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Background: Sleep disturbance has a prevalence of 30-78% in patients with advanced cancer. While pharmacotherapy is common, randomized controlled studies (RCTs) investigating available agents are limited. This study examines the efficacy and safety of temazepam or melatonin versus placebo for sleep in advanced cancer. Methods: This is a multicenter, randomized, double-blind, placebo-controlled study of temazepam, melatonin prolonged release (PR) or placebo for insomnia in patients with advanced cancer, and an insomnia severity index (ISI) score of >11. Results: Twenty-one participants were randomized: nine to temazepam, eight to melatonin, and four to placebo. Baseline characteristics between groups were similar. The adjusted mean difference in day 8 ISI score versus placebo was -9.1 (95% confidence interval [CI] -17.5, 0.7, p = 0.04) for temazepam and -9.6 (95% CI -18,-1.2, p = 0.03) for melatonin PR. There was no improvement in global quality of life. Both agents were well tolerated. Conclusion: Temazepam and melatonin PR were associated with a clinically significant improvement in patient-reported insomnia severity compared with placebo. Findings need confirmation with larger patient numbers.

Study Objectives: The Multiple Sleep Latency Test (MSLT) is a key diagnostic component in the diagnosis of central disorders of hypersomnolence. Due to time constraints, it is common practice to wake patients at a standard time from overnight polysomnography (PSG) prior to the MSLT. This has the potential to influence MSLT results due to sleep deprivation. We describe the impact of allowing ad libitum sleep on the night prior to the MSLT in patients being assessed for hypersomnolence., Methods: 580 consecutive patients undergoing PSG/MSLT for assessment of hypersomnolence were analyzed: 290 either side of a change in laboratory protocol which allowed patients ad libitum sleep during the PSG, rather than being woken at a pre-specified time. Baseline characteristics, PSG and MSLT results were compared between the groups., Results: Groups were similar at baseline, other than there being more females in the ad libitum group. After adjusting for confounding variables, ad libitum patients had later sleep offset time (+58.7 minutes; p<0.001), longer PSG total sleep time (+47.8 minutes; p<0.001), longer MSLT mean sleep latency (+1.3 minutes; p=0.002) and 23% fewer MSLT with mean sleep latency less than 8 minutes (p=0.004) when compared with patients who were woken at a standard time., Conclusions: The common practice of waking patients from their PSG at a standard time has the potential to curtail sleep and impact MSLT results by reducing mean sleep latency. Patients being assessed for hypersomnolence should be allowed ad libitum sleep during the PSG on the night prior to their MSLT., (© 2024 American Academy of Sleep Medicine.)

Background: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis., Aims: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects., Methods: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed., Results: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV 1 1.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups., Conclusion: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations., Competing Interests: Declaration of competing interest All the authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Gaps in the treatment of patients with acute asthma have been repeatedly described in Australia. We conducted a retrospective audit of acute asthma care at a Victorian tertiary institution., Aims: To describe acute asthma care at a large health network in metropolitan Melbourne, and evaluate the extent to which Emergency Department (ED) care was consistent with National Asthma Council guidelines., Methods: A retrospective audit was performed of medical records between July 2017 and June 2019. We included adult patients admitted to campuses within the Western Health network in Melbourne, Victoria, where the length of stay was at least 12 h, and the primary discharge diagnosis was asthma., Results: Four hundred and ninety-three admissions were included in the analysis, representing 392 individual patients. Seventy-one percent of patients were female and 27% were current smokers. Ninety-six percent of patients had a prior asthma diagnosis, 63% had a previous hospital presentation and 75% were prescribed an inhaled preventer. In the ED, systemic corticosteroids and inhaled salbutamol were prescribed in 65% and 82% admissions respectively; adjunctive treatments included ipratropium (67% of admissions), magnesium sulfate (30%), adrenaline (11%) and non-invasive ventilation (9%). Overall, ED care was guideline concordant in 59% of admissions. On the wards, treatments prescribed within 24 h of admission included corticosteroids (90% of admissions), salbutamol (84%), ipratropium (64%) and inhaled preventers (63%). The proportion of patients prescribed these treatments, as well as documented follow up (e.g. asthma action plans), varied significantly depending on the treating specialty., Conclusion: The emergency treatment of patients with acute asthma frequently deviated from guidelines and there was significant variation in inpatient treatment. Quality improvement initiatives that incorporate structural changes are required to improve asthma care., (© 2022 Royal Australasian College of Physicians.)

Introduction: Recurrent asthma admissions are frequent in our patients at a tertiary Australian hospital and are commonly related to poor health literacy and medication adherence. A need exists to improve these asthma self-management skills within our current model of care, especially during the vulnerable postdischarge period., Aim: To examine if the addition of a nurse-led Asthma Care Transition Team (ACTT) compared with usual care alone (UC) (1) improves asthma control at 12 weeks posthospital discharge; the number of patients using a Written Action Plan (WAP), compliance with inhaler therapy at 12 weeks, and readmission rates at 6 months., Methods: Adults admitted with asthma were randomised to either: UC: involving review of asthma medication and self-management skills by the ward team prior to discharge; a standard 6-week post discharge clinic visit and a 12-week study visit where an independent assessor assessed outcomes; or ACTT: In addition to UC, involved ACTT nurse-led review at 1 week and 6 weeks. Key aspects included a pre defined, structured review reinforcing education and self-management skills, and telephone support during working hours., Result: Sixty participants (UC and ACTT) had similar baseline characteristics: Mean age: 41 vs 38 years, asthma duration: 20 vs 18 years, baseline Asthma Control Questionnaire 3.1 vs 3.4. At 12 weeks Asthma Control Questionnaire (ACQ) improved significantly in both groups but more so with ACTT; ACTT group had a higher uptake of WAP and a trend to reduced readmissions., Conclusion and Practice Implication: A nurse-led ACTT improves asthma control and self-management skills following discharge and may lead to fewer readmissions., (© 2022 Australian Health Promotion Association.)

Little is known about the extent of cultural and linguistic diversity among people with chronic obstructive pulmonary disease (COPD) in Australia and if ethno-cultural factors influence engagement in pulmonary rehabilitation (PR). We conducted a prospective cohort study to evaluate the extent of cultural and linguistic diversity among people with COPD and identify variables that influence engagement in PR. Patients with COPD attending the respiratory outpatient clinic at a metropolitan health service completed a study-specific questionnaire with results descriptively analysed. Access issues of awareness, referrals, attendance and completion of PR were examined. A multiple regression analysis was conducted to identify variables that influenced engagement in PR. Ninety-seven participants were recruited, of whom 36 (37%) self-identified a culturally and linguistically diverse (CALD) community. While participants from CALD communities had less awareness of PR as compared with the English Australian group (χ 2 (df) = 5.3 (1), p = 0.02), there were no significant between-group differences in number of observed referrals (p = 0.30), attendance (p = 0.50) and completions of PR (p = 0.90). Only 11 (11%) out of 97 participants completed PR. Age (p = 0.006) and being from a CALD community (p = 0.03) were independent factors impacting on the awareness of PR while English proficiency (p = 0.04) was an independent factor impacting on referrals to PR. While older age and being from a CALD community were associated with having less awareness in PR, referrals to, attendance and completion rates of PR were similar regardless of ethnicity., (© 2022 John Wiley & Sons Ltd.)

Background: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population., Objective: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR., Methods: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR., Results: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV 1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV 1 value of 90% or lower to be biomarkers of increased H-TA risk., Conclusion: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications., Methods: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes., Results: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05)., Conclusions: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It has been suggested that interprofessional tracheostomy teams improve safety, enhance outcomes and promote excellence. This study evaluated the effect of a Tracheostomy Review Service (TRS) on patient outcomes and staff attitudes. The TRS reviewed patients with a tracheostomy tube (TT) in situ on our wards. Data was collected via medical record audit. Two years of retrospective data (n = 39) was compared with 12 months of prospective data (n = 28) for: length of cannulation (LOC); length of ward-based cannulation (LOWBC); length of stay (LOS); ICU LOS (ICU-length of stay); the frequency and time to trial one way valve (PMV); and tracheostomy-related adverse events (AE). Staff were also surveyed regarding their knowledge and confidence in tracheostomy management. No significant difference was seen in LOC, LOWBC, LOS, ICU-LOS, and AE. A significant increase was seen in the frequency of PMV use (pre-TRS 74%; post-TRS 100%). Staff reported an improvement in knowledge and confidence in more complex areas of tracheostomy management. Limited measureable improvements in patient outcomes were seen following the implementation of a TRS. Limitations of this study include a small sample size and heterogeneous patient characteristics.

Background: Current dosing of intrapleural fibrinolytic therapy (IPFT) in adults with complicated parapneumonic effusion (CPE) / empyema is empiric, as dose-escalation trials have not previously been conducted. We hypothesized that LTI-01 (scuPA), which is relatively resistant to PA inhibitor-1 (PAI-1), would be well-tolerated., Methods: This was an open-label, dose-escalation trial of LTI-01 IPFT at 50,000-800,000 IU daily for up to 3 days in adults with loculated CPE/empyema and failed pleural drainage. The primary objective was to evaluate safety and tolerability, and secondary objectives included assessments of processing and bioactivity of scuPA in blood and pleural fluid (PF), and early efficacy., Results: LTI-01 was well tolerated with no bleeding, treatment-emergent adverse events or surgical referrals (n=14 subjects). uPA antigen increased in PFs at 3 hours after LTI-01 (p<0.01) but not in plasma. PF saturated active PAI-1, generated PAI-1-resistant bioactive complexes, increased PA and fibrinolytic activities and D-dimers. There was no systemic fibrinogenolysis, nor increments in plasma D-dimer. Decreased pleural opacities occurred in all but one subject. Both subjects receiving 800,000 IU required two doses to relieve pleural sepsis, with two other subjects similarly responding at lower doses., Conclusion: LTI-01 IPFT was well-tolerated at these doses with no safety concerns. Bioactivity of LTI-01 IPFT was confirmed, limited to PFs where its processing simulated that previously reported in preclinical studies. Preliminary efficacy signals including reduction of pleural opacity were observed.

Background: The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016., Objective: Among thunderstorm-affected patients presenting to emergency rooms (ERs), we investigated risk factors predicting severe attacks requiring admission to hospital., Methods: Thunderstorm-affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed., Results: We interviewed 1435/2248 (64%) of thunderstorm-affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [aOR] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission (aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non-Asian patients (aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia (OR = 5.42, 95% CI 1.56, 18.83)., Conclusions: In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background and Objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk., Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months., Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea., Conclusion: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits., (© 2018 Asian Pacific Society of Respirology.)

Background: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood., Objective: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma., Methods: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated., Results: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01)., Conclusion and Clinical Relevance: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age., (© 2018 John Wiley & Sons Ltd.)

Background: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies., Methods: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions., Findings: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m 3 ). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died., Interpretation: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma., Funding: None., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs)., Objective: To establish the impact of exercise training in patients with ILDs of differing aetiology and severity., Methods: 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months., Measurements and Main Results: Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension., Conclusions: Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease., Trial Registration Number: Results, ACTRN12611000416998., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Achalasia cardia is a motility disorder of the oesophagus characterized by aperistalsis of the oesophageal body and incomplete relaxation of the lower oesophageal sphincter. It usually presents with dysphagia, regurgitation and heartburn. It may have various respiratory manifestations. Rarely, it may be complicated by acute airway compromise causing stridor. This case report presents an elderly woman with massive dilatation of the oesophagus secondary to achalasia, who presented with a short history of heartburn and rapid deterioration of her respiratory status due to tracheal compromise and stridor as a result of achalasia. The various hypotheses regarding the pathogenesis of this rare complication are described.

Study Objectives: The role of upper airway surgery as a treatment for adult obstructive sleep apnea (OSA) remains controversial, with perspectives on treatment efficacy varying considerably. Though debate may occur in the clinical sphere, it is necessary to appreciate the ever-increasing funding and policy focus on cost effectiveness and "efficacy" in health care., Design: In this review, we examine contemporary evidence that highlights the importance of "highly effective treatment" over "sub-therapeutic treatment" as a necessity to confer improved health outcomes in OSA. We highlight that assumptions of surgical success inherent in most articles fail to assimilate contemporary, clinically significant indicators of success. We performed a literature search and present interpolated meta-analyses data from 18 surgical articles. Statistical meta-analyses highlight how surgical success decreases when new evidence-based criteria of success are applied., Measurements and Results: Specifically, when the traditional definition is applied (50% reduction in apnea-hypopnea index [AHI] and/or < or = 20) the pooled success rate for Phase I procedures is 55% (45% fail). However, at AHI < or = 10, success reduces to 31.5% (68.5% fail) and, at AHI < or = 5, success is reduced to 13% (87% fail). According to these definitions, Phase II success (fail) rates decrease from 86% (14%) to 45% (55%) and 43% (57%), respectively., Conclusions: The evidence for clinical efficacy must define treatment "success". We propose all future surgical audits report "objective cure" rates with success based on AHI outcomes of < or = 5 and/or < or = 10. We hope this paper serves as a catalyst for debate and consensus.

Rationale, Aims and Objectives: Currently there are multiple surgical interventions utilized in the treatment of adult obstructive sleep apnoea (OSA). The role of these operations remains controversial, with perspectives on treatment efficacy varying considerably. Despite this, their use is proliferating., Objectives: In this paper, we present the degree of variability that occurs in the application of these procedures, and examine the effectiveness of surgical intervention as a treatment for OSA., Method: A multi-centre retrospective clinical audit of consecutive, unselected surgical cases presenting at the sleep disorder clinics of two teaching hospitals in a major Australian city. Patients acted as their own historical controls, undergoing polysomnography pre and post surgery to gauge effectiveness., Results: On variability demonstrate 94 individuals in this cohort received 220 individual upper airway surgical procedures, 184 occurred in their first operation (mean 2.5 per person; range 1-7) and 36 occurred in a second operation (n=18; cumulative mean of 4 per person; range 3-7). These 94 individuals received 41 varying combinations of surgery. Results on effectiveness demonstrate an overall physiological success rate of 13% (87% fail). One operation reduced OSA severity by 20% (patients still had severe OSA), and two operations by 35% (still moderate OSA). In contrast, conventional Continuous Positive Airway Pressure therapy controlled OSA (n=64)., Conclusions: This case study demonstrates substantial procedural variability and limited effectiveness. This raises questions as to the quality of care, the treatment-derived health outcomes of this population and of efficient resource allocation. This issue requires greater policy attention.

In Australia, unmet demand for sleep study services is resulting in protracted waiting lists and treatment delays for those in need. This present study gauged efficiency gains that could be achieved by implementing a split-night protocol within the laboratory. Results demonstrate improved technical efficiency by at least 15%, reducing time to treatment for the most severe cases and increasing patient throughput within the clinic. With over 56,000 sleep studies carried out annually, this technique has significant utility in evidence-based practice.

Aims: Chronic obstructive pulmonary disease (COPD) is a common condition associated with considerable morbidity, mortality and hospital admissions. However, published COPD management guidelines have major limitations and lack practical summaries. We aimed to optimally develop, implement, and evaluate a multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts for comprehensive day one assessments through to a discharge criteria checklist., Method: Two intervention and two control public teaching hospitals in Adelaide, South Australia, took part, with pre-intervention (721 COPD admissions over 7 months) and intervention phases (509 COPD admissions over 7 months). During the intervention stage the ACCORD guideline was placed in the case notes on the day of admission or soon after. Readmissions were categorized as either emergency or elective and compared between the study arms, as were mortality and potential confounders (age, gender, number of comorbidities), with Poisson regression analysis., Results: Of case notes of eligible COPD patients, 60% had the ACCORD guideline placed, of which 76% had evidence of use as judged by completion of guideline entry and tick boxes. The ACCORD guideline was associated with an increase in elective admissions and a reduction in emergency admissions in the intervention group in relation to the control group (P < 0.01), with no difference in overall admissions or death rates., Conclusions: The ACCORD guideline was associated with a shift from emergency admissions to more planned elective care, suggesting more proactive care of health problems, but without overall reduction in admissions.

Tumour necrosis factor (TNF)-alpha is thought to be a key early cytokine in the pathogenesis of sarcoidosis, despite conflicting data. Largely the product of mononuclear phagocyte activation, it is unclear whether TNF-alpha production at disease sites is a feature of all mononuclear phagocytes that accumulate there or whether it is secreted by a subset of these cells. Using the reverse haemolytic plaque assay, the aims of this study were to determine if the upregulation of TNF-alpha could be confirmed and to investigate whether this was monocyte or macrophage specific. The reverse haemolytic plaque assay allows the measurement of cytokine production at a single cell level. A greater number of alveolar macrophages produced TNF-alpha compared to autologous monocytes in sarcoidosis but not in controls and, based on cell size, it was confirmed that this was the product of more mature macrophages and that the secretion of TNF-alpha by monocytes and macrophages was heterogeneous: not all monocytes and macrophages secrete TNF-alpha. No differences in the average levels of TNF-alpha secretion by peripheral blood monocytes or alveolar macrophages were observed. This study has demonstrated that a subset of mononuclear phagocytes, mature macrophages, are responsible for tumour necrosis factor secretion and this could have implications for targeted management in sarcoidosis in the future.

Study Objectives: Lung volume reduction surgery (LVRS) for emphysema has a variable effect on spirometry with improvement linked to increases in lung elastic recoil. The mechanism by which recoil increases following LVRS has not been described completely. This study examines preoperative and postoperative pulmonary function to describe a mechanism for changes in airflow obstruction., Design: Change in pulmonary function following LVRS. Setting : Public teaching hospital in Australia., Patients: Patients with severe emphysema and pulmonary function measurements made before and after LVRS., Measurements: Routine pulmonary function testing performed with ventilated lung alveolar volume (VA) derived from the gas transfer measurement used as a proxy for the effective lung volume., Results: Pulmonary function tests from 36 consecutive patients with measurements made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD, 1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by 0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in those patients whose VAs did not increase (n = 7) was not significant., Conclusions: The increase in VA reflects an increase of functional or ventilating lung volume and is associated with an improvement in spirometry following LVRS.

Background: Previous studies have revealed that tumour necrosis factor (TNF)-alpha is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-alpha secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-alpha levels differ between SSc patients with FA (FASSc) and a nonfibrotic group., Methods: The reverse haemolytic plaque assay was used to evaluate the secretion of cytokine at a single cell level while immunostaining allowed subtyping of AMs and Mos., Results: This study demonstrated a difference in total TNF-alpha levels produced by AMs when the levels in subjects with FA (cryptogenic FA and FASSc) were compared to levels in either SSc patients without FA (P = 0.0002) or normal healthy controls (P < 0.001). In addition, AMs from patients with FASSc secreted more TNF-alpha than those of patients with no FA (P = 0.003). In contrast, there were no significant differences in Mo TNF-alpha secretion between the groups. A positive correlation was found between total TNF-alpha level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r = 0.49, P < 0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-alpha secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-alpha production., Conclusion: By demonstrating the primary cell source of TNF-alpha in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future.

Background: Lung volume reduction surgery (LVRS) has been a frequent literature topic in emphysema management recently. Opinions differ in regard to usefulness, efficacy, and selection criteria., Aims: To present the results of our first 55 bilateral videoscopically resected group, with follow-up of up to three years, and to present some of the local methodology problems faced., Methods: Thirty-nine men and 16 women, age range 40-77, had either upper lobe (42), mixed (two), or lower lobe (11) resections without buttressing (except for unilateral buttressing in several of the latter patients as part of an intrapatient comparison trial) according to their pattern of emphysema determined by CT and perfusion scanning., Results: Thirty day mortality was 5.5%. Follow-up pulmonary function is available for 44 patients, and demonstrates a mean 51% improvement in FEV1, and significant improvement in FVC, PaO2, dyspnoea indices and walking distance, with a reduction in mean RV, TLC, PaCO2. FEV1 improvement is maintained above baseline at three years. Lower lobe surgery outcomes are at least as good as their upper lobe counterparts., Conclusions: Outcomes confirm improvements reported elsewhere, and suggest that videoscopic resection may provide worthwhile benefit to lower lobe patterns of emphysema. Other managment issues are discussed.

Study Objectives: Previous studies have shown that it is possible to improve the health-related quality of life (HRQoL) of chronic lung disease (CLD) patients without a concurrent change in morbidity. A valid CLD index that discriminates between different levels of CLD severity and is associated with HRQoL status is an important tool for primary care settings. In this study a symptom-based CLD index was assessed for its validity and relationship with HRQoL in a representative Australian population sample. The study also measured the prevalence of self-reported CLD., Design: Representative population survey of adults aged 18 years and over using a multistage, systematic, clustered area sample., Setting: Metropolitan Adelaide and country centres in South Australia with a population of over 1000 persons., Participants: Three hundred twenty-nine adults with CLD identified through a representative population survey of 3010 South Australians., Measurements and Results: The CLD index and the SF-36 were administered to participants to assess the association between each subscale of the CLD index with each HRQoL scale. The CLD index was also used to assess the prevalence of CLD and the distribution of severity in self-reported CLD in the South Australian population. Each symptom sub-scale of the CLD index was significantly correlated with all scales of the SF-36. The prevalence of CLD as measured by the CLD index was 7.7% (mild), 2.2% (moderate) and 1.0% (severe)., Conclusions: In the Australian context the CLD index is a reliable patient interview instrument that can be used to assess the effects of CLD on general HRQoL, improve assessment, and lead to interventions for physicians and their patients.

Objective: To examine the relationships between ownership of written asthma action plans, asthma morbidity, use of devices, and patients' perceptions of their asthma management., Design and Setting: A random population survey (in 1996) of the South Australian population aged 15 years or over, using interviewers to administer a questionnaire., Participants: People who reported that they had current, doctor-diagnosed asthma., Main Outcome Measures: Prevalence of written asthma action plans; night-time awakenings from asthma; ownership of peak flow meters; and people's perceptions of their asthma management., Results: The ownership of asthma action plans by people with self-reported asthma was 33% and has declined since 1995 (42%; P < 0.001). Fifteen per cent were awakened weekly or more frequently by asthma symptoms. These people were more likely to have a peak flow meter and a written action plan, but less likely to consider they had been provided with enough information about their asthma, to feel comfortable managing their asthma, or to find it easy to see their doctor. Having a written asthma action plan was associated with regular corticosteroid use, understanding asthma, having enough information and owning a peak flow meter., Conclusions: Ownership of asthma action plans in South Australia is suboptimal. Before we develop new strategies to improve asthma outcomes, we must determine whether there is a need to target people with less severe asthma and/or improve the use of guidelines by health professionals.

Background: Chronic obstructive pulmomary disease (COPD) is associated with substantial mortality, morbidity, and costs to the health care system. With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services, for conditions such as COPD., Aim: To determine the effectiveness of an outreach respiratory nurse in a shared care approach, with collaboration between general practitioners and hospital services, in the management of patients with severe COPD., Methods: Patients with severe COPD attending The Queen Elizabeth Hospital, Adelaide participated in a randomised controlled trial of a home based nursing intervention (HBNI) over 12 months with outcome measures including mortality rate, hospital service utilisation, FEV1 and health related quality of life (HRQL) using a modified Dartmouth Primary Care Co-operative Quality of Life questionnaire., Results: There were 48 subjects in each study arm, with no differences in mortality rate (eight deaths in the HBNI group and seven in the control group), hospital admissions, length of stay, number of outpatient and Emergency Service visits. The study had inadequate follow-up of FEV1 and HRQL within the control group. Within the HBNI group, a small improvement in HRQL (in three of ten indices measured) was demonstrated, despite a deterioration in FEV1 (11% reduction, p=0.04) compared to baseline. Quality of life of HBNI subjects' carers did not change., Conclusion: An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation.

Background: Fibrosing alveolitis is characterized by inflammation, fibrosis and increased numbers of activated CD4+ T-cells in the lower respiratory tract. The aims of this study were to compare the T-cell antigen receptor repertoire in the lungs of subjects with fibrosing alveolitis systemic sclerosis (FASSc) with cryptogenic fibrosing alveolitis (CFA) and normal control subjects, to determine whether FASSc is driven by a specific T-cell trigger and is determined by a T-cell driven immune response, and to assess the clonality of CD4+ and CD8+ TcR usage in subjects with FASSc., Materials and Methods: We used reverse transcription polymerase chain reaction with specific V alpha- and V beta-chain primers to identify the TcR gene usage in biopsy material, bronchoalveolar lavage fluid or peripheral blood from our subjects., Results: We found individual-specific restriction of V alpha- and V beta-chain usage in lung biopsies from patients and control subjects. To establish whether this was due to expression bias in the CD4+ or CD8+ T-cells and was restricted to the lung, the alpha beta-T-cell receptor chain usage was assessed in T-cell subsets separated from the lungs of patients with fibrosing alveolitis and was compared with that of the peripheral blood. There was no consistent difference in the expression of any variable family chain among the population studied, although there was a significant difference between lung and peripheral blood lymphocyte V beta-families in CD8+ T-cells (P = 0.0007)., Conclusion: We conclude that there is individual TcR V alpha- and V beta-expression bias in subjects with fibrosing alveolitis.

Alternative non-chlorofluorocarbon (CFC) propellants have been developed and have been shown to be safe alternatives to CFC propellants. Salbutamol (albuterol) and beclomethasone dipropionate (BDP) in metered dose inhalers (MDIs) have been most studied. Salbutamol sulfate non-CFC MDIs have remained as a suspension formulation, and there is good evidence that salbutamol sulfate non-CFC MDIs are equivalent to salbutamol sulfate CFC MDIs. BDP non-CFC MDIs have a new formulation which is a solution and has a significantly smaller particle size than BDP delivered from CFC MDIs. This has resulted in more of the metered dose from the non-CFC MDI reaching the lower respiratory tract, with a consequent reduction of the dose deposited in the throat. This change allows a smaller dose of the non-CFC BDP to be equivalent to the CFC formulation. However, efficacy studies will be needed with other medications that are delivered in non-CFC MDIs because this finding with BDP relates to the solution formulation and particle size. The non-CFC propellant hydrofluoroalkane (HFA)-134a functions better at a lower temperature than its CFC comparator.

Neutrophil accumulation in the lower respiratory tract of patients with fibrosing alveolitis is thought to be facilitated by IL-8, a neutrophil chemoattractant primarily secreted by mononuclear phagocytes. The aims of this study were: (i) to explore IL-8 secretion by lung and blood mononuclear phagocytes in subjects with cryptogenic fibrosing alveolitis, systemic sclerosis with and without fibrosing alveolitis, sarcoidosis and normal individuals; (ii) to examine IL-8 secretory heterogeneity in alveolar macrophages and peripheral blood monocytes; and (iii) to correlate alveolar macrophage phenotypic profile to IL-8 secretion. We observed that more monocytes secreted IL-8 than autologous macrophages and that there was heterogeneity in the in vitro IL-8 secretion by alveolar macrophages and peripheral blood monocytes. IL-8 secretion by alveolar macrophages was significantly higher in subjects with fibrosing alveolitis compared with subjects without fibrosing alveolitis, due to a higher percentage of IL-8-secreting alveolar macrophages in the fibrotic group both in the absence (P < 0.002) and presence of lipopolysaccharide (LPS) (P < 0.04) and correlated with bronchoalveolar lavage neutrophil percentage. Using the MoAbs RFD1, RFD7 and RFD9, that distinguish subsets of alveolar macrophages, we have been able to identify associations between secretion of IL-8 and smaller cells and the cells identified by the MoAb RFD7. In situ hybridization of the bronchoalveolar lavage cell population revealed that alveolar macrophages are the predominant source of IL-8 in the lung. We conclude that there is an increased number of IL-8-secreting alveolar macrophages in the lungs of patients with fibrosing alveolitis, and IL-8 secretion by these cells is associated with specific phenotypic profile expression.

Sarcoidosis is a chronic granulomatous disorder, which is characterized by the accumulation of activated CD4+ T lymphocytes (T cells) at disease sites. There is up-regulation of cell surface expression of MHC molecules in sarcoidosis, and it has been suggested that specific MHC class II alleles are associated with the disease. A study of chronic beryllium disease (CBD), a granulomatous disorder which is pathologically similar to sarcoidosis, has identified an association between this disease and the presence of a glutamine residue at position 69 (Glu 69+) of the B1 chain of the HLA-DPB molecule. A further study also suggested the importance of Glu at position 55 of the same chain. The aims of the present study were to attempt to define MHC class II alleles associated with sarcoidosis by comparison of their frequency in two groups of subjects and to compare the frequency of HLA-DPB1 Glu 69+/- and Glu 55+/-alleles in the same subjects. Forty-one subjects with sarcoidosis and 76 normal subjects were studied. The polymorphic regions of the class II MHC were identified by PCR in association with sequence-specific oligonucleotide probes. There were no significant differences in the phenotype frequencies of MHC class II or Glu 55+ alleles between the two groups of subjects. However, there was a significant increase (P = 0.02) in the frequency of HLA-DPB1* Glu 69+ alleles compared with the control population. We therefore suggest that the presence of a Glu residue at position 69 on the DPB1 chain may play an important role in antigen presentation and recognition in chronic granulomatous diseases.

Pulmonary fibrosis commonly develops in systemic sclerosis. We assessed the role of thrombin in promoting fibroblast proliferation in the lungs in this disorder. Bronchoalveolar lavage fluid (BALF) thrombin concentrations were higher in ten patients with systemic sclerosis than in 12 healthy controls (14.6 vs 3.6 nmol/L, p < 0.02), but values in patients with cryptogenic fibrosing alveolitis (n = 10) or sarcoidosis (n = 10) were not increased. BALF from all patients induced fibroblast proliferation. This proliferation was attenuated by thrombin inhibitors for BALF from systemic sclerosis patients only. We suggest thrombin contributes to lung fibroblast proliferation in this disorder.

Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and compared it with that in normal individuals and sarcoidosis and systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8 protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and IL-8 mRNA expression was assessed using Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of lung parenchyma. Compared with normal subjects, IL-8 concentration was significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA expression evaluated by Northern analysis was seen only in patients with CFA and FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8 within the lower respiratory tract.

Background: Interstitial lung diseases are characterised by the recruitment of mononuclear cells to disease sites where maturation occurs and activation products, including lysozyme (LZM), are released. Analysis of in vitro cell culture supernatants for activation products masks the functional heterogeneity of cell populations. It is therefore necessary to examine the secretion of activation products by single cells to assess whether the activation of newly recruited mononuclear phagocytes at the sites of disease in the lung is uniform and controlled by the local microenvironment., Methods: The reverse haemolytic plaque assay was used to evaluate, at a single cell level, the ability of bronchoalveolar lavage (BAL) fluid from seven patients with sarcoidosis to activate Ficoll-Hypaque-separated peripheral blood mononuclear cells by comparison with BAL fluid from six normal volunteers and nine patients with systemic sclerosis. Monolayers of peripheral blood mononuclear cells and sheep red blood cells were cultured either alone or in the presence of 20% (v/v) BAL fluid with a polyclonal anti-LZM antibody. LZM/anti-LZM complexes bound to red blood cells surrounding the secreting cells were disclosed following complement lysis of red blood cells and quantification of plaque dimensions using microscopy and image analysis., Results: Bronchoalveolar lavage fluid from all the patients with sarcoidosis increased LZM secretion by peripheral blood mononuclear cells compared with unstimulated mononuclear cells. By contrast, BAL fluid from the other individuals had no effect on LZM secretion., Conclusions: Single cells activated by BAL fluid can be evaluated by the reverse haemolytic plaque assay. BAL fluid from patients with sarcoidosis, but not from patients with systemic sclerosis or normal individuals, contains components capable of activating mononuclear phagocytes to secrete lysozyme.

Pulmonary fibrosis is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). The pathogenesis of this condition is poorly understood, but one of the earliest pathologic features is endothelial and epithelial cell injury with subsequent regeneration. Endothelial and epithelial cells can release several mediators, including endothelin-1 (ET-1). In this study, we investigated the levels of ET-1 in bronchoalveolar lavage fluid (BALF) from patients with SSc and assessed the contribution of ET-1 to the fibroblast mitogenic activity induced by these fluids. A total of 26 patients were evaluated and divided into those with evidence of pulmonary fibrosis, assessed by thin-section computed tomography (group I, n = 16), and those with a normal scan (group II, n = 10). BALF from both groups of patients stimulated fibroblast proliferation. Values expressed as median (range) percentage increase above media controls were 25.5% (5.0 to 47.8%) and 27.6% (10.9 to 51.6%) for groups I and II, respectively (P < 0.02 in both cases). Mitogenic activity was inhibited by about 40% in the presence of either a neutralizing antibody to ET-1 or two synthetic ET-1 receptor ligands. Levels of ET-1 in BALF, expressed as medians (range) were 2.90 ng/mg albumin (0.68 to 5.75) in patients with SSc and 1.23 ng/mg albumin (0.84 to 2.0) in control patients (P < 0.02). Furthermore, ET-1 levels in BALF from patients in group II (3.83 ng/mg albumin, range 1.76 to 5.75) were elevated compared with those in group I (2.62 ng/mg albumin, range 0.68 to 3.81; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)