A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection.

Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1-4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01-peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.

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.

Patterns of care for people with small cell lung cancer in Victoria, 2011-19: a retrospective, population-based registry data study.

OBJECTIVES: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC). DESIGN: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR). SETTING, PARTICIPANTS: All people diagnosed with SCLC in Victoria during 1 April 2011 - 18 December 2019. MAIN OUTCOME MEASURES: Stage-specific management and treatment of people with SCLC; median survival time. RESULTS: During 2011-19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range [IQR], 62-77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I-III, 268 [30%]; TNM stage IV, 628 [70%]) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 [49%]; 2-4, 174 [17%]). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2-16 months; stage I-III: 16.3 [IQR, 9.3-30] months; stage IV: 7.2 [IQR, 3.3-12] months). Multidisciplinary meeting presentation (hazard ratio [HR], 0.66; 95% CI, 0.58-0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36-0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48-0.94) were each associated with lower mortality during follow-up. CONCLUSION: Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC-specific management and outcomes data could improve the quality and safety of care.

Safety and efficacy of bronchial thermoplasty in Australia 5 years post-procedure.

BACKGROUND AND OBJECTIVE: Outside clinical trials, there is limited long-term data following bronchial thermoplasty (BT). In a cohort of real-world severe asthmatics in an era of biological therapy, we sought to evaluate the safety and efficacy of BT 5 years post-treatment. METHODS: Every patient treated with BT at two Australian tertiary centres were recalled at 5 years, and evaluated by interview and record review, Asthma Control Questionnaire (ACQ), spirometry and high-resolution CT Chest. CT scans were interpreted using the modified Reiff and BRICS CT scoring systems for bronchiectasis. RESULTS: Fifty-one patients were evaluated. At baseline, this cohort had a mean age of 59.0 ± 11.8 years, mean ACQ of 3.0 ± 1.0, mean FEV1 of 55.5 ± 18.8% predicted, and 53% were receiving maintenance oral steroids in addition to triple inhaler therapy. At 5 years, there was a sustained improvement in ACQ scores to 1.8 ± 1.0 (p < 0.001). Steroid requiring exacerbation frequency was reduced from 3.8 ± 3.6 to 1.0 ± 1.6 exacerbations per annum (p < 0.001). 44% of patients had been weaned off oral steroids. No change in spirometry was observed. CT scanning identified minor degrees of localized radiological bronchiectasis in 23/47 patients with the modified Reiff score increasing from 0.6 ± 2.6 at baseline to 1.3 ± 2.5 (p < 0.001). However, no patients exhibited clinical features of bronchiectasis, such as recurrent bacterial infection. CONCLUSION: Sustained clinical benefit from BT at 5 years was demonstrated in this cohort of very severe asthmatics. Mild, localized radiological bronchiectasis was identified in a portion of patients without clinical features of bronchiectasis.

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics.

BACKGROUND AND OBJECTIVE: This study compared the clinical outcomes of severe asthmatics treated with mepolizumab and benralizumab in a tertiary care severe asthma service setting. METHODS: Patient data at baseline, six and 12 months were collected prospectively at two large tertiary hospital severe asthma clinics following treatment initiation. Two hundred and four patients received treatment with mepolizumab (117) or benralizumab (87). Baseline characteristics between groups were similar in regard to age, gender, body mass index, steroid dose and blood eosinophil count. However, the mepolizumab cohort had a higher Asthma Control Questionnaire Score (ACQ) at baseline (4.0 ± 1.1 vs. 3.6 ± 0.9, p = 0.018), accompanied by more frequent reliever medication usage and lower prebronchodilator FEV1 % (56.0 ± 20.1 vs. 63.8 ± 18.9, p = 0.008). RESULTS: After 6 months treatment, both treatments induced significant improvements in (i) ACQ of 2.3 ± 0.1 (p < 0.001), (ii) oral steroid requiring exacerbations (incident rate ratio 0.26 (0.18-0.37), p < 0.001) and (iii) FEV1 . However, the improvement in FEV1 was 0.18 (0.05-0.30) litres greater with benralizumab than with mepolizumab (p = 0.002) even when adjusting statistically for baseline differences between groups. These differences were even more pronounced at 12 months post-treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64% greater than with mepolizumab (p = 0.01). Whilst both treatments significantly reduced the blood eosinophil count at 6 and 12 months, this reduction was substantially greater with benralizumab than mepolizumab (-260 cells/µL [-400 to -110, p = 0.001]). CONCLUSION: In this large group of severe eosinophilic asthmatics, mepolizumab and benralizumab both improved disease parameters. However, benralizumab treatment appeared significantly more effective than mepolizumab in reducing exacerbations, improving FEV1 and depleting blood eosinophils.

Safety of delivering bronchial thermoplasty in two treatment sessions.

BACKGROUND: Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach. METHODS: Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment. RESULTS: The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p < 0.001). ICU monitoring was required on 5 occasions with ABT (16.1%), compared to 0.9% with CBT (p = 0.002). Subgroup analysis demonstrated that females were more likely to require prolonged admission (OR 11.6, p = 0.0025). The 30-day hospital readmission rate was similar for both groups (6.4% vs 5.4%, p = 0.67). All patients made a complete recovery after treatment with similar outcomes at the 6-month follow-up reassessment. CONCLUSION: This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment.

Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

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.

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.

Bronchial thermoplasty reduces ventilation heterogeneity measured by multiple breath nitrogen washout.

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 cmH2O.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 reduces airway resistance.

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.

Phenotype- and patient-specific modelling in asthma: Bronchial thermoplasty and uncertainty quantification.

Theoretical models can help to overcome experimental limitations to better our understanding of lung physiology and disease. While such efforts often begin in broad terms by determining the effect of a disease process on a relevant biological output, more narrowly defined simulations may inform clinical practice. Two such examples are phenotype-specific and patient-specific models, the former being specific to a group of patients with common characteristics, and the latter to an individual patient, in view of likely differences (heterogeneity) between patients. However, in order for such models to be useful, they must be sufficiently accurate, given the available data about the specific characteristics of the patient. We show that, for asthma in particular, this approach is promising: phenotype-specific targeting may be an effective way of selecting patients for treatment based on their airway remodelling phenotype, and patient-specific targeting may be viable with the use of a clinically-plausible dataset. Specifically we consider asthma and its treatment by bronchial thermoplasty, in which the airway smooth muscle layer is directly targeted by thermal energy. Patient-specific and phenotype-specific models in this context are considered using a combination of biobank data from ex vivo tissue samples, CT imaging, and optical coherence tomography which allows more detailed resolution of the airway wall structures.

Bronchial thermoplasty: Redefining its role.

In this review, we trace (i) the origins of bronchial thermoplasty, (ii) the development of a solid evidence base for efficacy and safety, (iii) the emerging understanding of the pathophysiological mechanisms of action and (iv) the place in therapy today. Future challenges are then discussed.

Bronchial thermoplasty versus mepolizumab: Comparison of outcomes in a severe asthma clinic.

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, FEV1 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 FEV1 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.

Boundary line models for soil nutrient concentrations and wheat yield in national-scale datasets.

In boundary line analysis a biological response (e.g., crop yield) is assumed to be a function of a variable (e.g., soil nutrient concentration), which limits the response in only some subset of observations because other limiting factors also apply. The response function is therefore expressed by an upper boundary of the plot of the response against the variable. This model has been used in various branches of soil science. In this paper we apply it to the analysis of some large datasets, originating from commercial farms in England and Wales, on the recorded yield of wheat and measured concentrations of soil nutrients in within-field soil management zones. We considered boundary line models for the effects of potassium (K), phosphorus (P) and magnesium (Mg) on yield, comparing the model with a simple bivariate normal distribution or a bivariate normal censored at a constant maximum yield. We were able to show, using likelihood-based methods, that the boundary line model was preferable in most cases. The boundary line model suggested that the standard RB209 soil nutrient index values (Agriculture and Horticulture Development Board, nutrient management guide (RB209), 2017) are robust and apply at the within-field scale. However, there was evidence that wheat yield could respond to additional Mg at concentrations above index 0, contrary to RB209 guidelines. Furthermore, there was evidence that the boundary line model for yield and P differs between soils at different pH and depth intervals, suggesting that shallow soils with larger pH require a larger target P index than others. HIGHLIGHTS: Boundary line analysis is one way to examine how soil variables influence crop yield in large datasets.We showed that boundary line models could be applied to large datasets on soil nutrients and crop yield.The resulting models are consistent with current practice for P and K, but not for Mg.Models suggest that more refined recommendations for P requirement could be based on soil pH and depth.

12-month randomised controlled trial of ginseng extract for moderate COPD.

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.

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.

Bronchodilator responsiveness as a predictor of success for bronchial thermoplasty.

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 (FEV1 )/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 FEV1 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 FEV1 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.

Measuring the effects of bronchial thermoplasty using oscillometry.

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 (FEV1 ) 55.5 ± 20.1% predicted, forced expiratory ratio 53.0 ± 14.5% and FEV1 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.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

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.

Airway smooth muscle as an underutilised biomarker: a case report.

BACKGROUND: Severe asthma and chronic obstructive pulmonary disease (COPD) can be challenging to manage, particularly when the clinical features may be similar. With the increased availability of advanced therapies for both entities, it is more important than ever to diagnose and phenotype accurately to inform appropriate treatment decisions. This case highlights the use of endobronchial biopsies to allow for histological evaluation of airways disease, and in particular the role of airway smooth muscle mass as an additional biomarker that could facilitate the diagnostic process. CASE PRESENTATION: A 65 year old woman presented with a diagnosis of severe COPD on the background of previous smoking and mild childhood asthma. Despite taking maximal inhaled pharmacotherapy, she had frequent exacerbations requiring corticosteroids and remained dyspnoeic on mild exertion. Lung function tests showed severe obstruction on spirometry (forced expiratory ratio 43%, forced expiratory volume in 1 s 47% predicted), and single breath Diffusing Capacity for Carbon Monoxide was moderately reduced at 45% predicted. Computed tomography revealed hyperinflation without marked emphysema. Quantitative CT for emphysema distribution demonstrated a relatively small lung fraction of 9.35% with <- 950 Hounsfield units. Bronchoscopy with endobronchial biopsy was undertaken to further determine the underlying pathology, and airway mucosa histology was consistent with typical findings of asthma. The patient was treated with bronchial thermoplasty as she did not meet prescribing criteria for monoclonal antibodies. Six months post treatment, she had a significant improvement in symptom control and medication usage, without any exacerbations. CONCLUSIONS: Airway smooth muscle histology is an underutilised biomarker that has a valuable role in phenotyping airways disease in the era of individualised medicine.