Paediatric Respiratory Reviews最新文献

Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respiratory distress syndrome, childhood wheeze and asthma. In addition to genetics, these poor outcomes are likely due to the mediating influence of maternal asthma on the in-utero environment, altering fetal lung and immune development and predisposing the offspring to later lung disease. Maternal asthma may impair glucocorticoid signalling in the fetus, a process critical for lung maturation, and increase fetal exposure to proinflammatory cytokines. Therefore, interventions to control maternal asthma, increase glucocorticoid signalling in the fetal lung, or Vitamin A, C, and D supplementation to improve alveologenesis and surfactant production may be beneficial for later lung function. This review highlights potential mechanisms underlying maternal asthma and offspring respiratory morbidities and describes how pregnancy interventions can promote optimal fetal lung development in babies of asthmatic mothers.

Objectives

Aim of this study was to identify risk factors for a progression to cystic fibrosis (CF) in individuals detected as CF Screening Positive, Inconclusive Diagnosis (CFSPID).

Methods

This is a systematic review through literature databases (2015–2023). Blood immunoreactive trypsinogen (b-IRT) values, CFTR genotype, sweat chloride (SC) values, isolation of Pseudomonas aeruginosa (Pa) from respiratory samples, Lung Clearance Index (LCI) values in CFSPIDs who converted to CF (CFSPID > CF) and age at CF transition were assessed.

Results

Percentage of CFSPID > CF varies from 5.3 % to 44 %. Presence of one CF-causing CFTR variant in trans with a variant with variable clinical consequences (VVCC), an initial SC ≥ 40 mmol/L, an increase of SC > 2.5 mmol/L/year and recurrent isolation of pseudomonas aeruginosa (Pa) from airway samples could allow identification of subjects at risk of progression to CF.

Conclusions

CFSPIDs with CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up.

Melioidosis is a tropical infectious disease caused by the saprophytic gram-negative bacterium Burkholderia pseudomallei. Despite the infection being endemic in southeast Asia and northern Australia, the broad clinical presentations and diagnostic difficulties limit its early detection, particularly in children. Melioidosis more commonly affects the immunocompromised and adults. Melioidosis is increasingly being diagnosed around the world and whole-genome sequencing indicates that these cases are not linked with travel to endemic areas. Research has concentrated on the adult population with limited experience reported in the care of this uncommon, but potentially fatal condition in children presenting with bacteraemia and pneumonia.

Race-based and skin pigmentation-related inaccuracies in pulse oximetry have recently been highlighted in several large electronic health record-based retrospective cohort studies across diverse patient populations and healthcare settings. Overestimation of oxygen saturation by pulse oximeters, particularly in hypoxic states, is disparately higher in Black compared to other racial groups. Compared to adult literature, pediatric studies are relatively few and mostly reliant on birth certificates or maternal race-based classification of comparison groups. Neonates, infants, and young children are particularly susceptible to the adverse life-long consequences of hypoxia and hyperoxia. Successful neonatal resuscitation, precise monitoring of preterm and term neonates with predominantly lung pathology, screening for congenital heart defects, and critical decisions on home oxygen, ventilator support and medication therapies, are only a few examples of situations that are highly reliant on the accuracy of pulse oximetry. Undetected hypoxia, especially if systematically different in certain racial groups may delay appropriate therapies and may further perpetuate health care disparities. The role of biological factors that may differ between racial groups, particularly skin pigmentation that may contribute to biased pulse oximeter readings needs further evaluation. Developmental and maturational changes in skin physiology and pigmentation, and its interaction with the operating principles of pulse oximetry need further study. Importantly, clinicians should recognize the limitations of pulse oximetry and use additional objective measures of oxygenation (like co-oximetry measured arterial oxygen saturation) where hypoxia is a concern.

Summary

Cystic fibrosis liver disease (CFLD) is characterised by a wide heterogenity of manifestations and severity. It represents a major cause of morbidity in people with cystic fibrosis (PwCF), which will be of increasing relevance as survival increases in the new era of cystic fibrosis care. No medical therapy currently available has evidence to treat or prevent progression of liver disease. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators may be transformative on pulmonary, nutritional and quality of life, but direct effect on long term liver disease outcomes is not yet established. Drug-associated hepatic adverse effects may be common, and clinician familiarity with drug-monitoring recommendations is essential. Longitudinal studies are required to understand the effect of CFTR modulators on the incidence and natural history of CFLD, including with early treatment initiation, in established advanced liver disease, and post liver transplantation.

Objective

To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD).

Study design

Preterm infants < 29 weeks’ gestation born 2007–2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks’ postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18–42 months corrected age using the Bayley Scales of Infant Development, 3rd edition.

Results

1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants.

Conclusion

The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.

Cystic fibrosis (CF) is a monogenic disorder cause by mutations in the CF Transmembrane Regulator (CFTR) gene. The prognosis of cystic fibrosis has been transformed by the discovery of highly effective modulator therapies (HEMT). Treatment has changed from reactive therapy dealing with complications of the disease to pro-active correction of the underlying molecular functional abnormality. This has come about by discovering the detailed biology of the different CF molecular sub-endotypes; the development of biomarkers to assess response even in mild disease or young children; the performance of definitive large randomised controlled trials in patients with a common mutation and the development of in vitro testing systems to test efficacy in those patients with rare CFTR mutations. As a result, CF is now an umbrella term, rather than a specific diagnostic label; we have moved from clinical phenotypes to molecular subendotypes. Children’s Interstitial Lung Diseases (chILDs) comprise more than 200 entities, and are a diverse group of diseases, for an increasing number of which an underlying gene mutation has been discovered. Many of these entities are umbrella terms, such as pulmonary alveolar proteinosis or hypersensitivity pneumonitis, for each of which there are multiple and very different endotypes. Even those chILDs for which a specific gene mutation has been discovered comprise, as with CF, different molecular subendotypes likely mandating different therapies. For most chILDs, current treatment is non-specific (corticosteroids, azithromycin, hydroxychloroquine). The variability of the different entities means that there is little evidence for the efficacy of any treatment. This review considers how some of the lessons of the success story of CF are being applied to chILD, thus opening the opportunities for truly personalised medicine in these conditions. Advances in knowledge in the molecular biology of surfactant protein C and Adenosine triphosphate binding cassette subfamily A member 3 (ABCA3), and the possibilities of discovering novel therapies by in vitro studies will especially be highlighted.