Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tested the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms. Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in the presence of culture medium alone or with RA, basophils, or AFS cells. In vivo green fluorescent protein-expressing (GFP⁺) rat AFS cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds, and the frequency of bronchial contractions were assessed. Protein gene product 9.5 (PGP 9.5) and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP 9.5, and TTF-1. The levels of FGF-10, VEGFα, and TGF-β1 secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by ANOVA. In vitro, the surface, the number of terminal buds, and the bronchial peristalsis were increased in nitrofen + AFS cell explants in comparison with nitrofen-exposed lungs. While nitrofen + RA lungs were similar to nitrofen + AFS ones, basophils did not normalize these measurements. PGP 9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo, the surface, number of terminal buds, and peristalsis were similar to control after injection of AFS cells in nitrofenexposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF-10 and VEGFα were increased in nitrofen + AFS cell explants, while the levels of TGF-β1 were similar to controls. Lung growth, bronchial motility, and innervation were decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to that observed before with RA. The AFS cell beneficial effect was probably related to paracrine action of growth factor secretion.

Background: Although there is agreement on surgically removing symptomatic congenital lung malformations (CLMs), the management of asymptomatic cases remains controversial. Some paediatric surgeons suggest conservative management for asymptomatic cases due to the low perceived risk of developing symptoms or malignancy. This study aimed to investigate the characteristics and management of adults with CLMs.Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted to find studies reporting on adult patients (aged ≥15 years) with CLMs.Results: Out of 12 908 studies reviewed from 1947 to 2024, 653 studies met the inclusion criteria, covering 980 patients. None of the patients had a prenatal diagnosis. The mean±sdage at surgery was 39.4±15.7 years (range 15–86). A total of 74.4% of adults with CLMs presented with symptoms, leading to the detection of CLM. Pneumonia was the most common symptom in congenital pulmonary airway malformation (CPAM) and intralobar sequestration, with over 30% of these patients experiencing recurrent respiratory infections. In 11.7% of adults, CLMs harboured tumours at the time of surgical removal, with CPAM associated with lung tumours in over 20% of cases.Conclusions: Thoracic surgeons recommend surgical resection for all adult CLM patients, including asymptomatic cases, due to risks of infections and malignancy. Conservative management was considered only when surgery was not feasible

Aim: Respiratory failure secondary to pulmonary hypoplasia is the main cause of death in congenital diaphragmatic hernia (CDH). Lung growth is regulated by growth factors (GFs), whose imbalances are reported in pathological conditions. We measured amniotic fluid levels of GFs, regulating lung development, in pregnancies with CDH and compared them with normal gestations. Methods: Amniotic fluid was collected at amniocentesis and delivery from 4 women carrying fetuses with CDH and 12 with normal pregnancy. GFs were isolated and quantified. Same GFs were measured in lung biopsies collected during autopsy of three newborns dead of CDH. Results: Impairment expression of lung GFs in the amniotic fluid of CDH pregnancies in comparison with normal was found. Fibroblast growth factor 10 (FGF10), fibroblast growth factor 7, vascular endothelial growth factor and transforming growth factor β (TGFβ) were decreased at amniocentesis, while platelet-derived growth factor (PDGF) increased. While FGF10 and PDGF tended to normalize at delivery, epidermal growth factor increased and TGFβ was still decreased. Same GFs were similarly expressed in both lungs of babies dead of CDH. Conclusion: Anomalies in lung GFs expression of embryos and fetuses with CDH can be detected by measuring their levels in the amniotic fluid during pregnancy. Further investigation would help to correlate prenatal expression of GFs and clinical outcome of babies with CDH after birth.