ABSTRACT
OBJECTIVE: We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control. METHODS: A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma. KEY RESULTS: The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.
Subject(s)
Asthma/genetics , Epoxide Hydrolases/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin-4/genetics , Tumor Necrosis Factor-alpha/genetics , Adolescent , Asthma/drug therapy , Child , Child, Preschool , Epistasis, Genetic , Female , Gene Frequency , Genetic Association Studies , Genetic Heterogeneity , Haplotypes , Humans , Infant , Linkage Disequilibrium , MaleABSTRACT
BACKGROUND: The use of portable fractional exhaled nitric oxide (FENO) devices is increasingly common in the diagnosis and management of allergic airways inflammation. METHODS: We tested two handheld FENO devices, to determine (a) if there was adequate intradevice repeatability to allow the use of single breath testing, and (b) if the devices could be used interchangeably. In a mixed pediatric population, including normal, asthmatic, and children with peanut allergies, 858 paired values were collected from the NIOX-MINO® and/or the NObreath® devices. RESULTS: The NIOX-MINO® showed excellent repeatability (mean difference of 0.1 with 95% limits of agreement between -7.93 to 7.72 ppb), while the NObreath® showed good repeatability (mean difference of -1.61 with 95% limits of agreement between -14.1 and 10.8 ppb). Intradevice repeatability was good but not adequate and the NIOX-MINO® systematically produced higher results than the NObreath® [mean difference of 7.8 ppb with 95% limits of agreement from -11.55 to 27.52 ppb (-33% to 290%)]. CONCLUSIONS: Our results support the manufacturer's advice that single breath testing is appropriate for the NIOX-MINO®. NObreath® results indicate that the mean of more than one breath should be utilized. The devices cannot be used interchangeably.
