Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease.

Variation in lung alveolar development is strongly linked to disease susceptibility. However, underlying cellular and molecular mechanisms are difficult to study in humans. We have identified an alveolar-fated epithelial progenitor in human fetal lungs, which we grow as self-organizing organoids that model key aspects of cell lineage commitment. Using this system, we have functionally validated cell-cell interactions in the developing human alveolar niche, showing that Wnt signaling from differentiating fibroblasts promotes alveolar-type-2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. We identify a Wnt-NKX2.1 axis controlling alveolar differentiation. Moreover, we show that differential binding of NKX2.1 coordinates alveolar maturation, allowing us to model the effects of human genetic variation in NKX2.1 on alveolar differentiation. Our organoid system recapitulates key aspects of human fetal lung stem cell biology allowing mechanistic experiments to determine the cellular and molecular regulation of human development and disease.

Alterações respiratórias relacionadas à prematuridade em terapia intensiva neonatal / Respiratory changes related to prematurity in neonatal intensive care

Identificar alterações clínicas respiratórias em recém-nascidos pré-termo internados em Unidade de Terapia Intensiva Neonatal. Métodos: pesquisa documental, com145 prontuários, por meio de instrumento com variáveis sociodemográficas de recém-nascidos pré-termo e respectivas mães. Resultados: a maioria dos nascidos era do sexo masculino, 66,9% nascidos por via cirúrgica, 64,8% com prematuridade moderada e peso de nascimento entre 1.500 e 2.500 gramas. Dentre as alterações respiratórias, destacaram-se disfunção respiratória precoce, membrana hialina e apneia. Em relação aos fatores obstétricos relacionados à prematuridade, constatou-se prevalência de mulheres em trabalho de parto prematuro (42,8%), bolsa rota (32,4%) e pré-eclâmpsia (20,7%), além de outros. Conclusão: constatou-se incidência elevada de nascidos prematuros, com alterações respiratórias importantes.

Objective: to identify respiratory clinical changes in preterm newborns hospitalized in the Neonatal Intensive Care Unit. Methods: this is a documentary research with 145 medical records by an instrument with sociodemographic variables of preterm newborns and their mothers. Results: most of the newborn were male, 66.9% were born surgically, 64.8% were moderately premature, and the birth weights were between 1,500 and 2,500 grams. Among the respiratory changes, there were early respiratory dysfunction, hyaline membrane, and apnea. There was the prevalence of women in preterm labor (42.8%), water breaking (32.4%) and pre-eclampsia (20.7%) among others were found to be related to obstetric factors related to prematurity. Conclusion: a high incidence of preterm births was observed, with significant respiratory changes.

Maternal and fetal origins of lung disease in adulthood.

This review focuses on genetic and environmental influences that result in long term alterations in lung structure and function. Environmental factors operating during fetal and early postnatal life can have persistent effects on lung development and so influence lung function and respiratory health throughout life. Common factors affecting the quality of the intrauterine environment that can alter lung development include fetal nutrient and oxygen availability leading to intrauterine growth restriction, fetal intrathoracic space, intrauterine infection or inflammation, maternal tobacco smoking and other drug exposures. Similarly, factors that operate during early postnatal life, such as mechanical ventilation and high FiO(2) in the case of preterm birth, undernutrition, exposure to tobacco smoke and respiratory infections, can all lead to persistent alterations in lung structure and function. Greater awareness of the many prenatal and early postnatal factors that can alter lung development will help to improve lung development and hence respiratory health throughout life.

Is maternal smoking more determinant than paternal smoking on the respiratory symptoms of young children?

BACKGROUND: It is generally accepted that maternal smoking has more detrimental effects than paternal smoking on the respiratory health of children. The objective of this study was to assess the effects of postnatal exposure due to the smoking behaviour by father and mother in the home, and prenatal exposure from maternal smoking during pregnancy, on the respiratory symptoms in children. METHODS: The parents of 484 children, aged 3-6 years, completed a questionnaire about smoking and respiratory symptoms in children. Bivariate and logistic regression analyses were used to examine the associated factors with respiratory symptoms. RESULTS: The final model of logistic regression analysis showed that prenatal exposure by maternal smoking during pregnancy increased the risk of wheezing with colds (adjusted OR=2.00, 95% CI:1.13-3.55) with respect to those children whose mothers reported no smoking during pregnancy. Postnatal exposure by maternal smoking in the home, in the presence of the child, increased the risk of cough with phlegm (adjusted OR=2.79, 95% CI:1.23-6.30) with respect to those children whose mothers did not smoke in their presence. Paternal smoking was associated with wheezing and cough in the bivariate analysis, but did not remain significant in the multivariate analysis. CONCLUSIONS: Our results underline a greater influence of exposure to maternal smoking (prenatal and postnatal) than postnatal paternal smoking on the development of respiratory symptoms in young children.