J Sastre

Fundación Jiménez Díaz, Madrid, Madrid, Spain

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Publications (289)1696.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Diisocyanates, reactive chemicals used to produce polyurethane products, are the most common causes of occupational asthma. The aim of this study is to identify susceptibility gene variants that could contribute to the pathogenesis of diisocyanate asthma (DA) using a Genome Wide Association Study (GWAS) approach. Genome-wide SNP genotyping was performed in 74 diisocyanate -exposed workers with DA and 824 healthy controls using Omni-2.5 and Omni-5 SNP microarrays. We identified 11 SNPs that exceeded genome-wide significance; the strongest association was for the rs12913832 SNP located on chromosome 15, which has been mapped to the HERC2 gene (p=6.94×10(-14)). Strong associations were also found for SNPs near the ODZ3 and CDH17 genes on chromosomes 4 and 8 (rs908084, p=8.59×10(-9) and rs2514805, p=1.22×10(-8), respectively). We also prioritized 38 SNPs with suggestive genome-wide significance (p <1×10(-6)). Among them, 17 SNPs map to the PITPNC1, ACMSD, ZBTB16, ODZ3, and CDH17 gene loci. Functional genomics data indicate that two of the suggestive SNPs (rs2446823 and rs2446824) are located within putative binding sites for the CEBPA/B and HNF4A transcription factors (TF), respectively. The present study identified SNPs mapping to the HERC2, CDH17 and ODZ3 genes as potential susceptibility loci for DA. Pathway analysis indicated that these genes are associated with antigen processing and presentation, and other immune pathways. Overlap of two suggestive SNPs with likely transcription factor binding sites suggests possible roles in disruption of gene regulation. These results provide new insights into the genetic architecture of DA and serve as a basis for future functional and mechanistic studies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Toxicological Sciences 04/2015; DOI:10.1093/toxsci/kfv084 · 4.48 Impact Factor
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    ABSTRACT: Shrimp are highly allergenic foods. Current management are limited to the avoidance of foods. Therefore, there is an unmet need for a safe and effective therapy using modified allergens. This study focuses on assessing the potential for modification of the allergenicity of shrimp proteins following heat treatment or simulated gastric digestion. Shrimp proteins do not reduce their IgE reactivity after heat treatment but it is reduced by simulated gastric digestion in a time- and dose-dependent manner. Tropomyosin in shrimp extract is worse digested than purified tropomyosin. After 60min of 10U/μg pepsin digestion, a strong inhibition was produced in the in vivo skin reactivity of shrimp extracts and in activation of basophils from allergic patients. Immunisation experiments performed in rabbits demonstrated that digested boiled shrimp extract is able to induce IgG antibodies that block the IgE binding to the untreated boiled shrimp extract in shrimp-allergic patients. Building on our observations, digestion treatment could be an effective method for reducing shrimp allergenicity while maintaining the immunogenicity. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Food Chemistry 04/2015; 173:475-81. DOI:10.1016/j.foodchem.2014.10.063 · 3.26 Impact Factor
  • Marina Sastre-Ibañez, Joaquín Sastre
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    ABSTRACT: Defining the allergen sensitization of a patient with asthma at the molecular level by measuring specific IgE to purified natural or recombinant allergens can improve diagnostic accuracy and improve asthma phenotyping. Molecular diagnosis is possible thanks to the specificity of some markers of species-specific sensitization and resolve cross-reactivity phenomena from a true co-sensitization. None of this precision is possible with conventional allergy tests, and such information will eventually give clinicians the possibility to individualize the actions taken, including indications on reducing targeted-allergen exposure or selection of suitable allergens for specific immunotherapy, thereby increasing the safety and efficacy of immunotherapy. Nevertheless, all in vitro tests should be assessed alongside clinical history, as allergen sensitization does not necessarily imply clinical responsiveness.
    Expert Review of Molecular Diagnostics 04/2015; DOI:10.1586/14737159.2015.1036745 · 4.27 Impact Factor
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    ABSTRACT: The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup of shrimp allergy. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    03/2015; DOI:10.1016/j.jaip.2015.02.001
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    ABSTRACT: Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.
    International Journal of Molecular Sciences 03/2015; 16(3):5434-5451. DOI:10.3390/ijms16035434 · 2.34 Impact Factor
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    ABSTRACT: Abstract Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA(+), n = 95) and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5' nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the PTGS1 rs5788 and TGFB1 rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74, respectively) while the TNFα rs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, the PTGS2 rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75). These results suggest that genetic variations in TNFα, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility.
    Journal of Immunotoxicology 02/2015; DOI:10.3109/1547691X.2015.1017061 · 1.91 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB190. DOI:10.1016/j.jaci.2014.12.1557 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB189. DOI:10.1016/j.jaci.2014.12.1554 · 11.25 Impact Factor
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    ABSTRACT: Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.
    Revue Française d Allergologie 02/2015; DOI:10.1016/j.reval.2014.10.001 · 0.22 Impact Factor
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    ABSTRACT: The aim of the study was to investigate if adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens.192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week up-dosing with 5-injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association of the number of grass allergens sensitized by the patients and the total number of ADRs (p=0.004) occurred locally (p=0.003) and systemically (p=0.01) Sensitization to Phl p1+ Phl p5 or Phl p1+ Phl p5+ Phl p12 was significantly associated with a higher frequency of local or systemic reactions (p=0.001,both).Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.This article is protected by copyright. All rights reserved.
    Allergy 01/2015; 70(5). DOI:10.1111/all.12575 · 6.00 Impact Factor
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    ABSTRACT: Eosinophils secrete several granules that are involved in the propagation of inflammatory responses in patients with pathologies such as asthma. We hypothesized that some of these granules are exosomes, which, when transferred to the recipient cells, could modulate asthma progression. Eosinophils were purified from peripheral blood and cultured with or without IFN-γ or eotaxin. Multivesicular bodies (MVBs) in eosinophils were studied by using fluorescence microscopy, transmission electron microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome characterization was performed with TEM, Western blotting, and NanoSight analysis. Generation of MVBs in eosinophils was confirmed by using fluorescence microscopy and flow cytometry and corroborated by means of TEM. Having established that eosinophils contain MVBs, our aim was to demonstrate that eosinophils secrete exosomes. To do this, we purified exosomes from culture medium of eosinophils and characterized them. Using Western blot analysis, we demonstrated that eosinophils secreted exosomes and that the discharge of exosomes to extracellular media increases after IFN-γ stimulation. We measured exosome size and quantified exosome production from healthy and asthmatic subjects using nanotracking analysis. We found that exosome production was augmented in asthmatic patients. Our findings are the first to demonstrate that eosinophils contain functional MVBs and secrete exosomes and that their secretion is increased in asthmatic patients. Thus exosomes might play an important role in the progression of asthma and eventually be considered a biomarker. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Journal of Allergy and Clinical Immunology 01/2015; 135(6). DOI:10.1016/j.jaci.2014.11.026 · 11.25 Impact Factor
  • Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2015; 25(1):59-60. · 2.64 Impact Factor
  • Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2015; 25(1):55-6. · 2.64 Impact Factor
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    ABSTRACT: Fluticasone propionate and formoterol fumarate have been combined in a single inhaler (fluticasone/formoterol; flutiform(®)) for the maintenance treatment of asthma. This pooled analysis assessed the efficacy of fluticasone/formoterol versus fluticasone in patients who previously received inhaled corticosteroids. Data were pooled from five randomised studies in patients with asthma (aged ≥12 years) treated for 8 or 12 weeks with fluticasone/formoterol (100/10, 250/10 or 500/20 μg b.i.d.; n = 528 delivered via pMDI) or fluticasone alone (100, 250 or 500 μg b.i.d.; n = 527). Fluticasone/formoterol provided significantly greater increases than fluticasone alone in mean morning forced expiratory volume in 1 second (FEV1) from pre-dose at baseline to 2 hours post-dose at study end (least-squares mean [LSM] treatment difference: 0.146L; p < 0.001) and in pre-dose FEV1 from baseline to study end (LSM treatment difference: 0.048 L; p = 0.043). Compared with fluticasone, fluticasone/formoterol provided greater increases in the percentage of asthma control days (no symptoms, no rescue medication use and no sleep disturbance due to asthma) from baseline to study end (LSM treatment difference: 8.6%; p < 0.001), and was associated with a lower annualised rate of exacerbations (rate ratio: 0.71; p = 0.014). In summary, fluticasone/formoterol provides clinically significant improvements in lung function and asthma control measures, with a lower incidence of exacerbations than fluticasone alone. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Respiratory Medicine 12/2014; 109(2). DOI:10.1016/j.rmed.2014.10.019 · 2.92 Impact Factor
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    ABSTRACT: To date, no studies have assessed nasal and bronchial response to diisocyanates during specific inhalation challenges (SIC). This study was performed to assess nasal response during SIC with diisocyanates (nasal and oral breathing) in patients with suspected occupational asthma due to these agents. Fourteen patients with suspected clinical history of diisocyanate-induced asthma were challenged with diisocynates in a 7m3 chamber. Nasal response testing during challenges was assessed by acoustic rhinometry, peak nasal inspiratory flow (PNIF), and visual analog scale (VAS), alongside bronchial responses. Eleven patients had a significant asthmatic response to diisocyanates. None reported clear work-related nasal symptoms. In patients with positive bronchial response to diisocyanates, nasal mean minimal cross-sectional area (MCA) decreased by 26.9%, nasal volume at 5 cm decreased by 33.5%, and PNIF decreased by 28.3%, all from baseline. A positive nasal response was elicited in 45%, 54%, and 45% of patients, respectively. A significant increase in VAS was observed in 4 patients. Three patients with negative bronchial response had a negative nasal response. SIC revealed an objective nasal response in around 50% of patients with occupational asthma due to diisocyanates, in spite of the fact that none of them reported work-related nasal symptoms. The clinical significance of this finding is a poor association between nasal symptoms at work and an objective nasal response during positive SIC with diisocyanates.
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    ABSTRACT: In spite of being an old disease and apparently easy to diagnose, chronic spontaneous urticaria (CSU) is still perceived as an uncontrollable and difficult to manage disease. The perception of the patient is that his/her condition is not well understood and that is suffering from a disorder with hidden causes that doctors are not able to tackle. Sometimes patients go through a number of clinicians until they found some CSU expert who is familiar with the disease. It is surprising that myths and believes with no scientific support still persist. Guidelines are not widely implemented and recent tools to assess severity are infrequently used. European and American recent guidelines do not agree in several key points related to diagnosis and treatment, which further contributes to confusion. With the aim to clarify some aspects of the CSU picture, a group of allergists and dermatologists from the Spanish Dermatology and Allergy societies developed a Frequent Asked Questions leaflet that could facilitate physicians work in daily practice and contribute to a better knowledge of common clinical scenarios related to patients with CSU. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 11/2014; 45(4). DOI:10.1111/cea.12465 · 4.32 Impact Factor
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    ABSTRACT: Aim To assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent. Methods Study in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis. Results Of the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively (p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent. Conclusions Avoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines.
    Respiratory Medicine 09/2014; 108(9). DOI:10.1016/j.rmed.2014.08.001 · 2.92 Impact Factor
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    ABSTRACT: Scope: Shrimp is a seafood consumed worldwide and the main cause of severe allergenic reactions to crustaceans. Seafood allergy has been related to mite sensitization, mainly mediated by tropomyosin, but other proteins could be involved. The aim of the study was to identify new shrimp allergens implicated in mite-seafood cross-reactivity (CR) in two different climate populations: dry and humid climates. Methods and results: Shrimp and mite IgE-binding profiles of patients from continental dry and humid climates were analyzed by immunoblotting, and the most frequently recognized Solenocera melantho shrimp proteins were identified by MS as alpha-actinin, beta-actin, fructose biphosphate aldolase, arginine kinase, sarcoplasmic calcium-binding protein, and ubiquitin. Using inhibition immunoblot assays, we demonstrate that tropomyosin and ubiquitin were responsible for mite-seafood CR from both climates; but also alpha-actinin and arginine kinase are implicated in dry-and humid-climate populations, respectively. Reciprocal inhibition assays demonstrated that mites are the primary sensitizer in humid-climate, as shrimp is in continental dry-climate population. Conclusion: Several new shrimp allergens have been identified and should be considered in the diagnosis and treatment of shrimp allergy and mite-seafood CR. Differences in mite-seafood CR were founded to be based on the climate.
    Molecular Nutrition & Food Research 09/2014; 58(9). DOI:10.1002/mnfr.201400122 · 4.91 Impact Factor
  • Gianna Moscato, Gianni Pala, Joaquin Sastre
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    ABSTRACT: Purpose of reviewOccupational allergy represents a substantial health, social, and financial burden for the society. Its management is a complex task that, in selected cases, may also include allergen-specific immunotherapy. The purpose of this article is to review clinical data on allergen immunotherapy and biological treatments applied to occupational allergy in 2013.Recent findingsImmunotherapy in occupational allergic diseases has been scarcely used, and only for a few sensitizers, such as latex, flour, and Hymenoptera venom, partly due to the lack of standardized extracts. The recent use of the molecular diagnosis can improve the indication and selection of suitable allergens for preparing new standardized and powerful extracts for immunotherapy. Some recent reports suggest a beneficial role of treatment with omalizumab in workers with occupational asthma who continue to be exposed to the causal agent.SummaryAlthough scarce, available data suggest that immunotherapy and biological treatments may allow allergic workers to continue their work activity, but further studies are needed to standardize extracts and to evaluate the cost-effectiveness of these treatments, when exposure at the workplace cannot be avoided.
    Current Opinion in Allergy and Clinical Immunology 08/2014; 14(6). DOI:10.1097/ACI.0000000000000105 · 3.66 Impact Factor
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    ABSTRACT: The most frequent pet allergy is allergy to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is increasing. The list of new pets includes hamsters, and one of the most popular hamster is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine and salivary glands of 4 hamster species (European, golden, Siberian and Roborovski). IgE-binding proteins were detected by immunobloting and identified by mass spectrometry. The recombinant protein was produced in E.coli. and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obteined from the hair, urine and salivary glands of the Siberian hamster. All proteins correspond to the same protein, which was identified as a lipocalin. This lipocalin has no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to protein extracts from Siberian hamster. Also, the recombinant allergen is capable of producing a biological activation in vivo. The major allergen from Siberian hamster was cloned and allergenic properties have been characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.
    Journal of Biological Chemistry 07/2014; 289(34). DOI:10.1074/jbc.M114.579060 · 4.60 Impact Factor

Publication Stats

3k Citations
1,696.11 Total Impact Points

Institutions

  • 1994–2015
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 2010–2014
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • Ministry of Health, Madrid
      Madrid, Madrid, Spain
  • 2013
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 2011–2012
    • Centro de Investigacion Biomédica en Red de Enfermedades Respiratorias
      Bunyola, Balearic Islands, Spain
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2007–2012
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1996–2012
    • Universidad Autónoma de Madrid
      • Department of Medicine
      Madrid, Madrid, Spain
  • 2008–2011
    • Hospital Universitario La Paz
      • Servicio de Alergología
      Madrid, Madrid, Spain
  • 2007–2011
    • Universidad de Salamanca
      Helmantica, Castille and León, Spain
  • 2006–2011
    • Hospital de Basurto
      Bilbo, Basque Country, Spain
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2009
    • Clínica Universidad de Navarra
      Madrid, Madrid, Spain
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain
  • 2006–2009
    • Clínica Dr. Lobatón
      Cádiz, Andalusia, Spain
    • Hospital de La Plana
      Vila-real, Valencia, Spain
  • 2005
    • National University of Cordoba, Argentina
      • Faculty of Medical Science
      Córdoba, Cordoba, Argentina
  • 2004
    • Hospital Universitario Marques de Valdecilla
      Santander, Cantabria, Spain
    • University of Oxford
      • Department of Public Health
      Oxford, ENG, United Kingdom
  • 1994–2004
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
  • 2000
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 1988–1990
    • Tulane University
      • Department of Medicine
      New Orleans, Louisiana, United States