ABSTRACT
BACKGROUND: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. METHODS: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. RESULTS: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. CONCLUSION: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.
Subject(s)
Hypersensitivity , Interleukin-10 , Allergens , Allergoids , Animals , Dander , Dogs , Humans , Immunoglobulin E , Immunoglobulin G , Interleukin-10/metabolism , Plant Extracts/pharmacology , RabbitsABSTRACT
OBJECTIVE: to identify lethality and mortality rates and, mortality risk factors in ventilator associated pneumonia (VAP) on 114 patients treated between 2000 and 2007. METHOD: Twenty five risk factors were analyzed, emphasizing age, gender, APACHE score, associated diseases, hypotension at intake, coma, hospitalization time, length of time of ventilation, emergency intubation, reintubation, previous antibiotics, and resistant microrganisms. RESULTS: Lethality was 25.4 %, and mortality was 2.4 %. Association between lethality, and APACHE score was found (p: 0.04). Critical APACHE value was 22. Also, in early pneumonia, association between lethality and nasogastric tube (p: 0.01, I.C. 95 % 1.39 - 6.35) was found. No association with late pneumonia was found among mortality and clinical practices. Death's RR (relative risk) increase in following values with: previous neurological disease 2.7 (p: 0.15, IC 95 % 1.15 - 6.5), neurological comaRR 2 (p: 0.2, IC 95 % 0.54 - 7.53). Nevertheless, at multivariate analysis no mortality risk factors were identified. Fair association with time in ICU (p: 0.051 IC 95 % 0.99 - 1.17) and, male sex (p: 0.051, IC 95 % 0.99 - 6.72) was found. CONCLUSIONS: We observed multiple factors associated to mortality in VAP: use of nasogastric catheter, longer stay in ICU and male sex.
Subject(s)
Pneumonia, Ventilator-Associated/mortality , Chile/epidemiology , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/microbiologyABSTRACT
Objective: to identify lethality and mortality rates and, mortality risk factors in ventilator associated pneumonia (VAP) on 114 patients treated between 2000 and 2007. Method: Twenty five risk factors were analyzed, emphasizing age, gender, APACHE score, associated diseases, hypotension at intake, coma, hospitalization time, length of time of ventilation, emergeney intubation, reintubation, previous antibiotics, and resistant microrganisms. Results: Lethality was 25.4 percent, and mortality was 2.4 percent. Association between lethality, and APACHE score was found (p: 0.04). Critical APACHE valué was 22. Also, in early pneumonia, association between lethality and nasogastric tube (p: 0.01, I.C. 95 percent 1.39 - 6.35) was found. No association with late pneumonia was found among mortality and clinical practices. Death's RR (relative risk) increase in following valúes with: previous neurological disease 2.7 (p: 0.15, IC 95 percent 1.15 - 6.5), neurological comaRR2 (p: 0.2, IC 95 percent 0.54 - 7.53). Nevertheless, at multivariate analysis no mortality risk factors were identified. Fair association with time in ICU (p: 0.051 IC 95 percent 0.99 - 1.17) and, male sex (p: 0.051, IC 95 percent 0.99 - 6.72) was found. Conclusions: We observed múltiple factors associated to mortality in VAP: use of nasogastric catheter, longer stay in ICU and male sex.
Objetivo: Identificar la tasa de letalidad, mortalidad y factores de riesgo de mortalidad en neumonía asociada a ventilación mecánica (NAVM) en 114 pacientes de la cohorte 2000-2007. Se estudiaron 25 factores de riesgo del paciente y de las prácticas clínicas. Resultados: La tasa de letalidad fue 25,4 por ciento) y la tasa de mortalidad de 2,4 por ciento>. Se encontró asociación entre el puntaje APACHE al momento del diagnóstico de neumonía y mortalidad (p: 0,04). El valor crítico de APACHE de alto riesgo fue igual o mayor a 22. En neumonía precoz se identificó como factor de letalidad la presencia de sonda naso-gástrica (p: 0,01, IC 95 por ciento> 1,39-6,35). Para las variables categóricas no se encontró asociación significativa entre la exposición y mortalidad. El RR en presencia de enfermedad neurológica previa (accidente vascular encefálico) fue 2,7 (p: 0,15, IC 95 por ciento 1,15-6,5), coma al ingreso 2 (p: 0,2, IC 95 por ciento 0,54-7,53). En neumonía tardía, no se identificaron factores de riesgo asociados a la atención. El análisis multivariado de todas esas exposiciones no identificó factores significativos asociados a mortalidad. Identificamos una asociación débil con días de estada en UCI (p: 0,051 IC 95 por ciento 0,99-1,17) y sexo masculino (p: 0,051, IC 95 por ciento 0,99-6,72). Conclusiones: Los resultados muestran una relación multifactorial de prácticas clínicas y del paciente para fallecer por NAVM. Como factor de prácticas clínicas encontramos asociado a mortalidad el uso de sonda nasogástrica y mayor permanencia en UCI. Dependiente del paciente encontramos una débil asociación entre mortalidad y sexo masculino.
Subject(s)
Female , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/mortality , Chile/epidemiology , Epidemiologic Methods , Pneumonia, Ventilator-Associated/microbiologyABSTRACT
Contiene: Generalidades, antibioticos, sulfonamidas, drogas antituberculosas, agentes antifungicos, drogas antiparasitarias, agentes antivirales
