Nirsevimab and Hospitalization for RSV Bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).

Specialized proresolving mediator resolvin E1 corrects the altered cystic fibrosis nasal epithelium cilia beating dynamics.

In cystic fibrosis (CF), impaired mucociliary clearance leads to chronic infection and inflammation. However, cilia beating features in a CF altered environment, consisting of dehydrated airway surface liquid layer and abnormal mucus, have not been fully characterized. Furthermore, acute inflammation is normally followed by an active resolution phase requiring specialized proresolving lipid mediators (SPMs) and allowing return to homeostasis. However, altered SPMs biosynthesis has been reported in CF. Here, we explored cilia beating dynamics in CF airways primary cultures and its response to the SPMs, resolvin E1 (RvE1) and lipoxin B4 (LXB4). Human nasal epithelial cells (hNECs) from CF and non-CF donors were grown at air-liquid interface. The ciliary beat frequency, synchronization, orientation, and density were analyzed from high-speed video microscopy using a multiscale Differential Dynamic Microscopy algorithm and an in-house developed method. Mucins and ASL layer height were studied by qRT-PCR and confocal microscopy. Principal component analysis showed that CF and non-CF hNEC had distinct cilia beating phenotypes, which was mostly explained by differences in cilia beat organization rather than frequency. Exposure to RvE1 (10 nM) and to LXB4 (10 nM) restored a non-CF-like cilia beating phenotype. Furthermore, RvE1 increased the airway surface liquid (ASL) layer height and reduced the mucin MUC5AC thickness. The calcium-activated chloride channel, TMEM16A, was involved in the RvE1 effect on cilia beating, hydration, and mucus. Altogether, our results provide evidence for defective cilia beating in CF airway epithelium and a role of RvE1 and LXB4 to restore the main epithelial functions involved in the mucociliary clearance.

Comparison of telerobotic and conventional ultrasonography in children: a crossover bicentric pilot study.

Background: The MELODY system allows for performing ultrasonography on a patient remotely and has been proposed to assess disease characteristics in the context of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this interventional crossover study was to address the feasibility of the system in children aged 1 to 10 years old. Methods: Children underwent ultrasonography with a telerobotic ultrasound system followed by a second conventional examination by a different sonographer. Results: In total, 38 children were enrolled, and 76 examinations were performed, with 76 scans analyzed. The mean [standard deviation (SD)] age of participants was 5.7 (2.7) years (range, 1-10 years). We found substantial agreement between telerobotic and conventional ultrasonography [κ=0.74 (95% CI: 0.53-0.94), P<0.005]. The mean (SD) duration was longer for telerobotic than conventional examinations [26.0 (2.5) vs. 13.9 (11.2) min, P<0.0001]. Abdominal organs and abnormalities were similarly visualized on telerobotic and conventional ultrasonography. Cardiac echocardiography provided reliable diagnoses, with non-significantly different measurements with both techniques, although the visualization score was significantly higher with conventional than telerobotic ultrasonography (P<0.05). On lung analysis, both examinations identified consolidations and pleural effusion, whereas visualization and total lung score were similar with the 2 techniques. Overall, 45% of parents reported that their children felt less pressure with the telerobotic system. Conclusions: Telerobotic ultrasonography may be effective, feasible, and well-tolerated in children.

CF Patients' Airway Epithelium and Sex Contribute to Biosynthesis Defects of Pro-Resolving Lipids.

Specialized pro-resolving lipid mediators (SPMs) as lipoxins (LX), resolvins (Rv), protectins (PD) and maresins (MaR) promote the resolution of inflammation. We and others previously reported reduced levels of LXA4 in bronchoalveolar lavages from cystic fibrosis (CF) patients. Here, we investigated the role of CF airway epithelium in SPMs biosynthesis, and we evaluated its sex specificity. Human nasal epithelial cells (hNEC) were obtained from women and men with or without CF. Lipids were quantified by mass spectrometry in the culture medium of hNEC grown at air-liquid interface and the expression level and localization of the main enzymes of SPMs biosynthesis were assessed. The 5-HETE, LXA4, LXB4, RvD2, RvD5, PD1 and RvE3 levels were significantly lower in samples derived from CF patients compared with non-CF subjects. Within CF samples, the 12-HETE, 15-HETE, RvD3, RvD4, 17-HODHE and PD1 were significantly lower in samples derived from females. While the mean expression levels of 15-LO, 5-LO and 12-LO do not significantly differ either between CF and non-CF or between female and male samples, the SPMs content correlates with the level of expression of several enzymes involved in SPMs metabolism. In addition, the 5-LO localization significantly differed from cytoplasmic in non-CF to nucleic (or nuclear envelope) in CF hNEC. Our studies provided evidence for lower abilities of airway epithelial cells derived from CF patients and more markedly, females to produce SPMs. These data are consistent with a contribution of CF airway epithelium in the abnormal resolution of inflammation and with worse pulmonary outcomes in women.

The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease.

Cystic Fibrosis (CF) is a recessive genetic disease due to mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encoding the CFTR chloride channel. The ion transport abnormalities related to CFTR mutation generate a dehydrated airway surface liquid (ASL) layer, which is responsible for an altered mucociliary clearance, favors infections and persistent inflammation that lead to progressive lung destruction and respiratory failure. The inflammatory response is normally followed by an active resolution phase to return to tissue homeostasis, which involves specialized pro-resolving mediators (SPMs). SPMs promote resolution of inflammation, clearance of microbes, tissue regeneration and reduce pain, but do not evoke unwanted immunosuppression. The airways of CF patients showed a decreased production of SPMs even in the absence of pathogens. SPMs levels in the airway correlated with CF patients' lung function. The prognosis for CF has greatly improved but there remains a critical need for more effective treatments that prevent excessive inflammation, lung damage, and declining pulmonary function for all CF patients. This review aims to highlight the recent understanding of CF airway inflammation and the possible impact of SPMs on functions that are altered in CF airways.