Subcutaneous allergen immunotherapy for asthma: A randomized, double-blind, placebo-controlled study with a standardized Blomia tropicalis vaccine.

BACKGROUND: Sensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. OBJECTIVE: To assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. METHODS: A double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). RESULTS: The 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26-61) of placebo values, whereas medication was 34.5% (22.4%-63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. CONCLUSIONS: Subcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).

Is peanut causing food allergy in Cuba? Preliminary assessment of allergic sensitization and IgE specificity profile to peanut allergens in Cuban allergic patients.

BACKGROUND: Peanut allergy is increasing at an alarming pace in developed countries. Peanut (Arachis hypogaea) is a common food in Cuba. Nevertheless, reported values of sensitization and symptom severity are usually low. As our objective, we carried out an evaluation of allergic sensitivity to perform an assessment of allergic sensitization and IgE specificity profile to peanut allergens in Cuban allergic patients. METHODS: The Skin Prick Test (SPT) was performed for each patient, using two glycerinated allergenic extracts, prepared from raw or roasted peanuts. Overall, 316 food allergic patients (159 adults and 157 children) attending allergy services at four hospitals in Havana were included, as well as 303 adult non- allergic volunteers. The IgE binding profile of 26 selected SPT positive patients was further analyzed by immunoblotting. RESULTS: The prevalence of sensitization to peanut was 4.6% in general adult population, whereas in adult food-allergic patients it was 18.6%. Prevalence rates were even greater in food allergic children achieving 25.8%. Sensitization frequencies were apparently greater for roasted, as compared to raw peanuts, although the difference was not significant (p> 0.05, Mc Nemar's). IgE binding was shown mostly by the 15 and 17 kDa bands, tentatively identified as the major allergens Ara h 2 and Ara h 6. The IgG4 binding profile was similar to IgE, although with more prominence of the bands at 37 and 28 KDa, corresponding to an Ara h 3 fragment and Peanut Agglutinin. DISCUSSION: The study estimated a relatively high prevalence of peanut sensitization in population. Data reported here suggest that IgE sensitization in Cuban patients is focused mostly on MW bands corresponding to the major allergens Ara h 6 and Ara h 2. CONCLUSIONS: Sensitization to peanut allergen is indeed relatively frequent in Cuba. The IgE profile is congruent to a sensitization pattern by ingestion of roasted peanuts and is directed to well-known major allergens.

[Sensitivity and specificity of prick skin test with two concentrations of standardized extract of Culex quinquefasciatus in allergic children]. / Sensibilidad y especificidad de la prueba cutánea por punción con dos concentraciones del extracto estandarizado de Culex quinquefasciatus en niños alérgicos.

BACKGROUND: Diagnostic options for immune reactions to mosquito bites are limited. In Cuba, IgE-mediated reactions are frequently related to Culex quinquefasciatus bite. OBJECTIVE: To determine the sensitivity and specificity of skin prick test with two doses of standardized extract in nitrogen protein units (PNU of Culex quinquefasciatus (BIOCEN, Cuba). MATERIAL AND METHOD: An analytical study was conducted on 100 children between 2 and 15 years old. Fifty atopic patients with a history of allergy to mosquito bite and positive specific serum IgE Culex quinquefasciatus and fifty atopic patients without a history of allergy to mosquito bite and negative specific serum IgE to Culex quinquefasciatus. Skin prick tests (SPT) were performed by duplicates on the forearms of the patients. Investigated doses were 100 PNU/mL and 10 PNU/mL. RESULTS: SPT with the highest concentration obtained a mean wheal size of 22.09 mm2 and for lower doses of 8.09 mm2, a statistically significant difference (p=0.001, Student's t test). Positive skin test correlated in 100% of patients with the presence of specific IgE. Testing with both doses showed a 94% of specificity and 88% of sensitivity. CONCLUSION: The diagnostic accuracy of SPT using both doses of standardized extract was similar, which justifies its use for diagnosis of sensitization to Culex quinquefasciatus in patients with symptoms of allergy to mosquito bite.

Antecedentes: las opciones diagnósticas de las reacciones inmunológicas a la picadura del mosquito son limitadas. En Cuba, las reacciones mediadas por IgE más frecuentes son por picadura de Culex quinquefasciatus. Objetivo: determinar la sensibilidad y especificidad de la prueba cutánea por punción con dos dosis del extracto estandarizado en unidades de nitrógeno proteico (UNP) de Culex quinquefasciatus (BIOCEN, Cuba). Material y método: estudio analítico efectuado en 100 niños entre 2 y 15 años de edad: 50 pacientes atópicos con antecedentes de alergia a la picadura de mosquito e IgE sérica específica positiva a Culex quinquefasciatus y 50 pacientes atópicos sin antecedentes de alergia a la picadura de mosquito e IgE sérica específica negativa a Culex quinquefasciatus. La prueba cutánea por punción se realizó por duplicado en los antebrazos de los pacientes. Las dosis investigadas fueron 100 y 10 UNP/mL. Resultados: en la prueba cutánea por punción con el extracto de mayor concentración se obtuvo un tamaño del área del habón de 22.09 mm2 y con la menor concentración de 8.19 mm2; una diferencia estadísticamente significativa (p=0.001, prueba t de Student). La prueba cutánea positiva se correlacionó en el 100% de los pacientes con la existencia de IgE específica. La prueba con ambas dosis mostró 94% de especificidad y 88% de sensibilidad. Conclusión: la alta coincidencia en el resultado de la prueba cutánea nos muestra que puede sustituirse la concentración del extracto a 100 UNP/mL por la de menor concentración, sin perder confiabilidad en el diagnóstico de sensibilización al mosquito Culex quinquefasciatus, utilizando ese método in vivo.

[Dust mites as occupational allergens in two bakeries of La Habana, Cuba]. / Ácaros del polvo como alérgenos ocupacionales en dos panaderías de La Habana, Cuba.

BACKGROUND: Occupational allergies are becoming more frequent. The allergens present in the working environment of bakeries, such as mites, are not well identified despite being known risk factors of respiratory diseases. OBJECTIVES: To isolate and identify the species of mites present in two bakeries in La Habana, Cuba, with high sensitization of mites on their workers. MATERIAL AND METHOD: A descriptive study was done in which samples were taken by tripled from potential sources of mites in bakeries -as flourin use, spills of wheat on the floors, wheat flour stored in sealed bags, sugar, yeast, granulated baker- that were processed, according to the method of flotation of Hart and Fain (1987) to isolate, identify and count the mites present. RESULTS: Mites were found in samples of wheat flourin use, spills on the floorsand in the wheat flourstored in sealed bags. The species identified were Blomia tropicalis (70%), Tyrophagus putrescentiae (20%) and to a lesser degree Dermatophagoides pteronyssinus and Dermatophagoides siboney. CONCLUSIONS: There is a high exposure to house dust mites, particularly to store mites, which constitute a risk factor of occupational allergy to consider.

Antecedentes: las alergias ocupacionales son cada vez más frecuentes. Los alergenos del ambiente laboral de panaderías, como los ácaros, no están bien identificados a pesar de ser factores de riesgo conocidos de enfermedades respiratorias. Objetivos: aislar e identificarlas especies de ácaros en dos panaderías de La Habana, Cuba, con alta sensibilización a ácaros en sus trabajadores. Material y método: estudio descriptivo en el que se tomaron muestras por triplicado de las posibles fuentes de ácaros en las panaderías ­como harina de trigo en uso, derrames de harina de trigo en los pisos, harina de trigo almacenada en sacos sellados, azúcar, levadura panadera granulada­ que fueron procesadas, según el método de flotación de Hart and Fain (1987) para aislar, identificar y contar los ácaros presentes. Resultados: se encontraron ácaros en las muestras de harina de trigo en uso, en los derrames de ésta en los pisos y en la harina de trigo almacenada en sacos sellados. Las especies identificadas fueron Blomia tropicalis (70%), Tyrophagus putrescentiae (20%) y en mucho menor grado Dermatophagoides pteronyssinus y Dermatophagoides siboney. Conclusiones: existe elevada exposición a ácaros del polvo doméstico, particularmente a ácaros de almacén, en las panaderías analizadas, lo que constituye un factor de riesgo de alergia ocupacional a considerar.

[Sensitization to three house dust mites in a children allergic population of cuba]. / Sensibilización a tres ácaros domésticos en una población infantil alérgica de Cuba.

BACKGROUND: Allergic diseases constitute a worldwide health problem and mites are among the main etiological agents. OBJECTIVE: To characterize the sensitization to the mites Dermatophagoides pteronyssinus, Dermatophagoides siboney, and Blomia tropicalis, by skin tests in a children allergic sample from Cuba. METHODS: This is a descriptive transversal investigation that included 103 allergic children, with ages ranging from 3 to 15 years, who underwent skin prick tests with D. pteronyssinus, D. siboney, and B. tropicalis allergenic extracts. For the analysis of the results, sex, place of residence and degree of exposure to house dust were considered. RESULTS: The greater sensitization was to D. pteronyssinus (36,9%), followed by D. siboney (35%) and B. tropicalis (33%). The greater geometric mean of the wheal diameter was 5,14 mm for D. pteronyssinus (IC95%: 4.52-5.76 mm); 4.82 mm for D. siboney (IC95%: 4.22-5.43 mm) and 4.25 mm for B. tropicalis (IC95%: 3.93-4.58 mm). Fifty six children (54.3%) were not sensitive to none of the three mites. In 45.7% we found sensitization at least to one mite, and 21.4% were sensitive to the three mites. There were no significant differences (p >0.05) in the sensitization according to sex, place of residence and degree of exposure to house dust. The percentage of sensitive patients with rhinitis plus asthma was more significant (p < 0.001), and in them, the geometric mean of the wheal diameter was significant for D. pteronyssinus (p=0.028) and D. siboney (p=0. 027). CONCLUSIONS: A third of our studied child population, residing in a non-industrialized tropical area, presented sensitization to one or some of the three tested mites. There was a different pattern of sensitization with mites in relation to gender. Patients with asthma plus rhinitis showed more sensitization concerning the number and intensity of the skin tests.

Sensibilización a tres especies de ácaros en pacientes alérgicos de lazona costera de la ciudad de La Habana

Antecedentes: en diferentes estudios se ha reportado la sensibilización de pacientes a los ácaros Dermatophagoides pteronyssinus,Dermatophagoides siboney y Blomia tropicalis (alergénicos del polvo doméstico en Cuba). Objetivo: determinar la sensibilización a Dermatophagoides pteronyssinus, Dermatophagoides siboney y Blomia tropicalis en pacientesde la costa norte de la ciudad de La Habana, Cuba. Pacientes y métodos: se seleccionaron 210 pacientes alérgicos, clasificados en dos grupos (de 1 a 14 y de 15 a 55 años de edad).Se realizaron pruebas por punción cutánea con extractos alergénicos estandarizados VALERGEN-BT (B. tropicalis), VALERGENDS(D. siboney) y VALERGEN-DP (D. pteronyssinus) de producción nacional (BIOCEN). La prueba se consideró positiva cuando el diámetro del habón fue mayor o igual a 3 mm. Resultados: ambos grupos mostraron mayor sensibilización para D. pteronyssinus (>78 porciento), mientras que para los otros ácaros fue por debajo de 60 porciento. En los pacientes mayores de 14 años la sensibilización fue aparentemente más alta, aunque no significativa estadísticamente (p > 0.05). Sin embargo, la reactividad cutánea en ese grupo fue significativamente mayor (p < 0.05) para los tres alergenos. Inusitadamente, el tamaño promedio del habón fue superior (p < 0.05) para B. tropicalis.Conclusiones: aunque la sensibilización para D. pteronyssinus fue mayor, B. tropicalis mostró ser un aeroalérgeno de importancia por su mayor reactividad cutánea y más de 50 porciento de sensibilización. En los pobladores de la ciudad de La Habana sería recomendablerealizar la prueba cutánea por punción con los tres extractos de ácaros, simultáneamente, y combinarlos en la inmunoterapia específica(AU)

Background: Sensitization to three allergic mite species Dermatophagoides pteronyssinus, Dermatophagoides siboney and Blomia tropicalis) from house dust in Cuba has been reported in different studies. Objective: To assess allergic sensitization to these mites in a north coast area of Havana city.Patients and methods: A total of 210 allergic patients were selected, classified in two groups: from 1 to 14 years, and from 15 to 55 years. Skin Prick Test (SPT) was performed on all patients using standardized allergenic extracts VALERGEN-BT (B. tropicalis),VALERGEN-DS (D. siboney) and VALERGEN-DP (D. pteronyssinus) manufactured by BIOCEN, Cuba. The test was considered positive when the average wheal diameter was greater or equal to 3 mm. Results: Both groups showed higher sensitization to D. pteronyssinus (>78 percent), while for the remaining mites it was below 60 percent. In patients older than 14 years, the sensitization was apparently higher, although not statistically significant (p>0.05). Nevertheless, theskin reactivity in this group was significantly greater (p <0.05) for the three allergens. Unusually, mean wheal size in both groups was significantly superior toward B. tropicalis (p <0.05).Conclusions: In spite of being D. pteronyssinus the mite showing the highest sensitization, Blomia tropicalis showed to be also an important aeroallergen with more than 50 percent sensitization and greater skin reactivity. Therefore, in our population it would be advisable to perform SPT with the three mites extracts, simultaneously and to combine it in allergen-specific immunotherapy(AU)