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1.
J Allergy Clin Immunol Pract ; 9(1): 275-282.e1, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33038591

RESUMEN

BACKGROUND: Safe and cost-effective biological surrogate markers to evaluate the severity and threshold dose of peanut allergy (PA) reactions during an oral food challenge (OFC) are lacking. OBJECTIVE: To evaluate biological markers associated with the severity and threshold dose of an allergic reaction during an OFC in a population of children with PA. METHODS: Demographic and biological parameters of children with peanut OFC and basophil activation test (BAT) results were collected. Patients were stratified into 2 severity groups (mild-to-moderate and severe) and 2 cumulative threshold dose groups: low (LCTG) ≤100 mg crushed peanut and high >100 mg. RESULTS: Among the 68 children included, there was a 96% concordance between the OFC and BAT result for the diagnosis of PA. Of the 56 children with a positive OFC and BAT to peanut (median age: 8.8 years), the severity of an allergic reaction and the cumulative threshold dose were not correlated (P = .24). Higher Ara h 2-specific IgE and FcεRI-positive control values were both associated with severe reactions to peanut. Combining these 2 markers led to a 92% sensitivity (84%-97%) and an 82% specificity (71%-89%) for severe reactions in all subjects. For children in the LCTG, a 4-variable composite marker, including age, normalized basophil sensitivity (EC50), and FcεRI- and fMLP-positive control values, resulted in a 97% sensitivity (89%-99%) and 61% specificity (49%-71%). CONCLUSION: Distinct composite markers including BAT allergen-specific and non-allergen-specific parameters appear to be associated with severity and cumulative threshold dose in children with PA.


Asunto(s)
Hipersensibilidad al Cacahuete , Alérgenos , Antígenos de Plantas , Arachis , Basófilos , Biomarcadores , Niño , Humanos , Hipersensibilidad al Cacahuete/diagnóstico
2.
Ann Biol Clin (Paris) ; 78(3): 329-342, 2020 06 01.
Artículo en Francés | MEDLINE | ID: mdl-32420887

RESUMEN

Accreditation of an in vitro diagnostic assay according to the NF/EN/ISO 15189 standard requires to analyze its technical performance before implementation for routine use, and annually when reviewing effectiveness of quality controls. Performance is evaluated through repeatability, intermediate fidelity, accuracy and uncertainty of measurement. The coefficients of variation (CV) of the intra-assay and inter-assay precision tests must be compared with those of "peers" (results from laboratories employing the same method) and also with those obtained with "all methods", i.e., results from all laboratories performing the same assay, irrespective of the method. To our best knowledge, there is currently no French or international recommendation on what the acceptable limits of performance for specific IgE and tryptase assays should be. Therefore, the AllergoBioNet network of hospital allergy laboratories set out to characterize the performance of their current methods as a basis for the development of recommendations. The results provided by 24 centers were analyzed and led to consensus recommendations for specific IgE, total IgE and tryptase assays.


Asunto(s)
Bioensayo/métodos , Inmunoglobulina E/análisis , Triptasas/análisis , Acreditación , Bioensayo/normas , Consenso , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/normas , Francia , Humanos , Laboratorios/normas , Control de Calidad , Reproducibilidad de los Resultados
3.
Allergy Asthma Immunol Res ; 11(1): 143-151, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30479084

RESUMEN

A pollen/food-associated syndrome (PFAS) has been described between peach and cypress pollen. Cross-reactive allergens were characterized which belong to the Gibberellin-regulated protein (GRP) family, BP14 in cypress pollen and Pru p 7 in peach. GRP are small cationic protein with anti-microbial properties. A patient suffering from a peach/cypress syndrome was explored clinically and biologically using 2 types of immunoglobulin E (IgE) multiarray microchip, immunoblots and a basophil activation test to assess the clinical relevance of various extracts and purified allergens from fruits or cypress pollen. In addition to PR10 sensitization, the patient showed specific IgE to Pru p 7, BP14 and allergen from pomegranate. These last 3 allergens and allergenic sources are able to induce ex vivo basophil activation characterized by the monitoring of the expression of CD63 and CD203c, both cell surface markers correlated with a basophil mediator release. Up to 100% of cells expressed CD203c at 50 ng/mL of BP14 protein. In contrast, snakin-1, a GRP from potato sharing 82% sequence identity with Pru p 7 did not activate patient's basophils. These results strongly suggest that, like Pru p 7, BP14 is a clinically relevant allergenic GRP from pollen. Allergen members of this newly described protein family are good candidates for PFAS where no cross-reactive allergens have been characterized.

5.
Ann Biol Clin (Paris) ; 75(6): 646-652, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29072174

RESUMEN

Strong epidemiological evidence supports a causal relationship between dyslipidemia and atherosclerotic cardio-vascular disease, which remains the leading cause of death and morbidity worldwide. A lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) is recommended at the initial evaluation for the assessment of the cardio-vascular risk. A commentary of the lipid profile for the clinician and mostly for the patient should be stated on the lab report. Quantifying the cardio-vascular risk using the SCORE (systematic coronary risk estimation) system, as recommended by the Haute autorité de santé (HAS), is the starting point to establish therapeutic goals and treatment strategies. It may be important to emphasize therapeutic goals in lipid reports in order to better monitor lipid profiles at appropriate intervals to assess compliance and therapeutic efficacy for patients on lipid lowering therapy.


Asunto(s)
Análisis Químico de la Sangre/métodos , Análisis Químico de la Sangre/tendencias , Lípidos/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/sangre , Dislipidemias/diagnóstico , Humanos , Factores de Riesgo , Triglicéridos/sangre
6.
Pediatr Pulmonol ; 52(11): 1435-1442, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28950434

RESUMEN

BACKGROUND: Childhood recurrent wheezing and consequently asthma corresponds to various phenotypes. Our aim was to link genetic variants of asthma candidate genes to the phenotypes of early onset wheezing. STUDY DESIGN: We included very young consecutive children presenting with recurrent wheezing who had been evaluated for the severity of wheezing, associated atopic comorbidities, and tested for biomarkers of atopy and inflammation. All were genotyped for 16 single nucleotide polymorphisms (SNPs) linked with asthma or atopy. An unsupervised hierarchical bottom-up method was used for clustering the phenotypes and a multinomial logistic regression was performed for each individual SNP. RESULTS: We replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.5 ± 7.9 months: cluster 1 (nonatopic uncontrolled severe wheeze), n = 207, a severe viral-induced wheeze, cluster 2 (atopic multiple trigger wheeze), n = 61, with multiple allergic comorbidities, and cluster 3 (episodic viral wheeze), n = 49, a mild viral-induced wheeze. The TT-genotype of the IL-4 rs2070874 polymorphism was significantly associated with the nonatopic uncontrolled severe wheeze compared to the episodic viral wheeze (OR 7.9; CI95% [2.5-25.3]; P = 0.001). CONCLUSION: Association between the TT-genotype of IL-4 rs2070874 polymorphism and a severe phenotype of viral-induced wheeze further underlines the role IL-4 plays in the inflammation pathway leading to viral respiratory infections.


Asunto(s)
Asma/genética , Interleucina-4/genética , Ruidos Respiratorios/genética , Infecciones del Sistema Respiratorio/genética , Virosis/genética , Preescolar , Femenino , Genotipo , Humanos , Hipersensibilidad Inmediata/genética , Lactante , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Recurrencia
7.
Respir Med ; 129: 16-23, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28732825

RESUMEN

We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms.


Asunto(s)
Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/patología , Proteinosis Alveolar Pulmonar/genética , Proteína B Asociada a Surfactante Pulmonar/deficiencia , Factor Nuclear Tiroideo 1/genética , Adolescente , Adulto , Atetosis/complicaciones , Atetosis/genética , Atetosis/patología , Líquido del Lavado Bronquioalveolar/química , Niño , Corea/complicaciones , Corea/genética , Corea/patología , Hipotiroidismo Congénito/complicaciones , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/patología , Femenino , Francia/epidemiología , Genes Homeobox , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/terapia , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/terapia , Masculino , Mutación , Pronóstico , Proteinosis Alveolar Pulmonar/complicaciones , Proteína B Asociada a Surfactante Pulmonar/genética , Surfactantes Pulmonares/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
8.
BMC Cancer ; 17(1): 419, 2017 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-28619014

RESUMEN

BACKGROUND: Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. METHODS: Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). RESULTS: Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival. CONCLUSIONS: Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series. OS 2006 TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT00470223; date of registration: May 3th 2007.


Asunto(s)
Inductores de la Angiogénesis/sangre , Inductores de la Angiogénesis/orina , Biomarcadores , Neoplasias Óseas/metabolismo , Neoplasias Óseas/mortalidad , Osteosarcoma/metabolismo , Osteosarcoma/mortalidad , Adolescente , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/terapia , Niño , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Factor 2 de Crecimiento de Fibroblastos/orina , Humanos , Masculino , Estadificación de Neoplasias , Osteosarcoma/diagnóstico , Osteosarcoma/terapia , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Carga Tumoral , Factores de Crecimiento Endotelial Vascular/sangre , Factores de Crecimiento Endotelial Vascular/orina , Adulto Joven
9.
J Allergy Clin Immunol Pract ; 5(5): 1351-1361.e2, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28363401

RESUMEN

BACKGROUND: Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children. OBJECTIVES: The aim of the Severe Asthma Molecular Phenotype cohort was to characterize phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness. METHODS: Children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively. They underwent standardized clinical and blood workup, and bronchoalveolar lavage (BAL) evaluation. Cluster analysis was applied to 350 children with 34 variables. RESULTS: Three clusters were identified: cluster 1, Neutrophilic steroid-refractory recurrent wheeze phenotype, with 138 children uncontrolled despite high-dose inhaled corticosteroids (ICS) (92%, P < .001), with more history of pneumonia (31%, P < .001), more gastroesophageal reflux disease (37%, P < .001), and the highest blood neutrophil count (mean 4.524 cells/mm3, P = .05); cluster 2, Severe recurrent wheeze with sensitization to a single aeroallergen (12%, P = .002), with 104 children controlled with high-dose ICS (63%, P < .001); cluster 3, Eosinophilic steroid-refractory asthma phenotype, with 108 children uncontrolled despite high-dose ICS (76%, P < .001) with more allergic rhinitis, atopic dermatitis, and food allergies (82%, 40%, 31%, P < .001, respectively). They also had a higher blood eosinophil count and a higher percentage of BAL eosinophil (506/mm3, 2.6%, P < .001 respectively). CONCLUSIONS: Inflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.


Asunto(s)
Asma/inmunología , Eosinófilos/inmunología , Neutrófilos/inmunología , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Resistencia a Medicamentos , Femenino , Humanos , Lactante , Masculino , Recurrencia , Ruidos Respiratorios , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
ACS Omega ; 2(9): 5962-5972, 2017 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-30023757

RESUMEN

Early diagnosis of dopamine and serotonin metabolic defects is of importance notably because of the availability of therapeutic strategies able to prevent the associated progressive brain dysfunction. The diagnosis of these diseases relies on the determination of monoamine metabolites and pterins in cerebrospinal fluid (CSF). Current methods involve at least two high-performance liquid chromatography runs of CSF analysis. The first one is devoted to the quantification of dopamine and serotonin metabolites and the second one to the quantification of pterins. Here, we describe a single-step method to measure monoamine neurotransmitter metabolites and pterins of interest in less than 10 min by ultrahigh-performance liquid chromatography coupled to sequential coulometric oxidation and fluorescence detections. All target compounds were quantified in CSF with a small volume (50 µL) and a single filtration step for sample preparation and analysis. After validation, the proposed method was applied to the determination of age-related reference ranges in the CSF of target compounds from a series of 1372 samples collected in France from 2008 to 2014. In the same period, the results obtained for 19 CSF samples from patients with known neurotransmitter disorders and 115 CSF samples with known immune system activation confirmed the expected pattern of changes in monoamine metabolites and pterins.

11.
Turk J Pediatr ; 59(4): 483-486, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29624232

RESUMEN

Takci S, Anuk-Ince D, Louha M, Couderc R, Çakar N, Köseoglu RD, Ates Ö. A rare large mutation involving two exons of the SP-B gene in an infant with severe respiratory distress. Turk J Pediatr 2017; 59: 483-486. Hereditary surfactant protein-B (SP-B) deficiency is a rare autosomal recessive disease of newborn infants causing severe respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) in the gene encoding SP-B. We report a term infant with unremitting respiratory distress who was unresponsive to all treatment modalities. The parents were consanguineous and a term sibling of the infant had died due to respiratory failure without a certain diagnosis. In the first step of the diagnostic work-up, common genetic mutations for SP-B, surfactant protein C and ATP-binding cassette s3 were absent, however sequencing of SP-B gene revealed a large homozygous genomic deletion covering exon 8 and 9. In this case report, we aimed to emphasize further genetic evaluation in all cases suggestive of surfactant dysfunction, even if common mutations are absent.


Asunto(s)
Exones , Proteína B Asociada a Surfactante Pulmonar/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Eliminación de Secuencia , Consanguinidad , Resultado Fatal , Homocigoto , Humanos , Lactante , Recién Nacido , Masculino
12.
Ann Allergy Asthma Immunol ; 117(5): 527-534, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27788883

RESUMEN

BACKGROUND: The most emblematic members of Urticaceae at allergic risk level are wall pellitories (Parietaria), whereas nettle (Urtica) pollen is considered as poorly allergenic. No allergen from nettle pollen has yet been characterized, whereas 4 are listed for Parietaria pollen by the International Union of Immunological Societies. Clinical and biological profiles of 2 adult men who developed symptoms against nettle pollen and/or leaves were studied. OBJECTIVE: To characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens. METHODS: IgE-mediated reaction to nettle pollen extract was evaluated by skin prick test, immunoassay, nasal provocation, and basophil activation test. To characterize specific nettle pollen allergens, an allergomic (IgE immunoproteomic) analysis was performed combining 1- and 2-dimensional electrophoresis, IgE immunoblots of nettle pollen extract, identification of allergens by mass spectrometry, and database queries. RESULTS: The results of biological and immunochemical analyses revealed that the allergic rhinitis was due to Urtica dioica pollen in both patients. The allergomic analysis of nettle pollen extract allowed the characterization of 4 basic protein allergens: a thaumatin-like protein (osmotin) with a relative molecular mass of 27 to 29 kDa, a pectinesterase (relative molecular mass, 40 kDa), and 2 other basic proteins with relative molecular masses of 14 to 16 kDa and 43 kDa. There is no or only very weak allergen associations between pellitory and nettle pollen. CONCLUSION: Exposure to nettle pollen can be responsible of allergic symptoms, and several allergens were characterized. Unravelling the allergens of this underestimated allergy might help to improve diagnosis and care for patients, to predict cross-reactivities and design adapted specific immunotherapy.


Asunto(s)
Alérgenos/inmunología , Conjuntivitis/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Urtica dioica/inmunología , Conjuntivitis/sangre , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Pruebas de Provocación Nasal , Rinitis Alérgica Estacional/sangre , Pruebas Cutáneas
13.
Int J Hyg Environ Health ; 219(8): 792-800, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27649627

RESUMEN

BACKGROUND: Allergic sensitisation is poorly documented in infants. This study aims to provide new insights into allergic sensitisation patterns and related factors in infancy. METHODS: This study concerns 1860 infants involved in the Pollution and Asthma Risk: an Infant Study (PARIS) population-based birth cohort who had a standardised health examination when 18 months old, from 2004 to 2008. Sensitisation was assessed by measurements of serum specific IgE to 12 food and 4 inhalant allergens and defined by IgE≥0.35kUA/L. Information regarding lifestyle and environment were obtained from questionnaires prospectively administered. RESULTS: Prevalence of allergic sensitisation to any allergen, to food allergens, and to aeroallergens was 13.8%, 12.3%, and 2.3%, respectively. Multiple sensitisation (to at least two allergens) concerned 6.2% of toddlers. Intrinsic factors such as male gender, family history of allergy, and high birth weight increased the risk of food allergen sensitisation and multiple sensitisation. Caesarean section was also positively associated with multiple sensitisation. Day-care attendance was negatively related to food allergen, aeroallergen, and multiple sensitisation. A cat entering the baby's room in early life was strongly associated with aeroallergen sensitisation (ORa 3.21, 95%CI: 1.29-8.01). An introduction of meat in infant's diet after 6 months of age was negatively related to food allergen sensitisation (ORa 0.46, 95%CI: 0.24-0.91). CONCLUSION: Our results suggest that intrinsic factors and indicators of exposure to microorganisms such as caesarean section and day-care attendance may be associated with inhalant as well as food allergen sensitisation in infancy. For example, male gender, family history of allergy, high birth weight, and caesarean section could be positively related whereas day-care attendance could be negatively related to both aeroallergen and food allergen sensitisation. Conversely, early life exposure to inhalant allergens or food allergens may be specifically linked to either aeroallergen sensitisation or food allergen sensitisation, respectively.


Asunto(s)
Hipersensibilidad/epidemiología , Alérgenos/inmunología , Animales , Peso al Nacer , Gatos , Cesárea , Estudios de Cohortes , Centros de Día , Femenino , Alimentos , Humanos , Inmunoglobulina E/sangre , Lactante , Masculino , Anamnesis , Prevalencia , Factores de Riesgo
14.
Pediatr Allergy Immunol ; 27(8): 831-837, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27501330

RESUMEN

BACKGROUND: Profiles of allergic sensitization are poorly documented in infancy. Relations between early sensitization and allergic morbidity need to be clarified. METHODS: This study dealt with children involved in the Pollution and Asthma Risk: an Infant Study (PARIS), a population-based prospective birth cohort. Allergic sensitization to twelve food and four inhalant allergens was assessed at 18 months and defined by a specific immunoglobulin E (IgE) level ≥0.35 kUA /l. Health data were collected by standardized questionnaires at 2 and 6 years. Early allergic profiles were identified by an unsupervised cluster analysis based on health data at 2 years and IgE measurements. Profiles were compared with regard to allergic morbidity and multimorbidity at 6 years. RESULTS: Sensitization to any allergen concerned 13.6% of infants. By cluster analysis, 1525 infants were grouped into three profiles: 89.2% not or rarely sensitized (only 3.7% of sensitized), 9.2% mainly sensitized to one or few allergens (45.2% of monosensitized and 45.9% of paucisensitized) and 1.6% all polysensitized. The prevalence of doctor-diagnosed asthma, rhinitis, eczema, food allergy and multimorbidity at 2 years increased from profile one to profile three (p-trend <0.001). At 6 years, symptoms of current asthma, rhinitis, eczema and multimorbidity were significantly more frequent in the last two profiles. CONCLUSIONS: This study highlights, as early as 18 months of age, three profiles of increasing severity with regard to allergic sensitization and diseases. These profiles also differ in terms of allergic morbidity at 6 years. Early sensitization can predict allergic multimorbidity in childhood, and in the case of early polysensitization, multimorbidity is more frequent as soon as infancy.


Asunto(s)
Alérgenos/inmunología , Hipersensibilidad/epidemiología , Inmunización , Preescolar , Estudios de Cohortes , Reacciones Cruzadas , Femenino , Estudios de Seguimiento , Alimentos , Humanos , Hipersensibilidad/diagnóstico , Inmunoglobulina E/sangre , Lactante , Masculino , Grupos de Población , Prevalencia , Pronóstico , Estudios Prospectivos
15.
PLoS One ; 10(6): e0131369, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26107938

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term "atopic march". However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma. METHODS: We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6. RESULTS: We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called "AD with low sensitization"; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called "AD with multiple sensitizations" - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called "AD with familial history of asthma". Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01). CONCLUSION: Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.


Asunto(s)
Asma/diagnóstico , Asma/etiología , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Alérgenos/inmunología , Niño , Preescolar , Análisis por Conglomerados , Femenino , Estudios de Seguimiento , Hipersensibilidad a los Alimentos/inmunología , Francia , Humanos , Inmunoglobulina E/inmunología , Lactante , Masculino , Fenotipo , Estudios Prospectivos , Encuestas y Cuestionarios , Centros de Atención Terciaria
16.
Int J Mol Sci ; 16(6): 12230-42, 2015 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-26035753

RESUMEN

UNLABELLED: Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. METHODS: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. RESULTS: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. DISCUSSION: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.


Asunto(s)
Anticolesterolemiantes/administración & dosificación , Arginina/análogos & derivados , Arginina/sangre , Atorvastatina/administración & dosificación , Hipercolesterolemia/terapia , Placa Aterosclerótica/prevención & control , Animales , Anticolesterolemiantes/farmacología , Arginina/administración & dosificación , Atorvastatina/farmacología , Colesterol/sangre , Suplementos Dietéticos , Hipercolesterolemia/sangre , Óxido Nítrico/sangre , Óxido Nítrico Sintasa/antagonistas & inhibidores , Placa Aterosclerótica/sangre , Conejos
17.
Br J Nutr ; 113(1): 120-4, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25391524

RESUMEN

In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortality. This may result from the associated decreased plasma concentration of arginine, an amino acid that plays an important role in immunity. In vitro, increasing arginine availability leads to an improvement in macrophage function; however, arginine supplementation in diabetic obese patients may be detrimental. The aim of the present study was to assess in vitro whether citrulline, an arginine precursor, could replace arginine in the regulation of macrophage function under a condition of diabetes and obesity. Peritoneal macrophages from diabetic obese or lean rats were incubated for 6 h in an arginine-free medium, in the presence of increasing citrulline concentrations (0·1, 0·5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal macrophages from either lean or diabetic obese rats produced NO, and at higher levels in the cells from lean rats. In diabetic obese rats, TNF-α production decreased with increasing citrulline concentrations, but was higher than that in the cells from lean rats. In contrast, IL-6 production increased with increasing citrulline concentrations. The present experiment shows that citrulline is effectively used for NO production and regulates cytokine production in macrophages from diabetic obese rats. This effect warrants in vivo evaluation in T2D-related inflammation.


Asunto(s)
Antiinflamatorios/farmacología , Citrulina/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Animales , Arginina/química , Arginina/farmacología , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Interleucina-6/metabolismo , Macrófagos Peritoneales/metabolismo , Masculino , Óxido Nítrico/metabolismo , Obesidad/tratamiento farmacológico , Ratas , Ratas Zucker , Factor de Necrosis Tumoral alfa/metabolismo
18.
ScientificWorldJournal ; 2015: 940243, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26819967

RESUMEN

This review summarizes the available data related to the effects of air pollution on pollen grains from different plant species. Several studies carried out either on in situ harvested pollen or on pollen exposed in different places more or less polluted are presented and discussed. The different experimental procedures used to monitor the impact of pollution on pollen grains and on various produced external or internal subparticles are listed. Physicochemical and biological effects of artificial pollution (gaseous and particulate) on pollen from different plants, in different laboratory conditions, are considered. The effects of polluted pollen grains, subparticles, and derived aeroallergens in animal models, in in vitro cell culture, on healthy human and allergic patients are described. Combined effects of atmospheric pollutants and pollen grains-derived biological material on allergic population are specifically discussed. Within the notion of "polluen," some methodological biases are underlined and research tracks in this field are proposed.


Asunto(s)
Contaminación del Aire/efectos adversos , Polen/efectos adversos , Rinitis Alérgica Estacional/inmunología , Animales , Humanos , Polen/inmunología , Rinitis Alérgica Estacional/epidemiología , Rinitis Alérgica Estacional/etiología
20.
PLoS One ; 9(5): e97236, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24831804

RESUMEN

BACKGROUND: In the preschool period, allergic rhinitis (AR) is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma. METHODS: We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema) were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens) and environmental parameters were also collected. RESULTS: Forty one of the children (18.1%) had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002); food allergy (OR = 4.31; p = 0.026); mold exposure (OR = 3.81 p<0.01) and parental history of AR (OR = 1.42; p = 0.046). Due to the strong link between food allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR. CONCLUSIONS & CLINICAL RELEVANCE: These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.


Asunto(s)
Asma/complicaciones , Rinitis Alérgica/complicaciones , Alérgenos/inmunología , Asma/diagnóstico , Estudios de Casos y Controles , Preescolar , Eccema/inmunología , Ambiente , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Hipersensibilidad Inmediata/complicaciones , Hipersensibilidad Inmediata/inmunología , Lactante , Masculino , Análisis Multivariante , Rinitis Alérgica/diagnóstico , Factores de Riesgo , Encuestas y Cuestionarios
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