Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma.

BACKGROUND: Blood eosinophils and fractional exhaled nitric oxide (Feno) are prognostic biomarkers for exacerbations and predict lung function responses to dupilumab in adolescents and adults with asthma. OBJECTIVE: We evaluated the relationship between baseline blood eosinophils and Feno and response to dupilumab in children with asthma. METHODS: Children aged 6 to 11 years with uncontrolled moderate-to-severe asthma (n = 408) were randomized to receive dupilumab 100/200 mg by body weight or volume-matched placebo every 2 weeks for 52 weeks. Annualized exacerbation rate (AER) reduction and least squares mean change in prebronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) at week 12 were assessed according to cutoff baseline levels for Feno (<20 ppb vs ≥20 ppb) and blood eosinophil count (<150, ≥150 to <300, ≥300 to <500, and ≥500 cells/µL). Quadrant analyses in populations defined by biomarker thresholds and spline models across continuous end points assessed the relationship with Feno and eosinophil count. Interaction testing evaluated the independent roles of Feno and blood eosinophils as predictive markers. RESULTS: Exacerbation risk and magnitude of AER reduction increased in subgroups with higher baseline biomarker levels. Quadrant analyses revealed that disease of patients with either elevated Feno or eosinophil counts demonstrated a clinical response to dupilumab. Interaction testing indicated blood eosinophil counts or Feno independently added value as predictive biomarkers. CONCLUSIONS: In children with uncontrolled moderate-to-severe asthma, blood eosinophil counts and Feno are clinically relevant biomarkers to identify those at risk for asthma exacerbations, as well as those with disease with clinical response to dupilumab. TRIAL REGISTRATION: Liberty Asthma VOYAGE ClinicalTrials.gov NCT02948959.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

Management of CRSwNP in Latin America: A multidisciplinary consensus from an expert working group.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. While etiology and pathogenetic mechanisms are heterogeneous and complex, in most patients, disease is mediated predominantly through type 2 inflammatory processes. Clinical management is challenging, and a multidisciplinary approach is preferred. Principal treatment approaches are the use of local/systemic corticosteroids and sinonasal surgery, although outcomes can be unsatisfactory. Recent availability of biological therapies targeting underlying inflammatory processes can offer effective treatment options in uncontrolled disease. Specialist guidelines greatly assist clinical decision-making, although as these are chiefly written from a global/international perspective, they may not wholly accommodate disease patterns and clinical practice at a regional level. An expert panel of specialists from Latin America was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations which can provide guidance for clinicians in the Latin American region.

Dupilumab improves pediatric type 2 asthma outcomes independent of patient baseline characteristics.

CLINICAL IMPLICATIONS: Dupilumab, a biological therapy that blocks the shared receptor component for interleukins-4/13, reduced exacerbations and improved lung function in children with uncontrolled moderate-to-severe type 2 asthma independent of most baseline patient and asthma characteristics.

Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study.

BACKGROUND: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years. OBJECTIVE: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028). METHODS: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. RESULTS: A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. CONCLUSIONS: Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Rinitis alérgica en pediatría: recomendaciones para su diagnóstico y tratamiento / Allergic rhinitis in pediatrics: recommendations for diagnosis and treatment

La rinitis alérgica (RA) es una de las enfermedades crónicas más frecuentes de la infancia. Sin embargo, permanece subdiagnosticada y subtratada. Su prevalencia ha aumentado en los últimos años y varía del 2 % al 25 %. Los síntomas de la RA incluyen estornudos, prurito, rinorrea y congestión nasal. Un correcto diagnóstico y tratamiento de la RA y sus comorbilidades, tales como rinosinusitis con o sin poliposis nasal, conjuntivitis, otitis media, asma bronquial e infecciones del tracto respiratorio, son importantes para reducir el impacto negativo en la afectación de la calidad de vida del paciente y sus familiares, y los gastos sanitarios que ocasiona. La inmunoterapia alérgeno específica, en pacientes correctamente seleccionados, previene nuevas sensibilizaciones y reduce la hiperreactividad bronquial asociada a la RA. Considerando todos estos factores, el Comité Nacional de Alergia de la Sociedad Argentina de Pediatría propone recomendaciones basadas en la evidencia actual.

Allergic rhinitis (AR) is one of the most common chronic diseases in children. However, it remains underdiagnosed and undertreated. Its prevalence has increased in recent years and varies from 2 to 25 %. Symptoms include sneezing, itching, runny nose, and nasal congestion. A correct diagnosis and treatment of AR and its comorbidities such as rhinosinusitis with or without nasal polyposis, conjunctivitis, otitis media, bronchial asthma and respiratory tract infections, are important to reduce the negative impact on the quality of life of the patient and their relatives, and in medical costs. Specific allergen immunotherapy, in correctly selected patients, prevents new sensitizations and reduces bronchial hyperreactivity associated with AR. Taking into account all these reasons, the National Allergy Committee of the Sociedad Argentina de Pediatría proposes current evidence based recommendations

Estudio aleatorizado, cruzado, de no inferioridad para evaluar la eficacia, la seguridad y la tolerabilidad de dos formulaciones de budesonida/fumarato de formoterol en adultos asmáticos / Randomized, Crossover, Non-Inferiority Study to Evaluate the Efficacy, Safety and Tolerability of Two Budenoside/Formoterol Fumarate Formulations in Asthmatic Adults

RESUMEN El asma es un grave problema de salud mundial. Según el último informe del Ministerio de Salud, 1 380 000 sujetos padecen asma en la Argentina.1 Las guías internacionales (Europa, Estados Unidos, OMS) varían en su enfoque para definir la equivalencia y la posibilidad de intercambio de los productos para inhalación respiratorios. Si bien es posible un enfoque in vitro, en general las guías recomiendan brindar más indi cios clínicos que avalen la posibilidad de intercambiar el producto innovador por otro posteriormente desarrollado con iguales principios activos en polvo seco para inhalar. Este estudio, aleatorizado de fase IV, se realizó para establecer la eficacia, seguridad y tolerabilidad de Neumoterol® 400 en comparación con el producto medicinal de refe rencia Symbicort forte budesonida/fumarato de formoterol 320/9 μg, indicados 2 veces al día en pacientes asmáticos. Además, se evaluó la preferencia de los pacientes por uno u otro dispositivo. Se demostró la no inferioridad de la formulación evaluada en comparación con el pro ducto medicinal de referencia. El límite inferior del IC del 95% para la diferencia entre los tratamientos fue mayor que el margen predefinido de no inferioridad de -125 mL (diferencia: 0,044 l [IC del 95%: -0,008 a 0,096]). Asimismo, se comprobaron valores más altos para el AUC0-10h del FEV1 y un mayor cambio respecto del puntaje basal en la prueba de control del asma el día 29 para las cápsulas de budesonida/fumarato de formoterol 400/12 μg. En un análisis exploratorio sobre la preferencia de los pacientes por los dispositivos, una mayor proporción de participantes expresaron su preferencia global por la cápsula de budesonida/fumarato de formoterol 400/12 μg. No se informa ron diferencias en la incidencia de AE o SAE (del inglés Adverse event: evento adver so y Severe Adverse Event: evento adverso severo) graves durante el tratamiento o después de este. El perfil de seguridad de ambos productos en general concordó con el perfil comprobado de budesonida/fumarato de formoterol.

ABSTRACT Asthma is a serious worldwide health problem. According to the last report of the Min istry of Health, 1,380,000 subjects suffer from asthma in Argentina.1 The International Guidelines (Europe, United States, WHO [World Health Organization]) have varying approaches to define the equivalence and possibility of switching respiratory inhalation products. Whereas an in vitro approach is possible, in general Guidelines recommend providing more clinical evidence that support the possibility of switching from the inno vative product to another one subsequently developed with the same active ingredient in the form of dry powder inhaler. This randomized, phase IV study has been conduct ed to establish the efficacy, safety and tolerability of Neumoterol® 400 compared to the reference medicinal product Symbicort forte, budenoside/formoterol fumarate 320/9 μg twice a day in asthmatic patients. Also, the patients' preference for one device or the other has been evaluated. The evaluated formulation has proven to be non-inferior compared to the reference medicinal product. The lower 95% CI (confidence interval) limit for the difference be tween treatments was higher than the predefined non-inferiority margin of -125 mL (difference: 0.044 l [95% CI: -0.008 to 0.096]). Also, higher values were evidenced for the AUC0-10h (are under the curve) of the FEV1 (forced expiratory volume in the first second) and a more important change of the baseline score in the asthma control test on day 29 for the budenoside/formoterol fumarate capsules of 400/12 μg. In one exploratory test about the patients' preference for one device or the other, a higher pro portion of participants expressed their global preference for the budenoside/formoterol fumarate capsule of 400/12 μg. No differences were reported in the incidence of AEs (adverse events) or SAEs (serious adverse events) during or after the treatment. The safety profile of both products in general agreed with the verified profile of budenoside/ formoterol fumarate.

Alergia e intolerancia a antiinflamatorios no esteroideos en pediatría / Allergy and intolerance to nonsteroidal anti-inflammatory drugs in children

Los antiinflamatorios no esteroideos son ampliamente recetados en niños. Constituyen la segunda causa de reacciones a medicamentos en pediatría después de los antibióticos betalactámicos; sin embargo, solo una parte de estas son reacciones de hipersensibilidad. La prevalencia de dichas reacciones a antiinflamatorios no esteroideos en niños es del 0,3 % y aumenta al 5 % en asmáticos.Los mecanismos fisiopatológicos involucrados (inhibición de la ciclooxigenasa, hipersensibilidad mediada por inmunoglobulina E, linfocitos T reactivos y/o afectación de la inmunidad innata) darán lugar a diferentes entidades clínicas con sintomatología dispar.La confusión con síntomas propios de procesos virales y la variabilidad clínica hacen del diagnóstico de certeza un verdadero desafío. Una historia clínica detallada, análisis de laboratorio, pruebas cutáneas y de provocación controlada permitirán definir estrategias para cada paciente en particular sin etiquetar como alérgico a un niño que no lo es ni exponer a riesgos innecesarios a quien está sensibilizado.

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug ́s reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics.The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms.The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge.A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized.

Intervención ambiental en las enfermedades respiratorias / Environmental intervention in respiratory disease

En los últimos años hubo un aumento significativo en la prevalencia de las enfermedades alérgicas pese a los avances en la comprensión de la patogénesis, la divulgación de guías para su control y tratamiento y la aparición de nuevos fármacos. La raz ón para este aumento no está totalmente estable cida, pero se considera que múltiples factores ambientales podrían estar involucrados en ello. El aire inspirado contiene numerosos agentes nocivos además de alérgenos ambientales; el asma y la rinitis alérgica son las principales expresiones clínicas respiratorias inmediatas posteriores a su inhalación. En la antropósfera, el entorno de la superficie terrestre habitada por los humanos, se han alterado los equilibrios naturales por la emisión de múltiples sustancias y se ha producido un creciente cambio climático. Este fenómeno global influye en la calidad del aire y consecuentemente en el desarrollo de enfermedades respiratorias. Dado que la bibliografía sobre el tema del control ambiental es muy amplia, y en ocasiones difícil de interpretar para poder realizar indicaciones precisas, válidas y sencillas de cumplir por parte de los pacientes, cuatro sociedades científicas de la República Argentina, dedicadas a este tipo de enfermedades, elaboraron un documento con información de fácil acceso a todo profesional médico que trate asma y/o rinitis, que expone medidas prácticas para los enfermos y alerta a los distintos actores involucrados en la salud pública acerca de las necesidades insatisfechas en este tema tan complejo, a fin de poder elaborar una agenda para su posible resolución.

In recent years there has been a significant increase in the prevalence of allergic diseases despite advances in the understanding of the pathogenesis, the dissemination of guidelines for its management and the emergence of new drugs. The reasons for this increase are not fully established, but it is suggested that multiple environmental factors may be involved. Inhaled air contains numerous harmful agents in addition to environmental allergens. The main immediate respiratory clinical expression after inhaling this contaminated air is asthma and rhinitis. The activity of human beings has altered the outdoor environment by the emission of multiple pollutants and has produced an increasing climate change. It also has a notable impact on the development of respiratory pathology and the modification of air quality. The bibliography on the subject of environmental control is very broad and sometimes difficult to interpret. In order to be able to make precise, valid and simple indications for patients to accomplish with, four scientific societies of the Argentine Republic that deal with this type of diseases, have elaborated a document that contains information of easy access to all medical personal involved in the treatment of patients with asthma and / or rhinitis, that provides practical measures for the patients and the different public health systems about unmet needs in this complex issue.

Guía argentina de urticaria y angioedema / Argentine guidelines for urticaria and angioedema

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20

of the population at some point in their lives. Acute urticaria (less than 6 weeks’ duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU’s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40

of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.

Guía Argentina de urticaria y angioedema

Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks' duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU´s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.

Asma de difícil control en niños y adolescentes: Estrategias diagnóstico-terapéuticas / Poorly controlled asthma: diagnosis and therapeutics in children and adolescents

El asma es una de las enfermedades crónicas más frecuentes en los niños. Si bien la mayoría de los niños con asma responden a bajas dosis de corticoides inhalados y/o antagonistas del receptor de leucotrienos, algunos de ellos permanecen sintomáticos independientemente de cualquier esfuerzo terapéutico, presentando una elevada morbilidad e inclusive mortalidad. Aunque la mayoría de los pacientes controlan los síntomas de forma adecuada, existe un grupo importante que presenta síntomas graves de la enfermedad difíciles de controlar (ADC). El objetivo de la presente revisión es discutir los aspectos clínicos, diagnósticos y terapéuticos del ACD en los menores de 18 años y su implicancia en la práctica clínica diaria.

Asthma is one of the most common chronic diseases in children. While most children with asthma respond to low doses of inhaled corticosteroids and /or leukotriene receptor antagonists, some of them remain symptomatic regardless of any therapeutic effort, showing a high morbidity and even mortality. While most of the patients control symptoms adequately, there is a large group with severe symptoms of the disease and difficult to control. The aim of this review is to discuss the clinical aspects, diagnosis and treatment of poorly controlled asthma in children and adolescents and its implications in daily clinical practice.

Urticaria crónica autoinmunitaria: tratamiento con omalizumab / Chronic autoimmune urticaria: treatment with omalizumab

Se presenta el caso de una niña con diagnóstico de urticaria autoinmunitaria y su evolución terapéutica con omalizumab. Caso clínico. Paciente de sexo femenino de 12 años de edad con un cuadro de urticaria crónica grave y angioedema de 14 meses de evolución, escasa respuesta a dosis máximas de 3 antihistamínicos combinados, antileucotrienos y corticoides, y gran afectación de su calidad de vida. Se realizó una prueba de suero autólogo, que fue positiva hasta la dilución 1:100, llegándose al diagnóstico de urticaria crónica autoinmunitaria. La falta de respuesta al tratamiento lleva a indicar terapia con omalizumab, con una reducción notable de los síntomas hacia la tercera dosis y ausencia de ellos tras 12 meses de tratamiento. Conclusión. El omalizumab podría ser una opción terapéutica para pacientes con urticaria autoinmunitaria que no responden a otros tratamientos.

We report the case of a child with diagnosis of chronic urticaria/angioedema and its evolution upon omalizumab treatment. Case report. Our patient is a 12-years-old female who suffered for 14 months severe chronic urticaria/angioedema. She had a poor response to the highest doses of combined therapy with 3 antihistamines, steroids and anti-leukotrienes and great impairmentof her quality of life. An autologous serum skin test was positive until 1:100 dilutions, leading to the diagnosis of chronic autoimmune urticaria. Due to the lack of response to treatment, therapy with omalizumab was administered. A notable reduction in symptoms toward the third dose was observed. After 12 months of this treatment, the patient is asymptomatic and has a negative autologousserum test. Conclusion. Omalizumab could be a therapeutic option for patients with autoimmune urticaria unresponsive to other treatments.

O que é um alergista? / What is an allergist?

Introdução: O alergista é o médico que concluiu com êxito um período de treinamento especializado em alergia e imunologia e um período de treinamento em medicina interna e/ou pediatria. Os alergistas também são imunologistas clínicos especializados, devido à base imunológica das doenças que diagnosticam e tratam. Na maioria dos países, o período aprovado de formação na especialidade em alergia e imunologia é de dois a três anos de treinamento intenso e específico. Dependendo dos sistemas de credenciamento nacionais, a conclusão desse treinamento será reconhecida por um certificado de treinamento especializado em alergia, em alergia e imunologia ou em alergia e imunologia clínica, outorgado por uma comissão diretiva. Em alguns países, isso acompanha a conclusão bem-sucedida de um exame de qualificação e, em outros, as competências apresentadas por um supervisor de treinamento. Os alergistas totalmente treinados fazem uma importante contribuição para o delineamento dos sistemas de atendimento local e proporcionam o atendimento necessário aos pacientes com doenças alérgicas. Os alergistas agem como defensores do paciente, e apóiam e questionam o caso para melhorar a educação dos médicos de atendimento primário e secundário, assim como de outros profissionais de saúde que também atendem pacientes alérgicos. Os alergistas devem estar disponíveis para fazer o atendimento dos casos mais complicados, que estão além do campo de ação de médicos de atendimento primário e secundário e de outros profissionais de saúde com bom treinamento. As principais características que definem um alergista são a apreciação da importância dos desencadeantes externos que causam a doença e o conhecimento de como identificar e tratar essas doenças, juntamente com a experiência nas terapias imunológicas e fármacos apropriados. Essa conduta no diagnóstico e na terapia é um valor essencial do especialista em alergia, e destaca o alergista entre muitos especialistas cujas bases de pacientes podem sobrepor-se com a especialidade...

Requisitos para treinamento médico em alergia: competências clínicas essenciais para o tratamento de pacientes com doenças alérgicas ou imunológicas: declaração da posição provisória da word allergy organization (WAO) / Requirements for physician training in allergy: key clinical competencies appropriate for the care of patients with allergic or immunologic diseases: a provisional position statement of the world allergy organization

Introdução: As doenças alérgicas têm prevalência extraordinária em todo o mundo, e a incidência de alergia é crescente em to¬dos os lugares!-7. Como os processos alérgicos e imunol¬gicos sobrepõem todos os sistemas orgânicos, nem sempre a alergia é ensinada nas escolas de medicina como uma disciplina separada. Realmente, a falta de reconhecimento da especialidade e da necessidade de ensinar as doenças alérgicas e imunológicas resulta no fato de a alergia não ser incluída em certos currículos de medicinas. Com a estimativa de que 22 pt por cento da população global tem doenças alérgicas e imunológicas, está na hora de reconhecer e fortalecer a educação em alergia e imunologias. A World Aflergy Organization, uma aliança de 74 sociedades nacionais e regionais de alergia, criou este documento consensual para estabelecer diretrizes educacionais que aplicadas mundialmente, para identificar e corrigir as deficiências do treinamento em alergia e para definir metas de treinamento apropriadas. Ao criar este consenso, é reconhecido que cada país tem seus próprios princípios e metas de educação médica nos níveis de graduação e pós-graduação. Este documento define o que um médico deve saber para tratar pacientes alérgicos.