Drug allergy in primary care: systematic review to support quality improvement initiative of management and optimization of healthcare pathways.

PURPOSE OF REVIEW: The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients. RECENT FINDINGS: DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists. SUMMARY: DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs.

Food allergy in the World Health Organization's International Classification of Diseases (ICD)-11.

There are increasing global data regarding the prevalence of food allergy and food-induced anaphylaxis. However, knowledge in morbidity and mortality epidemiological data is still not optimal, and international comparable standards remain poorly accessed. This information could in turn support better clinical practice and possibly prevent future severe reactions and avoidable fatalities. The International Classification of Diseases (ICD) is the standard diagnostic tool used for epidemiology, health management, and clinical purposes supported by the World Health Organization (WHO). It is also used to determine health care payment and reimbursement of providers and health care services in hospitals. Thanks to the academic and technical efforts under the ALLERGY in ICD-11 initiative the pioneer "Allergy and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter of the ICD-11. The "Food hypersensitivity" (FH) subsection is classified under the "Complex allergic or hypersensitivity conditions" section and "Food-induced anaphylaxis" is under the "Anaphylaxis" section. In order to inform the development of strategies to reduce preventable FHs/food allergies, the burden of disease in different healthcare settings and patient populations and their common etiologies need to be understood. Besides, greater specificity regarding clinical conditions and services delivered will provide payers, policy makers, and providers with better information to make major refinements to countries payment and reimbursement systems, including the design and implementation of pay-for-performance program.The new classification addressed to FHs will enable the collection of more accurate epidemiological data to support quality management of patients with FHs/food allergies, and better facilitate health care planning and decision-making and public health measures to prevent and reduce their morbidity and mortality. The improved logic and standardized definitions through the ICD-11 (and other WHO classifications) will also facilitate international comparisons of quality care and the sharing of best practice globally.

Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Real-life impact of uncontrolled severe asthma on mortality and healthcare use in adolescents and adults: findings from the retrospective, observational RESONANCE study in France.

OBJECTIVE: To characterise uncontrolled severe asthma and compare the disease burden with the general and asthmatic populations. DESIGN: Retrospective observational study using a national sample of a French healthcare database (Echantillon Généraliste des Bénéficiaires (EGB)). SETTING: The EGB, an anonymised permanent sample of health insurance databases, representing 1/97th of the French population. PARTICIPANTS: Patients (≥12 years) were selected in year 2014 and followed 2 years. A cohort of patients with uncontrolled severe asthma was defined using an algorithm based on peer-reviewed literature and Global Initiative for Asthma recommendations. Index date was the occurrence of the first marker of uncontrolled asthma. This cohort was matched with two control cohorts, general population and asthmatic controls, on baseline characteristics. MAIN OUTCOMES MEASURES: Mortality, healthcare use and associated costs were studied in the 2 years of follow-up. RESULTS: Among 467 716 individuals in the EGB, 16 588 patients with asthma were identified, including 739 (4.5%) with uncontrolled severe disease. The survival probability at 2 years for patients with uncontrolled severe asthma (92.0%) was lower than in the general population cohort (96.6%; relative risk of death: 2.35; 95% CI: 1.70 to 3.29; p<0.0001) and tended to be lower than in the control asthmatic cohort (94.3%; p=0.07). Emergency department visits and hospitalisations were higher in patients with uncontrolled severe asthma than in the general population (64.7% vs 34.9%; p<0.0001) and asthmatic controls (64.7% vs 55.2%; p=0.0002). Other components of healthcare use (medical and paramedical visits, medications) were increased in patients with uncontrolled severe asthma compared with control populations. These increases translated into higher costs (p<0.0001 for both comparisons). CONCLUSIONS: This study demonstrates the huge burden of uncontrolled severe asthma in terms of mortality, morbidity and healthcare resource consumption compared with other patients with asthma and with the general population and emphasises the importance of appropriate management in this high-risk population.

Economic burden of drug-induced anaphylaxis: what can we do better?

PURPOSE OF REVIEW: This systematic review evaluates published data related to the economic burden of drug-induced anaphylaxis (DIA) to understand preventive cost saving measures that could reduce the burden of these conditions. RECENT FINDINGS: Although DIA has a relevant societal impact, there are limited and heterogenous available data related to its cost. Direct costs related to the management of acute phase of DIA was estimated by $529.6 to $3125, depending on the number of emergency room visits/hospitalizations, emergency kits and transports in ambulance. Direct costs of investigations of DIA varied from $288 to $2292.95 and the desensitization was estimated by $6796. Main variables for this were: personnel, allergy screening procedures, medical consumables and space cost. The mean indirect cost was based on a mean absenteeism of 3 days per DIA corresponding to $381.2. SUMMARY: More than reviewing the published data, we were able to identify variables that, if correctly managed, can reduce the economic burden of DIA, such as adjusting the timing of referral and etiological diagnosis, identification of potential risk and/or co-factors, correct written recommendations to patients. The evidence presented highlights the need of optimization of healthcare patients to patients suffering from DIA.

Mobile Technology in Allergic Rhinitis: Evolution in Management or Revolution in Health and Care?

Smart devices and Internet-based applications (apps) are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability, and cost-effectiveness. Second, they should be evaluated in the frame of the digital transformation of health, their impact on health care delivery, and health outcomes. This review (1) summarizes some existing mobile health apps for allergic rhinitis and reviews those in which testing has been published, (2) discusses apps that include risk factors of allergic rhinitis, (3) examines the impact of mobile health apps in phenotype discovery, (4) provides real-world evidence for care pathways, and finally (5) discusses mobile health tools enabling the digital transformation of health and care, empowering citizens, and building a healthier society.

Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey.

BACKGROUND: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. METHODS: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. RESULTS: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (ß: - 49 ml; 95%-CI: -132, 35 for FEV1 and ß: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. CONCLUSION: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.

The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

BACKGROUND: Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. METHODS: Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. RESULTS: A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). CONCLUSIONS: In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs.

Comparison of outcome measures in allergic rhinitis in children, adolescents and adults.

BACKGROUND: Grass pollen-induced allergic rhinoconjunctivitis (AR) is very common worldwide. However, its symptoms may vary with the patient's age. The present study compared symptom profiles and quality of life (QoL) in children, adolescents and adults with grass pollen-induced AR. METHODS: This was a four-week, multicentre, observational study of children (aged 6-11), adolescents (12-17) and adults (18-65) consulting specialist physicians in France. The management of AR was at the physicians' discretion. Participants regularly rated their symptoms (the rhinoconjunctivitis total symptom score (RTSS) and a visual analogue scale (VAS)) and QoL (the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: A total of 806 patients (253 children, 250 adolescents and 303 adults, of whom 83.5% suffered from moderate-to-severe, persistent AR) provided data for at least the first 2 weeks of the study. Ocular pruritus (the most bothersome symptom in children (35%), adolescents (22%) and adults (16%)) was associated with poor QoL in all groups, whereas nasal obstruction and pruritus were associated with poor QoL in adolescents and children. Over 4 weeks, the weekly mean RTSS and VAS scores fell by around half. This change was associated with an improvement in the RQLQ scores. In all age groups, the VAS score was well correlated with the weekly mean RTSS score (Pearson's r: 0.79-0.88) and moderately correlated with the weekly mean RQLQ score (Pearson's r: 0.64-0.80). CONCLUSIONS: In moderate-to-severe grass pollen-induced AR, symptom perception differs in children vs. older patients. However, the assessments of treatment outcomes (using the RTSS, VAS and RQLQ) were similar in all age groups.

International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics.

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.

[The implementation gap in asthma prevention and control?]. / Prévenir et contrôler l'asthme, quels sont les obstacles ? Comment les surmonter ?

Asthma and allergic diseases generally start early in life and persist throughout life but, for reasons we do not yet understand, they sometimes appear later Prevention, early diagnosis and treatment of these major chronic respiratory diseases is a recognized priority for EU public health policy and for the United Nations. As factors favoring allergy (rapid urbanization, pollution, climate change and infections) are not expected to change in the foreseeable future, it is crucial to develop, strengthen and optimize prevention and treatment. We have developed tools to control asthma but are still unable to prevent children from developing asthma and allergic diseases. This article examines what works and what does not, and analyzes the "missing links" between the creation and effective implementation of a prevention program, otherwise known as the implementation gap.

Assessment of disease control in allergic rhinitis.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative has had a significant impact, by raising awareness of allergic rhinitis (AR) and improving the diagnosis and treatment of AR sufferers. ARIA classifies the severity of AR as "mild" or "moderate/severe" on the basis of "yes"/"no" answers to four questions. This two-point classification has been criticized as providing little guidance on patient management; patients with "mild" AR are unlikely to consult a physician, whereas the group of patients with "moderate/severe" seen by specialists is heterogeneous. These perceived shortcomings have prompted attempts to improve the ARIA classification or, by analogy with the Global Initiative for Asthma (GINA), adopt approaches based on "disease control" in AR. Even though "disease severity", "disease control" and "responsiveness to treatment" are different (albeit related) metrics, they are not mutually exclusive. Currently, there is no single, accepted definition, but we propose that "disease control" in AR can combine (i) measurements of the severity and/or frequency of daily or nocturnal symptoms, (ii) impairments in social, physical, professional and educational activities, (iii) respiratory function monitoring and (iv) exacerbations (e.g. unscheduled medical consultations and rescue medication use). Although control-based classifications have a number of limitations (e.g. their dependence on treatment compliance and the patient's psychological status), these instruments could be used as an adjunct to the ARIA severity classification and regional practice parameters. Here, we assess the strengths and weaknesses of the current two-level ARIA classification, analyze published proposals for its modification and review the literature on instruments that measure AR control. We conclude that there is a need for research in which severity is compared with control in terms of their effects on patient management.

[ARIA (Allergic Rhinitis and its Impact on Asthma). Achievements in 10 years and future needs in Latin America]. / ARIA (Rinitis Alérgica y su Impacto en Asma). Logros en 10 años y necesidades futuras en América Latina.

Allergic rhinitis and asthma represent global problems of public health affecting all age groups; asthma and allergic rhinitis frequently coexist in the same patients. In Latin American prevalence of allergic rhinitis, although variable, is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a workshop of the World Health Organization performed in 1999 and was published in 2001. ARIA proposed a new classification of allergic rhinitis in intermittent or persistent and mild or moderate-severe. This approach of classification reflects more nearly the impact of allergic rhinitis in patients. In its review of 2010 ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of clinical practices for management of comorbidities of allergic rhinitis and asthma based on GRADE (Grading of Recommendations, Development and Evaluation). ARIA has been spread and implemented in more than 50 countries. In Latin American an intense activity has been developed to spread these recommendations in almost all the countries of the region and it is important to record the obtained goals in the diffusion and implementation of ARIA, as well as to identify the unsatisfied needs from the clinical, research and implementation points of view. Final objective is to reinforce the priority that allergy and asthma should have, especially in children, in the programs of public health, as they have been prioritized in European Union in 2011.

La rinitis alérgica y el asma representan problemas globales de salud pública que afectan a todos los grupos etarios; el asma y la rinitis alérgica frecuentemente coexisten en los mismos pacientes. En América Latina la prevalencia de rinitis alérgica, aunque variable, es muy elevada. La iniciativa Rinitis Alérgica y su Impacto en Asma (globalmente conocida como ARIA, de su nombre en inglés Allergic Rhinitis and its Impact on Asthma) comenzó durante un taller de la Organización Mundial de la Salud (OMS) realizado en 1999 que se publicó en el año 2001. ARIA propuso una nueva clasificación de rinitis alérgica en intermitente o persistente y leve o moderada-severa. Este esquema de clasificación refleja más estrechamente el impacto de la rinitis alérgica en los pacientes. En su revisión de 2010, la guía ARIA desarrolló pautas para el diagnóstico y tratamiento de la rinitis alérgica y de prácticas clínicas para el manejo de las comorbilidades de la rinitis alérgica y el asma basadas en GRADE (Gradación de Recomendaciones, Desarrollo y Evaluación). ARIA se ha diseminado e implantado en más de 50 países. En América Latina se ha desarrollado una intensa actividad para diseminar estas recomendaciones en casi todos los países de la región y es importante llevar un registro de los logros obtenidos en la difusión e implantación de ARIA, además de identificar las necesidades insatisfechas desde el punto de vista clínico, de la investigación y de la implantación. El objetivo final es reforzar la prioridad que deben tener la alergia y el asma ­especialmente en niños­ en los programas de Salud Pública, tal como los priorizó la Unión Europea en 2011.

Classification and epidemiology of hypersensitivity drug reactions.

Nonimmune hypersensitivity reactions are unpredictable adverse drug reactions that are clinically similar to allergic reactions for which no drug-specific antibodies or T lymphocytes are identified. Few tools allow a definite diagnosis, and most of the available ones need to be validated. True epidemiologic data are limited, and most of the available information on the incidence, mortality, and socioeconomic impact should be discussed with caution.