Objective
Long‐term respiratory consequences of bronchopulmonary dysplasia (BPD) in preterm infants born in the post‐surfactant era (“new” BPD) remain partially unknown. The present study aimed to evaluate the respiratory outcomes of “new” BPD in adolescents who were born preterm.
Methods
This multicenter, cross‐sectional study included 286 adolescents born between 2003 and 2005 (mean age: 14.2 years); among them, 184 and 102 were born extremely preterm (EP; <28 weeks' gestation) and moderate–late preterm (32 to <37 weeks' gestation), respectively. Among EP adolescents, 92 had BPD, and 92 did not. All participants underwent lung function tests, skin prick testing, and questionnaires on asthma symptoms and quality of life.
Results
EP adolescents with BPD had significantly lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC than other included adolescents. FEV1/FVC ratios were below the lower limit of normal (z‐score <−1.645) in 30.4% of EP adolescents with BPD, 13.0% of EP adolescents without BPD, and 11.8% of adolescents who were born moderate–late preterm. Bronchodilator response and air‐trapping were significantly higher in BPD adolescents than in other adolescents. Diffusion capacity was significantly lower in EP adolescents than in moderate–late preterm adolescents. Asthma symptoms and quality‐of‐life scores were similar among groups.
Conclusion
EP adolescents with “new” BPD had poorer pulmonary function than EP adolescents without BPD or moderate–late preterm adolescents. Further studies are needed to determine whether “new” BPD is associated with early‐onset chronic obstructive pulmonary disease in adulthood.
Objectives
Post‐infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post‐transcriptional gene regulation in order to characterise PiBO.
Methods
A total of 39 patients with well‐defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next‐generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein–protein interaction network analysis respectively.
Results
Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL‐1β, IL‐6, IL‐8 and TGF‐β compared to controls.
Next‐generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR‐335‐5p, miR‐186‐5p, miR‐30b‐5p and miR‐30c‐5p were further validated using qRT‐PCR. Interestingly, these miRNAs are functionally implicated in cytokine–cytokine receptor interaction, TGF‐β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1).
Conclusion
Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics.
Pulmonary hypertension (PH) in children is a serious disorder, for which the major goal of treatment is to prevent progressive vascular remodeling, and improve clinical status and survival. Iloprost is approved for the treatment of PH in adults; however, few studies have evaluated its effects in children. The objective of this study is to analyze the long-term effects of inhaled iloprost treatment in children with PH. A retrospective study was conducted in patients treated with iloprost between 2000 and 2012. Patients with left-right cardiac shunt and persistent PH of the newborn were excluded. The cohort comprised 22 patients (15 females) with a median age of 2.6 years. Twelve patients had pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2) and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]). One patient had pulmonary veno-occlusive disease, six patients had PH secondary to lung disease and three had multifactorial PH. Median mean pulmonary arterial pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood units. Good tolerability was observed, with the exception of one case of recurring abdominal pain. PH resolved in two patients, with functional capacity improvement in 10 patients and stabilization in three patients. The clinical condition of six patients deteriorated; two died, and two received lung transplants. In conclusion, the results of this uncontrolled study showed that iloprost was effective and well tolerated in children. However, further research is needed to support this study, as PH is a serious condition that can require organ transplantation or result in death.
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