Perceived QOL by children with HMV and their families is lower than that of healthy children. Parents are happy to care for their children at home, even though it negatively affects family life. What is Known: • The use of home mechanical ventilation (HMV) in children has increased over the last years. • Normal family functioning is usually disrupted by HMV. What is New: • The aim of HMV is to provide a lifestyle similar to that of healthy children, but perceived quality of life by these patients and their parents is low. • Most of the families caring for children on HMV agree that support and resources provided by national health institutions is insufficient.

Background: Data addressing short-and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. | 125MORENO-GALDÓ Et AL.

RationaleSubstantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.MethodsA genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 European-descent children treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.ResultsTen independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078, p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.ConclusionsThe intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.

In this study, several non-modifiable parameters (family history of asthma, low birthweight, need for mechanical ventilation) and modifiable parameters (young maternal age, DCA, or exposure to school-age siblings) were identified as significant risk factors for the development of bronchiolitis and recurrent wheezing during the first year of life in MLP infants.