J Sastre

Fundación Jiménez Díaz, Madrid, Madrid, Spain

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Publications (304)1795.52 Total impact

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    ABSTRACT: Background: The great majority (60-80 %) of patients consulting specialist physicians for allergic respiratory disease are polysensitized and thus may be potentially clinically polyallergic. However, management approaches to allergen immunotherapy (AIT) in polysensitized and polyallergic patients are not standardized. Methods: An international group of clinicians with in-depth expertise in AIT product development, clinical trials and clinical practice met to generate up-to-date, unambiguous, pragmatic guidance on AIT in polysensitized and polyallergic patients. The guidance was developed after reviewing (1) the current stance of regulatory bodies and learned societies, (2) the literature data on single- and multi-AIT and (3) the members' confirmed clinical experience with polysensitized patients. Results: AIT is safe and effective in polysensitized and polyallergic patients, and should always be based on the identification of one or more clinically relevant allergens (based on the type and severity of symptoms, the duration of induced symptoms, the impact on quality of life and how difficult an allergen is to avoid). Single-AIT is recommended in polyallergic patients in whom one of the relevant allergens is nevertheless clearly responsible for the most intense and/or bothersome symptoms. Parallel 2-allergen immunotherapy or mixed 2-allergen immunotherapy is indicated in polyallergic patients in whom two causal relevant allergens have a marked clinical and QoL impact. In parallel 2-allergen immunotherapy (whether subcutaneous or sublingual), high-quality, standardized, single-allergen formulations must be administered with an interval of 30 min. Mixing of allergen extracts may be considered, as long as (1) the mixture is technically feasible, (2) the mixture is allowed from a regulatory standpoint, (3) the allergen doses are reduced in proportion to the number of components but are still at concentrations with demonstrated efficacy. Conclusions: Physicians can prescribe AIT (preferably with high-quality, standardized, single-allergen formulations) with confidence in polysensitized and polyallergic patients by focusing on clinical/QoL relevance and safety.
    Preview · Article · Dec 2016 · Allergy Asthma and Clinical Immunology
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    ABSTRACT: Objective: To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). Methods: The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. Results: The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). Conclusions: These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.
    No preview · Article · Dec 2015 · Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine
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    ABSTRACT: Video E1. Three of 3 viable GFP-CD63+ eosinophils treated with IFN-γ were analyzed and showed that translocation to the plasma membrane of GFP-CD63 began at 8 minutes. The transmittance video shows viable cells.
    Full-text · Dataset · Nov 2015

  • No preview · Article · Aug 2015 · Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología
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    ABSTRACT: The fifth Jack Pepys Workshop on Asthma in the Workplace focused on the similarities and differences of work-related asthma (WRA) and non-work-related asthma (non-WRA). WRA includes occupational asthma (OA) and work-exacerbated asthma (WEA). There are few biological differences in the mechanisms of sensitization to environmental and occupational allergens. Non-WRA and OA, when due to high-molecular-weight agents, are both IgE mediated; it is uncertain whether OA due to low-molecular-weight agents is also IgE mediated. Risk factors for OA include female sex, a history of upper airway symptoms, and a history of bronchial hyperresponsiveness. Atopy is a risk factor for OA due to high-molecular-weight agents, and exposure to cleaning agents is a risk factor for both OA and non-WRA. WEA is important among workers with preexisting asthma and may overlap with irritant-induced asthma, a type of OA. Induced sputum cytology can confirm airway inflammation, but specific inhalation challenge is the reference standard diagnostic test. Inhalation challenges are relatively safe, with the most severe reactions occurring with low-molecular-weight agents. Indirect health care costs account for about 50% of total asthma costs. Workers with poor asthma control (WRA or non-WRA) are less likely to be employed. Income loss is a major contributor to the indirect costs of WRA. Overall, asthma outcomes probably are worse for adult-onset than for childhood-onset asthma but better for OA than adult-onset non-WRA. Important aspects of management of OA are rapid and proper confirmation of the diagnosis and reduction of exposure to sensitizers or irritants at work and home.
    No preview · Article · Jul 2015 · Annals of the American Thoracic Society
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    ABSTRACT: A patient's knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness. To assess patients' understanding of allergy and acceptance of allergen immunotherapy on the basis of (i) information given by their physician at the time of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent "early abandoners" (having discontinued allergen immunotherapy before the end of the prescribed course) or "non-starters" (having decided not to initiate a course of allergen immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study's main objectives were to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume allergen immunotherapy. We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 "early abandoners" and 134 "non-starters". The mean time since symptom onset and selection for the study was 14.5 years. Subcutaneous allergen immunotherapy had been prescribed in 60 % of cases. Twenty-eight percent of the participants did not know for which allergy they were being treated. Early abandoners reported a perception of low effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt better informed afterwards, and 67 % stated that viewing the communication template would have made them more likely to continue or initiate allergen immunotherapy (overall willingness score: 5.65 out of 10 before viewing and 7.1 out of 10 afterwards). After viewing a new communication template on allergy and allergen immunotherapy, patients participating in the survey felt better informed and more likely to initiate or complete this therapy. It now remains to investigate the communication template's effect on actual acceptance of and adherence to allergen immunotherapy.
    Full-text · Article · May 2015 · Allergy Asthma and Clinical Immunology
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    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.
    No preview · Article · Apr 2015 · Toxicological Sciences

  • No preview · Article · Apr 2015 · Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología

  • No preview · Article · Apr 2015 · Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología
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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.
    No preview · Article · Apr 2015 · Food Chemistry
  • 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.
    No preview · Article · Apr 2015 · Expert Review of Molecular Diagnostics
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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.
    Full-text · Article · Mar 2015
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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.
    Full-text · Article · Mar 2015 · International Journal of Molecular Sciences
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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.
    Full-text · Article · Feb 2015 · Journal of Immunotoxicology

  • No preview · Article · Feb 2015 · Journal of Allergy and Clinical Immunology

  • No preview · Article · Feb 2015 · Journal of Allergy and Clinical Immunology
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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.
    No preview · Article · Feb 2015 · Revue Française d Allergologie
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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.
    No preview · Article · Jan 2015 · Allergy
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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.
    Full-text · Article · Jan 2015 · Journal of Allergy and Clinical Immunology
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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.
    No preview · Article · Dec 2014 · Respiratory Medicine

Publication Stats

4k Citations
1,795.52 Total Impact Points

Institutions

  • 1994-2016
    • Fundación Jiménez Díaz
      • Servicio de Inmunología
      Madrid, Madrid, Spain
  • 2010-2015
    • Instituto de Salud Carlos III
      • CIBER of Respiratory Diseases (CIBERES)
      Madrid, Madrid, Spain
    • Ministry of Health, Madrid
      Madrid, Madrid, Spain
  • 1996-2015
    • Universidad Autónoma de Madrid
      • • Department of Medicine
      • • Enfermería de la Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 2014
    • Centre Hospitalier Universitaire Mont-Godinne
      Yvoir, Wallonia, Belgium
  • 2012-2014
    • Centro de Investigacion Biomédica en Red de Enfermedades Respiratorias
      Bunyola, Balearic Islands, Spain
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2011
    • University of California, Los Angeles
      Los Ángeles, California, United States
    • Clínica Universidad de Navarra
      Madrid, Madrid, Spain
    • Hospital de Basurto
      Bilbo, Basque Country, Spain
  • 2008
    • Hospital Universitario La Paz
      Madrid, Madrid, Spain
  • 2006
    • Clínica Dr. Lobatón
      Cádiz, Andalusia, Spain
  • 2005
    • National University of Cordoba, Argentina
      • Faculty of Medical Science
      Córdoba, Cordoba, Argentina
  • 2004
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
  • 2000
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 1989-1990
    • Tulane University
      • Department of Medicine
      New Orleans, Louisiana, United States