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BACKGROUND: There is evidence that global anthropogenic climate change may be impacting floral phenology and the temporal and spatial characteristics of aero-allergenic pollen. Given the extent of current and future climate uncertainty, there is a need to strengthen predictive pollen forecasts. METHODS: The study aims to use CatBoost (CB) and deep learning (DL) models for predicting the daily total pollen concentration up to 14 days in advance for 23 cities, covering all five continents. The model includes the projected environmental parameters, recent concentrations (1, 2 and 4 weeks), and the past environmental explanatory variables, and their future values. RESULTS: The best pollen forecasts include Mexico City (R2(DL_7) ≈ .7), and Santiago (R2(DL_7) ≈ .8) for the 7th forecast day, respectively; while the weakest pollen forecasts are made for Brisbane (R2(DL_7) ≈ .4) and Seoul (R2(DL_7) ≈ .1) for the 7th forecast day. The global order of the five most important environmental variables in determining the daily total pollen concentrations is, in decreasing order: the past daily total pollen concentration, future 2 m temperature, past 2 m temperature, past soil temperature in 28-100 cm depth, and past soil temperature in 0-7 cm depth. City-related clusters of the most similar distribution of feature importance values of the environmental variables only slightly change on consecutive forecast days for Caxias do Sul, Cape Town, Brisbane, and Mexico City, while they often change for Sydney, Santiago, and Busan. CONCLUSIONS: This new knowledge of the ecological relationships of the most remarkable variables importance for pollen forecast models according to clusters, cities and forecast days is important for developing and improving the accuracy of airborne pollen forecasts.
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Alérgenos , Previsões , Pólen , Pólen/imunologia , Previsões/métodos , Humanos , Mudança Climática , Modelos Teóricos , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: Grasses populate most biogeographical zones, and their diversity influences allergic sensitisation to pollen. Previously, the contribution of different Poaceae subfamilies to airborne pollen has mostly been inferred from historical herbarium records. We recently applied environmental (e)DNA metabarcoding at one subtropical site revealing that successive airborne grass pollen peaks were derived from repeated flowering of Chloridoid and Panicoid grasses over a season. This study aimed to compare spatiotemporal patterns in grass pollen exposure across seasons and climate zones. METHODS: Airborne pollen concentrations across two austral pollen seasons spanning 2017-2019 at subtropical (Mutdapilly and Rocklea, Queensland) and temperate (Macquarie Park and Richmond, New South Wales) sites, were determined with a routine volumetric impaction sampler and counting by light microscopy. Poaceae rbcL metabarcode sequences amplified from daily pollen samples collected once per week were assigned to subfamily and genus using a ribosomal classifier and compared with Atlas of Living Australia sighting records. RESULTS: eDNA analysis revealed distinct dominance patterns of grass pollen at various sites: Panicoid grasses prevailed in both subtropical Mutdapilly and temperate Macquarie Park, whilst Chloridoid grasses dominated the subtropical Rocklea site. Overall, subtropical sites showed significantly higher proportion of pollen from Chloridoid grasses than temperate sites, whereas the temperate sites showed a significantly higher proportion of pollen from Pooideae grasses than subtropical sites. Timing of airborne Pooid (spring), Panicoid and Chloridoid (late spring to autumn), and Arundinoid (autumn) pollen were significantly related to number of days from mid-winter. Proportions of eDNA for subfamilies correlated with distributions grass sighting records between climate zones. CONCLUSIONS: eDNA analysis enabled finer taxonomic discernment of Poaceae pollen records across seasons and climate zones with implications for understanding adaptation of grasslands to climate change, and the complexity of pollen exposure for patients with allergic respiratory diseases.
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DNA Ambiental , Poaceae , Humanos , Poaceae/genética , Estações do Ano , Alérgenos/análise , Pólen/genéticaRESUMO
BACKGROUND: Widening of subtropical climate zones globally and increasing grass-pollen exposure provide the impetus for developing a more precise and accessible diagnosis of allergy. OBJECTIVE: To evaluate the utility of recombinant allergen components of Panicoideae and Chloridoideae pollens for specific IgE testing in a rapid, point-of-care device. METHODS: Recombinant (r) Pas n 1 and Cyn d 1 were expressed, purified, and tested in the nanofluidic device for measuring serum specific IgE (spIgE) in a well-characterized Australian cohort. Concentrations and classes of spIgE to rPas n 1 and rCyn d 1, and total IgE were compared with skin prick test results and spIgE with grass pollen. RESULTS: Correlations between commercial and academic laboratories for 21 sera were high for rPas n 1 spIgE (r = 0.695) and total IgE (r = 0.945). Higher spIgE to rPas n 1 and rCyn d 1 fluorescence was detected in the patients with grass-pollen allergy and with clinician-diagnosed allergic rhinitis (n = 134) than in participants with other allergies (n = 49) or no allergies (n = 23). Correlation between spIgE concentrations to rPas n 1 (r = 0.679) and rCyn d 1 (r = 0.548), with Bahia and Bermuda grass-pollen spIgE, respectively, was highly significant (p<0.0001). The positive/negative predictive agreements of spIgE classes for rPas n 1 (73%/82.5%) and rCyn d 1 (67.8%/66.3%) between the nanofluidic and ImmunoCAP measurements for Bahia and Bermuda grass pollen, respectively, were substantial. CONCLUSION: Point-of-care nanofluidic tests for spIgE to rPas n 1 and rCyn d 1 could increase access to more precise clinical diagnosis for patients with allergies in subtropical regions.
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Sistemas Automatizados de Assistência Junto ao Leito , Rinite Alérgica , Humanos , Austrália , Pólen , Alérgenos , Rinite Alérgica/diagnóstico , Imunoglobulina E , PoaceaeRESUMO
BACKGROUND: Grass pollen is considered a major outdoor aeroallergen source worldwide. It is proposed as a mechanism for thunderstorm asthma that lightning during thunderstorms promotes electrical rupture of pollen grains that leads to allergic airway inflammation. However, most evidence of associations between grass pollen and asthma comes from temperate regions. The objective of this study was to investigate short-term associations between airborne grass pollen exposure and asthma emergency department presentations in a subtropical population. METHODS: Episode level public hospital presentations for asthma (2016-2020) were extracted for greater Brisbane, Australia, from Queensland Health's Emergency Data Collection. Concentrations of airborne pollen were determined prospectively using a continuous flow volumetric impaction sampler. Daily time series analysis using a generalised additive mixed model were applied to determine associations between airborne grass pollen concentrations, and lightning count data, with asthma presentations. RESULTS: Airborne grass pollen showed an association with asthma presentations in Brisbane; a significant association was detected from same day exposure to three days lag. Grass pollen exposure increased daily asthma presentations up to 48.5% (95% CI: 12%, 85.9%) in female children. Lightning did not modify the effect of grass pollen on asthma presentations, however a positive association was detected between cloud-to-cloud lightning strikes and asthma presentations (P = 0.048). CONCLUSION: Airborne grass pollen exposure may exacerbate symptoms of asthma requiring urgent medical care of children and adults in a subtropical climate. This knowledge indicates an opportunity for targeted management of respiratory allergic disease to reduce patient and health system burden. For the first time, an influence of lightning on asthma was detected in this context. The outcomes support a need for continued pollen monitoring and surveillance of thunderstorm asthma risk in subtropical regions.
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Asma , Poaceae , Adulto , Criança , Feminino , Humanos , Pólen , Asma/epidemiologia , Asma/etiologia , Alérgenos/análise , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: Allergic rhinitis affects half a billion people globally, including a fifth of the Australian population. As the foremost outdoor allergen source, ambient grass pollen exposure is likely to be altered by climate change. The AusPollen Partnership aimed to standardize pollen monitoring and examine broad-scale biogeographical and meteorological factors influencing interannual variation in seasonality of grass pollen aerobiology in Australia. METHODS: Daily airborne grass and other pollen concentrations in four eastern Australian cities separated by over 1700 km, were simultaneously monitored using Hirst-style samplers following the Australian Interim Pollen and Spore Monitoring Standard and Protocols over four seasons from 2016 to 2020. The grass seasonal pollen integral was determined. Gridded rainfall, temperature, and satellite-derived grassland sources up to 100 km from the monitoring site were analysed. RESULTS: The complexity of grass pollen seasons was related to latitude with multiple major summer-autumn peaks in Brisbane, major spring and minor summer peaks in Sydney and Canberra, and single major spring peaks occurring in Melbourne. The subtropical site of Brisbane showed a higher proportion of grass out of total pollen than more temperate sites. The magnitude of the grass seasonal pollen integral was correlated with pasture greenness, rainfall and number of days over 30 °C, preceding and within the season, up to 100 km radii from monitoring sites. CONCLUSIONS: Interannual fluctuations in Australian grass pollen season magnitude are strongly influenced by regional biogeography and both pre- and in-season weather. This first continental scale, Southern Hemisphere standardized aerobiology dataset forms the basis to track shifts in pollen seasonality, biodiversity and impacts on allergic respiratory diseases.
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Alérgenos , Pólen , Austrália , Humanos , Conceitos Meteorológicos , Poaceae , Estações do AnoRESUMO
BACKGROUND: While health services and their clinicians might seek to be innovative, finite budgets, increased demands on health services, and ineffective implementation strategies create challenges to sustaining innovation. These challenges can be addressed by building staff capacity to design cost-effective, evidence-based innovations, and selecting appropriate implementation strategies. A bespoke university award qualification and associated program of activities was developed to build the capacity of staff at Australia's largest health service to implement and evaluate evidence-based practice (EBP): a Graduate Certificate in Health Science majoring in Health Services Innovation. The aim of this study was to establish the health service's pre-program capacity to implement EBP and to identify preliminary changes in capacity that have occurred as a result of the Health Services Innovation program. METHODS: A mixed methods design underpinned by the Consolidated Framework for Implementation Research informed the research design, data collection, and analysis. Data about EBP implementation capacity aligned to the framework constructs were sought through qualitative interviews of university and health service executives, focus groups with students, and a quantitative survey of managers and students. The outcomes measured were knowledge of, attitudes towards, and use of EBP within the health service, as well as changes to practice which students identified had resulted from their participation in the program. RESULTS: The Health Services Innovation program has contributed to short-term changes in health service capacity to implement EBP. Participating students have not only increased their individual skills and knowledge, but also changed their EPB culture and practice which has ignited and sustained health service innovations and improvements in the first 18 months of the program. Capacity changes observed across wider sections of the organization include an increase in connections and networks, use of a shared language, and use of robust implementation science methods such as stakeholder analyses. CONCLUSION: This is a unique study that assessed data from all stakeholders: university and health service executives, students, and their managers. By assembling multiple perspectives, we identified that developing the social capital of the organization through delivering a full suite of capacity-building initiatives was critical to the preliminary success of the program.
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Grass pollens have been identified as mediators of respiratory distress, capable of exacerbating respiratory diseases including epidemic thunderstorm asthma (ETSA). It is hypothesised that during thunderstorms, grass pollen grains swell to absorb atmospheric water, rupture, and release internal protein content to the atmosphere. The inhalation of atmospheric grass pollen proteins results in deadly ETSA events. We sought to identify the underlying cellular mechanisms that may contribute towards the severity of ETSA in temperate climates using Timothy grass (Phleum pratense). Respiratory cells exposed to Timothy grass pollen protein extract (PPE) caused cells to undergo hypoxia ultimately triggering the subcellular re-organisation of F-actin from the peri junctional belt to cytoplasmic fibre assembly traversing the cell body. This change in actin configuration coincided with the spatial reorganisation of microtubules and importantly, decreased cell compressibility specifically at the cell centre. Further to this, we find that the pollen-induced reorganisation of the actin cytoskeleton prompting secretion of the pro-inflammatory cytokine, interleukin-8. In addition, the loss of peri-junctional actin following exposure to pollen proteins was accompanied by the release of epithelial transmembrane protein, E-cadherin from cell-cell junctions resulting in a decrease in epithelial barrier integrity. We demonstrate that Timothy grass pollen regulates F-actin dynamics and E-cadherin localisation in respiratory cells to mediate cell-cell junctional integrity highlighting a possible molecular pathway underpinning ETSA events.
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Asma , Phleum , Citoesqueleto de Actina , Actinas , Alérgenos , Caderinas , Humanos , Poaceae , PólenRESUMO
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.
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Asma , Rinite Alérgica Sazonal , Adulto , Alérgenos , Asma/diagnóstico , Humanos , Imunoglobulina E , Pólen , Rinite Alérgica Sazonal/complicaçõesRESUMO
BACKGROUND: The most severe thunderstorm asthma (TA) event occurred in Melbourne on the 21st November 2016 and during this period, daily pollen information was available and accessible on smart devices via an App. An integrated survey within the App allows users to self-report symptoms. OBJECTIVE: To explore patterns of symptom survey results during the period when the TA event occurred. METHODS: Symptom data from the Melbourne Pollen Count and Forecast App related to asthma history, hay fever symptoms, and medication use was explored. A one-week control period before and after the event was considered. Chi-square tests and logistic regression were used to assess associations between sex, age, symptoms, and medication use. RESULTS: Of the 28,655 responses, during the 2016 pollen season, younger (18 to 40 years) males, with no hay fever and no asthma were the most single and regular responders. During the TA event for new users, sex was only significantly associated with hay fever (p = 0.008) of which 60.2% of females' responses reported having hay fever, while 43% of males' responses did not. Those with mild symptoms peaked during the TA event. CONCLUSIONS: Many individuals completed the survey on the app for the first time during the TA event indicating the potential of digital technologies to be used as indicators of health risk among populations at risk of TA events.
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OBJECTIVE: Patient characteristics with exacerbation of asthma accessing care in the ED who are at risk of hospital admission have not been determined in subtropical climates. The objective of the study was to investigate the spatiotemporal burden of asthma hospital admissions across Queensland (QLD) and model risk factors for asthma hospital admission following an ED visit. METHODS: Six years of routinely collected data (2012-2017) from 28 QLD public hospitals were extracted from Queensland Health's Emergency Data Collection. The dataset contained individual, episode-level ED presentations having asthma-like diagnoses, and an indicator of hospital admission, including to short-stay unit (SSU). A generalised additive model was used to examine the risk of asthma hospital admission. RESULTS: Asthma hospital admissions increased from a weekly median of 79 (interquartile range [IQR] 66-99) in 2012 to 104 (IQR 81-135) in 2017. A higher incidence of asthma hospital admission was observed among males (median age 9, IQR 5-32) in childhood and females in adulthood (median age 32, IQR 11-51). Compared to the state capital Brisbane, the odds of asthma hospital admission ranged from 0.48 (95% CI 0.42-0.54) to 1.34 (95%CI 1.21-1.48) in other regions of QLD. CONCLUSION: Asthma hospital admissions appear to be increasing in QLD, largely driven by utilisation of the SSU admissions for asthma. With large variation in both incidence and proportion admitted across different regions, routinely collected data can in part be used to understand risk factors for asthma-related hospital admission following an ED presentation and further inform public health policy development.
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Asma , Serviço Hospitalar de Emergência , Adulto , Asma/epidemiologia , Austrália , Criança , Estudos de Coortes , Feminino , Hospitalização , Hospitais Públicos , Humanos , Masculino , Queensland/epidemiologiaRESUMO
Objective The aim of this study was to quantify the direct and indirect costs of asthma and allergic rhinitis (AR) for 2018 in Tasmania. Methods We used publicly available data, and Tasmanian-specific values where available, to estimate direct and indirect costs of both diseases. Direct costs included outcomes such as emergency department (ED) presentations, hospitalisations, general practice visits and medication use. Indirect costs included premature mortality and lost productivity. Results Direct health impacts for both conditions combined included 1454 ED presentations, 682 hospitalisations, 72446 general practice visits and 7122 specialist visits. Indirect health impacts included 13 deaths and between 483000 and 2.8 million days of lost productivity. Total costs ranged between A$126.5 million and A$436.7 million for asthma and between A$65.3 million and A$259.7 million for AR. Per-person annual costs ranged between A$1918 and A$6617 for asthma and between A$597 and A$2374 for AR. Conclusions The main financial burden due to asthma and AR was related to productivity losses from presenteeism and absenteeism. The magnitude of the economic impacts of AR and asthma warrants further analysis to produce a national-level assessment. Such analyses could identify cost-effective interventions that produce highest benefits for the management of these conditions in our community. What is known about the topic? Allergic respiratory diseases, and particularly asthma and AR, pose a significant health burden, with effects including asthma-related hospital admissions, significant pharmaceutical expenditure and lost workforce and school education productivity. Australia, and particularly Tasmania, has a high prevalence of these conditions, but no recent studies have appraised or estimated their health impacts and costs. What does this paper add? This paper proposes a unique and transparent costing model that allows the costs of these conditions to be estimated while accounting for restrictions in data availability. The model is used to provide the first comprehensive costings of asthma and AR in Tasmania, Australia. We identified that the estimated health costs are dominated by productivity losses from presenteeism and absenteeism, and that total per person costs are higher for a person with asthma compared to one with AR. What are the implications for practitioners? This analysis has the potential to guide cost-effective interventions by identifying where the highest benefits may be obtained when managing these conditions in our community.
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Asma , Custos de Cuidados de Saúde , Asma/epidemiologia , Austrália , Efeitos Psicossociais da Doença , Humanos , Fatores Socioeconômicos , Tasmânia/epidemiologiaRESUMO
Grass pollen is the major outdoor trigger of allergic respiratory diseases. Climate change is influencing pollen seasonality in Northern Hemisphere temperate regions, but many aspects of the effects on grass pollen remain unclear. Carbon dioxide and temperature rises could increase the distribution of subtropical grasses, however, medium term shifts in grass pollen in subtropical climates have not yet been analysed. This study investigates changes in grass pollen aerobiology in a subtropical city of Brisbane, Australia, between the two available monitoring periods, 1994-1999 and 2016-2020. Potential drivers of pollen change were examined including weather and satellite-derived vegetation indicators. The magnitude of the seasonal pollen index for grass showed almost a three-fold increase for 2016-2020 over 1994-1999. The number and proportion of high and extreme grass pollen days in the recent period increased compared to earlier monitoring. Statistically significant changes were also identified for distributions of CO2, satellite-derived seasonal vegetation health indices, and daily maximum temperatures, but not for minimum temperatures, daily rainfall, or seasonal fraction of green groundcover. Quarterly grass pollen levels were correlated with corresponding vegetation health indices, and with green groundcover fraction, suggesting that seasonal-scale plant health was higher in the latter period. The magnitude of grass pollen exposure in the subtropical region of Brisbane has increased markedly in the recent past, posing an increased environmental health threat. This study suggests the need for continuous pollen monitoring to track and respond to the possible effects of climate change on grass pollen loads.
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Climatic change will have an impact on production and release of pollen, with consequences for the duration and magnitude of aeroallergen seasonal exposure and allergic diseases. Evaluations of pollen aerobiology in the southern hemisphere have been limited by resourcing and the density of monitoring sites. This review emphasizes inconsistencies in pollen monitoring methods and metrics used globally. Research should consider unique southern hemisphere biodiversity, climate, plant distributions, standardization of pollen aerobiology, automation, and environmental integration. For both hemispheres, there is a clear need for better understanding of likely influences of climate change and comprehending their impact on pollen-related health outcomes.
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Mudança Climática , Hipersensibilidade , Alérgenos , Humanos , Hipersensibilidade/epidemiologia , PólenRESUMO
OBJECTIVE: Sudden acute episodes of asthma exacerbation are often treated by hospital EDs. It is hypothesised that determinants of acute asthma would differ across geographic regions. The objective of the present study was to detail seasonality, trends and spatiotemporal patterns of asthma ED presentations across Queensland (QLD), Australia, a state covering 1.8 million square kilometres, spanning multiple climates. METHODS: Six years of routinely collected data (2012 to 2017) from 28 major QLD public hospitals were extracted from Queensland Health's Emergency Data Collection. The dataset contained individual, episode-level asthma-like diagnoses of ED presentations. Seasonality and trends of acute asthma were assessed through multiplicative time-series analysis. RESULTS: The study consisted of 2192 days with a total of 65 012 asthma ED presentations in QLD. The 6-year average daily incidence rate was 270 asthma ED presentations per 100 000 population. The highest morbidity of asthma ED presentations occurred during the southern hemisphere winter months. Children showed a higher incidence rate compared to adults with males experiencing a higher incidence compared to females up until the age of 13, after which an inversion was observed persisting through adulthood. Seasonality of asthma ED presentations differed with latitude across QLD. CONCLUSION: Asthma-related ED presentations exhibit spatiotemporal variation across QLD, which appears to be related to climate. Furthermore, aeroallergens and respiratory viruses may be responsible for asthma ED peaks outside the winter period. Socioeconomic status may influence asthma ED presentation rates between regions. This knowledge can guide ongoing management and assist public health policy response.
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Asma , Serviço Hospitalar de Emergência , Adulto , Asma/epidemiologia , Austrália , Criança , Feminino , Hospitais Públicos , Humanos , Masculino , Queensland/epidemiologiaRESUMO
INTRODUCTION: Epidemic thunderstorm asthma (ETSA) is due to a complex interaction of environmental and individual susceptibility factors, with outbreaks reported globally over the last four decades. Australia has been particularly susceptible with nearly half of episodes reported internationally, culminating in the catastrophic Melbourne 2016 event. AREAS COVERED: Reported ETSA episodes are reviewed for common environmental and meteorological risk factors. Allergen aerobiology interaction with thunderstorm activity and rapid weather condition changes is examined. Assessment of the clinical and immunological data highlights risk factors for ETSA presentation, hospital admission, and intensive care admission. Risk factors associated with ETSA deaths are evaluated. Public health strategies, as well as pharmacological and immunological management approaches to reduce individual susceptibility and prevent ETSA are discussed. EXPERT OPINION: Improved understanding of the specific meteorological factors predisposing to the greatest risk of ETSA to improve forecasting is required. Better monitoring of aeroallergen levels in areas of greatest geographic risk, with further research into allergen aerobiology underpinning mechanisms of allergen exposure is needed. The role of climate change in increasing the risk of ETSA outbreaks requires further research. Public awareness and education are required to reduce exposure, and to improve uptake of pharmacological and immunological risk reduction and preventive strategies.
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Asma/imunologia , Dessensibilização Imunológica/métodos , Poluentes Atmosféricos/imunologia , Alérgenos/imunologia , Asma/terapia , Mudança Climática , Previsões , Interação Gene-Ambiente , Humanos , Educação de Pacientes como Assunto , Saúde Pública , Risco , Tempo (Meteorologia)RESUMO
BACKGROUND AIMS: Pathological activation and collaboration of T and B cells underlies pathogenic autoantibody responses. Existing treatments for autoimmune disease cause non-specific immunosuppression, and induction of antigen-specific tolerance remains an elusive goal. Many immunotherapies aim to manipulate the T-cell component of T-B interplay, but few directly target B cells. One possible means to specifically target B cells is the transfer of gene-engineered BM that, once engrafted, gives rise to widespread specific and tolerogenic antigen expression within the hematopoietic system. METHODS: Gene-engineered bone marrow encoding ubiquitous ovalbumin expression was transferred after low-dose (300-cGy) immune-preserving irradiation. B-cell responsiveness was monitored by analyzing ovalbumin-specific antibody production after immunization with ovalbumin/complete Freund's adjuvant. Ovalbumin-specific B cells and their response to immunization were analyzed using multi-tetramer staining. When antigen-encoding bone marrow was transferred under immune-preserving conditions, cognate antigen-specific B cells were purged from the recipient's preexisting B-cell repertoire and the repertoire that arose after bone marrow transfer. RESULTS: OVA-specific B-cell deletion was apparent within the established host B-cell repertoire as well as that developing after gene-engineered bone marrow transfer. OVA-specific antibody production was substantially inhibited by transfer of OVA-encoding BM and activation of OVA-specific B cells, germinal center formation and subsequent OVA-specific plasmablast differentiation were all inhibited. Low levels of gene-engineered bone marrow chimerism were sufficient to limit antigen-specific antibody production. RESULTS: These data show that antigen-specific B cells within an established B-cell repertoire are susceptible to de novo tolerance induction, and this can be achieved by transfer of gene-engineered bone marrow. This adds further dimensions to the utility of antigen-encoding bone marrow transfer as an immunotherapeutic tool.
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Formação de Anticorpos , Antígenos/metabolismo , Antígeno de Maturação de Linfócitos B/metabolismo , Linfócitos B/imunologia , Transplante de Medula Óssea , Medula Óssea/imunologia , Depleção Linfocítica , Animais , Diferenciação Celular , Centro Germinativo/citologia , Centro Germinativo/metabolismo , Tolerância Imunológica/imunologia , Camundongos Endogâmicos C57BL , Ovalbumina/biossíntese , Ovalbumina/imunologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: Globally, grass pollens (GP) are major aeroallergen triggers of allergic rhinitis (AR) and asthma. However, patterns of allergic sensitisation to pollen of temperate (Pooideae: Lolium perenne) and subtropical (Chloridoideae: Cynodon dactylon and Panicoideae: Paspalum notatum) subfamilies in diverse climates remain unclear. This study aims to evaluate the level of allergic sensitisation and IgE specificity for major GP allergens representing the three subfamilies in biogeographically distinct regions. METHODS: Participants (GP-allergic with AR, 330; non-atopic, 29; other allergies, 54) were recruited in subtropical: Queensland, and temperate: New South Wales, Western and South Australia, regions. Clinical history, skin prick test (SPT), total and specific IgE to GP and purified allergens (ImmunoCAP) were evaluated. Cross-inhibition of sIgE with Pas n 1, Cyn d 1 and Lol p 1 by GP extracts was investigated. RESULTS: Queensland participants showed higher sensitisation to P. notatum and C. dactylon than L. perenne GP. sIgE was higher to Pas n 1 and Cyn d 1, and sIgE to Pas n 1 and Cyn d 1 was inhibited more by Panicoideae and Chloridoideae, respectively, than Pooideae GP. Conversely, participants from temperate regions showed highest sensitisation levels to L. perenne GP and Lol p 1, and sIgE to Lol p 1 was inhibited more by Pooideae than other GP. CONCLUSION: Levels and patterns of sensitisation to subtropical and temperate GP in AR patients depended on biogeography. Knowledge of the specificity of sensitisation to local allergens is important for optimal diagnosis and choice of allergen-specific immunotherapy to maximise benefit.