Beyond bronchopulmonary dysplasia: Pathophysiology and management of chronic lung disease of prematurity

Chronic lung disease (CLD) of prematurity, historically termed bronchopulmonary dysplasia (BPD), is a complex and evolving disorder that extends far beyond isolated pulmonary injury. BPD was first described by Northway and colleagues in 1967, characterized by diffuse pulmonary fibrosis, radiographic cystic changes with dense streaking, and a progressive clinical course marked by persistent wheezing, respiratory distress, respiratory failure, and right-sided heart failure. Advances in neonatal care have dramatically altered the disease phenotype, giving rise to what is commonly referred to as the “new” BPD or Chronic Lung Disease of Prematurity that is characterized by disrupted lung development, including alveolar simplification, impaired pulmonary vascular growth or pulmonary vascular hypoplasia, airway injury like trachea-bronchomalacia, and heterogeneous abnormalities in lung compliance, often with minimal fibrosis and subtle or absent radiographic findings. Increasing recognition of the interactions between immature organ systems has further highlighted the multifaceted nature of the disease and its contribution to long-term respiratory morbidity. Reflecting these evolving concepts, terminology and classification systems continue to be refined, with growing adoption of the term chronic lung disease of prematurity and the development of contemporary severity-based grading frameworks.Despite these advances, important questions remain regarding the complex interplay among pulmonary, cardiovascular, lymphatic, renal, immune, gastrointestinal, and nutritional systems once established disease is present. Although current evidence supports multisystem pathophysiology, these domains are frequently studied and managed in isolation. A focused synthesis is therefore needed to integrate emerging mechanistic insights with practical approaches to clinical assessment and management.This Research Topic seeks to explore contemporary concepts in the pathophysiology, evaluation, and management of established CLD of prematurity. Particular emphasis will be placed on the interactions between pulmonary parenchymal and airway disease, pulmonary vascular abnormalities, hemodynamic instability, fluid overload and lymphatic dysfunction, inflammation, infection, aerodigestive disorders, and nutritional vulnerability. We will examine how these interconnected mechanisms contribute to distinct clinical phenotypes and influence respiratory support strategies, pharmacologic therapies, feeding interventions, procedural approaches, and long-term outcomes.In addition, the collection will highlight emerging advances in biomarkers, clinical risk prediction, artificial intelligence, and precision-medicine approaches to risk stratification. Rather than focusing primarily on disease prevention, this Research Topic will center on the evaluation and care of infants and children with established CLD of prematurity, while recognizing the need for individualized management and high-quality evidence to guide therapeutic decisions. We welcome review articles addressing, but not limited to, the following themes:I. Chronic lung disease of prematurity; Pulmonary Pathophysiology & Ventilation Strategy. Revisiting the spectrum of pulmonary and airway injury in the era of “new BPD,”. Discuss the pulmonary compliance and mechanics of the new disease. Spectrum of lung injury starting from paradoxical airways including trachea-bronchomalacia, segments of heterogeneous lung compliance, pulmonary vascular hypoplasia due to alveolar simplification and altered pulmonary vasoreactivity or vascular remodelling to caused increased pulmonary vascular resistance. Discuss the prevention of hyperinflation and atelectasis for optimized gas exchange. Rationale for adequate PEEP, longer, larger and few breaths ventilation strategy, potential role of cuffed endotracheal tubes or using relatively larger size ETT to help ventilation through Tracheo-bronchomalacia, indications for diuretics, bronchodilators, intermittent corticosteroids, sedation, paralysis, bronchoscopy, tracheostomy and tracheopexy.II. Phenotypes of the Pulmonary vascular disease and unstable hemodynamics in the Chronic Lung Disease of Prematurity. Examining the different phenotypes of the pulmonary vascular disease associated with the CLD of prematurity, discuss pathophysiology of the “Blue Spells” secondary to the ventilation-perfusion (V-Q) mismatch caused by decreased pulmonary blood flow in pulmonary hypertension, decreased intrathoracic venous return or cardiac dysfunction. Discuss physiology based interventions to improve pre-diastolic filling, improve ejection fraction & cardiac output, inhaled or systemic pulmonary vasodilators. Second variant of unstable hemodynamics could be due to the increased pulmonary blood flow secondary to the significant left to right shunts i.e. PDA, VSD, ASD or pulmonary vein stenosis. Similar physiology can be noted when infants on systemic pulmonary dilators develop atelectasis. These infants require medical or surgical treatment of the underlying etiology. Treatment with pulmonary vasodilators will be counterproductive in these patients.III. Lymphatic dysfunction and fluid homeostasis in CLD of Prematurity: Infants on chronic high pressure ventilation develop high central venous pressure due to high intrathoracic pressure that creates a functional obstruction to the lymphatic flow that starts leaking in sub-cutaneous tissues, cause pleural effusion, ascites, anasarca or even protein losing enteropathy that will be reflected as chronic hypoalbuminemia. Treating this edema with diuretics results in intravascular hypovolemia while edema doesn’t resolve. Discuss the fluid retention, renal physiology, differential diagnosis of edema, the role and limitations of diuretic therapy, and the potential use of medium-chain triglyceride-based feeding formulations in selected patients.IV. Immune Dysregulation and Recurrent Infections in Chronic Lung Disease of Prematurity: Considering inflammatory mechanisms, susceptibility to tracheitis, pneumonia, urinary tract infection, and sepsis, as well as immune dysfunction, infection-prevention strategies, immunisation, and the role of antibiotic prophylaxis.V. Aerodigestive dysfunction and Nutritional vulnerability: Exploring suboptimal growth, nutritional deficits, gastroesophageal reflux, microaspiration, oral-feeding readiness, swallow study/ speech assessment, transpyloric feeding, gastrostomy, and fundoplication.VI. Precision Medicine & Emerging Technologies in the Management of the Chronic Lung Disease of Prematurity: Discuss the new or emerging innovative interventions, Serum Biomarkers, Advanced Imaging, Ventilation Tools, New Airway skills, Role of Pulmonary Function Testing. Role of Artificial Intelligence in the Risk Stratification, and Long Term Outcomes Topic editors: Hussnain S Mirza. MB. FAAP. MBA, Steven Abman, Leif D Nelin Source: https://www.frontiersin.org/research-topics/85718/beyond-bronchopulmonary-dysplasia-pathophysiology-and-management-of-chronic-lung-disease-of-prematurity