Bronchial Thermoplasty Improves Ventilation Heterogeneity Measured by Functional Respiratory Imaging in Severe Asthma.

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

The impact of femoral head size on the wear evolution at contacting surfaces of total hip prostheses: A finite element analysis.

Total Hip Arthroplasty has been a revolutionary technique in restoring mobility to patients with damaged hip joints. The introduction of modular components of the hip prosthesis allowed for bespoke solutions based on the requirements of the patient. The femoral stem is designed with a conical trunnion to allow for assembly of different femoral head sizes based on surgical requirements. The femoral head diameters for a metal-on-polyethylene hip prosthesis have typically ranged between 22 mm and 36 mm and are typically manufactured using Cobalt-Chromium alloy. A smaller femoral head diameter is associated with lower wear of the polyethylene, however, there is a higher risk of dislocation. In this study, a finite element model of a standard commercial hip arthroplasty prosthesis was modelled with femoral head diameters ranging from 22 mm to 36 mm to investigate the wear evolution and material loss at both contacting surfaces (acetabular cup and femoral stem trunnion). The finite element model, coupled with a validated in-house wear algorithm modelled a human walking for 10 million steps. The results have shown that as the femoral head size increased, the amount of wear on all contacting surfaces increased. As the femoral head diameter increased from 22 mm to 36 mm, the highly cross-linked polyethylene (XLPE) volumetric wear increased by 61% from 98.6 mm3 to 159.5 mm3 while the femoral head taper surface volumetric wear increased by 21% from 4.18 mm3 to 4.95 mm3. This study has provided an insight into the amount of increased wear as the femoral head size increased which can highlight the life span of these prostheses in the human body.

Aseptic loosening of the option stemmed tibial tray in the Zimmer NexGen LPS total knee arthroplasty system.

BACKGROUND: We investigated the relationship between the backside deformation of polyethylene (PE) tibial inserts and aseptic loosening of the Option stemmed tibial tray used with Zimmer NexGen posterior-stabilised (PS) devices. We hypothesized that explanted inserts used in PS designs would exhibit greater extents of PE backside deformation than those used in equivalent cruciate retaining (CR) designs and that PE inserts retrieved from total knee arthroplasties (TKAs) revised for aseptic tibial tray loosening would exhibit greater extents of backside deformation than TKAs revised for other reasons. METHODS: A total of 73 explanted fixed-bearing TKAs (42 CR and 31 PS) were examined. PE components underwent geometric examination with a coordinate measuring machine using validated techniques. Multiple regression modelling was used to identify variables associated with revision secondary to aseptic loosing and to determine factors associated with increased PE backside deformation. RESULTS: PE inserts retrieved from TKAs with aseptic loosening had significantly greater backside deformation than those retrieved from TKAs revised for other reasons (p < 0.001). Greater PE backside deformation was significantly associated with larger tray/insert clearance heights (p < 0.001), thinner inserts (p < 0.001) and PS TKAs (p = 0.001). CONCLUSION: PE backside deformation was significantly greater in the PS TKAs. This may provide one explanation for the increased rate of aseptic loosening reported with the Option tibial tray used with the Legacy Posterior Stabilised (LPS) system.

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.

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.

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.

Metal debris release is commonly seen from explanted total ankle replacements.

This study aimed to characterise the damage mechanisms present on the metal components used in various contemporary total ankle replacements. Twenty-seven explanted total ankle replacements comprising 8 different designs (3 fixed bearing and 5 mobile bearing) were analysed using various explant analysis techniques. Pitting and scratching were the most commonly observed wear features. Microscopic analysis revealed metallic pitting on 52% of tibial components and 95% of talar components. Pitting was identified on more cobalt-chromium than titanium alloy tibial components (63% versus 0%). Non-contact profilometry confirmed the presence of pitting, with significant (p < 0.05) differences in the measured average surface roughness values of pitted and unpitted areas for tibial and talar components. There was macroscopically visible sliding plane scratching, indicating the presence of hard third body particles, on 78% of talar components. Changes to the non-articulating surfaces coatings in terms of coating loss and/or changes in reflectivity was identified visually on 80% of metal components. Scanning electron microscopy with energy dispersive X-ray spectroscopy identified metallic embedded debris in 19% of polyethylene inserts. This explant study demonstrates the release of metal debris from both the metallic tibial and talar component articulating surfaces and non-articulating surface coatings of various contemporary total ankle replacements. Metal particulate debris release from total ankle replacements may be more common than previously recognised. Metal debris should be considered in further study into the aetiology of failed total ankle arthroplasty.

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.

Impact of Landscape Fire Smoke Exposure on Patients With Asthma With or Without Laryngeal Hypersensitivity.

BACKGROUND: Individuals with asthma experienced severe and prolonged symptoms after the Australian 2019 to 2020 landscape fire. Many of these symptoms, such as throat irritation, occur in the upper airway. This suggests that laryngeal hypersensitivity contributes to persistent symptoms after smoke exposure. OBJECTIVE: This study examined the relationship between laryngeal hypersensitivity and symptoms, asthma control, and health impacts on individuals exposed to landscape fire smoke. METHOD: The study was a cross-sectional survey of 240 participants in asthma registries who were exposed to smoke during the 2019 to 2020 Australian fire. The survey, completed between March and May 2020, included questions about symptoms, asthma control, and health care use, as well as the Laryngeal Hypersensitivity Questionnaire. Daily concentration levels of particulate matter less than or equal to 2.5 µm in diameter were measured over the 152-day study period. RESULTS: The 49 participants with laryngeal hypersensitivity (20%) had significantly more asthma symptoms (96% vs 79%; P = .003), cough (78% vs 22%; P < .001), and throat irritation (71% vs 38%; P < .001) during the fire period compared with those without laryngeal hypersensitivity. Participants with laryngeal hypersensitivity had greater health care use (P ≤ .02), more time off work (P = .004), and a reduced capacity to participate in usual activities (P < .001) during the fire period, as well as poorer asthma control during the follow-up (P = .001). CONCLUSIONS: Laryngeal hypersensitivity is associated with persistent symptoms, reports of lower asthma control, and increased health care use in adults with asthma who were exposed to landscape fire smoke. Management of laryngeal hypersensitivity before, during, or immediately after landscape fire smoke exposure might reduce the symptom burden and health impact.

Functional lung imaging using novel and emerging MRI techniques.

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

The establishment of winter wheat root system architecture in field soils: The effect of soil type on root development in a temperate climate.

Winter wheat (Triticum aestivum L.) is an important cereal crop in the temperate climates of western Europe. Root system architecture is a significant contributor to resource capture and plant resilience. However, the impact of soil type on root system architecture (RSA) in field structured soils is yet to be fully assessed. This work studied the development of root growth using deep cultivation (250 mm) during the tillering phase stage (Zadock stage 25) of winter wheat across three soil types. The three sites of contrasting soil types covered a geographical area in the UK and Ireland in October 2018. Root samples were analysed using two methods: X-ray computed tomography (CT) which provides 3D images of the undisturbed roots in the soil, and a WinRHIZO™ scanner used to generate 2D images of washed roots and to measure further root parameters. Important negative relationships existed between soil bulk density and root properties (root length density, root volume, surface area and length) across the three sites. The results revealed that despite reduced root growth, the clay (Southoe) site had a significantly higher crop yield irrespective of root depth. The loamy sand (Harper Adams) site had significantly higher root volume, surface area and root length density compared with the other sites. However, a reduction in grain yield of 2.42 Mt ha-1 was incurred compared with the clay site and 1.6 Mt ha-1 compared with the clay loam site. The significantly higher rooting characteristics found in the loamy sand site were a result of the significantly lower soil bulk density compared with the other two sites. The loamy sand site had a lower soil bulk density, but no significant difference in macroporosity between sites (p > 0.05). This suggests that soil type and structure directly influence crop yield to greater extent than root parameters, but the interactions between both need simultaneous assessment in field sites.

How does bicycling affect the longevity of Total Hip Arthroplasty? A finite element wear analysis.

As the number of young and active individuals undergoing Total Hip Arthroplasty (THA) are increasing yearly, there is a need for hip prostheses to have increased longevity. Current investigations into the longevity of these prostheses only include walking as the patient's activity as there is limited data on the amount and intensity of other activity performed by the patient. To further understand the evolution of wear and increase the longevity of these implants, the impact of different activities on the hip prosthesis needs to be investigated. In this study, a finite element model and wear algorithm was developed to simulate both walking and bicycling over a 5-year period. The XLPE acetabular cup volumetric wear rate was found to be 33 mm3/yr while the femoral head taper wear rates were between 0.01 - 0.39 mm3/yr. The results showed that by adding bicycling of up to 80 km per week with normal walking activity, the XLPE mean volumetric wear rate increased by 67% and the metallic mean volumetric wear rate by 11%. However, the patient may gain further health benefits from this additional activity. Assistive electric bikes may also be used to further reduce the loads on the hip joint, allowing for lower amounts of wear.

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.

Periarticular metal hypersensitivity complications of hip bearings containing cobalt-chromium.

Hip joints with bearings composed of cobalt-chromium alloy (metal-on-metal bearings) have been one of the most widely used implants in joint replacement arthroplasty. Unfortunately, these implants can contribute to a complication called aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL), a type IV metal hypersensitivity response around the joint. Consistent with such bearings, increased metal debris can be found in the surrounding fluids and in remote tissues and organs, due to wear and corrosion. It is hypothesized that metal ions released from the prosthesis (including Co2+) can potentially form haptens with proteins such as serum albumin in synovial fluid that in turn elicit ALVAL. Generally, elevated cobalt and chromium levels in synovial fluids may indicate implant failure. However, such measurements cannot be used as a reliable tool to predict the onset of ALVAL. To detect ALVAL, some diagnostic tests, questionnaires and imaging techniques have been used clinically with some success, but a standardized approach is lacking. At present, guidelines for implant usage and patient management are ambiguous and inconsistent across health care authorities. To reduce and better manage the development of ALVAL, further research into the precise molecular mechanism(s) by which ALVAL develops is urgently needed. Identification of diagnostic and prognostic biomarkers for ALVAL is required, as are more standardized guidelines for surgery and patient management.

Erratum: Author Correction: The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

[This corrects the article DOI: 10.1038/s43856-022-00137-0.].

'Breathing Fire': Impact of Prolonged Bushfire Smoke Exposure in People with Severe Asthma.

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 µg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

Background: Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods: At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves. Results: Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively. Conclusions: The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient's genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials.

Plethysmography-derived gas trapping lacks utility in predicting response to bronchial thermoplasty.

There is a paucity of literature on measurable baseline parameters predicting response and guiding selection for bronchial thermoplasty. This study examines whether baseline gas trapping, as assessed by plethysmography, is associated with a response to bronchial thermoplasty at 12 months. 43 consecutive patients with severe asthma (mean±sd age 57.6±13.3 years) were evaluated at baseline and 12 months post bronchial thermoplasty. Data collected at both time points included spirometry, body plethysmography and four clinical outcome measures, namely Asthma Control Questionnaire (ACQ) score, annual exacerbation frequency, maintenance oral corticosteroid requirement and short-acting ß-agonist use. At baseline, participants had severe airflow obstruction (forced expiratory volume in 1 s 49.1±15.8%) with marked gas trapping (residual volume (RV) 150.3±40.8%, RV/total lung capacity (TLC) 51.3±10.5%), poor symptom control (ACQ 3.3±1.0) and frequent exacerbations (median 4, interquartile range 8). 12 months after bronchial thermoplasty, significant improvements were observed in all four clinical outcome measures. However, baseline RV and RV/TLC were not significantly associated with changes in ACQ nor any other clinical outcome measure, and changes in RV and RV/TLC did not significantly correlate with a change in any clinical outcome measure. Plethysmography-derived gas trapping does not demonstrate utility in predicting response and guiding selection for bronchial thermoplasty. An improvement in gas trapping was not associated with positive clinical outcomes, suggesting that this may not be the dominant mode of action of bronchial thermoplasty in generating clinical improvement.