A randomised controlled trial comparing high-flow nasal oxygen with standard management for conscious sedation during bronchoscopy.

Traditional conscious sedation for endobronchial ultrasound procedures places patients at risk of desaturation, and high-flow nasal oxygen may reduce the risk. We designed a parallel-group randomised controlled trial of high-flow nasal oxygen at a flow rate of 30-70 l.min-1 via nasal cannulae, compared with standard oxygen therapy at 10 l.min-1 via a bite block in adults planned for conscious sedation for endobronchial ultrasound. The primary outcome was the proportion of patients experiencing desaturation (defined as SpO2 < 90%). Secondary outcomes included oxygen saturation after pre-oxygenation, lowest oxygen saturation during procedure, number of hypoxic episodes, duration of hypoxia, end-procedure end-tidal CO2 , satisfaction scores and complications. Thirty participants were allocated to each group. Baseline patient characteristics, procedure time and anaesthetic agents used were similar between the groups. Desaturation occurred in 4 out of 30 patients allocated to the high-flow nasal oxygen group, compared with 10 out of 30 allocated to the standard oxygenation group, a non-significant difference (p = 0.07) with intention to treat analysis. The difference was significant (p = 0.047) when using a per-protocol analysis. Oxygen saturation after pre-oxygenation and the lowest oxygen saturation during procedure were significantly higher in the high-flow nasal oxygen group compared with the standard oxygenation group; median (IQR [range] 100 (99-100 [93-100]) vs. 98 (97-99 [94-100]), p = 0.0001 and 97.5 (94-99 [77-100]) vs. 92 (88-95 [79-98]), p < 0.001, respectively. There were no differences in other secondary outcomes. Although high-flow nasal oxygen may prevent desaturation due to some causes, it does not protect against hypoxaemia in all circumstances.

Outcomes of exertional rhabdomyolysis following high-intensity resistance training.

BACKGROUND: High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. AIMS: To compare the clinical outcomes of ER with other causes of rhabdomyolysis. METHODS: Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. RESULTS: Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). CONCLUSION: ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies.

Beta-blockers are under-prescribed in patients with chronic obstructive pulmonary disease and co-morbid cardiac disease.

The use of beta-blockers in patients with chronic obstructive pulmonary disease and co-morbid cardiovascular disease is controversial, despite increasing evidence to support their use as safe and efficacious. This study retrospectively assessed the rates of beta-blocker prescription in patients admitted to two Australian tertiary hospitals for acute exacerbation of chronic obstructive pulmonary disease. This revealed that less than half of patients (45%) with known cardiac indications were receiving beta-blocker therapy, evident across all degrees of airways disease severity. Further work is needed to ensure that medical management of this patient group is optimised.

Prevalence of incidental pulmonary nodules on computed tomography of the thorax in trauma patients.

BACKGROUND/AIMS: Lung cancer is the third leading cause of death in high-income countries. Early detection leads to improved clinical outcomes, with evidence showing that lung cancer screening reduces lung cancer mortality. Knowledge of the population prevalence of pulmonary nodules affects the efficacy and cost-effectiveness of a local screening programme. METHODS: We performed a retrospective review of our trauma database looking for the prevalence of incidental pulmonary nodules on computed tomography of the thorax. Prevalence of nodules and follow up according to Fleischner Guidelines were reviewed. RESULTS: Two hundred and forty-eight patients underwent a computed tomography thorax as part of their trauma assessment. 8.5% (21/248) had incidental pulmonary nodules. Eighty-one per cent of these (17/21) required follow up according to the Fleischner Society Guidelines. One was subsequently diagnosed with primary lung cancer, one with metastatic sigmoid cancer and one with invasive aspergillus. CONCLUSIONS: Incidental pulmonary nodules are common in the general population. This has implications for possible lung cancer screening recommendations in the Australian population. Referral and/or review systems are essential to ensure adequate follow up of incidental findings, as it is likely some patients are not receiving adequate follow up at present.

Direct ultrasound localisation for pleural aspiration: translating evidence into action.

BACKGROUND: There is strong evidence that direct ultrasound localisation for pleural aspiration reduces complications, but this practice is not universal in Australia and New Zealand. AIMS: To describe the current utilisation and logistical barriers to the use of direct ultrasound localisation for pleural aspiration by respiratory physicians from Australia and New Zealand, and to determine the cost benefits of procuring equipment and training resources in chest ultrasound. METHODS: We surveyed all adult respiratory physician members of the Thoracic Society of Australia and New Zealand regarding their use of direct ultrasound localisation for pleural aspiration. We performed a cost-benefit analysis for acquiring bedside ultrasound equipment and estimated the capacity of available ultrasound training. RESULTS: One hundred and forty-six of 275 respiratory physicians responded (53% response). One-third (33.6%) of respondents do not undertake direct ultrasound localisation. Lack of training/expertise (44.6%) and lack of access to ultrasound equipment (41%) were the most frequently reported barriers to performing direct ultrasound localisation. An average delay of 2 or more days to obtain an ultrasound performed in radiology was reported in 42.7% of respondents. Decision-tree analysis demonstrated that clinician-performed direct ultrasound localisation for pleural aspiration is cost-beneficial, with recovery of initial capital expenditure within 6 months. Ultrasound training infrastructure is already available to up-skill all respiratory physicians within 2 years and is cost-neutral. CONCLUSION: Many respiratory physicians have not adopted direct ultrasound localisation for pleural aspiration because they lack equipment and expertise. However, purchase of ultrasound equipment is cost-beneficial, and there is already sufficient capacity to deliver accredited ultrasound training through existing services.

Clinical utility of sequential venous blood gas measurement in the assessment of ventilatory status during physiological stress.

BACKGROUND: Venous blood gases (VBG) are commonly utilised, particularly in the emergency setting, to assess and monitor patients at risk of ventilatory failure with limited evidence regarding their clinical utility in the assessment of ventilatory status over time. AIMS: This study aims to assess agreement between arterial and venous pH and partial pressure of carbon dioxide (pCO2) both before and after physiological stress, at each time point, and within the same subject between paired samples before and after bronchoscopy. METHODS: Prospective study of 30 patients undergoing flexible bronchoscopy under conscious sedation. Paired arterial and venous samples taken before and after bronchoscopy were analysed utilising descriptive statistics and bias plot (Bland-Altman) analysis to assess limits of agreement. RESULTS: Compared with baseline, post-bronchoscopy arterial blood gas and VBG showed reduced pH (-0.05 ± 0.05 and -0.04 ± 0.04 respectively) and increased arterial and venous pCO2 (5.9 ± 6.7 and 3.5 ± 5.5 mmHg respectively), the differences being statistically significant (P = 0.035). There was statistical agreement between arterial blood gas and VBG parameters; however, the limits of agreement were wide at rest and, for pCO2, widened further post-bronchoscopy. CONCLUSION: Sequential VBG provide an unpredictable means for assessing pCO2 in patients undergoing flexible bronchoscopy. Previously noted poor agreement between arterial and venous pCO2 worsens following physiological stress, with sequential VBG likely to underestimate changes in ventilatory status in patients with acute respiratory compromise, suggesting limited utility as a means for monitoring changes in ventilation.

Mediastinal staging of non-small-cell lung cancer among Australasian thoracic physicians: clinical practice and constraints on minimally invasive techniques.

BACKGROUND/AIM: We determined current practice among Australasian thoracic physicians in the mediastinal staging of non-small-cell lung cancer (NSCLC). We focused on the availability of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) and constraints to its use, as there has been no systematic analysis regarding the availability and uptake of this new technology among thoracic physicians. METHODS: Physician members of the Thoracic Society of Australia and New Zealand were emailed a survey seeking their current approach to three scenarios requiring mediastinal staging of NSCLC. Respondents were also asked for their preferred investigation for each scenario if any current constraints were removed. Relevant demographic information was sought. RESULTS: We received 164 responses from 512 Australasian physicians (34%). Without constraints, EBUS-TBNA was the preferred investigation for all three clinical scenarios, but only 33% of respondents had access to EBUS-TBNA. Constraints included lack of availability and lack of expertise. Reduced EBUS-TBNA access was associated with a number of clinician factors. CONCLUSIONS: Australasian thoracic physicians prefer EBUS-TBNA for the mediastinal staging of NSCLC, but access to EBUS-TBNA services is limited. We recommend targeted measures to improve access to EBUS-TBNA use and optimise mediastinal staging of NSCLC.

Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels.

BACKGROUND: Next-generation sequencing is used in cancer research to identify somatic and germline mutations, which can predict sensitivity or resistance to therapies, and may be a useful tool to reveal drug repurposing opportunities between tumour types. Multigene panels are used in clinical practice for detecting targetable mutations. However, the value of clinical whole-exome sequencing (WES) and whole-genome sequencing (WGS) for cancer care is less defined, specifically as the majority of variants found using these technologies are of uncertain significance. PATIENTS AND METHODS: We used the Cancer Genome Interpreter and WGS in 726 tumours spanning 10 cancer types to identify drug repurposing opportunities. We compare the ability of WGS to detect actionable variants, tumour mutation burden (TMB) and microsatellite instability (MSI) by using in silico down-sampled data to mimic WES, a comprehensive sequencing panel and a hotspot mutation panel. RESULTS: We reveal drug repurposing opportunities as numerous biomarkers are shared across many solid tumour types. Comprehensive panels identify the majority of approved actionable mutations, with WGS detecting more candidate actionable mutations for biomarkers currently in clinical trials. Moreover, estimated values for TMB and MSI vary when calculated from WGS, WES and panel data, and are dependent on whether all mutations or only non-synonymous mutations were used. Our results suggest that TMB and MSI thresholds should not only be tumour-dependent, but also be sequencing platform-dependent. CONCLUSIONS: There is a large opportunity to repurpose cancer drugs, and these data suggest that comprehensive sequencing is an invaluable source of information to guide clinical decisions by facilitating precision medicine and may provide a wealth of information for future studies. Furthermore, the sequencing and analysis approach used to estimate TMB may have clinical implications if a hard threshold is used to indicate which patients may respond to immunotherapy.

Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis.

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.

Bronchoscopic evaluation of the mediastinum using endobronchial ultrasound: a description of the first 216 cases carried out at an Australian tertiary hospital.

BACKGROUND: Performance of linear probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging non-small-cell lung cancer has been extensively studied. Alternate indications for its use are less well characterised, and performance in other clinical settings may differ. METHODS: We examined a prospectively collected cohort comprising the first 215 patients undergoing EBUS-TBNA at our institution. Patients were analysed according to the clinical and radiological indication for referral. We also examined the effect of the procedural learning curve on diagnostic sensitivity. RESULTS: A total of 215 patients underwent 216 EBUS-TBNA procedures. EBUS-TBNA returned adequate tissue for cytopathological analysis in 202 of 216 procedures (94%). Overall sensitivity for detection of malignancy was 0.92 (95% confidence interval 0.86-0.96); however, this varied according to the primary indication for EBUS-TBNA. Diagnostic sensitivity was high among all sub-groups, but the negative predictive value varied depending on the clinical indication for the procedure. We estimate 104 invasive surgical procedures and 32 inpatient admissions were avoided by use of EBUS-TBNA. Significant improvement in diagnostic performance was seen after 20 procedures were completed, and diagnostic accuracy did not peak until after 50 procedures. CONCLUSIONS: EBUS-TBNA is able to confirm accurately histologically a large number of disease processes, both malignant and benign, in all clinical indications studied. The procedure is safe even when carried out by proceduralists with minimal prior experience. Diagnostic performance continues to improve beyond 50 cases carried out.

Incidence of bacteraemia following endobronchial ultrasound-guided transbronchial needle aspiration.

Few data exist concerning possible infectious complications associated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The present prospective evaluation was undertaken in order to determine the incidence of bacteraemia and infectious complications associated with EBUS-TBNA. Consecutive patients undergoing EBUS-TBNA for evaluation of mediastinal or hilar lymph node lesions were studied. Venesection was performed within 60 s of TBNA for aerobic and anaerobic blood culture. Sterile saline washing of TBNA needles was also performed. Patients with positive blood cultures were reviewed immediately, and all patients underwent clinical review within 1 week of EBUS-TBNA. A total of 43 patients underwent EBUS-TBNA, with bacteraemia demonstrated in three (7%). All bacterial isolates were typical oropharyngeal commensal organisms. The TBNA needle washing culture was positive in 15 (35%) patients. None of the three bacteraemic patients had clinical features suggestive of infection, and no complications were seen among the cohort. The incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. Contamination of the TBNA needle with oropharyngeal commensal bacteria is common; however, clinically significant infection following EBUS-TBNA appears rare.

Cavitating lymph node metastasis demonstrated by endobronchial ultrasound.

Cavitation of primary non-small cell lung carcinoma (NSCLC) occurs in a small number of patients. We report a case of cavitation of lymph node metastases in NSCLC. CT chest showed central low attenuation of the subcarinal lymph node, suggestive of necrosis, and endobronchial ultrasound (EBUS) imaging demonstrated two cystic spaces within the lymph node. Transbronchial needle aspiration of the cystic space confirmed the presence of metastatic NSCLC. Cystic necrosis was only demonstrable by EBUS. The incidence of such findings is unknown, however with the increasing use of EBUS for evaluation of the mediastinum such images may be more commonly encountered in the future.

Endobronchial ultrasound staging of thyroid lesion in small cell lung carcinoma.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven its utility in the mediastinal staging of lung cancer. Its use in the evaluation of thyroid lesions has not previously been described. We report the safe and effective use of EBUS-TBNA to evaluate a thyroid lesion in a patient with suspected lung cancer at the time of diagnostic bronchoscopy. Use of this method in the evaluation of thyroid lesions may be considered in patients with coexistent mediastinal or hilar lesions, or for lesions not accessible to a percutaneous approach.

Absence of platinum salt sensitivity in autocatalyst workers exposed to tetraamine platinum dichloride.

BACKGROUND: Platinum salt sensitivity (PSS) is well recognized following occupational exposure to platinum salts, though specific platinum compounds have been suggested to be non-allergenic. We report on a cohort of autocatalyst workers exposed to tetraamine platinum dichloride (TPC) and other platinum-group elements. METHODS: All subjects employed at an autocatalyst production plant undertook medical surveillance with symptoms, examination findings and results of skin prick testing and spirometry prospectively recorded. Environmental testing of the workplace was also performed to determine the level of exposure. RESULTS: Twenty-six subjects had a mean duration of employment of 46 (+/-30) months and undertook a mean 6.8 (+/-4.3) examinations. No subjects described the development of new respiratory or dermatological symptoms. No patients developed positive skin reactivity to platinum salts. FEV(1) remained unchanged for all subjects over the course of the study period. CONCLUSIONS: TPC and platinum-group elements are not associated with the development of PSS or occupational asthma. Identification of chemical compounds is important when advising on occupational health screening. TPC and/or platinum-group elements should be used in preference to chloroplatinic acid in catalyst production to minimize the impact of occupational illness due to PSS.

Effect of long-term nebulized colistin on lung function and quality of life in patients with chronic bronchial sepsis.

Recurrent Gram-negative bacterial infection is a significant cause of death in patients with bronchiectasis and severe chronic obstructive pulmonary disease (COPD). Nebulized colistin in cystic fibrosis has shown maintenance of pulmonary function and improved symptom scores. We prospectively followed 18 patients with chronic bronchial sepsis treated with nebulized colistin 30 mg daily. Mean decline in forced expiratory volume in 1 s was significantly slower following commencement of inhaled colistin (44 mL/year vs 104 mL/year, P = 0.035). Mean decline in forced vital capacity was also significantly slower following commencement of colistin (48 mL/year vs 110 mL/year, P = 0.033). Patient-reported quality of life improved following commencement of colistin (3.6 vs 6.2, P = 0.001). No patient had isolates resistant to colistin. No side-effects were reported by patients in the cohort. Use of inhaled colistin in the treatment of bronchiectasis and severe (COPD) in patients with recurrent Gram-negative infections is safe. Inhaled colistin may improve quality of life and slow decline in forced expiratory volume in 1 s and forced vital capacity.

Analysis of multidisciplinary lung cancer practice.

BACKGROUND: The aim of this study was to describe the activity of a lung cancer multidisciplinary clinic (MDC) and examine whether this model of clinical practice results in adherence to best-practice guidelines. METHODS: Prospective analysis of demographic and clinical data in 431 patients referred to a lung cancer MDC for the management of known or suspected thoracic malignancy. Adherence was documented to clinically relevant guideline recommendations concerning timely and evidence-based lung cancer management. RESULTS: Of 431 patients, 257 were diagnosed with primary lung cancer, mean age 68 years, 70% men and 90% current smokers or ex-smokers. Only 21% were referred with known malignancy and 28% were asymptomatic. Overall, 51% had stages I and II non-small-cell lung cancer, with this bias towards early-stage disease greatest in patients from rural areas. Histological confirmation of lung cancer was obtained in 92%. There was a high rate of adherence to international guideline recommendations concerning timely lung cancer diagnosis, staging and treatment implementation. Similarly, there was adherence to selected key evidence based recommendations for lung cancer management contained in national guidelines. CONCLUSION: Within a MDC, patients receive timely diagnosis, staging and treatment according to evidence-based guideline recommendations. The high proportion of patients receiving active treatment has implications for resource allocation. There is a referral bias towards patients with early non-small-cell lung cancer, particularly in rural patients, suggesting that further education about advances in metastatic lung cancer management is required. This study would support the establishment of regional lung cancer services with links to fully resourced MDC.

CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.

The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.