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We report the design, construction, and initial tests of a hyperpolariser to produce polarised 129 Xe and 3 He gas for medical imaging of the lung. The hyperpolariser uses the Spin-Exchange Optical Pumping method to polarise the nuclear spins of the isotopic gas. Batch mode operation was chosen for the design to produce polarised 129 Xe and polarised 3 He. Two-side pumping, electrical heating and a piston to transfer the polarised gas were some of the implemented techniques that are not commonly used in hyperpolariser designs. We have carried out magnetic resonance imaging experiments demonstrating that the 3 He and 129 Xe polarisation reached were sufficient for imaging, in particular for in vivo lung imaging using 129 Xe. Further improvements to the hyperpolariser have also been discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Epidemic thunderstorm asthma (ETSA) is a global health problem that can strike without sufficient warning and can have catastrophic consequences. Because of climate change, future events are likely to become more common, more disastrous, and more unpredictable. To prevent loss of life and avoid surge events on health care infrastructure, identifying at-risk individuals and their potential biomarkers is the most prophylactic approach that can be taken to mitigate the deadly consequences of ETSA. In this review, we provide an update on the clinical mechanism, global prevalence, and characteristics of those patients moderately or severely at risk of ETSA. Identifying these patient characteristics will aid clinical professionals to provide suitable and personalized treatment plans and, in turn, avoid future loss of life., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperpolarized helium-3 MRI ( 3 He MRI) provides detailed visualization of low- (hypo- and non-) ventilated lungs. Physiological measures of gas mixing may be assessed by multiple breath nitrogen washout (MBNW) and of airway closure by a forced oscillation technique (FOT). We hypothesize that in patients with asthma, areas of low-ventilated lung on 3 He MRI are the result of airway closure. Ten control subjects, ten asthma subjects with normal spirometry (non-obstructed), and ten asthmatic subjects with reduced baseline lung function (obstructed) attended two testing sessions. On visit one, baseline plethysmography was performed followed by spirometry, MBNW, and FOT assessment pre and post methacholine challenge. On visit two, 3 He MRI scans were conducted pre and post methacholine challenge. Post methacholine the volume of low-ventilated lung increased from 8.3% to 13.8% in the non-obstructed group ( P = 0.012) and from 13.0% to 23.1% in the obstructed group ( P = 0.001). For all subjects, the volume of low ventilation from 3 He MRI correlated with a marker of airway closure in obstructive subjects, Xrs (6 Hz) and the marker of ventilation heterogeneity Scond with r 2 values of 0.61 ( P < 0.001) and 0.56 ( P < 0.001), respectively. The change in Xrs (6 Hz) correlated well ( r 2 = 0.45, p < 0.001), whereas the change in Scond was largely independent of the change in low ventilation volume ( r 2  = 0.13, P < 0.01). The only significant predictor of low ventilation volume from the multi-variate analysis was Xrs (6 Hz). This is consistent with the concept that regions of poor or absent ventilation seen on 3 He MRI are primarily the result of airway closure. NEW & NOTEWORTHY This study introduces a novel technique of generating high-resolution 3D ventilation maps from hyperpolarized helium-3 MRI. It is the first study to demonstrate that regions of poor or absent ventilation seen on 3 He MRI are primarily the result of airway closure.

Since the first description of anaphylaxis in 1902, its clinical importance as an emergency condition has been recognized worldwide. Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life through respiratory or circulatory compromise. It is usually, although not always, associated with skin and mucosal changes. Although the academic/scientific communities have advocated to promote greater awareness and protocols for the management of anaphylaxis based on best evidence, there are few efforts documenting feedback as to the success of these efforts. In this article, we review the key unmet needs related to the diagnosis and management of anaphylaxis, and propose a public health initiative for prevention measures and a timetable action plan that intends to strengthen the collaboration among health professionals and especially primary care physicians dealing with anaphylaxis, which can encourage enhanced quality of care of patients with anaphylaxis. More than calling for a harmonized action for the best management of anaphylaxis to prevent undue morbidity and mortality, the Montpellier World Health Organization Collaborating Centre here proposes an action plan as a baseline for a global initiative against anaphylaxis. We strongly believe that these collaborative efforts are a strong public health and societal priority that is consistent with the overarching goals of providing optimal care of allergic patients and best practices of allergology., (Copyright © 2020. Published by Elsevier Inc.)

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma., (© 2020 Royal Australasian College of Physicians.)

Background and Objective: BT and interleukin-blocking monoclonal antibodies are both effective therapies for severe asthma, but there have been no direct comparisons between the two treatments. The aim of this study was to compare the efficacy and safety of BT and mepolizumab, in a real-world setting., Methods: Patients with severe asthma despite optimized inhaler therapy were drawn from a severe asthma clinic in a tertiary hospital. Every patient commencing therapy with BT or mepolizumab was prospectively included in a national registry. At predetermined assessment points over a 12-month period, assessments were made of ACQ, spirometry, oral corticosteroid requiring exacerbations, reliever medication and maintenance oral corticosteroid use., Results: A total of 91 patients with severe asthma participated: mean ACQ score 3.5 ± 1.0, FEV 1 51.4 ± 17.7%, maintenance oral steroids 48.3% and 11.5 ± 10.0 inhalations/day reliever therapy. Forty-seven patients received mepolizumab and 44 received BT. Baseline characteristics were similar except significantly higher blood eosinophil count in the mepolizumab group. At 12 months, there were no differences between treatment outcomes for ACQ (1.9 ± 1.3 mepolizumab vs 1.7 ± 1.3 BT), exacerbation rate (0.9 ± 1.1 vs 0.9 ± 1.5), reduction in reliever use (-6.3 ± 10.5 vs -5.0 ± 8.8 puffs/day) or reduction in oral corticosteroids (-3.3 ± 7.5 vs - 5.8 ± 6.7 mg/day). The FEV 1 improved equally (160 ± 290 vs 150 ± 460 mL). Readmission or prolonged admission was observed in 18.2% of BT patients, whilst 25.5% of mepolizumab patients had discontinued treatment at 12 months, 14.9% due to an adverse event or non-compliance., Conclusion: The results suggest that BT is as efficacious as mepolizumab for the treatment of severe asthma., (© 2020 Asian Pacific Society of Respirology.)

Background: Despite demonstrated symptomatic benefit from bronchial thermoplasty (BT), the underlying pathophysiological benefits have been uncertain. The purpose of the present study was to relate clinical benefit after BT to changes in lung physiology, focusing on ventilation homogeneity assessed using multiple breath nitrogen washout (MBNW), and how this may be affected by changes in airway volume and resistance., Methods: Consecutive patients (n = 21) with severe asthma scheduled for BT, were evaluated at baseline, 6 weeks and 6 months after completion of treatment. Assessments included the Asthma Control Questionnaire (ACQ), medication usage, exacerbation frequency, spirometry, plethysmography and MBNW. Eighteen of these patients underwent detailed CT evaluation for the estimation of airway volume at baseline and then after the left lung had received BT treatment but prior to right lung treatment. Data are mean ± STDEV., Results: Patients responded to BT with an improvement in ACQ from 3.4 ± 0.8 at baseline to 2.0 ± 1.1 at 6 months (p < 0.001). Steroid requiring exacerbations fell from 3.1 ± 2.9 in the 6 months prior to BT to 1.4 ± 1.7 following BT (p < 0.001). Significant reductions in maintenance oral steroid dosing and short acting beta agonist use were observed. Airway volume measured by CT scanning significantly increased after treatment. The FEV1 improved from 1.34 ± 0.65 l to 1.52 ± 0.76 l (p = 0.024). The Residual Volume fell from 2.87 ± 0.89 l to 2.71 ± 0.93 l (p = 0.008) and Total Airway Resistance (Raw) from 10.58 ± 6.56 to 7.64 ± 3.74 cmH 2 O.s.l -1 (p = 0.020). The Lung Clearance Index (LCI) was 187 ± 63% predicted at baseline and improved after treatment from 12.7 ± 3.3 to 11.8 ± 2.4 (p = 0.049). The improvement in LCI correlated with the improvement in Raw (r = 0.463, p = 0.035)., Conclusion: Clinical benefit after BT is accompanied by improvements in lung physiology, including normalisation of lung homogeneity that seems to be driven by airway dilation and reduced resistance.

Bronchial thermoplasty induces atrophy of the airway smooth muscle layer, but the mechanism whereby this improves patient health is unclear. In this study, we use computed tomography (CT) to evaluate the effects of bronchial thermoplasty on airway volume 12 months post-procedure. 10 consecutive patients with severe asthma were evaluated at baseline by the Asthma Control Questionnaire (ACQ), and high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC). The CT protocol was repeated 4 weeks after the left lung had been treated by bronchial thermoplasty, but prior to right lung treatment, and then again 12 months after both lungs were treated. The CT data were also used to model the implications of including the right middle lobe (RML) in the treatment field. The mean patient age was 62.7±7.7 years and forced expiratory volume in 1 s (FEV 1 ) 42.9±11.5% predicted. 12 months post-bronchial-thermoplasty, the ACQ improved, from 3.4±1.0 to 1.5±0.9 (p=0.001), as did the frequency of oral steroid-requiring exacerbations (p=0.008). The total airway volume increased 12 months after bronchial thermoplasty in both the TLC (p=0.03) and the FRC scans (p=0.02). No change in airway volume was observed in the untreated central airways. In the bronchial thermoplasty-treated distal airways, increases in airway volume of 38.4±31.8% at TLC (p=0.03) and 30.0±24.8% at FRC (p=0.01) were observed. The change in distal airway volume was correlated with the improvement in ACQ (r=-0.71, p=0.02). Modelling outputs demonstrated that treating the RML conferred no additional benefit. Bronchial thermoplasty induces long-term increases in airway volume, which correlate with symptomatic improvement., Competing Interests: Conflict of interest: D. Langton has nothing to disclose. Conflict of interest: C. Banks has nothing to disclose. Conflict of interest: P.B. Noble has nothing to disclose. Conflict of interest: V. Plummer has nothing to disclose. Conflict of interest: F. Thien has nothing to disclose. Conflict of interest: G.M. Donovan has nothing to disclose., (Copyright ©ERS 2020.)

Background: The issues and challenges in the diagnosis of drug allergy/hypersensitivity among children and adults in Asia are likely to be different from non-Asian countries., Objective: To study the diagnostic modalities used in the evaluation and management of drug allergy/drug hypersensitivity reactions (DHRs) among member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI)., Methods: A questionnaire comprising 41 questions was circulated electronically to member societies and individual members of APAAACI between January 23, 2020 and March 6, 2020., Results: Twenty-six respondents from 15 member societies and 1 individual member responded. European DHR guidelines were most commonly used. Skin prick and intradermal testing was used by 100%, with only 60% having access to commercial penicillin skin test reagents. In vitro -specific IgE tests were used by 75%, and basophil activation test by 56.3% for immediate DHR. Patch tests were used by 75% in contrast to lymphocyte transformation tests by 25% for nonimmediate DHR. Drug provocation tests were used by 68.8%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (93.3%). Human leukocyte antigen (HLA) genotype testing was mandatory among 25% respondents before new carbamazepine prescriptions, and 8.3% for allopurinol prescriptions., Conclusions: There was increased use of skin testing for iodinated contrast media hypersensitivity and patch testing for nonimmediate DHR. HLA genotype testing prior to new carbamazepine, allopurinol and abacavir prescriptions remain variable despite strong associations for severe cutaneous adverse reactions with Asian ethnicity. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across APAAACI member societies., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2020. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Introduction: Epidemic thunderstorm asthma (ETSA) is due to a complex interaction of environmental and individual susceptibility factors, with outbreaks reported globally over the last four decades. Australia has been particularly susceptible with nearly half of episodes reported internationally, culminating in the catastrophic Melbourne 2016 event., Areas Covered: Reported ETSA episodes are reviewed for common environmental and meteorological risk factors. Allergen aerobiology interaction with thunderstorm activity and rapid weather condition changes is examined. Assessment of the clinical and immunological data highlights risk factors for ETSA presentation, hospital admission, and intensive care admission. Risk factors associated with ETSA deaths are evaluated. Public health strategies, as well as pharmacological and immunological management approaches to reduce individual susceptibility and prevent ETSA are discussed., Expert Opinion: Improved understanding of the specific meteorological factors predisposing to the greatest risk of ETSA to improve forecasting is required. Better monitoring of aeroallergen levels in areas of greatest geographic risk, with further research into allergen aerobiology underpinning mechanisms of allergen exposure is needed. The role of climate change in increasing the risk of ETSA outbreaks requires further research. Public awareness and education are required to reduce exposure, and to improve uptake of pharmacological and immunological risk reduction and preventive strategies.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

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., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2020. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Although it is established that not all patients respond to bronchial thermoplasty (BT), the factors that predict response/nonresponse are largely unknown., Objectives: To identify baseline factors that predict clinical response., Methods: The records of 77 consecutive patients entered into the Australian Bronchial Thermoplasty Registry were examined for baseline clinical characteristics, and outcomes measured at 6 and 12 months after BT, such as change in the Asthma Control Questionnaire (ACQ) score, exacerbation frequency, the requirement for short-acting beta-2 agonist (SABA) medication and oral corticosteroids, and improvement in spirometry., Results: This was a cohort of patients with severe asthma: aged 57.7 ± 11.4 years, 57.1% females, 53.2% of patients taking maintenance oral steroids, 43% having been treated with an mAb, mean FEV 1 of 55.8% ± 19.8% predicted., Results: BT resulted in an improvement in the ACQ score from 3.2 ± 1.0 at baseline to 1.6 ± 1.1 at 6 months (P < .001). Exacerbation frequency in the previous 6 months reduced from 3.7 ± 3.3 to 0.7 ± 1.2 (P < .001). SABA requirement reduced from 9.3 ± 7.1 puffs/d to 3.5 ± 6.0 (P < .001), and 48.8% of patients were weaned completely off oral steroids. A significant improvement in FEV 1 was observed. Using multiple linear regression models, baseline ACQ score strongly predicted improvement in ACQ score (P < .001). Patients with an exacerbation frequency greater than twice in the previous 6 months showed the greatest reduction in exacerbations (-5.3 ± 2.8; P < .001). Patients using more than 10 puffs/d of SABA experienced the greatest reduction in SABA requirement (-12.4 ± 10.5 puffs, P < .001)., Conclusions: The most severely afflicted patients had the greatest improvements in ACQ score, exacerbation frequency, and medication requirement., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques., Methods: Eighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment., Results: The baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05). CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = - 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance., Conclusion: Symptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance.

Background: Randomized clinical trials of bronchial thermoplasty (BT) were conducted in patients with a baseline FEV 1 greater than 50%. There is a paucity of data regarding BT in patients with more severe obstruction, and consequently these patients are often excluded from receiving BT. The purpose of this study was to compare safety and efficacy outcomes in a large cohort of patients with an FEV 1 less than 50% with those of a cohort of less obstructed patients., Methods: Consecutive patients with severe asthma were drawn from the Australian BT Registry. Patients were grouped into (1) those with a baseline prebronchodilator FEV 1 % predicted < 50% (n = 32) or (2) those with an FEV 1  ≥ 50% (n = 36). Adverse outcomes were defined as (1) remaining in hospital longer than the planned 24-hour admission posttreatment or (2) being readmitted to hospital for any cause within 30 days of a treatment. Efficacy outcomes were evaluated 6 months after BT., Results: More severely obstructed patients were no more likely to have experienced any adverse event. Significant improvements in Asthma Control Questionnaire score, exacerbation frequency, reliever medication use, and requirement for daily oral steroids were observed in both groups, and were of a similar degree., Conclusions: This study demonstrates that BT can confidently be offered to patients with asthma with an FEV 1 that is 30% to 50% of predicted without risk of more frequent or more severe adverse events, and with the expectation of the same degree of response as patients with better lung function., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2020. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2020. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

High-resolution CT assessment of airway volumes after bronchial thermoplasty (BT), together with model predictions regarding the efficacy and underlying mechanism of action of the treatment, combine to help to elucidate the underlying mechanism of BT http://bit.ly/2WPHY6y., Competing Interests: Conflict of interest: D. Langton has nothing to disclose. Conflict of interest: P.B. Noble has nothing to disclose. Conflict of interest: F. Thien has nothing to disclose. Conflict of interest: G.M. Donovan has nothing to disclose., (Copyright ©ERS 2019.)

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., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2019. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

We review the history of the classification and coding changes for anaphylaxis and provide current and perspective information in the field. In 2012, an analysis of Brazilian data demonstrated undernotification of anaphylaxis-related deaths because of the difficulties of coding using the International Classification of Diseases, 10th Revision. This work triggered strategic international actions supported by the Joint Allergy Academies and the International Classification of Diseases World Health Organization (WHO) leadership to update the classification of allergic disorders for the International Classification of Diseases, 11th Revision (ICD-11), which resulted in construction of the pioneer "Allergic and hypersensitivity conditions" chapter. The usability of the new framework has been tested by evaluating the same data published in 2012 from the ICD-11 perspective. Coding accuracy was much improved, reaching 95% for definite anaphylaxis. As the results were provided to the WHO Mortality Reference Group, coding rules have been changed, allowing anaphylaxis to be recorded as an underlying cause of death in official mortality statistics. The mandatory use of ICD-11 from January 2022 for documenting cause of death could have 2 immediate consequences: (1) the reported number of anaphylaxis-related deaths might increase because of more appropriate coding and (2) the cross-sectional and longitudinal mortality data generated might ultimately lead to a better understanding of anaphylaxis epidemiology and improved health policies directed at reducing anaphylaxis-related mortality., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to use CT scanning with computational fluid dynamics to evaluate the mechanisms by which Bronchial Thermoplasty (BT) improves asthmatic symptoms., Methods: The study was conducted in a university teaching hospital, experienced in performing BT. Imaging studies were performed before, and after, BT of the left lung, and prior to treatment of the right lung, which therefore acted as a control. On each occasion, two high-resolution CT scans were performed, one at full inspiration (TLC) and the other at Functional Residual Capacity (FRC). The study protocol was offered to 10 patients, all of whom met the definition of severe asthma, despite high dose inhaled corticosteroids and dual long acting bronchodilators., Results: Significant increases in airway luminal volume were observed on the treated side, compared with control, at both full inspiration (by 27%) and at FRC (by 17%). The ratio of distal airway volume to lung volume significantly increased on the treated side. The change in airway volume with inspiration from FRC increased by 48% on the treated side compared to 5% in the control lung, suggesting treatment increased airway distensibility. No effect was observed on airway wall thickness, nor air trapping. There was a trend towards correlation between the improvement in airway volume at TLC and improvement in symptoms., Conclusion: This study demonstrates that BT increases the luminal airway volume on the treated side compared to the control lung. We suggest that this is an important link between the airway smooth muscle atrophy demonstrated pathologically, and the improvement in symptoms observed clinically.

Background: Panax ginseng (ginseng) is a therapeutic herb which might be beneficial in COPD. The study investigated if ginseng, compared with placebo, is effective and safe for people with moderate COPD., Methods: This multicentre, randomised, double-blind, placebo-controlled trial compared 24 weeks of ginseng capsules (100 mg twice daily) with placebo. Participants were followed up for a further 24 weeks. Participants were aged 40 years and over and had airflow limitation in the moderate (Global Initiative for Chronic Obstructive Lung Disease 2) COPD range. The coprimary endpoints were the St George's Respiratory Questionnaire, the COPD Assessment Test and the Short Form Health Survey. Secondary outcomes included lung function, exacerbation rate and use of relief medication., Findings: 168 participants were randomised 1:1 from five centres in Australia and China. Baseline characteristics were balanced between groups. There were no significant differences between ginseng and placebo, with overall results improving in both groups. Ginseng seemed safe for, and well tolerated by, people with COPD., Interpretation: There was no significant difference in improvement in health-related quality of life (primary outcome) between the ginseng and placebo groups., Trial Registration Number: ACTRN12610000768099., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Bronchial thermoplasty (BT) has been consistently shown to reduce symptoms, exacerbations and the need for reliever medication in patients with severe asthma. Paradoxically, no consistent improvement in spirometry has been demonstrated. It has been suggested that this is due to a reduction in peripheral resistance in small airways, not captured by spirometry. Therefore, in this study, we evaluate the response to BT using oscillometry., Methods: A total of 43 patients with severe asthma from two centres were evaluated at baseline, 6 weeks and 6 months post BT, using spirometry, plethysmography and oscillometry, in addition to medication usage, exacerbation frequency and the Asthma Control Questionnaire (5-item version) (ACQ-5)., Results: The mean age was 58.4 ± 11.2 years, forced expiratory volume in 1 s (FEV 1 ) 55.5 ± 20.1% predicted, forced expiratory ratio 53.0 ± 14.5% and FEV 1 response to salbutamol was 14.0 ± 14.5%. Following BT, the group responded to treatment with an improvement in ACQ-5 from 2.9 ± 0.9 at baseline to 1.7 ± 1.1 at 6 months (P < 0.005). There was an 81% reduction in exacerbation frequency (P < 0.001) and 50% of patients were weaned completely from maintenance oral corticosteroids. No changes after treatment were observed in spirometry but the residual volume reduced from 147 ± 38% to 139 ± 39% predicted (P < 0.01). Baseline oscillometry demonstrated high levels of resistance at 5 Hz with normal resistance at 20 Hz, indicating resistance in the small airways was elevated, but no changes were observed in any oscillometry parameter after BT treatment., Conclusion: Lung impedance measured with oscillometry did not change following BT despite marked clinical improvements in patients with severe asthma., (© 2018 Asian Pacific Society of Respirology.)

Derecruitment of air spaces in the lung occurs when airways close during exhalation and is related to ventilation heterogeneity and symptoms in asthma. The forced oscillation technique has been used to identify surrogate measures of airway closure via the reactance (Xrs) versus lung volume relationship. This study used a new algorithm to identify derecruitment from the Xrs versus lung volume relationship from a slow vital capacity maneuver. We aimed to compare two derecruitment markers on the Xrs versus volume curve, the onset reduction of Xrs (DR1 vol ) and the onset of more rapid reduction of Xrs (DR2 vol ), between control and asthmatic subjects. We hypothesized that the onset of DR1 vol and DR2 vol occurred at higher lung volume in asthmatic subjects. DR1 vol and DR2 vol were measured in 18 subjects with asthma and 18 healthy controls, and their relationships with age and height were examined using linear regression. In the control group, DR1 vol and DR2 vol increased with age ( r 2  = 0.68, P < 0.001 and r 2  = 0.71, P < 0.001, respectively). DR1 vol and DR2 vol in subjects with asthma [76.58% of total lung capacity (TLC) and 56.79%TLC, respectively] were at higher lung volume compared with control subjects (46.1 and 37.69%TLC, respectively) ( P < 0.001). DR2 vol correlated with predicted values of closing capacity ( r  = 0.94, P < 0.001). This study demonstrates that derecruitment occurs at two points along the Xrs-volume relationship. Both derecruitment points occurred at significantly higher lung volumes in subjects with asthma compared with healthy control subjects. This technique offers a novel way to measure the effects of changes in airways/lung mechanics. NEW & NOTEWORTHY This study demonstrates that the forced oscillation technique can be used to identify two lung volume points where lung derecruitment occurs: 1 ) where derecruitment is initiated and 2 ) where onset of rapid derecruitment commences. Measurements of derecruitment increase with age. The onset of rapid derecruitment was highly correlated with predicted closing capacity. Also, the initiation and rate of derecruitment are significantly altered in subjects with asthma.

Objective: To assess the association between the use of a flowchart incorporating Wells score, PERC rule and age-adjusted D-dimer and subsequent imaging and yield rates of computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion scans being ordered in the ED for the assessment of pulmonary embolism., Methods: A flowchart governing ED pulmonary embolism investigation was introduced across three EDs in Melbourne, Australia for a 12 month period. Comparison of pulmonary embolism imaging rates and yield with the preceding 12 months was performed., Results: A total of 1815 pre-implementation scans were performed compared with 1116 scans post-implementation. Because of growth in patient attendances over this time, this equated to an imaging rate of 14.5 per 1000 presentations pre-implementation and 8.6 per 1000 presentations post-implementation (P < 0.001). Overall pulmonary embolism imaging yield rates rose from 9.9% to 16.5% (P < 0.001). A total of 179 pre-implementation pulmonary embolisms were identified, with an incidence of 1.4 per 1000 presentations. This compared to 184 pulmonary embolisms post-implementation, with an incidence of 1.4 per 1000 presentations (P = 0.994)., Conclusion: The introduction of a clinical flowchart incorporating Wells score, PERC rule and age-adjusted D-dimer was associated with an increase in ED computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion yield rate from 9.9% to 16.5% across the three enrolment hospitals when investigating possible pulmonary embolism. This corresponded to a 40% relative reduction in pulmonary embolism imaging. Diagnosis rates remained unchanged and no cases of missed pulmonary embolism attributable to the flowchart were identified., (© 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Background: Epidemic thunderstorm asthma (ETSA) refers to large-scale acute bronchospasm events associated with thunderstorm. The most serious episode ever recorded occurred in Melbourne, Australia, in November 2016, where more than 3500 patients were treated in hospitals and 10 died. Previous work has been focused primarily on patient presentations to emergency departments. The prevalence of individuals with milder, non-emergent symptoms and who may be at risk of more serious episodes in the future has not previously been explored., Aim: To characterise the nature and extent of respiratory symptoms in healthcare workers during the Melbourne ETSA event., Methods: A survey was conducted among staff and volunteers across Eastern Health, distributed on the intranet homepage, by email and by word of mouth. Anonymous survey questions were constructed to assess prior and current diagnoses of relevance, symptoms, and demography., Results: There were 515 participants (80% female, n = 411) of approximately 9000 potential respondents (~6% response rate) who completed the survey; 132 (25.6%) had symptoms suggestive of asthma during the Melbourne ETSA event, the majority of whom did not seek professional medical help. Notably, of those with ETSA-like symptoms, only 58 (43.9%) had a history of asthma, while 97 (73.5%) had a history of allergic rhinitis. Specifically, a history of allergic rhinitis (OR 2.77, P < 0.001), a history of asthma (OR 1.67, P = 0.037) and being of self-identified Asian ethnicity (OR 3.24, P < 0.001) were all strong predictors of ETSA-like symptoms. Being predominantly indoors was not protective., Conclusions: Our study provides evidence of the presence of a large cohort of sufferers during the Melbourne ETSA event of 2016 that did not come to the attention of medical services, implying a potentially hidden and significant susceptible population. Further research should help clarify the true prevalence of vulnerability in the general population, with important public health implications., (© 2018 Royal Australasian College of Physicians.)

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 and Objective: A characteristic feature of asthma is hypertrophied airway smooth muscle, responsible for bronchoconstriction. This is the target of bronchial thermoplasty (BT). It is known that with increasing time and severity some patients develop remodelled airways with fixed airflow obstruction. The question arises whether these patients will still respond to BT., Methods: Forty-nine consecutive severe asthmatic patients were prospectively evaluated at baseline and then 6 months after BT. The characteristics recorded included medication usage, exacerbation history, spirometry and the Asthma Control Questionnaire 5-Item Version score (ACQ-5). Seven patients were excluded as they did not demonstrate airflow obstruction at baseline (forced expiratory ratio (forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC)) < 70%). The remaining 42 patients were divided into two cohorts based on their response to bronchodilator. Eighteen patients in whom the FEV 1 improved by at least 12% and 200 mL following bronchodilator were allocated to Group 1 (reversible). The remaining patients were allocated to Group 2 (fixed). The outcomes following BT in these two groups were then compared., Results: The patient age was 57.2 ± 12.4 years, the ACQ-5 was 3.2 ± 1.0 and the FEV 1 56.0 ± 16.4% predicted. At baseline, the patient cohorts were very similar, save for the response to bronchodilator, which was 28.1 ± 12.5% in Group 1 and 4.1 ± 5.3% in Group 2. Both groups responded to BT equally well, with significant improvements in ACQ-5, salbutamol usage, exacerbation frequency and the weaning of oral corticosteroids., Conclusion: In patients with severe asthma, the presence or absence of variable airflow obstruction as measured by spirometry does not appear to influence outcomes from BT., (© 2018 Asian Pacific Society of Respirology.)

Background: A significant correlation has been previously demonstrated between the quantum of radiofrequency treatment delivered at bronchial thermoplasty and the degree of improvement in an asthmatic patient's symptoms. The standard bronchoscope used for bronchial thermoplasty has an outer diameter of 4.8 mm at the distal tip. Thinner bronchoscopes are now available with the same internal channel size (2.0 mm). This study assesses whether using a thinner bronchoscope facilitates bronchial thermoplasty by increasing the radiofrequency activations delivered., Patients and Methods: This was a sequential study in a single center, conducted in 27 patients with very severe asthma. The first 12 patients (Group 1) underwent bronchial thermoplasty using the standard bronchoscope, Olympus BF-Q190. In the next group of eight patients (Group 2), the standard bronchoscope was used for all procedures except the left upper lobe, while the left upper lobe was treated with a smaller bronchoscope, Olympus BF-P190, with an outer diameter of 4.2 mm. In the last group of seven patients (Group 3), the smaller bronchoscope was used for every lobe. The quantum of radiofrequency treatment was measured by activations delivered to each lung lobe in each patient, and patient groups were compared by ANOVA., Results: In this group of 27 patients, the mean age was 56.5±12.9 years, the mean Asthma Control Questionnaire-5 item version score was 3.2±1.0 and the mean FEV 1 % predicted was 55.2±15.7. Bronchial thermoplasty treatment resulted in significant improvements in predicted Asthma Control Questionnaire-5 item version score (to 1.8±1.3, P <0.005), salbutamol rescue usage and oral corticosteroid requiring exacerbations, with no significant change in lung function. Use of the smaller bronchoscope resulted in greater radiofrequency treatment (total activations Group 1: 155±21, Group 2: 176±46, Group 3: 213±37; P <0.01). There were no significant differences in efficacy or safety outcomes among groups., Conclusion: Using a thinner bronchoscope facilitates access to the bronchial tree and increases the radiofrequency treatment delivered at bronchial thermoplasty., Competing Interests: Disclosure DL was the recipient of a postgraduate scholarship from Monash University. The authors report no other conflicts of interest in this work.

Background: There is increasing interest in the role of traffic-related air pollution (TRAP) in allergic airway diseases. Few studies investigate the relationship between TRAP exposure and acute exacerbations of asthma., Objective: The 2016 Melbourne thunderstorm asthma epidemic provided an opportunity to investigate the relationship between proxies of TRAP exposure and asthma exacerbation requiring urgent healthcare in the previous 12 months., Methods: Current asthmatics who presented to the 3 Emergency Departments of Melbourne's second-largest health service with epidemic thunderstorm asthma in November 2016 were identified and completed a standard questionnaire. Their residential addresses were geocoded and the annual average nitrogen dioxide (NO 2 ) exposure for each patient was assigned using a validated satellite-based land use regression model. Residential distance to the nearest major road was calculated using ArcGIS. Multivariate logistic regression was used to investigate the relationship between each TRAP proxy and healthcare use, adjusting for potential confounders., Results: From 263 thunderstorm asthma patients, 88 patients identified with current asthma were analysed. Those with higher mean annual residential NO 2 exposure had greater odds of urgent healthcare use in the previous year (odds ratio [OR], 3.45 per one interquartile-range increase; 95% confidence interval [CI], 1.31-9.10; p = 0.01), however distance from major road (OR, 0.95 per 100-m increase; 95% CI, 0.80-1.13; p = 0.57) and living <200 m from a major road (OR, 1.47; 95% CI, 0.29-7.45; p = 0.64) were not significantly associated., Conclusion: In current asthmatics who presented during an epidemic thunderstorm asthma event, greater exposure to residential NO 2 was significantly associated with greater odds of asthma exacerbations requiring urgent healthcare in the previous 12 months.

Airway closure has proved to be important in a number of respiratory diseases and may be the primary functional defect in asthma. A surrogate measure of closing volume can be identified using the forced oscillation technique (FOT), by performing a deflation maneuver and examining the resultant reactance (Xrs) lung volume relationship. This study aims to determine if a slow vital capacity maneuver can be used instead of this deflation maneuver and compare it to existing more complex techniques. Three subject groups were included in the study; healthy (n = 29), asthmatic (n = 18), and COPD (n = 10) for a total of 57 subjects. Reactance lung volume curves were generated via FOT recordings during two different breathing manoeuvres (both pre and post bronchodilator). The correlation and agreement between surrogate closing volume (Vol crit ) and reactance (Xrs crit ) at this volume was analysed. The changes in Vol crit and Xrs crit pre and post bronchodilator were also analysed. Across all three subject groups, the two different measures of Vol crit were shown to be statistically equivalent (p > 0.05) and demonstrated a strong fit to the data (R 2  = 0.49, 0.78, 0.59, for asthmatic, COPD and healthy subject groups, respectively). A bias was evident between the two measurements of Xrs crit with statistically different means (p < 0.05). However, the two measurements of Xrs crit displayed the same trends. In conclusion, we have developed an alternative technique for measuring airway closure from FOT recordings. The technique delivers equivalent and possibly more sensitive results to previous methods while being simple and easily performed by the patient.

Background: In randomized controlled trials, bronchial thermoplasty (BT) has been proven to reduce symptoms in severe asthma, but the mechanisms by which this is achieved are uncertain as most studies have shown no improvement in spirometry. We postulated that BT might improve lung mechanics by altering airway resistance in the small airways of the lung in ways not measured by FEV 1 . This study aimed to evaluate changes in measures of gas trapping by body plethysmography., Methods: A prospective cohort of 32 consecutive patients with severe asthma who were listed for BT at two Australian university hospitals were evaluated at three time points, namely baseline, and then 6 weeks and 6 months post completion of all procedures. At each evaluation, medication usage, symptom scores (Asthma Control Questionnaire, ACQ-5) and exacerbation history were obtained, and lung function was evaluated by (i) spirometry (ii) gas diffusion (KCO) and (iii) static lung volumes by body plethysmography., Results: ACQ-5 improved from 3.0 ± 0.8 at baseline to 1.5 ± 0.9 at 6 months (mean ± SD, p < 0.001, paired t-test). Daily salbutamol usage improved from 8.3 ± 5.6 to 3.5 ± 4.3 puffs per day (p < 0.001). Oral corticosteroid requiring exacerbations reduced from 2.5 ± 2.0 in the 6 months prior to BT, to 0.6 ± 1.3 in the 6 months after BT (p < 0.001). The mean baseline FEV 1 was 57.8 ± 18.9%predicted, but no changes in any spirometric parameter were observed after BT. KCO was also unaltered by BT. A significant reduction in gas trapping was observed with Residual Volume (RV) falling from 146 ± 37% predicted at baseline to 136 ± 29%predicted 6 months after BT (p < 0.005). Significant improvements in TLC and FRC were also observed. These changes were evident at the 6 week time period and maintained at 6 months. The change in RV was inversely correlated with the baseline FEV 1 (r = 0.572, p = 0.001), and in patients with a baseline FEV 1 of < 60%predicted, the RV/TLC ratio fell by 6.5 ± 8.9%., Conclusion: Bronchial thermoplasty improves gas trapping and this effect is greatest in the most severely obstructed patients. The improvement may relate to changes in the mechanical properties of small airways that are not measured with spirometry.

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: The most common adverse effect of bronchial thermoplasty (BT) is short-term aggravation of asthma immediately following the procedure. However, the magnitude and duration of this deterioration, and its predisposing factors are yet to be quantitated. This information will be particularly important as BT is extended to include more severely obstructed patients., Methods: In this prospective, observational study of 20 consecutive patients with very severe asthma undergoing BT, post bronchodilator FEV 1 was measured in the 30 min prior to surgery, and then 24 h following the 60 procedures. In half the patients, further spirometry was conducted on day 3 and day 7 post procedure., Results: This study enrolled 12 males and 8 females, mean age 59.7 ± 12.8 years, with mean prebronchodilator FEV 1 of 52.3 ± 15.2% predicted, mean forced expiratory ratio of 51.4 ± 12.6%, and mean improvement in FEV 1 post salbutamol of 19.5 ± 15.3%. All patients were taking inhaled corticosteroids, mean beclomethasone equivalent dose 1950 ± 857 mcg, and 7 patients required maintenance oral corticosteroids for control of their asthma. Twenty four hours after BT, the mean deterioration in post bronchodilator FEV 1 was 166 ± 237 mls (CI 102-224, p < 0.001) or 9.1 ± 15.2% of baseline. This deterioration was significantly greater after upper lobe procedures (p < 0.01, ANOVA repeated measures), where a mean fall in FEV 1 of 17.1 ± 12.6% was observed. The change in FEV 1 post procedure was significantly correlated with the number of radiofrequency activations applied, r = -0.376, p < 0.005. By multivariate analysis, the only factor other than activations predictive of the change in FEV 1 was age, which was protective. When the lower lobes were treated, the postbronchodilator FEV 1 had returned to baseline values by day 3, but patients took 7 days to recover after upper lobe treatments. Despite the severity of asthma in these patients, and the measured deterioration post treatment, there was only one instance of readmission in the 60 procedures., Conclusions: The deterioration in lung function after BT is transient and well tolerated, but is greatest after upper lobe treatment, and is significantly related to the number of radiofrequency activations applied., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rationale: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes., Objectives: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease., Methods: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit., Measurements and Main Results: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m 2 ), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m 2 /yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings., Conclusions: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).

Background: On 21st November 2016, Melbourne experienced an epidemic of 'thunderstorm asthma.' Although previously described in the literature, risk factors and natural history remain incompletely understood., Objective: Our aim was to follow up those presenting to the 3 Emergency Departments (EDs) in our health service during the epidemic, and assess their history for previous asthma, rhinitis, and allergies., Methods: ED notes of all respiratory presentations within 48 hours of the thunderstorm event were reviewed and patients with acute asthma included. A standardised questionnaire was devised encompassing asthma diagnosis, undiagnosed asthma symptoms and rhinitis severity. Patients were contacted by phone within 30 days of the event., Results: Three hundred forty-four patients were identified overall; 263 patients were contactable and completed a phone or mail questionnaire. The mean age was 32.7 ± 19.2 years (range, 6 months-87 years; 25% < 18 years) with 58% male sex. A previous diagnosis of asthma was present in 42% (n = 111), and there was no previous asthma diagnosis in 58% (n = 152). Of those who had no asthma diagnosis 53% had probable undiagnosed asthma. Overall, rhinitis prevalence was 88%, of which 72% were moderate or severe (Allergic Rhinitis and its Impact on Asthma guidelines) and 51% (n = 133) reported a history of grass pollen allergy., Conclusion: Our data highlights the importance of atopy and rhinitis as risk factors for epidemic thunderstorm asthma. Better identification of undiagnosed asthma, and implementing treatment of asthma and rhinitis may be important.

Background: Bronchial thermoplasty (BT) is an emerging bronchoscopic intervention for the treatment of severe asthma. The predictive factors for clinical response to BT are unknown. We examined the relationship between the number of radiofrequency activations applied and the treatment response observed., Methods: Data were collected from 24 consecutive cases treated at three Australian centres from June 2014 to March 2016. The baseline characteristics were collated along with the activations delivered. The primary response measure was change in the Asthma Control Questionnaire-5 (ACQ-5) score measured at 6 months post BT. The relationship between change in outcome parameters and the number of activations delivered was explored., Results: All patients met the ERS/ATS definition for severe asthma. At 6 months post treatment, mean ACQ-5 improved from 3.3 ± 1.1 to 1.5 ± 1.1, p < 0.001. The minimal clinically significant improvement in ACQ-5 of ≥0.5 was observed in 21 out of 24 patients. The only significant variable that differed between the 21 responders and the three non-responders was the number of activations delivered, with 139 ± 11 activations in the non-responders, compared to 221 ± 45 activations in the responders (p < 0.01). A significant inverse correlation was found between change in ACQ-5 score and the number of activations, r = -0.43 (p < 0.05)., Conclusions: The number of activations delivered during BT has a role in determining clinical response to treatment.

Opinion Statement: Allergy testing has been advocated for patients with eosinophilic esophagitis (EoE) as a means of defining food triggers and directing dietary therapy. Several recent and comprehensive studies have demonstrated the futility of skin prick (SPT), skin patch (APT) and serum food antigen specific IgE (SIgE) estimates in this context. Furthermore, if identification of food triggers is the endpoint (as opposed to the ability of an allergy test-directed diet merely to induce remission), previous positive studies have limitations. Evolving evidence that EoE may be a non-IgE-mediated disease has led to trials of new assays including serum IgG to food allergens, the cytokine thymic stromal lymphopoietin (TSLP) and basophil activation, all without success. Rather than using allergy test-directed diets, the clinician should use empirical elimination diets which are practical, and consider minimally invasive sampling of the oesophagus to facilitate dietary reintroduction. Research should be redoubled to consider not only assays to predict food triggers but also those that monitor disease activity. The anti-inflammatory effect of proton pump inhibitors and deficits in barrier integrity may influence the success of dietary therapy and the results of allergy tests and should be considered in future research design.

Eosinophilic esophagitis (EoE) is now considered to represent a form of food allergy and this is demonstrated by a response to elimination diet in many patients. A critical additional factor may be an inherent impairment in epithelial barrier integrity, possibly worsened by reflux of gastric contents and improved with proton pump inhibitor (PPI) use. Key clinic challenges are posed by the absence of reliable allergy tests to guide elimination diet, and the subsequent need for invasive endoscopic assessment following empirical food challenge, meaning that corticosteroids will remain the mainstay of therapy for many. From a research standpoint, determining if impairments in barrier integrity are innate, and how PPIs address this deficit (which may be pH independent) are important questions that when answered may allow future therapeutic advancement.

Background: Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE)., Aim: To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm., Methods: Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group)., Results: Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission., Conclusions: Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed., (© 2016 John Wiley & Sons Ltd.)

Rationale: To determine whether spirometry and regular medical review improved quality of life or other outcomes in children and adolescents with asthma., Methods: We conducted two cluster randomized controlled trials. We recruited 238 asthma patients aged between 7 and 17 years from 56 general practices in South Eastern Australia. Participants were randomized to receive an intervention that included spirometry or usual care. The main outcome measure was asthma related quality of life., Results: Baseline characteristics were well matched between the intervention and control groups. Neither trial found any difference in asthma related quality of life between groups. However because of measurement properties, a formal meta-analysis could not be performed. Nor were there any significant effects of the intervention upon asthma attacks, limitation to usual activities, nocturnal cough, bother during physical activity, worry about asthma, or written asthma action plans., Conclusions: The findings do not support more widespread use of spirometry for the management of childhood asthma in general practice, unless it is integrated into a complete management model., (© 2014 Wiley Periodicals, Inc.)