Have asthma symptoms in Mexico changed in the past 15 years? Time trends from the International Study of Asthma and Allergies in Childhood to the Global Asthma Network.

BACKGROUND: The Global Asthma Network (GAN) builds on the International Study of Asthma and Allergies in Childhood (ISAAC). OBJECTIVE: To compare asthma prevalence time trends in primary and secondary school children in four Mexican centers participating in ISAAC and GAN. METHODS: GAN is a cross-sectional, multicenter, epidemiological methodology carried out in groups of primary school children aged 6-7 and adolescents aged 13-14 following the ISAAC Phase Three protocol, with additional questions on risk factors and asthma management. RESULTS: Overall, the prevalence of asthma symptoms and diagnosis in primary school children was higher in males than in females both in ISAAC (p < 0.05) and in GAN (p < 0.01), while adolescent females had a higher prevalence, also both in ISAAC (p < 0.001) and in GAN (p < 0.001). CONCLUSION: The prevalence of asthma and its symptoms has increased from ISAAC Phase Three since 2003 to GAN Phase I in Mexico in 2019. These findings are in line with the increases observed in the centers with low asthma baseline prevalence in ISAAC Phase One in comparison with ISAAC Phase Three.

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

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.

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

BACKGROUND: A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma. OBJECTIVES: To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. METHODS: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). RESULTS: ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027). CONCLUSION: Variation in arginase genes may contribute to asthma and atopy in children.