Phenotypes and endotypes of uncontrolled severe asthma: new treatments.

Severe asthma is a heterogeneous disease that affects only 5%-10% of asthmatic patients, although it accounts for a significant percentage of the consumption of health care resources. Severe asthma is characterized by the need for treatment with high doses of inhaled corticosteroids and includes several clinical and pathophysiological phenotypes. To a large extent, this heterogeneity restricts characterization of the disease and, in most cases, hinders the selection of appropriate treatment. In recent years, therefore, emphasis has been placed on improving our understanding of the various phenotypes of severe asthma and the identification of biomarkers for each of these phenotypes. Likewise, the concept of the endotype has been gaining acceptance with regard to the various subtypes of the disease, which are classified according to their unique functional or pathophysiological mechanism. This review discusses the most relevant aspects of the clinical and inflammatory phenotypes of severe asthma, including severe childhood asthma and the various endotypes of severe asthma. The main therapeutic options available for patients with uncontrolled severe asthma will also be reviewed.

Natural pollen exposure increases the response plateau to adenosine 5'-monophosphate and bronchial but not alveolar nitric oxide in sensitized subjects.

BACKGROUND: The effect of allergen exposure on airway responsiveness and exhaled nitric oxide (NO) has been well documented, but no information is available on allergen-induced changes in the response plateau to adenosine 5'-monophosphate (AMP) and in bronchial NO flux (J'aw(NO)) and alveolar NO (CA(NO)). OBJECTIVES: To determine the effect of natural allergen exposure, a proinflammatory stimulus, on the shape of the concentration-response curve to AMP and NO production in airway and alveolar sites. METHODS: Airway responsiveness to high concentrations of methacholine and AMP, J'aw(NO) and CA(NO) values were obtained in 31 subjects with pollen allergy and in 11 healthy controls. Subjects with pollen allergy were studied before and at the height of the pollen season whereas healthy controls were tested on one occasion only. RESULTS: In the group with pollen allergy, natural pollen exposure increased J'aw(NO) (p = 0.03), but had no effect on CA(NO) (p = 0.12). In the 18 subjects with pollen allergy who showed a response plateau to AMP in at least one period, the response plateau to AMP increased from a mean of 13.4% (95% CI: 8.2-18.5) out of season to 22.5% (95% CI: 15.5-29.4, p = 0.004) during the pollen season. Similar results were obtained with methacholine. Compared with healthy controls, subjects with pollen allergy had a higher response plateau and higher J'aw(NO) values. CONCLUSIONS: These findings suggest that inflammatory changes induced by natural allergen exposure in sensitized subjects are predominantly located in the airways and associated with modifications in the shape of the concentration-response curve to direct and indirect agonists.

Consensus document on the diagnosis of severe uncontrolled asthma.

BACKGROUND: The concepts of asthma severity, control, and exacerbation are important in the evaluation of patients and their response to treatment. However, terminology is not standardized, and terms are often used interchangeably. Patients with uncontrolled severe asthma pose a major health care problem. Over the last decade, it has become increasingly clear that, in order to facilitate the development of novel targeted therapies, patients must be further characterized and classified. OBJECTIVE: To draft a consensus statement on the diagnosis, management, and treatment of severe uncontrolled asthma. The statement is meant to serve as a guideline for health professionals and clinical researchers. METHODS: The consensus was led by the Severe Asthma Working Group of the Spanish Society of Allergology and Clinical ImmunologyAsthma Committee. A review was conducted of the best available scientific evidence (until December 2011) on severe asthma in adults and children. RESULTS: Definitions for severe asthma, level of control, and exacerbation are developed. Different phenotypes and endophenotypes of severe uncontrolled asthma and new specific therapeutic interventions are presented. A systematic algorithm for the evaluation of patients presenting with severe persistent asthma symptoms is proposed. CONCLUSIONS: A consensus statement on the diagnosis, management, and treatment of severe uncontrolled asthma is presented.

[Analysis of clinical safety in the units of Allergy of the Valencian Community]. / Análisis de la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana.

The introduction of new diagnostic and therapeutic procedures involving allergen exposure may increase the risk of allergic reactions. We designed and distributed an anonymous questionnaire among the allergy units of the Valencian Community in order to collect information on measures to ensure clinical safety. Twelve hospital outpatient clinics and 8 ambulatory care centres reported similar patterns of activities, including the use of critical care units, emergency rooms or day hospitals for higher risk techniques. The provision of security-related instruments is broader in hospital outpatient clinics and included: oxygen (91.7%), pulse oximeter (75.0%) or vital signs monitor (8.3%), resuscitation material (91.7%) and defibrillator (83.3%). The response time for emergencies is set in 50% of clinics. The resuscitation material is systematically reviewed and informed consent signed. Security is more limited in ambulatory care centres. It is necessary to set down the conditions for clinical safety in allergology. Key words. Allergy. Ambulatory care. Clinical safety. Health services. Hospital outpatient clinic.

Pollen-induced allergic asthma and rhinoconjunctivitis: differences in outcome between seasonal and nonseasonal exposure to allergens under real-life conditions (The LANDSCAPE Study)

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Análisis de la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana / Analysis of clinical safety in the Allergy Units of the Valencian Community

La introducción de procedimientos diagnósticos y terapéuticos que implican exposición alergénica conlleva riesgos. Para evaluar la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana se diseñó y distribuyó un cuestionario anónimo, obteniendo respuesta de doce unidades hospitalarias y ocho centros de especialidades. La distribución de prestaciones entre los diversos entornos fue homogénea, así como la utilización de unidades de críticos, urgencias u hospitales de día para técnicas de mayor riesgo. La dotación de instrumentos relacionados con la seguridad es más amplia en las consultas hospitalarias e incluye fuente de oxígeno (91,7%), pulsioxímetro (75,0%) o monitor (8,3%), carro de paradas (91,7%) y desfibrilador (83,33%). El tiempo de respuesta para emergencias está pactado en el 50%. Sistemáticamente se revisa el material para resucitación y se firma consentimiento informado. La seguridad es más limitada en los centros de especialidades. Se deberían establecer las condiciones idóneas de seguridad clínica en Alergología (AU)

The introduction of new diagnostic and therapeutic procedures involving allergen exposure may increase the risk of allergic reactions. We designed and distributed an anonymous questionnaire among the allergy units of the Valencian Community in order to collect information on measures to ensure clinical safety. Twelve hospital outpatient clinics and 8 ambulatory care centres reported similar patterns of activities, including the use of critical care units, emergency rooms or day hospitals for higher risk techniques. The provision of security-related instruments is broader in hospital outpatient clinics and included: oxygen (91.7%), pulse oximeter (75.0%) or vital signs monitor (8.3%), resuscitation material (91.7%) and defibrillator (83.3%). The response time for emergencies is set in 50% of clinics. The resuscitation material is systematically reviewed and informed consent signed. Security is more limited in ambulatory care centres. It is necessary to set down the conditions for clinical safety in allergology (AU)

Effect of omalizumab on adenosine 5'-monophosphate responsiveness in subjects with allergic asthma.

BACKGROUND: The objective of this study was to evaluate the effects of omalizumab on bronchoconstriction induced by methacholine and adenosine 5'-monophosphate (AMP). METHODS: Thirty-four subjects with mild to moderate allergic asthma were randomized to receive placebo (n = 16) or omalizumab (n = 18) subcutaneously during 12 weeks. Airway responsiveness to AMP was measured at baseline and after 4 and 12 weeks of treatment, whereas the response to methacholine was measured at baseline and after 12 weeks of treatment. RESULTS: After 4 weeks of treatment, the increase in AMP PC(20) (provocative concentration required to produce a 20% fall in FEV(1)) was significantly greater in the omalizumab group than in the placebo group, the mean difference in the change between the groups being 1.52 doubling concentrations (95% CI, 0.25-2.79, p = 0.02). Compared with baseline, the mean AMP PC(20) values at 12 weeks were increased by 1.91 doubling concentrations with omalizumab (p < 0.001) and 1.01 doubling concentrations with placebo (p = 0.16), but changes were not significantly different between the treatment groups. Changes in methacholine PC(20) values were not significantly different between the omalizumab and placebo groups. CONCLUSIONS: In subjects with allergic asthma, omalizumab reduces the response to AMP without decreasing the response to methacholine. These findings are consistent with the conclusion that the contribution of IgE to the development of AMP bronchoconstriction is more important than their role in the induction of methacholine hyperresponsiveness.

Phenotypes and Endotypes of Uncontrolled Severe Asthma: New Treatments

El asma grave es una enfermedad heterogénea que constituye entre un 5-10% de los sujetos asmáticos, pero representan un porcentaje significativo del consumo de los recursos sanitarios. El asma grave se caracteriza por precisar tratamiento con altas dosis de corticosteroides, e incluye diversos fenotipos tanto clínicos como fisiopatológicos. Esta heterogeneidad dificulta en gran medida la caracterización de la enfermedad, y en la mayoría de los casos también la elección del tratamiento adecuado. Por esta razón, en los últimos años se ha hecho hincapié en la mejora en el conocimiento de los distintos fenotipos del asma grave, y en la identificación de biomarcadores para cada uno de ellos. Así mismo, también ha tomado fuerza el concepto de endotipo en referencia a los distintos subtipos de la enfermedad divididos en base a su mecanismo funcional o fisiopatológico único. En esta revisión serán discutidos los aspectos más relevantes de los fenotipos clínicos e inflamatorios del asma grave, incluyendo el asma grave infantil y los diferentes endotipos del asma grave serán discutidos en este capítulo. Así mismo, se revisan las principales opciones terapéuticas disponibles en este grupo de pacientes serán revisadas (AU)

Severe asthma is a heterogeneous disease that affects only 5%-10% of asthmatic patients, although it accounts for a significant percentage of the consumption of health care resources. Severe asthma is characterized by the need for treatment with high doses of inhaled corticosteroids and includes several clinical and pathophysiological phenotypes. To a large extent, this heterogeneity restricts characterization of the disease and, in most cases, hinders the selection of appropriate treatment. In recent years, therefore, emphasis has been placed on improving our understanding of the various phenotypes of severe asthma and the identification of biomarkers for each of these phenotypes. Likewise, the concept of the endotype has been gaining acceptance with regard to the various subtypes of the disease, which are classified according to their unique functional or pathophysiological mechanism. This review discusses the most relevant aspects of the clinical and inflammatory phenotypes of severe asthma, including severe childhood asthma and the various endotypes of severe asthma. The main therapeutic options available for patients with uncontrolled severe asthma will also be reviewed (AU)