation for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and co-morbid cardiovascular disease, emerging evidence suggests a benefit in commencing cardioselective beta-blockers. AIM: Our objective was to determine the safety of beta-blocker commencement during hospitalisation for acute exacerbation of COPD. METHODS: A retrospective cohort study of 1071 patients hospitalised for acute exacerbation of COPD was conducted across two tertiary hospitals over a 12-month period. We identified 36 patients in whom beta-blocker therapy was commenced during admission. The primary outcome of the study was to assess cardiovascular and respiratory adverse events related to the commencement of beta-blocker therapy. RESULTS: The most common indications for beta-blockers were atrial fibrillation (53%) and acute coronary syndrome (36%). Metoprolol was the most commonly prescribed beta-blocker (75%). No patients suffered clinically significant declines of respiratory function following the commencement of a beta-blocker, including worsening respiratory symptoms, oxygen, bronchodilator or ventilation requirements. These results were demonstrable in patients with reversible airways disease and advanced COPD. Only one patient (2.8%) experienced symptomatic hypotension after 48 h of therapy. CONCLUSION: The commencement of cardioselective beta-blockers during acute exacerbations of COPD appears to be well-tolerated.

Balance and Falls in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Prospective Study.

Individuals with chronic obstructive pulmonary disease (COPD) have demonstrated balance impairment and a higher fall incidence. However, these have not been investigated in acute exacerbations of the disease (ECOPD). This study evaluates balance in patients during an ECOPD compared to stable COPD and healthy controls, and examines the fall incidence rate after hospitalisation due to ECOPD compared to individuals with stable COPD. Balance performance of 26 hospitalised patients with ECOPD was compared to 26 community-dwelling participants with stable COPD and 25 matched healthy controls. Balance was evaluated using computerised posturography and the Berg Balance Scale (BBS). Prospective falls were monitored by monthly calendars for 12 months in both COPD groups. Compared to controls, greater balance impairment was observed during ECOPD for most posturography variables across standing conditions (p ≤ 0.05). Both COPD groups had worse BBS scores (p ≤ 0.05) compared to controls. Increased dyspnoea and reduced quadriceps' strength were associated with impaired balance performance. A higher fall incidence (1.76 falls/person/year) was observed following hospitalisation in patients with ECOPD compared to stable COPD (0.53 falls/person/year) at 12 months. Patients with ECOPD demonstrate balance impairments which are associated with increased dyspnoea and reduced muscle strength. Balance impairment during ECOPD may contribute to a high incidence of falls following hospitalisation.

Sequential multimodality bronchoscopic investigation of peripheral pulmonary lesions.

Multiple guidance modalities may be combined during bronchoscopic investigation of peripheral pulmonary lesions (PPLs). The relative contribution of each modality to diagnostic performance remains uncertain.Endobronchial ultrasound (EBUS) with virtual bronchoscopy (VB) was routinely performed, with electromagnetic navigation (EMN) utilised only where EBUS was unable to locate PPLs or where the probe was adjacent to the lesion and on-site cytologic examination was nondiagnostic.236 consecutive patients with 245 PPLs had lesion size 22.8±12.4 mm (mean±sd). PPLs were localised using EBUS+VB alone in 188 (77%) and was diagnostic in 134 of these (71.3%). EBUS localisation was predicted by PPL size (23.7±10.5 versus 19.7±9.8 mm, p=0.003), but not by bronchus sign, PPL-hilum distance or PPL-pleura distance. EMN in 57 patients achieved EBUS localisation in a further 17 patients (30.9%), improving overall visualisation yield to 85%. Nine of these 57 procedures achieved a definitive diagnosis (16%), improving overall diagnostic yield to 58.4%. Probe position and lesion type influenced overall diagnostic yield. Sensitivity for diagnosis of lung cancer was 70% (131/188; 95% CI 63-76%).Localisation rate and diagnostic sensitivity of radial probe EBUS+VB alone for diagnosis of PPLs is high. EBUS localisation rates and procedural yield are improved only modestly (by 8% and 4%, respectively) with addition of EMN. Sampling following EMN should include all available methods to maximise diagnostic yield.