Rodriguez-Fernandez R, Xu Z, Moreno-Galdó A, Sardón O, Rubi T, Castillo-Corullón S, Torres A, Corcuera P, Callejón Callejón A, Perez G, Cortell I, Rovira-Amigo S, Pastor-Vivero MD, Mondejar-Lopez P, Perez-Frias J, Velasco V, Torres-Borrego J, Figuerola J, de la Serna Blázquez O, Garcia-Hernandez G, Tang L, Mejias A, Ramilo O; SAREPREM 3235 investigators. Longitudinal transcriptional immune profiles and persistent wheezing in moderate-to-late preterm infants. Pediatr Allergy Immunol. 2024 Oct;35(10):e14261. doi: 10.1111/pai.14261. PMID: 39445663.
https://pubmed.ncbi.nlm.nih.gov/39445663/

Background: Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing.

Materials and methods: A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression.

Results: Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers.

Conclusions: Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Tan Z, Zhong W, Danielsson H, Arzoomand A, Lakshmikanth T, Chen Q, Mikes J, Wang J, Chen Y, James A, Nilsson AK, Elfvin A, Brusselaers N, Portlock T, Lundgren P, Sävman K, Wackernagel D, Hansen-Pupp I, Ley D, Uhlén M, Hellström A, Brodin P. Immune development differs between preterm newborns fed mothers' own milk and donor milk. iScience. 2025 Jun 17;28(7):112918. doi: 10.1016/j.isci.2025.112918. PMID: 40672699; PMCID: PMC12266545.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12266545/

Extremely preterm infants are at risk of immune-mediated complications such as infections and inflammatory conditions like bronchopulmonary dysplasia and necrotizing enterocolitis. Preterm infants are immunologically distinct from term infants at birth, but subsequently undergo adaptive postnatal changes resulting in immunological convergence during their first 3 months. Here, we performed a systems-level analysis of immune development in 72 preterm infants born as early as 22 weeks to investigate factors associated with variation. We find similar immune trajectories during early postnatal immune development but occurring more slowly in infants born at 22–24 weeks. Immune development showed a greater resemblance to that of term-born children in preterm infants fed mother’s own milk compared to donor milk. This developmental normalization was manifested by NK cell development and was not explained by differences in microbial colonization between feeding groups, possibly suggesting direct effects of bioactive milk molecules on developing immune cells in extremely preterm infants.

Faner R, Cho MH, Koppelman GH, et al. Towards early detection and disease interception of COPD across the lifespan. Eur Respir Rev 2025; 34: 240243 [DOI: 10.1183/16000617.0243-2024]. https://bit.ly/4jcQ95B

COPD is “a heterogeneous lung condition characterized by chronic respiratory symptoms due to abnormalities of the airways and/or alveoli that cause persistent, often progressive, airflow obstruction”. COPD has been traditionally associated with tobacco smoking and accelerated lung function decline. However, our understanding of the pathogenesis of COPD has changed significantly over the past few years due to the recognition that different lung function trajectories starting in early life and progressing across the lifespan are also important pathways to COPD. Further, today, it is well accepted that there are multiple genetic, host and environmental factors (i.e., aetiotypes) that can cause COPD and contribute to its clinical heterogeneity. Here, we review current understanding of the environmental, genomic and immune factors associated with the early-life origins of COPD. We also discuss the current knowledge gaps and how this new knowledge can facilitate earlier detection and disease interception of COPD across the lifespan, thus reducing its disease burden and improving the well-being and prognosis of COPD patients.

Gibbons et al