Purpose:Bronchial thermoplasty (BT) is a bronchoscopic intervention for the treatment of severe asthma. Despite demonstrated symptomatic benefit, the underlying mechanisms by which this is achieved remain uncertain. We hypothesize that the effects of BT are driven by improvements in ventilation heterogeneity as assessed using functional respiratory imaging (FRI).Patient and Methods:Eighteen consecutive patients with severe asthma who underwent clinically indicated BT were recruited. Patients were assessed at baseline, 4-week after treatment of the left lung, and 12-month after treatment of the right lung. Data collected included short-acting beta-agonist (SABA) and oral prednisolone (OCS) use, asthma control questionnaire (ACQ-5) and exacerbation history. Patients also underwent lung function tests and chest computed tomography. Ventilation parameters including interquartile distance (IQD; measure of ventilation heterogeneity) were derived using FRI.Results:12 months after BT, significant improvements were seen in SABA and OCS use, ACQ-5, and number of OCS-requiring exacerbations. Apart from pre-bronchodilator FEV1, no other significant changes were observed in lung function. Ventilation heterogeneity significantly improved after treatment of the left lung (0.18 ± 0.04 vs 0.20 ± 0.04, p=0.045), with treatment effect persisting up to 12 months later (0.18 ± 0.05 vs 0.20 ± 0.04, p=0.028). Ventilation heterogeneity also improved after treatment of the right lung, although this did not reach statistical significance (0.18 ± 0.05 vs 0.19 ± 0.04, p=0.06).Conclusion:Clinical benefits after BT are accompanied by improvements in ventilation heterogeneity, advancing our understanding of its mechanism of action. Beyond BT, FRI has the potential to be expanded into other clinical applications.

Background Respiratory tract infections (RTIs) are a major global health burden due to their high morbidity and mortality. This retrospective study described the epidemiology of respiratory pathogens in adults over a 5-year period at an Australian tertiary healthcare network. Methods All multiplex reverse transcription polymerase chain reaction respiratory samples taken between the 1st of November 2014 and the 31st of October 2019 were included in this study. Overall prevalence and variations according to seasons, age groups and sex were analysed, as well as factors associated with prolonged hospital and intensive care length of stay. Results There were 12,453 pathogens detected amongst the 12,185 positive samples, with coinfection rates of 3.7%. Picornavirus (Rhinovirus ), Influenza A and respiratory syncytial virus were the most commonly detected pathogens. Mycoplasma pneumoniae was the most commonly detected atypical bacteria. Significant differences in the prevalence of Chlamydia pneumoniae and Human metapneumovirus infections were found between sexes. Longest median length of intensive care and hospital stay was for Legionella species. Seasonal variations were evident for certain pathogens. Conclusions The high rates of pathogen detection and hospitalisation in this real-world study highlights the significant burden of RTIs, and the urgent need for an improved understanding of the pathogenicity as well as preventative and treatment options of RTIs.

Bronchial thermoplasty is a treatment option for patients with severe asthma. We report a case series of 6 patients who underwent bronchial thermoplasty on two separate occasions for poorly controlled asthma. The repeat procedures were well tolerated with no unexpected complications. One patient developed a focal area of mild bronchiectasis on imaging 6-months after repeat treatment, but this was not felt to be clinically relevant. Individual responses to repeat bronchial thermoplasty were varied, with some patients showing great improvement after treatment, whereas others did not. This series highlights the safety and feasibility of performing repeat ablation on previously ablated airways, as well as the potential clinical benefit in a select group of patients.

Aim: MRI ventilation defects in acute asthma are not homogeneous. We assessed topographical ventilation differences following direct (methacholine (MCh)) and indirect (mannitol) inhalational challenges in mild asthma to improve our understanding of their pathophysiology. Methods: Asthmatic subjects underwent spirometry and hyperpolarised helium MRI (He3MRI) ventilation scans pre and post inhalation of either MCh or mannitol (at their known provocative concentration/dose), with repeat scans using alternate challenge test on a separate day. He3MRI ventilation was quantified using k-means segmentation. Results: 8 subjects were studied. Mean age was 35.9±9.8 years and 75% were females. Baseline FEV1 was 95.3±12.8% and fell by 24±7% post MCh. Post mannitol, FEV1 fell by 18±11% from a baseline of 94.0±12.4%. Ventilation abnormalities seen at baseline were worse post-challenge. Regions of poor ventilation also increased from 10.3% to 17.8% with MCh and from 11.9% to 15.1% with mannitol. Overlap between regions affected by either challenge test was also noted. Conclusion: Direct and indirect airway challenges have different topographical distributions in ventilation defects despite a similar fall in FEV1. Certain airways also appear to be more susceptible to bronchial provocation regardless of the challenge method. This reinforces the notion that asthma is a heterogeneous disease.

Respiratory diseases are leading causes of death and disability in the world. While early diagnosis is key, this has proven difficult due to the lack of sensitive and non-invasive tools. Computed tomography is regarded as the gold standard for structural lung imaging but lacks functional information and involves significant radiation exposure. Lung magnetic resonance imaging (MRI) has historically been challenging due to its short T2 and low proton density. Hyperpolarised gas MRI is an emerging technique that is able to overcome these difficulties, permitting the functional and microstructural evaluation of the lung. Other novel imaging techniques such as fluorinated gas MRI, oxygen-enhanced MRI, Fourier decomposition MRI and phase-resolved functional lung imaging can also be used to interrogate lung function though they are currently at varying stages of development. This article provides a clinically focused review of these contrast and non-contrast MR imaging techniques and their current applications in lung disease.

Background: In 2016, Melbourne was struck by the world's largest and most devastating epidemic thunderstorm asthma (ETSA) episode. While affected individuals displayed worsened short-term asthma control, little is known about their longer-term natural history, nor about interventions that restore control. Objective: We assessed the asthma symptomatology and related behaviours of ETSA-affected individuals through a single-centre prospective 5-year longitudinal study. We embedded an open-label observational trial investigating the role of grass pollen sublingual tablet (Oralair) allergen immunotherapy in improving asthma and allergic rhinitis symptoms. Methods: Allergic rhinitis symptom severity, frequency of asthma symptoms and inhaled corticosteroid usage were assessed via questionnaire yearly. In 2018, a subgroup of participants was enrolled in an observational study of Oralair treatment compared to control. The active group received Oralair from 2019 to 2021; both groups were followed-up for 5 years. Subgroup analyses were performed for participants with complete datasets, and who completed the trial per-protocol. Results: Year-on-year data across 5 years was available for 30 participants. The rate of persistent asthma symptoms declined from 37% to 7% in 2016 to 2021. Only 10%-27% of participants reported being completely asymptomatic in any given year. The inhaled preventer prescription rate was 67%, with only 35% being adherent. Twenty-seven participants with available data completed the Oralair trial per-protocol. No significant difference was noted between control and active groups for allergic rhinitis symptoms or asthma control, although the Oralair group saw a significant improvement in asthma control comparing 2019 with 2021. Conclusion: This is the longest documented follow-up of ETSA- affected individuals. Five years following sentinel event, there was progressive reduction but some persistence in asthma symptoms. Oralair allergen immunotherapy did not further improve allergic rhinitis or asthma symptoms compared to control, but there were no further ETSA events to test a protective effect during the study period.

© Author(s) (or their employer(s)) 2021. No commercial reuse. See rights and permissions. Published by BMJ. A 60yearold man with a history of benign prostate hyperplasia was referred to our clinic for evaluation of persistent left lower lobe chest Xray (CXR) changes and symptoms suggestive of recurrent chest infection that did not improve with antibiotic therapy. On history, the patient vividly recalled an episode of violent coughing 3 months ago while eating peanuts. Thereafter, he reported daily cough with clear productive sputum and breathlessness on heavy exertion. The patient is a lifelong nonsmoker and reported no other infective or cardiac symptoms, or relevant environmental exposures. On examination, the patient was not dyspnoeic. Temperature was 37.2°C, respiratory rate 12 breaths/min and room air oxygen saturation 97%. Chest auscultation revealed left basal coarse crackles which did not clear on coughing. The remainder of the clinical examination was normal. Full blood count, C reactive protein, urea and electrolytes, and liver function test were normal. To further evaluate the CXR changes, a chest CT was performed. This showed an endobronchial lesion in the proximal left lower lobe bronchus associated with distal bronchiectasis, peribronchial consolidation and treeinbud opacities (figure 1). Bronchoscopy identified a peanut firmly wedged in the left lower lobe bronchus with surrounding mucosa erythema and oedema (figure 2). This was successfully extracted with a rat tooth forceps and washout of copious pus distally was performed. The patient’s symptoms promptly resolved and chest CT 2 months later showed marked improvement in the previously identified abnormalities, with residual smooth bronchial dilation and scattered ground glass (figure 1). Bronchiectasis is classically defined as a clinical syndrome of cough, sputum production and

Introduction/Aim: Malignant pleural effusion (MPE) often results in debilitating symptoms. Relief of dyspnoea and improvement in quality of life can be achieved with either thoracoscopic talc poudrage or insertion of an indwelling pleural catheter (IPC). The former requires a lengthy inpatient stay and the latter is associated with lower pleurodesis rates. Due to limited inpatient capacity, we developed a pragmatic approach in managing MPE by combining thoracoscopy, talc poudrage and insertion of IPC into a single day case procedure. We present data on the safety and efficacy of our approach. Methods: Patients who had undergone the abovementioned procedure between 2017 and 2020 were analysed. Demographic data, hospital length of stay (LOS), histological diagnosis, rates of pleurodesis success and procedural related complications were collated. Patients were followed-up for 6 months. Results: 45 patients underwent the procedure. Mean age was 68.5±10.4 years and 56% were male. Histological diagnosis was achieved in all cases. 86.7% (n=39) of patients were discharged on the day of the procedure. 13.3% (6) required admission. Mean and median LOS was 0.5±1.7 days and 0 (range 0-9) days respectively. Pleurodesis success rates of 71.1% (32/45) and 77.8% (35/45) were achieved at 3 and 6-months. 31.1% (14) of patients died within 6 months. No procedure related deaths or IPC related infections were observed. Conclusion: Day case rapid pleurodesis is a safe and effective option in the management of MPE. All patients received a definitive pleural intervention with 86.7% of them discharged on the same day and 77.8% pleurodesis success at 6-months. Future randomised trials are required to confirm these findings.

Retained haemothorax is a common sequela of traumatic haemothorax and refers to blood that cannot be drained from the pleural cavity. We report a case of trapped lung secondary to retained haemothorax in a patient who sustained a penetrating chest injury. Initial chest computed tomography (CT) showed a large haemothorax that was managed with an intercostal drain insertion (ICD). Repeat chest CT and thoracic ultrasonography performed after ICD removal showed an organized pleural space resembling haematoma. ICD was reinserted with administration of intrapleural fibrinolytic therapy (IPFT). Subsequent chest CT showed the development of a pleural rind and trapped lung. A second ICD was inserted, and further IPFT were administered together with aggressive negative pressure suction. Haemoglobin remained stable. The patient made a full recovery and imaging performed two weeks later showed minor blunting of the costophrenic angle. This case highlights the feasibility and safety of IPFT in the management of trapped lung associated with traumatic retained haemothorax as an alternative to surgery.

Malignant pleural effusion is common in mesothelioma. We report a case of viscous recurrent malignant mesothelioma pleural effusion. The viscosity was due to the presence of hyaluronic acid and resulted in prolonged drainage time. The use of intrapleural hyaluronidase significantly reduced fluid viscosity and drainage duration. No adverse reactions were noted. This novel case highlights the feasibility and safety of the use of intrapleural hyaluronidase in the management of hyaluronic acid-rich viscous malignant pleural effusion.

Background and Objective: Malignant pleural effusion (MPE) often results in debilitating symptoms. Relief of dyspnoea and improvement in quality of life can be achieved with either talc pleurodesis or insertion of an indwelling tunneled pleural catheter (IPC). The former requires a lengthy hospital stay and the latter is associated with lower pleurodesis rates. In response to limited hospital bed capacity, we developed a pragmatic approach in managing MPE by combining thoracoscopic talc poudrage and insertion of IPC into a single day case procedure. We present data on the safety and efficacy of this approach. Methods: Patients who had undergone the abovementioned procedure between 2017 and 2020 were analyzed. Demographic data, hospital length of stay (LOS), histological diagnosis, rates of pleurodesis success and procedural related complications were collated. Patients were followed-up for 6 months. Results: Forty-five patients underwent the procedure. Mean age was 68.5 ± 10.4 years and 56% were male. Histological diagnosis was achieved in all cases. 86.7% of patients were discharged on the day of the procedure. Median LOS was 0 (IQR 0–0) days. Successful pleurodesis was attained in 77.8% at 6-month follow-up. No procedure related deaths or IPC related infections were recorded. Conclusion: Ambulatory thoracoscopic poudrage and IPC insertion is a safe and effective option in the management of MPE. All patients received a definitive pleural intervention with 77.8% pleurodesis success at 6-months and majority of them discharged on the same day. Future randomized trials are required to confirm these findings.

Haemothorax is an accumulation of blood in the pleural space. Retained haemothorax refers to blood that cannot be drained from the pleural cavity and is associated with an increased risk of empyema and fibrothorax often necessitating surgical evacuation. We describe our experience of using intrapleural fibrinolytic therapy in three patients with different bleeding risk and acute non-traumatic retained haemothorax. The first was a 41-year-old female with disseminated Candida guilliermondii sepsis and an iatrogenic haemothorax, second was a 48-year-old female with transfusion-dependent acute myeloid leukaemia and spontaneous haemothorax, and the third was a 72-year-old female with spontaneous haemothorax from newly diagnosed lung cancer. All patients received one to two doses of intrapleural alteplase without any bleeding complications and resolution of retained haemothorax. This case series demonstrates the successful application and safety of this approach as an alternative to surgery in a well-resourced environment with close monitoring and ready access to blood transfusion.

Malignant pleural effusion (MPE) is common in lung cancer. We report a case of highly viscous recurrent MPE associated with lung cancer. The viscosity prohibited gravity-dependent drainage initially with a 6-Fr aspiration catheter and subsequently with a 12-Fr intercostal drain. The effusion was eventually evacuated after a single dose of intrapleural fibrinolytic therapy. This process was repeated a total of 13 times over a 12-month period in an ambulatory setting. No bleeding complications were observed. This case highlights the feasibility and safety of repeated intrapleural fibrinolysis in the management of highly viscous recurrent MPE in an ambulatory setting.

This study aimed to examine the environmental and operational factors that disrupt sleep in the acute, non-ICU hospital setting. This was a prospective study of adult patients admitted to an acute tertiary hospital ward (shared versus single room) and sleep laboratory (single room conducive to sleep). This study measured ambient light (lux) and sound (dB), number of operational interruptions, and questionnaires assessing sleep and mental health. Sixty patients were enrolled, 20 in a double bedroom located close to the nursing station (‘shared ward’), 20 in a single bedroom located distant to the nursing station (‘single ward’) and 20 attending the sleep laboratory for overnight polysomnography (‘sleep laboratory’). Sleep was disturbed in 45% of patients in the shared and single ward groups (Pittsburgh Sleep Quality Index > 5). Light levels were appropriately low across all 3 locations. Sound levels (significant effect of room F(1.38) = 6.452, p = 0.015) and operational interruptions (shared ward 5.6 ± 2.5, single ward 6.2 ± 2.9, sleep laboratory 2.7 ± 2.1 per night, p < 0.05 wards compared to sleep laboratory) were higher in the shared and single ward group compared to the sleep laboratory but not compared to each other. Noise was rated as the greatest environmental disturbance by 70% of ward patients compared to 10% in the sleep laboratory. Higher noise levels and frequent operational interruptions are potential barriers to sleep and recovery on an acute medical ward which are not ameliorated by being in a single bedroom located distant to the nursing station

BACKGROUND:The world's most catastrophic epidemic thunderstorm asthma event (ETSA) affected Melbourne in 2016. Little is known about the natural history of individuals affected by such extreme events. OBJECTIVE:In this single center prospective 3-year longitudinal study, symptomatology and behaviors of individuals affected by ETSA were assessed. METHODS:Standardized telephone questionnaire was used to evaluate frequency of asthma symptoms, inhaled corticosteroid preventer use, asthma action plan ownership, and healthcare utilization. Questionnaires were administered at 12, 24, and 36 months after 2016 ETSA. Subgroup analyses of the 'current', 'past', 'possible,' and 'no asthma' subgroups were also conducted. RESULTS:Two hundred and eight, 164, and 112 completed questionnaires were analyzed in 2017, 2018, and 2019, respectively. Seventy to eighty five percent of respondents reported ongoing asthma symptoms in any given year, of which 20%-28% experienced weekly symptoms. Nearly 50% of respondents were prescribed preventers, with approximately 45% adherent at least 5 days a week. Less than 40% had an asthma action plan and 15%-20% sought urgent medical attention for asthma over the follow-up period. Among 106 individuals with 3 consecutive years of completed questionnaires, those with no prior doctor diagnosis of asthma were significantly more likely to be asymptomatic on follow-up than those with a prior doctor diagnosis of asthma (p = 0.02). Subgroup analyses suggest that large proportions of respondents with 'past' and 'no asthma' continue to remain symptomatic throughout the 36-month period. CONCLUSION:In individuals affected by ETSA, we found evidence of ongoing loss of asthma control in those with previously well controlled asthma, and the persistence of symptoms suggestive of asthma in those with no history or symptoms suggestive of prior asthma, even after 36 months from initial ETSA. Low rates of inhaler adherence and asthma action plan ownership may contribute to increased morbidity and mortality from future ETSA events. Further research is required to confirm these findings.

Sir, In the past few decades, health and medical research encompassing clinical medicine, public health, and basic translational sciences have been the cornerstone of clinical advancement. The value of research has been recognized by governments worldwide, with billions of dollars invested in this industry annually. International collaborations have led to innumerable discoveries and therapies in the vast field of medical sciences. Observational studies fuelled the development of the first successful smallpox vaccination, eventually eradicating this disease worldwide.[1] The coronavirus-19 (COVID-19) pandemic has led to an unprecedented level of interest in research.[2]. Medical journals are receiving an overwhelming number of submissions in relation to COVID-19-including translational research, clinical perspectives, case reports, treatment trials, and review articles. Editorial boards and reviewers work tirelessly, evaluating and prioritizing key manuscripts to facilitate rapid dissemination of up-to-date information to its readers, enabling them to practice evidence-based medicine in these uncertain times. The surge in research activity may be due to several reasons. First, COVID-19 is a novel form of coronavirus that has never been encountered before, sparking intense interest from the scientific community seeking to understand and unravel its mysteries as quickly as possible. Second, in contrast to previous pandemics of influenza A virus subtype H1N1 and human immunodeficiency virus/acquired immune deficiency syndrome, the disruptions of COVID-19 on daily life are enormous. Laws and restrictions has affected the lives of everyone in the world regardless of age, gender and socioeconomic status. In addition, conferences and examinations have been cancelled, and all nonessential medical procedures and surgeries suspended. While this has severely limited trainees' scope of practice, the new exposure to public health, epidemiology, and health-care systems has presented an opportunity for clinicians to participate in early research. Regardless of reason, the improvement of health and health care through research, while maintaining the highest standards and ethical principles, is a step in the right direction. When the COVID-19 pandemic eventually comes to an end, we hope the passion for research will continue with scientific community forging ahead with enthusiasm and vigor to further the advancement of medicine. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Endobronchial tuberculosis (TB) is an uncommon manifestation ofMycobacterium tuberculosis.We report a case of endobronchial TB polyps in a patient from India presenting with cough, loss of weight and night sweats. Computed tomography chest revealed enlarged mediastinal lymph nodes, endobronchial invasion, and nodular infiltrates in the right lower lobe. Flexible bronchoscopy revealed two endobronchial polyps at the carina and left main bronchus which were biopsied. Histopathology showed non-caseating granulomas. Both the biopsy and bronchial washings did not identify acid-fast bacilli on Ziehl-Neelsen stain and had negative TB complex DNA polymerase chain reaction. One month after bronchoscopy,M. tuberculosiswas cultured from the bronchial washings. Following six months of TB treatment, there was full resolution of symptoms and significant radiological improvement. We highlight the diagnostic challenges in endobronchial TB which may impact on the timely institution of treatment.

Objective To evaluate the effectiveness of two different strategies designed to facilitate implementation of Choosing Wisely Australia guidelines, aiming to reduce unnecessary coagulation study blood tests in patients presenting to a metropolitan hospital ED. Method In this real-world quality improvement study, the first intervention tested was an education strategy. The second intervention was physically removing coagulation pathology tubes from the bedside trolleys in the ED. Data were collected about clinical appropriateness of testing, as per the Choosing Wisely Australia guideline and total volume of coagulation studies ordered. Results No reduction in inappropriate coagulation testing was observed following the education intervention whereas a significant reduction in inappropriate coagulation testing was seen after the second intervention (inappropriate testing reduced from 73.8% to 53.0%). Conclusion Physically removing coagulation pathology tubes from the trolleys was found to be effective at reducing unnecessary testing.

We report the first case of autoimmune pulmonary alveolar proteinosis (PAP) associated with and preceding myelodysplastic syndrome. A 74-year-old female with a history of polymyalgia rheumatica presented with six months history of progressive exertional breathlessness. Examination revealed bilateral chest crackles and exertional desaturation. A diagnosis of autoimmune PAP was made based on the presence of autoantibodies to granulocyte-macrophage colony-stimulating factor and characteristic findings on chest computed tomography, bronchoalveolar lavage, and transbronchial biopsies. Bilateral whole lung lavage was performed with prompt improvement in symptoms. Fourteen months later, she presented with new breathlessness and was diagnosed with myelodysplasia on bone marrow biopsy. No recurrence of alveolar proteinosis was detected. This case highlights the importance of follow-up and screening of patients with autoimmune PAP for haematological conditions.

BACKGROUND:Epidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA.OBJECTIVE:A multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals.METHODS:We used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the "current," "past," "probable," and "no asthma" subgroups defined according to their original 2016 survey responses.RESULTS:Four hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year.CONCLUSIONS:Following an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change.