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BACKGROUND AND OBJECTIVE: Inhalation of high concentrations of respirable crystalline silica (RCS) can lead to silicosis. RCS contains varying levels of iron, which can cause oxidative stress and stimulate ferritin production. This study evaluated iron-related and inflammatory markers in control and silicosis patients. METHODS: A cohort of stone benchtop industry workers (n = 18) were radiologically classified by disease severity into simple or complicated silicosis. Peripheral blood and bronchoalveolar lavage (BAL) were collected to measure iron, ferritin, C-reactive protein, serum amyloid A and serum silicon levels. Ferritin subunit expression in BAL and transbronchial biopsies was analysed by reverse transcription quantitative PCR. Lipid accumulation in BAL macrophages was assessed by Oil Red O staining. RESULTS: Serum iron levels were significantly elevated in patients with silicosis, with a strong positive association with serum ferritin levels. In contrast, markers of systemic inflammation were not increased in silicosis patients. Serum silicon levels were significantly elevated in complicated disease. BAL macrophages from silicosis patients were morphologically consistent with lipid-laden foamy macrophages. Ferritin light chain (FTL) mRNA expression in BAL macrophages was also significantly elevated in simple silicosis patients and correlated with systemic ferritin. CONCLUSION: Our findings suggest that elevated iron levels during the early phases of silicosis increase FTL expression in BAL macrophages, which drives elevated BAL and serum ferritin levels. Excess iron and ferritin were also associated with the emergence of a foamy BAL macrophage phenotype. Ferritin may represent an early disease marker for silicosis, where increased levels are independent of inflammation and may contribute to fibrotic lung remodelling.

Purpose To report on quantitative electroencephalograph (EEG) activity during polysomnography (PSG) in a rare case of confirmed Fatal Familial Insomnia (FFI). Methods Sleep/wake characteristics of a 32-year-old male patient were quantitatively analysed using central EEG recordings during two PSGs (FFI-1 and FFI-2) first, for investigation of insomnia and PLMS but with no suspicion of FFI and second, 120 days later with suspected but unconfirmed FFI at the time; 89 days prior to death. PSG metrics; absolute EEG power in specified frequency bands; EEG slowing ratio of slow-to-fast frequencies ((delta + theta)/ (alpha + sigma + beta)); and sleep spindle density were calculated. Results were compared with gender and age-matched insomnia and healthy controls (two of each). Results FFI-1 and FFI-2 PSGs revealed total time in bed of 413.5 and 392 minutes, total sleep times of 208.5 and 7.5 minute, including NREM 153.0 and 2.5 minutes, and REM 55.5 and 5.0 minutes, respectively. FFI-1 had approximately 1.5 times lower slow wave activity (SWA, 0.5–4.5Hz) during N3 than insomnia and controls.​ FFI-1 had 2 times and 1.8 times higher slowing ratio during REM than insomnia and controls, respectively. Spindle density (per minute of NREM sleep) for FFI-1 was 0.9, compared to pair-averages of 1.2 for insomnia disorder and 4.7 for healthy controls. Conclusions PSG in FFI revealed poor sleep efficiency that severely deteriorated with disease progression. Quantitative analysis of EEG revealed lower spindle density, lower SWA in N3, and higher slowing ratio in REM, when compared to insomnia patients and healthy sleepers.

Pulmonary embolus (PE) is a known complication of coronavirus disease 2019 (COVID-19). The diagnosis of PE in our hospitalised patients with COVID-19 correlated with more severe disease and occurred despite the use of routine thromboprophylaxis. Higher D-dimers were seen on admission in patients who developed PE and rose at PE diagnosis, suggesting a role for D-dimer in risk stratification.

A comparison of the clinical performance of the Elecsys Anti-SARS-CoV-2, Liaison SARS-CoV-2 S1/S2 IgG, Access SARS-CoV-2 IgG and Vitros Immunodiagnostic Products Anti-SARS-CoV-2 IgG immunoassays for the diagnosis of COVID-19 infection was performed. Patient sera were collected at least 6 weeks following onset of COVID-19 infection symptoms. Negative control specimens were stored specimens from those without COVID-19, collected in April–May 2019. Sensitivity and specificity with 95% confidence intervals (CI) were calculated. Linear regression was used to examine the relationship between the magnitude of serological response and clinical characteristics. There were 80 patients from whom 86 sera specimens were collected; six patients had duplicate specimens. There were 95 negative control specimens from 95 patients. The clinical sensitivity of the Elecsys assay was 98.84% (95% CI 93.69–99.97), specificity was 100% (95% CI 96.19–100.00); the Liaison assay clinical sensitivity was 96.51% (95% CI 90.14–99.27), specificity was 97.89% (95% CI 92.60–99.74); the Access assay clinical sensitivity was 84.88% (95% CI 75.54–91.70), specificity was 98.95% (95% CI 94.27–99.97); and the Vitros assay clinical sensitivity was 97.67% (95% CI 91.85–99.72), specificity was 100% (95% CI 96.15–100.00). A requirement for hospitalisation for COVID-19 infection was associated with a larger Vitros, Liaison and Access IgG response whilst fever was associated with a larger Elecsys response. All assays evaluated with the exception of the Access assay demonstrated similar performance. The Elecsys assay demonstrated the highest sensitivity and specificity.

Ventriculo-pleural (VPL) shunt insertion is performed in hydrocephalic patients when alternative sites of cerebrospinal fluid (CSF) diversion are contraindicated. These include patients with peritoneal complications from ventriculo-peritoneal shunts. Despite its utility, VPL shunts are uncommon. Hydrothoraces should be considered as a potential cause of dyspnoea in the setting of a VPL shunt. We present a case of worsening respiratory failure in the setting of a massive CSF hydrothorax in a hydrocephalic patient with a VPL shunt to highlight this potential complication of pleural CSF diversion, and present a potential management strategy in patients with premorbid underlying lung pathology. In this case, the hydrothorax was drained and the shunt was converted to ventriculo-atrial (VA) shunt.

Immune checkpoint inhibitors (ICIs) have become pivotal in the treatment of lung cancer. An increasing number of immune-related adverse events (irAEs) have been recognized with their use. To our knowledge, this is the first published case of sarcoid-like pulmonary lymphadenopathy associated with durvalumab, a monoclonal antibody against programmed death ligand-1 (PD-L1). A 76-year-old woman received adjuvant durvalumab for Stage IIA pT2aN1M0 (American Joint Committee on Cancer, Seventh edition) poorly differentiated lung adenocarcinoma. After three cycles, a sarcoid-like granulomatous reaction was identified in mediastinal and hilar lymph nodes. Although the lymphadenopathy remained stable in size with the ongoing treatment, progressive intracranial metastases were identified after a further three cycles of durvalumab. Sarcoid-like inflammation with the formation of non-caseating granulomas in the absence of systemic sarcoidosis is an irAE which may mimic disease progression. Although a subset of patients who experience this reaction may have a favourable response to checkpoint inhibition, progression of disease may occur contemporaneously.

Introduction: Obstructive sleep apnoea (OSA) commonly manifests with greater severity in the supine position. Over 60% of patients with OSA have supine predominant OSA (supine apnoea-hypopnoea index [AHI] greater than twice of non-supine AHI) and 25% have supine isolated OSA (non-supine AHI< 5 events/hour). Therefore, for the majority of patients, the proportion of total sleep time in the supine body position necessarily impacts on the severity of OSA assessed by polysomnography (PSG). We previously reported that the proportion of time in the supine position is significantly higher during laboratory PSG compared to habitual sleep. Here we report the interim results of our current study comparing sleeping position during unattended home PSG to habitual sleeping position. Material(s) and Method(s): This is a prospective observational study of patients referred for unattended PSG through our tertiary academic sleep unit. We use the Night ShiftTM positional therapy device to record body position during the unattended PSG and subsequently for up to three additional nights to sample habitual sleeping position. The Night ShiftTM was programmed to record only; the feedback intervention function was disabled. A paired t-test was used to compare the mean difference in proportion of sleep time in the supine position during unattended PSG compared to habitual sleep. We then calculated a modified AHI "corrected" for habitual sleeping position. Night-to-night variability in habitual sleeping position was assessed using a correlation matrix, and a repeated measures one-way ANOVA. Result(s): To date, fifty-two patients have been recruited, out of a target of 79 patients. 38.5% female, age 47 +/- 12.8 years, body mass index 30.9 (range: 27.5-37.5) kg/m2. Median total AHI 19 (range: 3.2-27.9) events/hour, supine AHI 22 (0.9-45.3) events/hour, non-supine AHI 9.4 (1.3-24.9) events/hour. Fifteen patients (29.4%) had supine predominant OSA and 1 (2%) had supine isolated OSA. Proportion o

Introduction: Obstructive sleep apnoea (OSA) is frequently worse when sleeping in the supine position. Previous data have shown that at least 60% of patients with OSA have supine predominant OSA (OSA that occurs at least twice as frequently in the supine position). In this context, the proportion of time patients spend sleeping supine will influence interpretation of OSA severity. Patients sometimes report that sleeping position during laboratory polysomnography (PSG) does not represent their habitual sleeping position at home. We therefore designed a study to compare sleeping position during PSG compared to home in OSA patients, and hypothesised that there will be less time spent supine when at home compared to PSG. Method(s): Prospective observational study at a large, tertiary academic sleep unit. Patients referred for diagnostic PSG were provided with a body position sensor (Night ShiftTM) to record sleeping position in the laboratory during PSG and at home over the subsequent 3 nights. Night ShiftTM was set to record position only and the feedback intervention function was disabled. Result(s): Since May 4th 2018, we have recruited 19 patients to date. Majority of patients were of male gender (63.2%). Mean age was 48 years (range 26-67). Mean body mass index (BMI) was 31.1kg/m2. Mean total AHI = 27.4 events/hour. Eighteen patients (94.7%) had supine predominant OSA. 89.5% of patients reported the PSG equipment did not alter their habitual sleeping position. When comparing data during PSG to that when the device was worn at home, 13 patients (68.4%) had a reduction in the amount of time spent in the supine position. Overall percentage time spent supine was 35.1 % (+/- 25.1) during PSG vs 25% (+/- 21.4) at home (P = 0.07). Discussion(s): Results to date suggest a greater proportion of time is spent supine in the sleep laboratory compared to home. Recruitment is ongoing with target n of 50 patients. Results from this study may have implications as to how we interpr

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. Method(s): 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. Result(s): 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(s): 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.Copyright © 2016 Royal Australasian College of Physicians

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.