Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

B subset cells in patients with chronic granulomatous disease in a Mexican population.

INTRODUCTION: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. MATERIALS AND METHODS: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. RESULTS: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. DISCUSSION: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease.

Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect its immunological profile?

BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.

Fungal Allergy: Pattern of sensitization over the past 11 years.

INTRODUCTION AND OBJECTIVES: Although the prevalence of sensitization to fungi is not precisely known, it can reach 50% in inner cities and has been identified as a risk factor in the development of asthma. Whereas the prevalence of allergic diseases is increasing, it is unclear whether the same occurs with sensitization to fungi. PATIENTS AND METHODS: A retrospective study was performed at the "Hospital Infantil de México Federico Gómez". From skin tests taken between 2004 and 2015, information was gathered about Alternaria alternata, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, Mucor mucedo and Penicillium notatum. The participating patients were 2-18 years old, presented some type of allergic condition, and underwent immediate hypersensitivity tests to the fungi herein examined. Descriptive analysis and chi-squared distribution were used. RESULTS: Of the 8794 patients included in the study, 14% showed a negative result to the entire panel of environmental allergens. The remaining 7565 individuals displayed sensitization to at least one fungus, which most frequently was Aspergillus, with a rate of 16.8%. When the patients were divided into age groups, the same trend was observed. The highest percentage of sensitization (58%) toward at least one type of fungus was found in 2014, and the lowest percentage (49.8%) in 2008. CONCLUSION: The rate of sensitization to at least one type of fungus was presently over 50%, higher than that detected in other medical centers in Mexico. This rate was constant over the 11-year study, and Aspergillus exhibited the greatest frequency of sensitization among the patients.

Composition of gut microbiota in obese and normal-weight Mexican school-age children and its association with metabolic traits.

BACKGROUND: Childhood obesity is a serious public health problem in Mexico. Adult gut microbiota composition has been linked to obesity, but few studies have addressed the role of gut microbiota in childhood obesity. OBJECTIVES: The aim of this study is to compare gut microbiota composition in obese and normal-weight children and to associate gut microbiota profiles with amino acid serum levels and obesity-related metabolic traits. METHODS: Microbial taxa relative abundance was determined by 16S rRNA sequencing in 67 normal-weight and 71 obese children aged 6-12 years. Serum amino acid levels were measured by mass spectrometry. Associations between microbiota composition, metabolic parameters and amino acid serum levels were tested. RESULTS: No significant differences in phyla abundances or Firmicutes/Bacteroidetes ratios were observed between normal-weight and obese children. However, Bacteroides eggerthii abundance was significantly higher in obese children and correlated positively with body fat percentage and negatively with insoluble fibre intake. Additionally, Bacteroides plebeius and unclassified Christensenellaceae abundances were significantly higher in normal-weight children. Abundance of both these species correlated negatively with phenylalanine serum levels, a metabolite also found to be associated with obesity in Mexican children. CONCLUSIONS: The study identified bacterial species associated with obesity, metabolic complications and amino acid serum levels in Mexican children.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Cross-over clinical trial for evaluating the safety of camel's milk intake in patients who are allergic to cow's milk protein.

BACKGROUND: Cow's milk protein allergy (CMPA) affects between 0.6 and 0.9% of the general population, and its treatment implies the total elimination of the intake of this protein. Camel's milk has been suggested as an alternative for patients over one year of age who suffer from CMPA due to the difference in the amino acid sequence from that of cow's milk. The objective of this study was to evaluate the safety and tolerability of camel's milk in children with CMPA. METHODS: Crossed clinical trial for the use of camel's milk vs. amino acid formula, carried out at the Dr. Federico Gómez Children's Hospital of Mexico (HIMFG) on patients between one and 18 years of age with diagnosed CMPA confirmed through double-blind, placebo-controlled food challenges (DBPCFCs). Only those whose allergies were confirmed were randomly placed into two groups: those to be administered camel's milk and those to be administered the amino-acid formula for two weeks, followed by a six-week wash-out period, and then a group crossing for a further two weeks. RESULTS: 49 patients with suspected CMPA were included in the study; the diagnosis was confirmed through DBPCFCs in 15 patients, who were those who participated in the study. After having been administered camel's milk, none of the patients presented adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Camel's milk is safe and tolerable in patients above one year of age with CMPA and can be considered as a good alternative given the benefit of its taste compared to other formulas.

Dermatophagoides pteronyssinus: Changes in sensitisation in the past 11 years and comparison with other centres in Mexico.

BACKGROUND: House dust mites are a ubiquitous air allergen in the human habitat. It has been shown that exposure to them is a fundamental factor in sensitisation and development of atopic disease. The objective of the study was to analyse changes in sensitisation to Dermatophagoides pteronyssinus (Der p.) in children treated in a tertiary level care hospital in Mexico City for a period of 11 years and compare with other studies carried out in Mexico. METHODS: A retrospective study was performed at the Hospital Infantil de México Federico Gómez (HIMFG). Information was gathered from skin tests for Der p. performed in the Allergy Laboratory from January 2004 to April 2015. Patients 2-18 years old who presented for examination of some type of allergic condition and who had immediate hypersensitivity tests to Der p. were included in the study. Results were compared with prior reports from other institutions. Descriptive analysis and χ2 statistics were used. RESULTS: A total of 8794 patients were included in the study; 49.3% of the tests (95% CI 48-50) were positive for Der p. The percentage of monosensitised to mites was 2.7% for Der p. (95% CI 2-3). A significant difference was found between the results of older patients and those <6 years old. The frequency of sensitisation had a tendency to decrease during the 11 years analysed in all age groups. CONCLUSIONS AND CLINICAL RELEVANCE: The frequency of sensitisation to Der p. increased with age until reaching adolescence. In the last 11 years a decrease in sensitisation to this air allergen was observed.

SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients.

BACKGROUND: Asthma is one of the most common respiratory diseases worldwide, and the complexity of its etiology has been widely documented. Chromosome 5q31-33 is one of the main loci implicated in asthma and asthma-related traits. IL13, CD14 and ADRB2, which are located in this risk locus, are among the genes most strongly associated with asthma susceptibility. OBJECTIVES: This study evaluated whether single-nucleotide polymorphisms or haplotypes at 5q31-33 conferred risk for asthma in Mexican-Mestizo pediatric patients. METHODS: We performed a case-controlled study including 851 individuals, 421 of them affected with childhood-onset asthma and 430 ethnically matched unaffected subjects. We used the TaqMan Allelic Discrimination Assay to genotype 20 single-nucleotide polymorphisms within IL5, RAD50, IL13, IL4, CD14, SPINK5, HTR4, ADRB2 and IL12B. RESULTS: Although no association was detected for any risk allele, three SPINK5 haplotypes (GGCT: p = 6 × 10(-6); AATC: p = 0.0001; AGTT: p = 0.0001) and five ADRB2 haplotypes (AGGACC: p = 0.0014; AGGAAG: p = 0.0002; TGAGAG: p = 0.0001; AGGAAC: p = 0.0002; AAGGAG: p = 0.003) were associated with asthma. Notably, the AGTT SPINK5 haplotype exhibited a male gender-dependent association (p = 7.6 × 10(-5)). CONCLUSION: Our results suggest that SPINK5 and ADRB2 haplotypes might play a role in the susceptibility to childhood-onset asthma.

Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay.

BACKGROUND: There are two inheritance patterns, the X-linked recessive (XL) pattern and the autosomal recessive pattern. There is no information on the predominant inheritance pattern of male patients with chronic granulomatous disease (CGD) in Mexico. OBJECTIVE: The aim of this study was to determine the inheritance pattern in a cohort of Mexican male patients with CGD by means of the detection of an XL status carrier among their female relatives, and to describe the frequency of discoid lupus (DL) among carriers. METHODS: We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. All carriers were questioned for current or past established DL diagnosis. RESULTS: We detected 33 families with one or more CGD male patients; we found an XL-CGD in 79% of the relatives from at least one female relative with a bimodal pattern. For the remaining seven relatives we were not able to confirm a carrier status by means of a DHR assay. Moreover, we detected one mother with CGD secondary to skewed X-chromosome inactivation. We also found 47 carriers, and only one carrier with DL among them. CONCLUSION: We concluded that XL-CGD is the most frequent form of CGD in a cohort of CGD male patients in Mexico. DHR assay is a fast and practical tool to determine the CGD form in the Latin-American countries. Finally, DL frequency in Mexico is lower than that reported in the literature for other regions of the world.

DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance.

OBJECTIVE: Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome. SUBJECTS: One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples. RESULTS: Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at -51 and -31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at -283 nt relative to the start site of the ADIPOQ promoter. CONCLUSIONS: These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to predict and follow up the physiological changes associated with obesity and insulin resistance.

MiR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients.

Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.

Elemental carbon exposure and lung function in school children from Mexico City.

Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air samplers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean ± sd of elemental carbon light absorption was 92.7 ± 54.7 Mm(-1). An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm(-1)) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV(1)) (-62.0 (95% CI -123.3- -1.2) mL) and forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF(25-75%)) (-111 (95% CI -228.3- -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively; and on FEV(1) (-95.0 (95% CI -182.3- -8.5) mL) and FVC (-105.0 (95% CI -197.0- -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.

Weight loss induced by 6-month lifestyle intervention improves early endothelial activation and fibrinolysis in obese adolescents.

BACKGROUND: Adolescent obesity is associated with an increased risk of adult obesity and subsequent cardiovascular diseases. The present study aimed to assess the effect of weight loss after 6-month lifestyle intervention in obese adolescents on biomarkers of endothelial activation and fibrinolytic system. METHODS: Eighty-five obese adolescents aged 10 to 16 years were assigned to a 6-month lifestyle intervention and 61 completed the programme. We examined the effect of the intervention on adhesion molecules (selectin E, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1) and fibrinolytic parameters [plasminogen activator inhibitor-1 (PAI-1) and fibrinogen]. Thirty-six lean adolescents were studied only at baseline as a comparison group. RESULTS: Compared with lean participants, obese adolescents at baseline demonstrated significantly higher levels of triglycerides, glucose, insulin, homeostasis model assessment, soluble intercellular adhesion molecule 1, PAI-1 and fibrinogen. After 6-month lifestyle intervention, those obese adolescents with decreased standard deviation score-body mass index (SDS-BMI) displayed significant decreases in insulin (19.2 ± 11.2 vs. 26.8 ± 13.2 mU/L, P≤ 0.01), homeostasis model assessment (4.24 ± 3.19 vs. 6.58 ± 4.08, P≤ 0.01), selectin E (100.2 ± 60.9 vs. 116.0 ± 69.0 ng/mL, P≤ 0.01) and PAI-1 (39.6 ± 38.0 vs. 51.8 ± 25.6 ng/mL, P≤ 0.05) with respect to the baseline levels. No changes in these parameters were observed in the obese adolescents with stable or increased SDS-BMI. The changes of triglycerides after intervention in subgroup with decreased SDS-BMI were significantly greater than those in subgroup with stable SDS-BMI. CONCLUSIONS: The present study demonstrated increased endothelial activation and impairment of the fibrinolytic system in early life, which is in part reversible by a 6-month lifestyle intervention.

The increase in seroprevalence to Toxocara canis in asthmatic children is related to cross-reaction with Ascaris suum antigens.

BACKGROUND: It has been suggested that the presence of Toxocara canis larvae in lungs is an underlying factor in the onset of asthma. Although the association of asthma and seropositivity to Toxocara has been observed, there are no studies that indicate whether these antibodies are specific against T. canis antigens. METHODS: Seroprevalence to T. canis excretion-secretion antigens (TcES Ag) were compared between asthmatic children (n=285) and non-asthmatic children (n=152), using IgG-ELISA and IgE-ELISA. The recognition patterns of TcES Ag were determined using Western blot (WB). RESULTS: IgG-ELISA seroprevalence was 30.8% for asthmatic children and 19.7% for non-asthmatic children (p<0.05). IgE-ELISA seroprevalence was 7.7% for asthmatic children and 6.5% for non-asthmatic children, respectively (p>0.05). Sera of both groups positive to IgG-ELISA recognised 11 TcES Ag bands for IgG. No differences between the groups were observed regarding recognition patterns; the asthmatic group, however, presented significantly higher cross-reaction to Ascaris suum somatic antigens (AsS Ag) than the non-asthmatic group. Sixty-three sera from asthmatic children positive to IgG-ELISA were evaluated by WB for IgE and 58.7% revealed a recognition pattern for IgE. In the group of non-asthmatic children positive to IgG-ELISA, 80% presented IgE band recognition. No differences were observed between the groups regarding recognition patterns. CONCLUSIONS: The results observed suggest that differences in seroprevalence determined by IgG-ELISA between groups of asthmatic and non-asthmatic children reported by other authors occur because of a higher frequency of cross-reaction in asthmatic children.

Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma.

BACKGROUND: A genome-wide association study identified ORM1-like 3 (orosomucoid 1-like 3, ORMDL3) as an asthma candidate gene. Single nucleotide polymorphisms (SNPs) in the region including ORMDL3 on chromosome 17q21 were related to childhood asthma risk and ORMDL3 expression levels in Europeans. OBJECTIVE: We examined whether polymorphisms in ORMDL3 and the adjacent gasdermin-like (GSDML) gene associated with asthma in the genome-wide association study are related to childhood asthma and atopy in a Mexico City population. METHODS: We genotyped rs4378650 in ORMDL3 and rs7216389 in GSDML in 615 nuclear families consisting of asthmatic children aged 4-17 years and their parents. Atopy was determined by skin prick tests to 25 aeroallergens. RESULTS: Individuals carrying the C allele of rs4378650 or the T allele of rs7216389 had increased risk of asthma [relative risk (RR) = 1.73, 95% confidence interval (CI) 1.19-2.53, P = 0.003 for one or two copies of rs4378650 C, and RR = 1.64, 95% CI 1.12-2.38, P = 0.009 for one or two copies of rs7216389 T). Linkage disequilibrium between the two SNPs was high (r(2) = 0.92). Neither of the SNPs was associated with the degree of atopy. A meta-analysis of five published studies on rs7216389 in nine populations gave an odds ratio for asthma of 1.44 (95% CI, 1.35-1.54, P < 0.00001). CONCLUSIONS: Our results and the meta-analysis provide evidence to confirm the finding from a recent genome-wide association study that polymorphisms in ORMDL3 and the adjacent GSDML may contribute to childhood asthma.

Study of the relationship between acetaminophen and asthma in Mexican children aged 6 to 7 years in 3 Mexican cities using ISAAC methodology.

OBJECTIVE: To establish the relationship between the use of acetaminophen and the frequency of asthma in Mexican children in 3 Mexican cities. METHODS: Ours was a multicenter, observational, descriptive, cross-sectional study. Patients from 6 to 7 years of age participating in Phase Three B of the ISAAC (International Study of Asthma and Allergies in Children) living in the north of Mexico City, Victoria City, and Merida were included. After adjusting for confounders, we calculated the odds ratios (OR) for the presence of wheezing ever, wheezing in the last 12 months, asthma ever, and the use of acetaminophen in the first year of life and during the last 12 months. RESULTS: The ORs for wheezing ever, wheezing in the last year, and asthma ever with respect to use of acetaminophen in the first year of life were not statistically significant (P > .05) in Mexico City, but they were significant in Victoria City (P < .05) and Merida (P < .05). The ORs (95% confidence intervals) for wheezing ever, wheezing in the last year, and asthma ever with respect to use of acetaminophen in the last year were 3.44 (2.96-4.0), 7.97 (5.89-10.78), and 6.10 (3.30-8.81) (P < .05) in Mexico City. Values forVictoria City were 1.36 (1.13-1.63), 3.80 (2.88-5.05), and 2.18(1.57-3.01) (P < .05). Those for Merida were 1.61 (1.40-1.85), 2.07 (1.73-2.48), and 1.53 (1.29-1.82) (P < .05). CONCLUSION: The use of acetaminophen is associated with the presence of wheezing and asthma in 3 different cities in Mexico.

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy.

G-protein-coupled receptor for asthma susceptibility (GPRA or GPR154) was identified as an asthma and atopy candidate gene by positional cloning. Some subsequent studies suggest associations of GPRA single nucleotide polymorphisms (SNPs) and haplotypes with asthma or atopy susceptibility. However, the associated SNPs or haplotypes vary among studies. The role of GPRA genetic variation in asthma and atopy remains unsolved. Published data on GRPA variants and asthma come exclusively from Caucasian and Asian populations. We examined whether GPRA SNPs and haplotypes are associated with asthma and atopy in a Mexican population. We genotyped and analyzed 27 GPRA SNPs in 589 nuclear families consisting of asthmatic children aged 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests to 25 aeroallergens. The 27 SNPs examined provided excellent coverage of the GPRA gene. GPRA SNPs and haplotypes were not associated with childhood asthma and the degree of atopy to aeroallergens in a Mexican population. Our review of studies of GPRA variants in relation to asthma phenotypes shows considerable heterogeneity. Accordingly, our results suggest that GPRA variants are not an important contributor to childhood asthma and atopy susceptibility in a Mexican population.

A case-control study of food hyper-sensitivity, timing of weaning and family history of allergies in young children with atopic dermatitis.

BACKGROUND: The aim of this study was to investigate the relationship between food hypersensitivity and atopic dermatitis (AD) in young children. MATERIAL AND METHODS: In a case-control design, 28 patients < 3 years old, with AD and 28 age-matched healthy children were included in the study. A detailed medical history of allergies and timing of weaning was obtained. Children underwent skin tests (prick and patch) to evaluate food hypersensitivity. The status of DA and food allergies in the study participants was investigated 4 years later. RESULTS: There were more children with positive skin tests for food hypersensitivity among cases than controls, OR 4.2 (95%CI 1.3 to 13.4). In contrast, there were no differences in the number of children with positive family history of allergic diseases or weaned at < or = 6 months of age between groups. Four years later, out of the 28 original cases, the state of AD was investigated in 13 (46.4%) infants. Of them, 11 followed an exclusion diet; 6 (46.1%) remained with AD. Of 28 original controls, 15 (51.7%) infants were investigated 4 years later; only one case developed AD. CONCLUSIONS: Young children who had hypersensitivity to cow's milk, hen egg, wheat, fish, soy, or legumes were found to have a higher risk of AD. Positive family history of allergies and early weaning were not found to be relevant risk factors.