Mauricio T. Caballero

Bronchopulmonary dysplasia (BPD) remains one of the most frequent and clinically relevant chronic respiratory complications of extreme prematurity. Although successive definitions have improved disease classification, most are still based on oxygen requirement and respiratory support assessed at 36 weeks postmenstrual age (PMA), an approach that fails to capture the biological heterogeneity, dynamic clinical trajectories and long-term consequences of the disease. This narrative review analyzes the evolution of BPD definitions, from early time-based criteria to contemporary classifications based on severity and respiratory support, highlighting their strengths and limitations for predicting outcomes and translational research. We argue for the need to move beyond BPD as a single clinical entity toward a framework based on phenotypes and endotypes, including the parenchymal, airway, vascular, inflammatory, and mechanical components of the disease. Although non-animal alternatives are rapidly evolving, animal models remain the primary tools for analyzing specific developmental windows, injurious exposures, and molecular pathways involved in impaired alveolarization, abnormal vascular growth, inflammation, and ventilator-induced lung injury. We propose an endotype-based approach to guide the selection of preclinical models, supported by standardized injury protocols, longitudinal multimodal measurements, and the integration of emerging technologies such as organoids, lung-on-a-chip platforms, multi-omics, and predictive modeling. Redefining BPD through a translational and mechanism-based framework may improve risk stratification and support precision neonatal therapies.

Apnea is a potentially life-threatening complication of severe acute respiratory infection (SARI) in early infancy; however, its determinants remain incompletely understood. Between 2011 and 2013, we conducted a population-based, cross-sectional, multicenter study in Buenos Aires, Argentina. We examined epidemiological, clinical, virological, and immunological factors associated with apnea in a population-based cohort of 2376 infants younger than five months hospitalized due to SARI. Using hierarchical multivariable logistic regression, we identified preterm birth, cesarean section, previous NICU admission, age under two months, and severe household crowding as independent predictors of apnea. RSV infection was inversely associated with apnea, and IL-5 levels in respiratory secretions were significantly lower among infants with apnea, suggesting a qualitatively different immune response in this group. Taken together, these findings indicate that apnea during SARI in early infancy is primarily driven by biological immaturity and adverse environmental conditions.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection (LRTI) in young children and imposes a substantial clinical and economic burden, particularly in low- and middle-income countries. However, prospective data capturing the full societal and health burden of RSV in Latin America remain scarce. We estimated the direct medical, direct non-medical, and indirect costs of severe RSV disease and quantified its health burden using disability-adjusted life years (DALYs) in three Latin American countries.Methods: We conducted a prospective multicenter cohort study between May 2023 and May 2025 among children aged 1–59 months hospitalized with severe LRTI in tertiary hospitals in Argentina, Brazil, and Colombia. RSV infection was confirmed by RT-PCR. Individual-level data on healthcare utilization, household out-of-pocket expenditures, and caregiver productivity losses were collected. Costs were estimated using a bottom-up micro-costing approach and expressed in June 2025 purchasing power parity–adjusted US dollars (USD PPP). DALYs per episode were calculated and summarized by country, RSV status, and level of care.Findings: Among 747 children, 368 (49.3%) were RSV-positive. ICU admission was the main driver of both costs and DALYs across all settings. Mean total societal costs per ICU episode reached USD PPP 22,016 (RSV-positive) and 12,192 (RSV-negative) in Argentina, 3,682 and 3,540 in Brazil, and 5,576 and 7,538 in Colombia, respectively. In contrast, mean costs for non-ICU admissions were substantially lower, ranging from approximately USD PPP 600–700 in Brazil, 1,700–2,000 in Colombia, and 3,000–3,200 in Argentina, with minimal differences by RSV status. Overall, ICU admissions were associated with three- to eightfold higher costs than ward admissions. Median DALYs per episode were consistently higher among ICU patients across all countries.Interpretation: Severe RSV disease imposes a substantial economic and health burden across Latin American hospital settings. ICU admission is the main determinant of both costs and DALYs, whereas RSV status alone does not substantially influence per-episode costs. These findings provide robust regional evidence to inform value assessments and policy decisions regarding RSV prevention strategies.

Understanding the distribution of respiratory syncytial virus (RSV) disease burden by more granular age bands in infants is necessary for optimising infant RSV immunisation strategies. Using a Bayesian model, we synthesised published data from a systematic literature review and unpublished data shared by international collaborators for estimating the distribution of infant RSV hospitalisations by month of age. Based on local RSV seasonality data, we further developed and validated a web-based prediction tool for estimating infant RSV hospitalisation distribution by birth month. Although RSV hospitalisation burden mostly peaked at the second month of life and was concentrated in infants under six months globally, substantial variations were noted in the age distribution of RSV hospitalisation among infants born in different months. Passive immunisation strategies should ideally be tailored to the local RSV disease burden distribution by age and birth month to maximise their per-dose effectiveness before a universal immunisation can be achieved.