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. 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. 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). 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. Subcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. Cuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).

Results A total of 88.4 % of patients were positive to D. siboney , 87.1 % to D. pteronyssinus , and 68.1 % to B. tropicalis . Sensitization to Dermatophagoides species was predominant, demonstrated by the fact that 31.9 % of patients showed positive SPT to either D. siboney or D. pteronyssinus only, whereas only 5.6 % was sensitized solely to B. tropicalis. Nevertheless, most patients (58.6 %) were polysensitized to the 3 species. The mean wheal size produced by the different allergens in positive patients was similar (n.s. p > 0.05). Reaction size was strongly correlated (r = 0.71, p = 5.3 × 10 −09 ) between D. siboney and D. pteronyssinus , whereas no significant correlation was found between D. pteronyssinus or D. siboney and B. tropicalis . Conclusions The results of this study support the need to include the 3 allergens in diagnostic panels and for combined allergen-specific immunotherapy. Key words Skin prick test Correlation Polysensitization Domestic mites References 1. R. Pawankar Allergic rhinitis and asthma: the link, the new ARIA classification and global approaches to treatment Current Opinion in Allergy and Clinical Immunology 4 2004 1 4 2. Rodríguez de la Vega A y otros. Investigaciones de la prevalencia nacional del asma bronquial en Cuba. Rev. Cubana Adm. Salud. 1983; Abril-Junio: 95-118. 3. Batista R. Comportamiento del Asma Bronquial en Cuba. Unidad de Análisis y Tendencias en Salud. MINSAP, Cuba, Reporte Técnico de Vigilancia 1996; 1, 3 (Diciembre): 1028-4338 4. D. Fabre P. Varona R. Suarez Prevalencia de asma en adolescentes cubanos por diferentes criterios Revista Alergia México 52 3 2005 132 137 5. R. Sporik M.D. Chapman TA. Pllats-Mills House dust mite exposure as a cause of asthma Clin Exp Allergy 22 1992 897 906 6. R. Ferrandiz R. Casas S Dreborg Sensitization to Dermatophagoides siboney, Blomia tropicalis and other domestic mites in asthmatic patients Allergy 51 1996 501 505 7. N. Cuervo F. Dusbabek J. De la Cruz R. Abreu Los ácaros (Acarina: Pyroglyphidae, Cheyletidae, Saproglyphidae y Glycyphagidae ) de los polvos domésticos en Cuba Rev Cub Med Trop 35 1983 83 103 8. N. Martinez R.E. Aranda R. Casas S. Garriga A. Labrada Epidemiological study of sensitization to common inhalant allergens in Cuba. Abstracts ICACI XVI, Cancún, México 1997; October Allergy Clin Immunol Intl Suppl 4 1997 148 9. R. Águila R.G. García F. de la Torre E. Fernández-Caldas A. Martínez Sensibilización a diferentes ácaros en niños asmáticos atendidos en el Hospital Pediátrico Docente del Cerro. 2001 Alergia, Asma e Inmunología Pediátricas 11 3 2002 83 87 10. R.E. Aranda A. Labrada E. Facenda R. Diéguez N. Martínez Respuesta IgE a Blomia tropicalis Revista Cubana de Medicina Tropical 52 1 2000 31 36 11. Sub Committee on Skin Test of the European Academy of Allergy and Clinical Immunology. In: Dreborg S, editor. Skin test used in type I allergy testing. Copenhagen: Munksgoard; 1989;44,10: 31-7. 12. Nordic Council on Medicines. Registration of allergen preparations, Nordic Guidelines 2nd edition, Uppsala, 1989;23:1-34. 13. L. Puerta E. Fernández- Caldas R.F. Lockey L.R. Caraballo Mite allergy in the tropics: Sensitization to six domestic mite species in Cartagena, Colombia J Invest Allergol Clin Immunol 3 1993 198 204 14. M. Sánchez-Borges A. Capriles-Hulett S. Malka Inhalant allergens clinically significant in Latin American Allergy Clin Immunol Int-J World Allergy Org 16 1 2004 28 32 15. F. Cheng L.P. Chi N. Cheong K.Y. Chua B.W. Lee Dust Mite Allergy in East Asia Allergy Clin Immunol Int-J World Allergy Org 16 4 2004 150 154 16. T.A. Manolio K.C. Barnes R.P. Naidu P.N. Levett T.H. Beaty A.F. Wilson Correlates of sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus in asthma in Barbados Int Arch Allergy Immunol 131 2 2003 119 126 17. F. Montealegre C. Quinones V. Michelen M. Bayona E. Fernandez-Caldas O. Vazques F. Colon D. Chardon M. Garcia Prevalence of skin reactions to aeroallergens in asthmatics of Puerto Rico P R Health Sci J 16 4 1997 359 367 18. R.L. Castro A. Labrada A. Abdo J. González C.A. Ulloa M.E. Falcón R.E. Aranda S Dreborg Diagnostic efficacy of skin prick test with mite allergen extracts of D. pteronyssinus D. siboney and Blomia tropicalis in a Cuban population Allergy Clin Immunol Intl-J World Allergy Org 12,5 Suppl 2000 234 19. R. Ferrándiz R. Casas S. Dreborg E. Einarsson B. Fernández Crossreactivity between Dermatophagoides siboney and other house dust mite allergens in sensitized asthmatic patients Clin Exp Allergy 25 1995 922 928 20. B.E. Stanaland E. Fernandez-Caldas C.M. Jacinto W.L. Trudeau R.F. Lockey Sensitization to Blomia tropicalis : skin test and cross-reactivity studies J Allergy Clin Immunol 94 3 1994 452 457 21. I.C. Kuo N. Cheong M. Trakultivakorn B.W. Lee K.Y. Chua An extensive study of human IgE cross-reactivity of Blot 5 and Der p 5 J Allergy Clin Immunol 111 3 2003 603 609

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. 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. 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. 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. 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.