Using high-flow nasal cannulas for infants with bronchiolitis admitted to paediatric wards is safe and feasible

Abstract Aim: Using a high‐flow nasal cannula (HFNC) for infant bronchiolitis is increasingly common, but insufficiently studied. In this retrospective study, we examined the outcomes of HFNC and compared infants who did and did not respond to this oxygen delivery method. Methods: This 2012–2015 study of six Finnish hospitals focused on 88 infants under 12 months who received HFNC: 53 on paediatric wards and 35 in paediatric intensive care units (PICUs). We reviewed patient files for underlying factors, clinical parameters and HFNC treatment. The treatment failed if the patient was transferred to another respiratory support. Results: We found HFNC treatment was successful in 76 (86%) infants, including all 53 on the paediatric wards and 23/35 PICU patients. The responders’ heart rates were significantly lower, and their oxygen saturation was significantly higher at 60 minutes after HFNC treatment started and then stayed relatively constant. Their respiratory rate was only significantly lower after 360 minutes. In non‐responders, the respiratory rate initially decreased but was higher at 180 and 360 minutes after the start of HFNC. Conclusion: We found preliminary evidence that oxygen support needs and heart rate were useful early predictors of HFNC therapy success in infants hospitalised with bronchiolitis, but respiratory rate was not

Haplotype of the Interleukin 17A gene is associated with osteitis after Bacillus Calmette-Guerin vaccination

Abstract Bacillus Calmette-Guerin (BCG) osteitis was more common in Finland than elsewhere at the time when universal BCG vaccinations were given to Finnish newborns. There is evidence that IL-17 plays a role in the defense against tuberculosis. The aim of this study was to evaluate the associations of IL17A rs4711998, IL17A rs8193036 and IL17A rs2275913 single-nucleotide polymorphisms (SNPs) with the risk of BCG osteitis after newborn vaccination. IL17A rs4711998, rs8193036 and rs2275913 SNPs were determined in 131 adults had presented with BCG osteitis after newborn BCG vaccination. We analyzed, using the HaploView and PLINK programs, whether allele or haplotype frequencies of these SNPs differ between the former BCG osteitis patients and Finnish population controls. Of the three IL17A SNPs studied, rs4711998 associated nominally with BCG osteitis; minor allele frequency was 0.215 in 130 BCG osteitis cases and 0.298 in 99 controls (p = 0.034). Frequency of the second common haplotype (GTA) differed significantly between BCG osteitis cases and controls (0.296 vs. 0.184, p = 0.040 after multi-testing correction). The GTA haplotype of the IL17A SNPs rs4711998, rs8193036 and rs2275913 was associated with osteitis after BCG vaccination

Genome-wide association study of polymorphisms predisposing to bronchiolitis

Abstract Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10⁻⁵) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size

NKG2D gene variation and susceptibility to viral bronchiolitis in childhood

Abstract Background: Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels. Methods: GWAS included a Finnish–Swedish case–control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10−⁴) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201). Results: Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population. Conclusions: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis