Mechanical computing.

Mechanical mechanisms have been used to process information for millennia, with famous examples ranging from the Antikythera mechanism of the Ancient Greeks to the analytical machines of Charles Babbage. More recently, electronic forms of computation and information processing have overtaken these mechanical forms, owing to better potential for miniaturization and integration. However, several unconventional computing approaches have recently been introduced, which blend ideas of information processing, materials science and robotics. This has raised the possibility of new mechanical computing systems that augment traditional electronic computing by interacting with and adapting to their environment. Here we discuss the use of mechanical mechanisms, and associated nonlinearities, as a means of processing information, with a view towards a framework in which adaptable materials and structures act as a distributed information processing network, even enabling information processing to be viewed as a material property, alongside traditional material properties such as strength and stiffness. We focus on approaches to abstract digital logic in mechanical systems, discuss how these systems differ from traditional electronic computing, and highlight the challenges and opportunities that they present.

Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma.

Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6, and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations, and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.We identified three trajectory groups: group 1, responsive asthma with less OCS use (n=170); group 2, responsive late-onset asthma (n=58); and group 3, obstructed and less responsive asthma (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to group 3 with 5.7% (p <0.001). Baseline predictors for assigned groups included lower OCS dose in group 1; greater FEV1% predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose, and nasal polyps in group 2; with group 3 as the reference.Treatment response to mepolizumab in severe eosinophilic asthma follows 3 trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.

Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Lagrangian approach to origami vertex analysis: kinematics.

The use of origami in engineering has significantly expanded in recent years, spanning deployable structures across scales, folding robotics and mechanical metamaterials. However, finding foldable paths can be a formidable task as the kinematics are determined by a nonlinear system of equations, often with several degrees of freedom. In this article, we leverage a Lagrangian approach to derive reduced-order compatibility conditions for rigid-facet origami vertices with reflection and rotational symmetries. Then, using the reduced-order conditions, we derive exact, multi-degree of freedom solutions for degree 6 and degree 8 vertices with prescribed symmetries. The exact kinematic solutions allow us to efficiently investigate the topology of allowable kinematics, including the consideration of a self-contact constraint, and then visually interpret the role of geometric design parameters on these admissible fold paths by monitoring the change in the kinematic topology. We then introduce a procedure to construct lower-symmetry kinematic solutions by breaking symmetry of higher-order kinematic solutions in a systematic way that preserves compatibility. The multi-degree of freedom solutions discovered here should assist with building intuition of the kinematic feasibility of higher-degree origami vertices and also facilitate the development of new algorithmic procedures for origami-engineering design.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Thunderstorm asthma in seasonal allergic rhinitis: The TAISAR study.

BACKGROUND: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. OBJECTIVE: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. METHODS: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR. RESULTS: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV1 value of 90% or lower to be biomarkers of increased H-TA risk. CONCLUSION: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

A nurse-led Asthma Care Team transitioning patients from hospital to home improves asthma control: A pilot study exploring an alternative model of care.

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

Origami mechanologic.

Robots autonomously interact with their environment through a continual sense-decide-respond control loop. Most commonly, the decide step occurs in a central processing unit; however, the stiffness mismatch between rigid electronics and the compliant bodies of soft robots can impede integration of these systems. We develop a framework for programmable mechanical computation embedded into the structure of soft robots that can augment conventional digital electronic control schemes. Using an origami waterbomb as an experimental platform, we demonstrate a 1-bit mechanical storage device that writes, erases, and rewrites itself in response to a time-varying environmental signal. Further, we show that mechanical coupling between connected origami units can be used to program the behavior of a mechanical bit, produce logic gates such as AND, OR, and three input majority gates, and transmit signals between mechanologic gates. Embedded mechanologic provides a route to add autonomy and intelligence in soft robots and machines.

Mepolizumab effectiveness and identification of super-responders in severe asthma.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission.

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.

Origami-Inspired Frequency Selective Surface with Fixed Frequency Response under Folding.

Filtering of electromagnetic signals is key for improved signal to noise ratios for a broad class of devices. However, maintaining filter performance in systems undergoing large changes in shape can be challenging, due to the interdependency between element geometry, orientation and lattice spacing. To address this challenge, an origami-based, reconfigurable spatial X-band filter with consistent frequency filtering is presented. Direct-write additive manufacturing is used to print metallic Archimedean spiral elements in a lattice on the substrate. Elements in the lattice couple to one another and this results in a frequency selective surface acting as a stop-band filter at a target frequency. The lattice is designed to maintain the filtered frequency through multiple fold angles. The combined design, modeling, fabrication, and experimental characterization results of this study provide a set of guidelines for future design of physically reconfigurable filters exhibiting sustained performance.

X-ray nanotomography and focused-ion-beam sectioning for quantitative three-dimensional analysis of nanocomposites.

Knowing the relationship between three-dimensional structure and properties is paramount for complete understanding of material behavior. In this work, the internal nanostructure of micrometer-size (∼10 µm) composite Ni/Al particles was analyzed using two different approaches. The first technique, synchrotron-based X-ray nanotomography, is a nondestructive method that can attain resolutions of tens of nanometers. The second is a destructive technique with sub-nanometer resolution utilizing scanning electron microscopy combined with an ion beam and `slice and view' analysis, where the sample is repeatedly milled and imaged. The obtained results suggest that both techniques allow for an accurate characterization of the larger-scale structures, while differences exist in the characterization of the smallest features. Using the Monte Carlo method, the effective resolution of the X-ray nanotomography technique was determined to be ∼48 nm, while focused-ion-beam sectioning with `slice and view' analysis was ∼5 nm.

Coexisting atopic conditions influence the likelihood of allergic bronchopulmonary aspergillosis in asthma.

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in asthma is often made in patients with total serum IgE levels greater than 1,000 IU/mL in conjunction with evidence of Aspergillus sensitization. The specificity of total serum IgE for the diagnosis of ABPA is low even when combined with serum Aspergillus specific IgE. OBJECTIVE: To determine the prevalence of ABPA and to identify alternative clinical predictors for ABPA among asthmatic patients with a total serum IgE level greater than 1,000 IU/ml. METHODS: This study was conducted in a tertiary hospital in Melbourne, Australia, with a large asthma and allergy service. Patients with asthma and total serum IgE levels greater than 1,000 IU/ml from January 1, 2005, through December 31, 2014, were included. Patients were considered to have concomitant allergic conditions if they had atopic eczema, allergic rhinitis, or both. The diagnosis of ABPA was based on the managing physician's documented diagnosis and referenced to criteria proposed by the International Society for Human and Fungal Mycology. RESULTS: The prevalence of ABPA in our cohort was 15.8%. Older age, elevated total serum IgE level, reduced lung function, and the absence of other concomitant allergic conditions increased the risk of ABPA. After multivariate logistic regression, patients without concomitant allergic conditions had an odds ratio of 4.4 (95% confidence interval, 1.9-10.1; P = .001) for ABPA when compared with patients with allergic conditions. CONCLUSION: The absence of atopic eczema and allergic rhinitis in these patients increases the likelihood of ABPA. Eliciting an accurate allergy history may be a useful bedside clinical tool when considering the diagnosis of ABPA.

Wearable high-density EMG sleeve for complex hand gesture classification and continuous joint angle estimation.

High-density electromyography (HD-EMG) can provide a natural interface to enhance human-computer interaction (HCI). This study aims to demonstrate the capability of a novel HD-EMG forearm sleeve equipped with up to 150 electrodes to capture high-resolution muscle activity, decode complex hand gestures, and estimate continuous hand position via joint angle predictions. Ten able-bodied participants performed 37 hand movements and grasps while EMG was recorded using the HD-EMG sleeve. Simultaneously, an 18-sensor motion capture glove calculated 23 joint angles from the hand and fingers across all movements for training regression models. For classifying across the 37 gestures, our decoding algorithm was able to differentiate between sequential movements with 97.3 ± 0.3 % accuracy calculated on a 100 ms bin-by-bin basis. In a separate mixed dataset consisting of 19 movements randomly interspersed, decoding performance achieved an average bin-wise accuracy of 92.8 ± 0.8 % . When evaluating decoders for use in real-time scenarios, we found that decoders can reliably decode both movements and movement transitions, achieving an average accuracy of 93.3 ± 0.9 % on the sequential set and 88.5 ± 0.9 % on the mixed set. Furthermore, we estimated continuous joint angles from the EMG sleeve data, achieving a R 2 of 0.884 ± 0.003 in the sequential set and 0.750 ± 0.008 in the mixed set. Median absolute error (MAE) was kept below 10° across all joints, with a grand average MAE of 1.8 ± 0 . 04 ∘ and 3.4 ± 0 . 07 ∘ for the sequential and mixed datasets, respectively. We also assessed two algorithm modifications to address specific challenges for EMG-driven HCI applications. To minimize decoder latency, we used a method that accounts for reaction time by dynamically shifting cue labels in time. To reduce training requirements, we show that pretraining models with historical data provided an increase in decoding performance compared with models that were not pretrained when reducing the in-session training data to only one attempt of each movement. The HD-EMG sleeve, combined with sophisticated machine learning algorithms, can be a powerful tool for hand gesture recognition and joint angle estimation. This technology holds significant promise for applications in HCI, such as prosthetics, assistive technology, rehabilitation, and human-robot collaboration.

Dupilumab-associated hypereosinophilia in severe asthma.

Dupilumab has been associated with adverse reactions including symptomatic hypereosinophilia. This study reports the incidence of dupilumab-related eosinophilia and adverse reactions in severe asthma patients at an Australian tertiary centre. https://bit.ly/3JgZ5Ya.

Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma.

BACKGROUND: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. OBJECTIVE: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. METHODS: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. RESULTS: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/µL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. CONCLUSIONS: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Plasmon-Mediated Chiroptical Second Harmonic Generation from Seemingly Achiral Gold Nanorods.

Throughout nature, simple rules explain complex phenomena, such as the selective interaction of chiral objects with circularly polarized light. Here, we demonstrate chiroptical signals from gold nanorods, which are seemingly achiral structures. Shape anisotropy due to atomic-level faceting and rounding at the tips of nanorods, which are free of chiral surface ligands, induces linear-to-circular polarization modulation during second harmonic generation. The intrinsic nanorod chiroptical response is increased by plasmon-resonant excitation, which preferentially amplifies circularly polarized harmonic signals. This structure-plasmon interplay is uniquely resolved by polarization-resolved second harmonic generation measurements. The material's second-order polarizability is the product of the structure-dependent lattice-normal susceptibility and local surface plasmon field vectors. Synthetically scalable plasmon-supporting nanorods that amplify small circular dichroism signals provide a simple, assembly-free platform for chiroptical transduction.

Mepolizumab and Oral Corticosteroid Stewardship: Data from the Australian Mepolizumab Registry.

BACKGROUND: Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship. OBJECTIVES: This study evaluated the trajectories of OCS exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy. METHODS: This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225). RESULTS: Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P < .001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P < .001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227). CONCLUSION: Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives.

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

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/m3). 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.

Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma. OBJECTIVE: The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial. METHODS: Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry. RESULTS: Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo. CONCLUSION: Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels.