Publications by authors named "Juan-Jose Sienra-Monge"

50 Publications

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

Cancers (Basel) 2021 Jan 30;13(3). Epub 2021 Jan 30.

Subdirección de Pediatría Ambulatoria Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Delegación Cuauhtémoc, Ciudad de Mexico 06720, Mexico.

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 ( = 0.014) and AA genotypes of rs4073 IL-8 ( = 0.002), as well as high levels of IL-6 ( = 0.009) and IL-8 ( = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.
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http://dx.doi.org/10.3390/cancers13030529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866803PMC
January 2021

An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

J Allergy Clin Immunol 2019 03 7;143(3):957-969. Epub 2018 Sep 7.

Veterans Caribbean Health Care System, San Juan, Puerto Rico.

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.

Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.

Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.

Results: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10, combined P = 2.6 × 10). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma.

Conclusion: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.
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http://dx.doi.org/10.1016/j.jaci.2016.08.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927816PMC
March 2019

[Knowledge of asthma: educational intervention with the 2014 GINA guide in primary care physicians].

Rev Alerg Mex 2016 Oct-Dec;63(4):358-364

Secretaría de Salud, Hospital Infantil de México Federico Gómez, Departamento de Alergia e Inmunología Clínica Pediátrica. Ciudad de México, México.

Background: Asthma is a public health problem in the world, so updating the guidelines for the diagnosis and treatment of asthma is based primarily on the practice of primary care physicians. Educational interventions are useful for increasing knowledge.

Objective: To compare the level of knowledge of asthma before and after an educational intervention.

Methods: A quasi-experimental prospective study was conducted in general and family practitioners and pediatricians who attended a training workshop on general aspects of asthma and current guidelines for diagnosis and treatment (GINA 2014). A questionnaire consisting of 11 multiple choice questions relating to fundamental aspects of the disease and diagnosis, classification, treatment and management of attacks, was used in two assessments, baseline and post-intervention.

Results: A total of 178 patients participated in the study, with knowledge pre-intervention at 25.5 points and post-intervention at 97.5 points on a scale of 100, with p < 0.05.

Conclusion: Educational interventions are inexpensive and effective tools to increase the knowledge of health professionals, and they have an impact on improving patient care.
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http://dx.doi.org/10.29262/ram.v63i4.196DOI Listing
December 2018

[Radiographic changes in children with primary immunodeficiency].

Rev Alerg Mex 2015 Jul-Sep;62(3):211-8

Hospital Infantil de México Federico Gómez, Secretaría de Salud, Distrito Federal, México.

Background: Although we have epidemiological information on primary immunodeficiencies (PID), the available information is meager in Mexico.

Objective: To provide epidemiological information on the delay in the diagnosis of PID and its correlation to chronic lung damage.

Material And Method: A retrospective, analytical study was done in patients 0-18 year old age diagnosed with PID for 11 years at the HIMFG (Hospital Infantil de Mexico Federico Gomez). The variables studied were: age at symptom onset, age at diagnosis, time from onset of symptoms to diagnosis, number of previous pneumonias and studies with radiographic chronic lung damage data.

Results: 48 patients were obtained after meeting inclusion criteria; 33 showed lung damage at diagnosis, antibody deficiency being the most affected group. Relating age of onset of symptoms and the time difference of the onset of symptoms to diagnosis showed a strong correlation (p < 0.001, Rho > 0.80). A moderate correlation between the observed time difference vs number of pneumonias (p=0.005, Rho=0.495) and correlation between number of pneumonia and lung damage was highly significant (p <0.001, Rho=0.704).

Conclusion: A strong relationship between the elapsed time from onset of symptoms and the number of pneumonia with lung injury time was found. So, the recurrent pneumonia (> 2) must make suspect the diagnosis of PID, as recommended in the literature.
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August 2015

[Antihistamines for the treatment of urticaria in Mexico].

Rev Alerg Mex 2015 Jul-Sep;62(3):157-74

Clínica de Alergia, Asma y Pediatría del Sur, Hospital Médica Sur, Distrito Federal, México.

There are four types of histamine receptors. Allergic symptoms, especially those in rhinoconjunctivitis and urticaria, are mainly caused by activation of histamine receptor 1 (H1). Consequently, oral H1-antihistamines form and integral part of the treatment of these diseases. Antihistamines are inverse agonists that stabilize the non-active configuration of the histamine receptor. First generation H1-antihistamines cause a variety of adverse effects via several mechanisms: sedation (accumulation in the central nervous system), dry mouth, urinary retention, weight gain (low selectivity: stimulation of serotonin/muscarinic/alpha-adrenergic receptors) and drug interactions (substrate of CYP450-3A4). Generally second generation H1-antihistamines have a better safety profile. New guidelines on allergic rhinitis and urticaria recommend second generation H1-antihistamines as first line drugs, with -if necessary- four-times updosing to obtain control in urticaria. The enhanced efficacy of quadruple doses in urticaria, while maintaining a good safety profile, has been shown for bilastine, desloratadine and levocetirizine (rupatadine). For ebastine and fexofenadine only the safety of quadruple doses has been shown till now. Extreme precaution should be taken with astemizol and terfenadine that never should be up-dosed, as high serum concentrations can cause potentially fatal ventricular tachycardia. First generation antihistamines are not recommended as first line treatment and updosing is not safe.
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August 2015

Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization.

World Allergy Organ J 2015 14;8(1):25. Epub 2015 Jul 14.

Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea.

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods - all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.
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http://dx.doi.org/10.1186/s40413-015-0073-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499913PMC
July 2015

[Mexican guidelines on the diagnosis and treatment of urticaria].

Rev Alerg Mex 2014;61 Suppl 2:S118-93

Clínica de Alergia, Asma y Pediatría, Hospital Médica Sur, México, DF.

Background: Urticaria is a disease that a fifth of the population shallsuffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups -both specialists and primary health care workers-, necessary in Mexico.

Material And Method: Internationally recognized tools for guidelinedevelopment were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline development) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development.

Results: By a formal process of discussion and voting during several working-sessions, experts and first level healthcare physicians determined the wording of the final guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as first line treatment is emphasized.

Conclusion: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, first line health care physicians and specialists.
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January 2014

[Frequency of allergy to cow's milk proteins and its association to other allergic diseases in patients of Hospital Infantil de Mexico Federico Gomez].

Rev Alerg Mex 2014 Oct-Dec;61(4):288-97

Hospital Infantil de México Federico Gómez, México, DF.

Background: The cow's milk protein allergy is the most common food allergy among children under two years and is associated with other atopic diseases.

Objectives: To evaluate cow's milk protein allergy frequency in patients sensitized to them, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, and its association with other atopic diseases.

Material And Method: A cross-sectional, analytical and descriptive study that reviewed medical records of patients aged 0-19 years, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, from January 2010 to January 2013, sensitized to the cow's milk protein by in vitro or in vivo studies, mediated or not by IgE, to determine its association with other atopic diseases during the course of their clinical evolution.

Results: We included 252 patients with symptoms suggestive of cow's milk protein allergy, which was diagnosed only in 15.1% by oral challenge. In relation to respiratory symptoms, about two-thirds of patients had rhinorrhea, nasal obstruction and nasal itching. Regarding gastrointestinal symptoms, about a third had abdominal pain, diarrhea and abdominal distension, being statistically significant. The most common dermatologic symptom, statistically significant, was xerosis. The most frequently associated atopic diseases were food allergy (76.3%), allergic rhinitis (65.8%), asthma (47.4%) and atopic dermatitis (23%).

Conclusions: The cow's milk protein allergy can be associated with other atopic diseases, such as allergy to other foods, allergic rhinitis, asthma and atopic dermatitis.
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December 2014

[ARIA Mexico 2014. Adaptation of the Clinical Practice Guide ARIA 2010 for Mexico. Methodology ADAPTE].

Rev Alerg Mex 2014;61 Suppl 1:S3-S116

Hospital Médica Sur, México, DF.

Background: The global prevalence of allergic rhinitis is high. International Study of Asthma and Allergies in Childhood (ISAAC) Phase III reports a total estimated prevalence of 4.6% in Mexico. There is evidence based on allergic rhinitis Clinical Practice Guidelines (CPG), but its promotion, acceptance and application is not optimal or adequate in Mexico.

Objective: To generate a guideline for the treatment of allergic rhinitis and its impact on asthma by adaptating the 2010 ARIA Guideline to Mexican reality, through a transculturation process applying the ADAPTE methodology.

Patients And Method: Using the ADAPTE Methodology, the original 2010 ARIA CPG recommendations were evaluated by the guideline development group (GDG) into which multiple medical specialities managing patients with allergic rhinitis were incoorporated. The GDG valorated the quality of 2010 ARIA, checked and translated key clinical questions. Moreover, the GDG adjusted recommendations, patient preferences and included comments in the context of the Mexican reality (safety, costs and cultural issues). To accomplish this, we ran Delphi panels with as many rounds as necessary to reach agreement. One extra question, not included in the original 2010 ARIA, on the use of Nasal Lavages for AR was created sustained by a systematic literature review.

Results: A total of 45 questions from the original 2010 ARIA were included and divided into six groups covering prevention, medical treatment, immunotherapy and alternative medicine to treat patients with allergic rhinitis with or without asthma. Most of the questions reached agreement in one or two rounds; one question required three rounds.

Conclusions: An easy-to-use, adaptated, up-to-date and applicable allergic rhinitis guideline for Mexico is now available.
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January 2014

Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

Science 2014 Jun 12;344(6189):1280-5. Epub 2014 Jun 12.

Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.
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http://dx.doi.org/10.1126/science.1251688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156478PMC
June 2014

[Food allergy].

Gac Med Mex 2011 ;147 Suppl 1:57-66

Departamento de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, SSA, México, D.F.

Food allergy is defined as an abnormal immunological reaction to food proteins, which causes an adverse clinical reaction. Most of the people become tolerant to many foods; however some time these tolerances fail and become an immunologic reaction. This is the first clinical expression of allergy, beginning with dermal o gastric manifestations and continues with asthma and rhinitis (the allergy march) and represents a very severe health problem, not only for many children and parents, but also for the entire medical and paramedical community. The evaluation of a child with suspected food allergy includes detailed medical history, physical examination, screening tests and response to elimination diet and to oral food challenge. None of the screening tests, alone or in combination, can definitively diagnose or exclude it. Regarding to the differential diagnosis, the clinician must know the different groups of foods. The treatment includes the exclusion of the involved food and the use of symptomatic medication when it is needed.
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April 2012

[Risk factors of food allergy].

Rev Alerg Mex 2009 Sep-Oct;56(5):158-64

Servicio de Alergia e Inmunología Clínica Pediátrica, México.

Food allergy or allergic food hypersensitivity is defined as an adverse immunologic reaction caused by immunologic mechanisms mediated or not by IgE. It is a complex disease influenced by polygenetic heritance and environmental factors. Many risk factors have been investigated, pre natal and post natal, and variable and controversial results have been obtained. The most important risk factors associated with food allergy are atopy, lack of breast feeding at least three to six months and early weaning (before four-six months).
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March 2010

Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans.

J Allergy Clin Immunol 2010 Feb 11;125(2):321-327.e13. Epub 2009 Nov 11.

Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Background: More than 200 asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs).

Objective: We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population.

Methods: From the literature, we identified candidate genes with at least 1 positive report of association with asthma phenotypes in human subjects or implicated in asthma pathogenesis using knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 550v3 BeadChip. Separate candidate gene analyses were performed for 2933 autosomal SNPs in the 237 selected genes by using the log-linear method with a log-additive risk model.

Results: Sixty-one of the 237 genes had at least 1 SNP with a P value of less than .05 for association with asthma. The 9 most significant results were observed for rs2241715 in the gene encoding TGF-beta1 (TGFB1; P = 3.3 x 10(-5)), rs13431828 and rs1041973 in the gene encoding IL-1 receptor-like 1 (IL1RL1; P = 2 x 10(-4) and 3.5 x 10(-4)), 5 SNPs in the gene encoding dipeptidyl-peptidase 10 (DPP10; P = 1.6 x 10(-4) to 4.5 x 10(-4)), and rs17599222 in the gene encoding cytoplasmic FMR1 interacting protein 2 (CYFIP2; P = 4.1 x 10(-4)). False discovery rates were less than 0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma.

Conclusions: This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes, including TGFB1, IL1RL1, IL18R1, and DPP10, might contribute to childhood asthma susceptibility in a Mexican population.
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http://dx.doi.org/10.1016/j.jaci.2009.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823974PMC
February 2010

[Difficult-to-control asthma. A bibliographical review].

Rev Alerg Mex 2009 Jul-Aug;56(4):115-23

Servicio de Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez.

Difficult-to-control asthma is a disease that causes serious exacerbations, near-fatal attacks, frequent hospitalizations, and needs chronic use of high doses of inhaled corticosteroids or daily oral corticosteroid therapy. On the basis of epidemiological studies, the risk factors for serious asthma are: female gender, high BMI, sensitivity to aspirin, gastro esophageal reflux, sinusitis, pneumonia history, and beginning of asthma symptoms in adult late age. It has been found that in severe asthma the inflammatory profile commonly changes with major participation of neutrophils, and evidence of destruction and remodelling. The first step in the care of these patients is an evaluation to determine that asthma is the right diagnosis. A systematic and rigorous evaluation helps to asses adequately the differential diagnoses, the comorbilities and the unusual triggers. The aim of the treatment is to achieve the best results with minimum adverse effects. New immunomodulatory therapies are needed for these patients management.
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October 2009

Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

PLoS Genet 2009 Aug 28;5(8):e1000623. Epub 2009 Aug 28.

Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.
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http://dx.doi.org/10.1371/journal.pgen.1000623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722731PMC
August 2009

[Diagnosis and treatment in the emergency room of acute asthma in childhood].

Rev Alerg Mex 2009 ;56 Suppl 1:S49-57

Neumóloga pediatra, profesora titular de la especialidad de neumologia pediátrica de la UNAM y Jefa del ServicIo de Neumología y Fisología Pulmonar.

Acute asthma is characterized by acute air way obstruction episodes presented as short breath, increased coughing, wheezing and difficult breathing, reversible with bronchodilator. It constitutes one of the most frequent causes of pediatric ER visits whose diagnosis and treatment is not always adequate. It is necessary to carry out a complete medical history searching for the number of previous attacks, risk factors, associated illnesses, triggers, prior hospitalizations, preventive and maintenance treatment used, along with a complete physical examination. During the management of moderate-severe attacks frequent systematic assessments are required to ensure treatment response. In children above 5 years old, monitoring of expiratory peak flow (EPF) during mild-moderate attacks is recommended. In general, a national consensus to classify and treat acute asthma in emergency services does not exist for which the need to develop a clinical practice guide of diagnosis and management arises.
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November 2010

Traffic-related air pollution and respiratory symptoms among asthmatic children, resident in Mexico City: the EVA cohort study.

Respir Res 2008 Nov 16;9:74. Epub 2008 Nov 16.

Instituto Nacional de Salud Pública, Mexico.

Background: Taffic-related air pollution has been related to adverse respiratory outcomes; however, there is still uncertainty concerning the type of vehicle emission causing most deleterious effects.

Methods: A panel study was conducted among 147 asthmatic and 50 healthy children, who were followed up for an average of 22 weeks. Incidence density of coughing, wheezing and breathing difficulty was assessed by referring to daily records of symptoms and child's medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression.

Results: Wheezing was found to relate significantly to air pollutants: an increase of 17.4 microg/m3 (IQR) of PM2.5 (24-h average) was associated with an 8.8% increase (95% CI: 2.4% to 15.5%); an increase of 34 ppb (IQR) of NO2 (1-h maximum) was associated with an 9.1% increase (95% CI: 2.3% to 16.4%) and an increase of 48 ppb (IQR) in O3 levels (1 hr maximum) to an increase of 10% (95% CI: 3.2% to 17.3%). Diesel-fueled motor vehicles were significantly associated with wheezing and bronchodilator use (IRR = 1.29; 95% CI: 1.03 to 1.62, and IRR = 1.32; 95% CI: 0.99 to 1.77, respectively, for an increase of 130 vehicles hourly, above the 24-hour average).

Conclusion: Respiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles.
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http://dx.doi.org/10.1186/1465-9921-9-74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613139PMC
November 2008

Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.

Environ Health Perspect 2008 Jun;116(6):832-8

Instituto Nacional de Salud Pública, Cuernavaca, México.

Background: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood.

Objective: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function.

Methods: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models.

Results: An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children.

Conclusions: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.
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http://dx.doi.org/10.1289/ehp.10926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430242PMC
June 2008

Assessment of personal exposure to ozone in asthmatic children residing in Mexico City.

Salud Publica Mex 2008 Jan-Feb;50(1):67-75

Instituto Nacional de Salud Pública, Universidad 655, Cuernavaca, Mexico.

Objective: A study was conducted to evaluate personal ozone exposure (O3p) among asthmatic children residing in Mexico City.

Material And Methods: A total of 158 children were recruited from December 1998 to April 2000. On average, three O3p measurements were obtained per child using passive badges. Time-activity patterns were recorded in a diary. Daily ambient ozone measurements (O3a) were obtained from the fixed station, according to children's residence. Levels of O3a and ozone, weighted by time spent in different micro-environments (O3w), were used as independent variables in order to model O3p concentrations using a mixed-effects model.

Results: Mean O3p was 7.8 ppb. The main variables in the model were: time spent indoors, distance between residence and fixed station, follow-up group, and two interaction terms (overall R(2)=0.50, p<0.05).

Conclusions: The O3w concentrations can be used as a proxy for O3p, taking into account time-activity patterns and the place of residence of asthmatic Mexican children.
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http://dx.doi.org/10.1590/s0036-36342008000100013DOI Listing
July 2008

[Uncommon manifestations of atopic dermatitis].

Rev Alerg Mex 2007 May-Jun;54(3):96-103

Departamento de Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez.

Atopic dermatitis is an inflammatory process characterized by a series of cutaneous alterations of typical morphology and distribution, with intense pruritus of nocturnal predominance, of chronic evolution, stational appearance, and with personal and family history of atopy. On genetically predisposed skin, dry and hypersensitive, the immune factors and other types are implicated in determining the abnormal reactions to multiple endogenous and environmental factors. The diagnosis is clinical, generally obtained by a group of signs and symptoms known as the Hanifin and Rajka criteria. The patients with atopic dermatitis can present with clinical typical manifestations, or minimized and localized variations as well, considered a stigma of atopic constituent. In some patients there can be observed clinical and morphological variations with special localizations denominated atypical variations of atopic dermatitis. The identification of these atypical presentations of atopic dermatitis leads to the differential diagnosis, with an early establishment of the disease's diagnosis and the appropriate and early treatment.
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October 2007

[Adverse reactions to vaccines].

Rev Alerg Mex 2007 May-Jun;54(3):86-95

Departamento de Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez, México, DF.

Vaccination is one of the medicine's achievements to control and/or eradicate certain infectious diseases. Vaccines contain antigenic doses derived from microorganisms and/or its toxins, besides they are composed of other substances such as aluminum, gelatin, egg proteins, mercury components (as thimerosal), and antibiotics; therefore, these substances can produce hypersensitivity reactions. The above-mentioned reactions can be evidenced with itch, edema, hives, asthmatic crisis, hypotension and even anaphylactic shock. Due to the importance of vaccination, especially in childhood, it is essential to know the benefits of vaccines, their impact in morbidity and mortality decrease of certain infected-contagious diseases, as well as the adverse effects and the allergic reactions to their application. As immunizations prevent natural infections, they might contribute to a free infectious environment that would allow atopic response. This paper reviews the allergic reactions to vaccines and their influence on the development of atopic disease.
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October 2007

Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma.

J Allergy Clin Immunol 2007 Aug 1;120(2):322-8. Epub 2007 Jun 1.

Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Background: S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge.

Objective: We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy.

Methods: We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing.

Results: Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy.

Conclusion: This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility.

Clinical Implications: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.
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http://dx.doi.org/10.1016/j.jaci.2007.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094003PMC
August 2007

[Urticaria and angioedema].

Rev Alerg Mex 2007 Mar-Apr;54(2):54-65

Departamento de Alergia e Inmunología Clinica, Hospital Infantil de México Federico Gómez.

Urticaria is considered a heterogeneous group of diseases that share different patterns of skin reactions. The wide diversity in urticaria subtypes have been identified and this reflects partial understanding of the causes or factors that trigger it, as well as the molecular and cellular mechanisms that are involved in their physiopathology. The objective of this article was to make an extensive review of the literature to be able to offer the readers a complete information and updating on the basic, ethiologic and physiophatologic mechanisms and mainly to make a special emphasis on diagnosis and treatment of urticaria, promoting the continuous medical education.
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December 2007

[Allergic conjunctivitis in children].

Rev Alerg Mex 2007 Mar-Apr;54(2):41-53

Hospital Infantil de México Federico Gómez.

Allergic conjunctivitis is a group of diseases that are frequent in childhood, associated to several allergic diseases affecting the ocular surface. It is related to type 1 hypersensitivity reactions. Two acute disorders: seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do three chronic diseases: vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. The ocular surface inflammation causes itching, tearing, lid and conjunctival edema-redness, and photophobia during the acute phase and can lead to a classic late-phase response (associated to eosinophilia and neutrophilia) in a subset of individuals. As in the case of several chronic allergic diseases, it can remodel the ocular surface tissue. This allergic disease is very frequent. Vernal keratoconjunctivitis could produce corneal lesions and visual illness; however, atopic keratoconjunctivitis does not permanently affect the vision. The aim of this review is to provide a current overview for a better understanding of the symptoms associated to this disease, to describe its classification, recent advances in its physiopathology and its treatment.
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December 2007

[Anaphylaxis and anaphylactic shock].

Rev Alerg Mex 2007 Mar-Apr;54(2):34-40

Hospital Infantil de México Federico Gómez.

Term anaphylaxis means an immediate hypersensitivity reaction mediated by IgE that produces a clinical syndrome with systemic affection of variable severity. Its prevalence varies according to the habits of each region and of the studied population from 3.2 to 7.6 cases per 100,000 inhabitants per year. Anaphylaxis secondary to the food ingestion accounts for 30-50% of the cases. Some risk factors have been defined, among them the most important are asthma, food allergy and previous reactions to the same food. Biphasic anaphylactic reactions are those presenting a recurrence of anaphylactic symptoms, after the initial remission of them. Success of treatment is based on the early recognition of signs and symptoms and the instauration of treatment with adrenaline.
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December 2007

Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma.

Environ Health Perspect 2007 Apr 16;115(4):616-22. Epub 2007 Jan 16.

Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, NC 27709, USA.

Background: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha (LTA, also called TNF-beta) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production.

Objectives: Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure.

Methods: We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests.

Results: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04-2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19-3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14-4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy.

Conclusions: Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.
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http://dx.doi.org/10.1289/ehp.9740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852663PMC
April 2007

Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

Hum Genet 2007 Jun 28;121(5):529-38. Epub 2007 Feb 28.

Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR)=1.42, 95% confidence interval (CI)=1.08-1.87 for one copy; RR (95%CI)=1.95 (1.36-2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09-1.98) for one and 2.00 (1.38-2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR=1.48, 95% CI=1.11-1.95 for one copy; RR=1.77, 95% CI=1.22-2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders.
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http://dx.doi.org/10.1007/s00439-007-0337-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865573PMC
June 2007

Asthma prevalence in children living in north Mexico City and a comparison with other Latin American cities and world regions.

Allergy Asthma Proc 2006 Jul-Aug;27(4):334-40

Allergy Department, Hospital Infantil de Mexico, Dr. Marquez 162, Mexico City 06720, Mexico.

Reports of previous studies done without following the international guidelines in different cities of Mexico showed a decrease in asthma prevalence. The aim of this study was to determine the prevalence and severity of asthma symptoms in children and teenagers living in north Mexico City and compare them with those of other Latin American cities and world regions. The cross-sectional survey followed the protocol of the International Study of Asthma and Allergies in Childhood IIIb phase survey. The study population included children 6-7 years old and teenagers 13-14 years old from randomly selected primary and secondary schools. There were 1629 boys and 1582 girls in the group of 6- to 7-year-old children and 2039 boys and 1860 girls in the 13- to 14-year-old group. "Wheezing or whistling in the chest at any time in the past" was present in 19.2% (95% confidence interval [CI], 17.9, 20.6) of the children and in 17.0% (95% CI, 15.8, 18.1) of the teenagers; "wheezing or whistling in the chest in the last 12 months" was reported in 6.8% (95% CI, 5.9, 7.6) of the children and 9.9% (95% CI, 9.0, 10.8) of the teenagers; "asthma ever" was claimed in 4.5% (95% CI, 3.8, 5.2) of the children and 8.0% (95% CI, 7.1, 8.8) of the teenagers. These prevalences were low compared with other ISAAC Latin American surveys and intermediate in comparison with worldwide regional prevalences reported by ISAAC surveys. The prevalence of asthma is low in Mexico City in comparison with other surveyed locations, but the number of patients with asthma makes it an important issue for Mexican public health programs.
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http://dx.doi.org/10.2500/aap.2006.27.2880DOI Listing
November 2006

[Cow-milk's protein allergy].

Rev Alerg Mex 2005 Sep-Oct;52(5):206-12

Hospital Infantil Federico Gómez, México, DF.

Milk contains more than 40 proteins and all of them may act like human species antigens. The main allergens are beta lactoglobulin, casein, alpha lactoalbumin and seroalbumin; beta lactoglobulin is a protein not existing in human species and is found in maternal milk in minimal quantities (mcg) due to milky products ingested by the mother, these small quantities are responsible of the highest number of sensitizations to this protein. This article reviews the allergy to the cow-milk's protein, also, a critical route to its diagnosis and management is planted.
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August 2006
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