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Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. Results: 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.
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BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.
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BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.
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Antiasmáticos/uso terapêutico , Asma/epidemiologia , Protocolos Clínicos/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Asma/tratamento farmacológico , Big Data , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Espanha/epidemiologia , Adulto JovemAssuntos
Alérgenos/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/epidemiologia , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Cupressaceae , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Testes de Provocação Nasal , Extratos Vegetais/imunologia , Estudos Prospectivos , Rinite Alérgica Sazonal/diagnóstico , Testes Cutâneos , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data.To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. METHODS: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). RESULTS: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58.5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. DISCUSSION: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.
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Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested-primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations, and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for (clinical) responders in AIT trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organizing two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural, and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies, and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.
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Alérgenos/imunologia , Dessensibilização Imunológica , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Animais , Ensaios Clínicos como Assunto , Consenso , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Gerenciamento Clínico , Prova Pericial , Humanos , Hipersensibilidade/diagnóstico , Resultado do TratamentoRESUMO
The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.
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Anafilaxia/diagnóstico , Hipersensibilidade/diagnóstico , Alérgenos/imunologia , Anafilaxia/imunologia , Gerenciamento Clínico , Necessidades e Demandas de Serviços de Saúde , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Guias de Prática Clínica como Assunto , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.
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Anafilaxia/epidemiologia , Fatores Etários , Alérgenos/imunologia , Anafilaxia/diagnóstico , Comorbidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Mastocitose , Vigilância em Saúde Pública , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.
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Dessensibilização Imunológica/normas , Hipersensibilidade/prevenção & controle , Guias de Prática Clínica como Assunto , Dessensibilização Imunológica/métodos , HumanosRESUMO
The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.
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Asma/epidemiologia , Rinite Alérgica/epidemiologia , Fatores Etários , Idoso , Tomada de Decisão Clínica , Comorbidade , Avaliação Geriátrica , Humanos , Avaliação de Resultados em Cuidados de Saúde , Vigilância da PopulaçãoRESUMO
The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.
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Dessensibilização Imunológica/normas , Dessensibilização Imunológica/tendências , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Medicina de Precisão/métodos , Vacinologia/métodos , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Sistemas de Liberação de Medicamentos/métodos , Descoberta de Drogas , Humanos , Terminologia como Assunto , Resultado do TratamentoRESUMO
In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two-third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high-quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools.
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Hipersensibilidade/diagnóstico , Padrões de Prática Médica/legislação & jurisprudência , Testes Cutâneos/métodos , Alérgenos , Atenção à Saúde/legislação & jurisprudência , Europa (Continente) , HumanosRESUMO
A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.
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Agonistas Adrenérgicos/provisão & distribuição , Anafilaxia/tratamento farmacológico , Epinefrina/provisão & distribuição , Saúde Global , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Avaliação das Necessidades , Agonistas Adrenérgicos/administração & dosagem , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Anafilaxia/mortalidade , Epinefrina/administração & dosagem , Humanos , InjeçõesAssuntos
Alérgenos/imunologia , Alérgenos Animais/imunologia , Cães/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Antígeno Prostático Específico/imunologia , Albumina Sérica/imunologia , Adolescente , Adulto , Animais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Lipid transfer protein (LTP) sensitization is the most common cause of food allergy in the Mediterranean area, with peach allergy acting as the primary sensitizer in most cases. Lettuce has been described as a common offending food in patients with LTP syndrome. The aim of the study was to investigate the frequency and clinical expression of LTP syndrome in a sample of lettuceallergic patients. METHODS: We determined specific IgE to Pru p 3 and lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms elicited by other LTP-containing plant-derived foods and the presence of cofactors were assessed. RESULTS: The clinical symptoms of lettuce allergy were frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the patients had allergic reactions to other plant foods. Cofactors were involved in the clinical reactions of 13 of the 30 patients. Sensitization to pollens was found in 90% of patients. CONCLUSIONS: Lettuce allergy is found not as an isolated condition but in the context of LTP syndrome and it is characterized by severe reactions and frequent cofactor association.
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Anafilaxia/imunologia , Antígenos de Plantas/efeitos adversos , Proteínas de Transporte/efeitos adversos , Hipersensibilidade Alimentar/imunologia , Lactuca/efeitos adversos , Folhas de Planta/efeitos adversos , Proteínas de Plantas/efeitos adversos , Adolescente , Adulto , Anafilaxia/sangue , Anafilaxia/diagnóstico , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Biomarcadores/sangue , Proteínas de Transporte/imunologia , Feminino , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/diagnóstico , Frutas/efeitos adversos , Frutas/imunologia , Humanos , Imunoglobulina E/sangue , Testes Imunológicos , Lactuca/imunologia , Masculino , Pessoa de Meia-Idade , Folhas de Planta/imunologia , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/imunologia , Valor Preditivo dos Testes , Prunus persica/efeitos adversos , Prunus persica/imunologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Allergic rhinitis and asthma constitute two clinical expressions of a single-condition, respiratory allergy. Allergen immunotherapy (AIT) is a form of treatment specifically aimed at modifying the response to sensitizing allergens. The inherent potential benefit of AIT is the simultaneous treatment of all clinical expressions of respiratory allergy. Current data support the effectiveness of subcutaneous and sublingual immunotherapy in rhinitis. Studies also provide proof for a beneficial effect in allergic asthma. Even more, substantial evidence points to the preventive effect on the progression from rhinitis to asthma. Despite the current knowledge on the basic mechanisms underlying the immunological effect of AIT is vast, the specific mechanisms for the preventive effect of primary sensitization or new sensitizations are poorly understood. This review aimed to provide a critical overview of the current knowledge on the effectiveness of AIT and its potential role in secondary prevention of respiratory allergy progression.
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Imunoterapia , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Alérgenos/imunologia , Asma/epidemiologia , Asma/etiologia , Asma/patologia , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Progressão da Doença , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Rinite Alérgica/epidemiologia , Rinite Alérgica/prevenção & controle , Resultado do TratamentoRESUMO
Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.