Daily Respiratory Research Analysis

Pulmonary type 2 innate lymphoid cells (ILC2s) exhibit immune memory, termed "trained immunity," which enhances their activation following exposure to an independent protease-containing allergen. The role of prostaglandin I2 (PGI2), a cyclooxygenase (COX) pathway metabolite, in modulating these trained ILC2 responses remains unclear. PGI2 acts through its G protein-coupled receptor IP. We hypothesized that IP signaling inhibits ILC2 training. To test this hypothesis, we used a mouse ILC2 training model in which we challenged wild-type (WT) and IP knockout (KO) mice with Alternaria alternata extract (Alt) to induce ILC2 activation and training. After a 33-d resting period, ILC2 responses subsided to a homeostatic level. Mice were then intranasally challenged with papain to evaluate responses to an unrelated allergen. IP KO mice displayed significantly heightened ILC2 interleukin (IL)-13 expression and with concomitant increased eosinophilia in the lungs post-papain challenge compared with WT control mice. Notably, neither WT nor IP KO mice challenged with papain only, devoid of ILC2 training, exhibited lung type 2 responses. The augmented type 2 inflammation observed in IP KO mice following both Alt and papain challenges correlated with increased numbers and percentages of IL-13-producing ILC2s and greater mean fluorescence intensity of IL-13 compared with WT mice. Furthermore, RNA sequencing of sorted ILC2s from WT and IP KO mice following Alt-papain challenges revealed heightened activation of immune response pathways and mitochondrial respiratory pathways in IP-deficient ILC2s. These findings reveal an inhibitory role of PGI2 signaling in trained ILC2 responses, emphasizing its pivotal contribution to innate immune responses and allergic inflammation.

This study aimed to compare the nasal continuous positive airway pressure (nCPAP) and bi-level positive airway pressure (BiPAP) in preterm infants with respiratory distress syndrome (RDS).Preterm infants (≤32 weeks of gestation) were randomly assigned, at birth, into two study groups: nCPAP or BiPAP. Primary outcomes (surfactant administration and failure of non-invasive respiratory support within the first 72 hours), and secondary outcomes (duration of ventilation support, pneumothorax, bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, intraventricular haemorrhage, retinopathy of prematurity, time to total enteral feeding, length of hospital stay, and mortality) were assessed.A total of 188 preterm infants with RDS were analysed. Mean gestational age was 28.8±1.8 weeks (nCPAP) versus 29±1.9 weeks (BiPAP). There were no statistically significant differences between groups in the failure of non-invasive respiratory support (25% vs. 33%, RR: 0.74, 95% CI: 0.47-1.17) or surfactant administration (35% vs. 38%, RR: 0.92, 95% CI: 0.49-1.71). No significant differences were observed in secondary outcomes between the two groups. Subgroup analysis of infants<30 weeks yielded similar results.Although two-level CPAP theoretically offers benefits, BiPAP was not superior to nCPAP as initial support in preterm infants with RDS. This underscores the continued value of the simpler, well-established nCPAP and the need for multicentre trials involving preterm infants of varying gestational ages.

BACKGROUND: The human microbiome is transmissible between individuals, including pathogens and commensals with metabolic and immune-modulating effects, which could influence susceptibility, severity, and outcomes of both infection and non-infection diseases. However, limited studies of respiratory microbiome transmission within populations have been conducted. Herein, we performed species- and strain-level metagenomic analyses on oropharyngeal (OP) swabs from 1046 healthy urban dwellers across 13 districts, including 111 households with at least two cohabitants, to elucidate the transmission dynamics of the respiratory microbiome within households and communities. RESULTS: We found that geographic districts accounted for the greatest variation in the OP microbiome, with unrelated individuals from the same district showing greater microbiome similarity and higher strain-sharing rates than those from different districts. Cohabitants, especially spouses and siblings, exhibited similar microbial abundances and shared more strains, with 16.7% (IQR 0.0-33.3%) of strains shared among cohabitants, compared to 0.0% (IQR 0.0-11.1%) in non-cohabiting pairs (p < 0.05). Both respiratory commensals and opportunistic pathogens were shared among cohabitants. In contrast, no evidence of vertical transmission was detected between mother-offspring pairs. Additionally, the OP microbiome contained diverse antibiotic resistance genes (ARGs), with 15.0% linked to mobile genetic elements (MGEs) or plasmids; the flanking sequences of these ARGs were more conserved across species than those of non-MGE-associated ARGs, suggesting horizontal transfer of ARGs among respiratory microorganisms. CONCLUSIONS: In summary, we characterized the transmissible nature of the OP microbiome and the risk of ARG dissemination among respiratory microorganisms. These findings underscore the role of respiratory microbes and ARGs exchange in shaping the microbiome of healthy populations and emphasize their relevance to public health strategies for respiratory health management. Video Abstract.