Cost-effectiveness and Budget Impact of Routine Use of Fractional Exhaled Nitric Oxide Monitoring for the Management of Adult Asthma Patients in Spain.

OBJECTIVES: Fractional exhaled nitric oxide (FeNO) is a marker for type 2 airway inflammation. The objective of this study was to evaluate the cost-effectiveness and budget impact of FeNO monitoring for management of adult asthma in Spain. METHODS: A cost-effectiveness analysis model was used to evaluate the effect on costs of adding FeNO monitoring to asthma management. Over a 1-year period, the model estimated the incremental cost per quality-adjusted life year and incremental number of exacerbations avoided when FeNO monitoring was added to standard guideline-driven asthma care compared with standard care alone. Univariate and multivariate sensitivity analyses were applied to explore uncertainty in the model. A budget impact model was used to examine the impact of FeNO monitoring on primary care costs across the Spanish health system. RESULTS: The results showed that adding FeNO to standard asthma care saved €62.53 per patient-year in the adult population and improved quality-adjusted life years by 0.026 per patient-year. The budget impact analysis revealed a potential net yearly saving of €129 million if FeNO monitoring had been used in primary care settings in Spain. CONCLUSIONS: The present economic model shows that adding FeNO to the treatment algorithm can considerably reduce costs and improve quality of life when used to manage asthma in combination with current treatment guidelines.

Cost-effectiveness and budget impact of routine use of fractional exhaled nitric oxide monitoring for the management of adult asthma patients in Spain

Objectives: Fractional exhaled nitric oxide (FeNO) is a marker for type 2 airway inflammation. The objective of this study was to evaluate the cost-effectiveness and budget impact of FeNO monitoring for management of adult asthma in Spain. Methods: A cost-effectiveness analysis model was used to evaluate the effect on costs of adding FeNO monitoring to asthma management. Over a 1-year period, the model estimated the incremental cost per quality-adjusted life year and incremental number of exacerbations avoided when FeNO monitoring was added to standard guideline-driven asthma care compared with standard care alone. Univariate and multivariate sensitivity analyses were applied to explore uncertainty in the model. A budget impact model was used to examine the impact of FeNO monitoring on primary care costs across the Spanish health system. Results: The results showed that adding FeNO to standard asthma care saved €62.53 per patient-year in the adult population and improved quality-adjusted life years by 0.026 per patient-year. The budget impact analysis revealed a potential net yearly saving of €129 million if FeNO monitoring had been used in primary care settings in Spain. Conclusions: The present economic model shows that adding FeNO to the treatment algorithm can considerably reduce costs and improve quality of life when used to manage asthma in combination with current treatment guidelines (AU)

Objetivos: La fracción exhalada del óxido nítrico (FeNO) es un marcador de la inflamación bronquial de tipo Th-2. El objetivo de este estudio ha sido evaluar el coste-efectividad e impacto presupuestario de la monitorización del FeNO en el manejo del asma del adulto en España. Métodos: Se ha utilizado un modelo de análisis de coste-efectividad para evaluar los resultados económicos cuando se utilizó el FeNO en el manejo del asma durante un año. El modelo estimó el incremento de coste por calidad de vida ajustada por año (QALY) y el número de exacerbaciones evitadas cuando se añadió el FeNO a la guía habitual de tratamiento del asma en comparación con la guía habitual. Se aplicó un análisis univariante y multivariante para valorar la posible incertidumbre del modelo. Se utilizó un modelo de impacto presupuestario para evaluar el impacto económico de la introducción de la monitorización con el FeNO en consultas de atención primaria del estado español y teniendo en cuenta el sistema sanitario español. Resultados: Se ha demostrado que el añadir el FeNO al tratamiento habitual del asma ahorra 62,53€ por paciente por año en adultos con asma y mejoró la QALYs en 0,026 por paciente y año. El análisis económico resultó en un ahorro estimado de 129 millones de euros netos por año en consultas de atención primaria. Conclusiones: El modelo económico utilizado ha mostrado que el añadir el FeNO al algoritmo habitual de tratamiento del asma conlleva a un importante ahorro en recursos económicos y un aumento de la calidad de vida (AU)

Cat allergen induces proinflammatory responses by human monocyte-derived macrophages but not by dendritic cells.

BACKGROUND: The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14-). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens. METHODS: Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. RESULTS: We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. CONCLUSION: These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.

Characterization of the human T cell response to antigen 5 from Vespula vulgaris (Ves v 5).

BACKGROUND: The T cell reactivity to the major allergen of bee venom, phospholipase A2, has been thoroughly characterized. In contrast, only little is known about the human cellular response to major allergens from wasp venom. OBJECTIVE: To characterize the human T cell response to antigen 5 from Vespula vulgaris, Ves v 5. METHODS: Recombinant Ves v 5 was used to establish allergen-specific T cell lines (TCL) and T cell clones (TCC) from the peripheral blood of vespid-allergic and non-allergic individuals. Ves v 5-specific TCL were mapped for T cell epitopes using overlapping synthetic peptides representing the complete amino acid sequence of Ves v 5. Ves v 5-specific TCC were analysed for antigen-induced secretion of IL-4, IFN-gamma and IL-10. RESULTS: Seventeen distinct T cell epitopes were recognized by allergic individuals among which Ves v 5(181-192) was identified as a dominant T cell epitope. Partially different epitopes were observed in TCL from non-allergic subjects and the dominant epitope Ves v 5(181-192) was not prevalent in these cultures. Ves v 5-specific TCC isolated from allergic individuals did not show the typical T helper type 2 (Th2)-like cytokine profile in response to specific stimulation, i.e. high amounts of IL-4 and low IFN-gamma. TCC from non-allergic individuals showed a Th1-like cytokine pattern. CONCLUSIONS: Our findings provide evidence that the allergic T cell response to Ves v 5 is not Th2-dominated and that different immunogenic sites on this major wasp venom allergen are recognized by allergic and non-allergic individuals.

Positive skin and oral challenge responses to potato and occurrence of immunoglobulin E antibodies to patatin (Sol t 1) in infants with atopic dermatitis.

The clinical significance and molecular specificity of hypersensitivity reactions to raw and cooked potatoes remain ambiguous. We therefore investigated the clinical hypersensitivity to raw and cooked potato in infants suspected to have potato allergy and compared the findings with the occurrence of immunoglobulin E (IgE) antibodies to patatin (Sol t 1), characterized as the primary allergen of potato. Twelve infants (10 to 24 months of age) suffering from atopic dermatitis (AD) and suspected to have adverse reactions to potato, were examined. As a skin exposure test we used rubbing with both raw and cooked potato, and used open oral challenge with cooked potato for 7 days. A special eczema scoring system (SCORAD) was used to assess the severity of symptoms and signs of AD. Skin-prick tests (SPTs) were performed with raw potato and natural Sol t 1, and serological studies included measurement of total serum IgE and IgE antibodies to Sol t 1, and potato radioallergosorbent testing (RAST). The skin-rubbing test with raw potato was positive in seven (58%) and the oral challenge positive in eight (67%) infants. One infant presented with an immediate reaction and seven with a delayed reaction, i.e. exacerbation of AD, after oral challenge responses to cooked potato. Nine (75%) infants had IgE antibodies to Sol t 1 in enzyme-linked immunosorbent assay (ELISA), and SPT to natural Sol t 1 was positive in six (50%) potato-allergic infants. In conclusion, we observed positive challenge responses to both raw and cooked potato in food-allergic atopic infants. The presence of IgE antibodies and concomitant positive SPTs to the heat-stable potato allergen, Sol t 1, suggest that cooked potato can be an allergenic food for infants suffering from AD.

Identification of four novel potato (Solanum tuberosum) allergens belonging to the family of soybean trypsin inhibitors.

BACKGROUND: We have previously identified patatin (Sol t 1) of potato tubers as a major food allergen among atopic children. In addition to Sol t 1, concomitant IgE binding to other, then unidentified, potato proteins was observed. METHODS: Purification and identification of the putative allergens were done by both standard and advanced methods of protein chemistry. The patient series comprised 39 children with positive skin prick test (SPT) to raw potato. Immunoblotting and ELISA were used to examine IgE-binding ability and skin prick testing to assess in vivo reactivity of the purified potato proteins. RESULTS: Four IgE-binding potato proteins with molecular masses ranging from 16 to 20 kDa were purified and identified as cathepsin D-, cysteine-, and aspartic protease inhibitors belonging to the family of soybean trypsin inhibitors (Kunitz type). The proteins were designated Sol t 2, Sol t 3.0101, Sol t 3.0102, and Sol t 4. In ELISA, 51% of the sera of the 39 atopic children showed specific IgE to Sol t 2, 43% to Sol t 3.0101, 58% to Sol t 3.0102, and 67% to Sol t 4, respectively. All these four allergens were able to produce positive wheal-and-flare responses in SPT. CONCLUSION: In addition to Sol t 1, potato tubers contain several proteins belonging to the family of soybean trypsin inhibitors against which atopic children with positive SPT responses to raw potato have in vitro and in vivo reactive IgE antibodies.

IgE reactivity to patatin-like latex allergen, Hev b 7, and to patatin of potato tuber, Sol t 1, in adults and children allergic to natural rubber latex.

BACKGROUND: Patients allergic to natural rubber latex (NRL) frequently show positive skin prick tests (SPT) and hypersensitivity reactions to various fruits, such as avocado, banana, and kiwi, as well as to vegetables such as potato. METHODS: Hev b 7 was purified from NRL "C-serum" and Sol t 1 from potato extract, and they were detected by immunoblotting. IgE antibodies to Hev b 7 and Sol t 1 were measured with ELISA in sera from 35 adults and 35 children allergic to NRL. ELISA inhibition and immunoblotting were used to study allergen cross-reactivity. The in vivo reactivity of Hev b 7 and Sol t 1 were demonstrated in the SPT. RESULTS: Seventeen (49%) of the 35 NRL-allergic adults had IgE antibodies to Hev b 7, in contrast to only one of the 35 NRL-allergic children. Fifteen (43%) of the NRL-allergic adults and 29 (83%) of the NRL-allergic children had IgE antibodies to Sol t 1. Ten (29%) of the adult sera showed IgE binding to both Sol t 1 and Hev b 7, and crosswise inhibition tests with pooled sera revealed marked cross-reactivity. In the SPT, both natural Hev b 7 and Sol t 1 were able to produce a wheal and flare reaction. CONCLUSIONS: One-half of the NRL-allergic adults, but only one of the NRL-allergic children, had IgE antibodies to natural Hev b 7. These results suggest that Hev b 7 is an important NRL allergen for adults, but not for children. Elucidation of the clinical importance of the observed cross-reactivity between Hev b 7 and Sol t 1 requires further studies.

Identification of patatin as a novel allergen for children with positive skin prick test responses to raw potato.

BACKGROUND: Peeling of raw potatoes may cause allergic symptoms, such as sneezing, wheezing, and contact urticaria, for adults. For children, potatoes as food may cause various allergic reactions. However, the identity and molecular structure of the putative allergens in potato have remained unknown. OBJECTIVE: The aim of our study was to identify possible major allergens in potato by using sera of atopic children suspected of having food allergy and having positive skin prick test responses to raw potato. METHODS: Potato proteins were purified by standard methods of protein chemistry and characterized with amino-terminal sequencing and mass spectrometry. The IgE-binding ability of the purified proteins was verified by immunoblotting and ELISA with IgE antibodies from the sera of atopic children having positive skin prick test responses to raw potato. RESULTS: Immunoblotting showed strong IgE binding to a 43-kd protein, identified as patatin, the main storage protein of potato tubers. In ELISA, 20 of 27 (74%) children with positive skin prick test responses to potato and none of the control subjects showed specific binding of IgE antibodies to purified patatin. A positive wheal-and-flare reaction was seen in 8 of 14 children prick tested with purified patatin. CONCLUSION: These results show that patatin in potatoes is a significant, previously unrecognized,IgE-binding protein for children with a positive skin prick test response to raw potato. Further studies are needed to confirm the clinical importance of potatoes, and especially patatin, as a food allergen.