Daily Respiratory Research Analysis
Analyzed 193 papers and selected 3 impactful papers.
Summary
Analyzed 193 papers and selected 3 impactful articles.
Selected Articles
1. Respiratory syncytial virus vaccination and risk of respiratory and cardiorespiratory hospitalization in adults with chronic kidney disease: a prespecified analysis of the DAN-RSV trial.
In a pragmatic nationwide randomized trial of 131,276 older adults, RSVpreF vaccination reduced RSV-related respiratory hospitalizations and broader cardiorespiratory hospitalizations, with consistent benefit in those with and without chronic kidney disease. Kidney-related hospitalizations were not reduced, and mortality estimates in CKD were imprecise due to few events.
Impact: This large, registry-linked pragmatic RCT provides high-quality effectiveness evidence for RSV vaccination in older adults at scale, including a vulnerable CKD subgroup, supporting deployment decisions.
Clinical Implications: Supports RSVpreF vaccination to reduce respiratory and cardiorespiratory hospitalizations in adults ≥60 years, including those with CKD; clinicians should not expect kidney outcome benefits, and mortality effects in CKD need further confirmation.
Key Findings
- RSVpreF reduced RSV-related respiratory hospitalizations (overall VE 83.3%, 95% CI 42.9–96.9%).
- Benefit extended to broader cardiorespiratory hospitalizations, irrespective of CKD status.
- No reduction in kidney-related hospitalizations; mortality estimates in CKD were imprecise.
Methodological Strengths
- Pragmatic, individually randomized design with nationwide registry linkage
- Large sample size enabling subgroup evaluation by CKD status
Limitations
- Open-label design may introduce behavior/ascertainment biases
- Fewer events in CKD limited precision for mortality estimates
Future Directions: Confirm mortality effects in CKD with longer follow-up and pooled analyses; assess durability, booster strategies, and cost-effectiveness across kidney function strata.
AIMS: Respiratory syncytial virus (RSV) is a common cause of severe illness in older adults and may cause extra-pulmonary complications. Individuals with chronic kidney disease (CKD) are at increased risk of severe outcomes from respiratory infections, but RSV-specific data are limited. This prespecified analysis of the DAN-RSV trial evaluated the RSV prefusion F protein-based vaccine (RSVpreF) effectiveness (VE) in adults aged ≥60 years with and without CKD. METHODS AND RESULTS: The DAN-RSV trial was a pragmatic, open-label, parallel-group, individually randomized clinical trial conducted during 2024/25. Adults aged ≥60 years were randomized 1:1 to receive respiratory syncytial virus prefusion F (RSVpreF) or no vaccine. Chronic kidney disease was identified using diagnosis codes and biomarkers. Outcomes were assessed through nationwide registry linkage from 14 days post-randomization to 31 May 2025. The primary outcome was RSV-related respiratory tract disease hospitalization; secondary outcomes included respiratory, cardiovascular, and kidney-related hospitalizations, and all-cause mortality. Among 131 276 participants (65 642 RSVpreF; 65 634 controls), 13 364 (10.2%) had CKD. Chronic kidney disease participants were older and had more comorbidities. Hospitalization rates were consistently higher among those with CKD. RSVpreF compared with no vaccine reduced RSV-related respiratory tract disease hospitalization [overall VE: 83.3% (95% confidence interval, CI: 42.9-96.9%); CKD VE: 66.4% (95% CI: -85.2 to 96.7%); no CKD VE: 91.7% (95% CI: 43.7 to99.8%), Pinteraction = 0.29], and cardiorespiratory hospitalization, irrespective of CKD status. Among participants with CKD, a numerical imbalance in mortality was observed; however, event numbers were limited. CONCLUSION: In this analysis of the DAN-RSV trial, RSVpreF vaccination reduced RSV-related, broader respiratory and cardiorespiratory hospitalizations in older including those with CKD. No significant differences were observed for acute kidney outcomes. In this nationwide Danish study of older adults, respiratory syncytial virus (RSV) vaccination reduced hospitalizations for respiratory and cardiorespiratory illness, with similar overall benefit in people with and without chronic kidney disease (CKD).Respiratory syncytial virus vaccination lowered the risk of hospitalization for RSV-related respiratory disease and other serious respiratory and heart–lung conditions in older adults overall, including those with CKD.In people with CKD, the estimates of benefit were less precise due to fewer events, and differences according to the level of kidney function should be considered exploratory.The vaccine did not reduce kidney-related hospitalizations. Mortality findings were based on a small number of events and need confirmation in a larger population.
2. Time-varying voriconazole clearance during extracorporeal membrane oxygenation.
Prospective popPK modeling in 31 ECMO patients demonstrated time-varying voriconazole clearance: early circuit sequestration followed by rising intrinsic clearance. Standard dosing achieved therapeutic exposure in only ~50% at 48 h, dropping by day 7. CYP2C19 genotype contributed to late-phase clearance variability, supporting early and repeated TDM and adaptive dosing.
Impact: Defines a mechanistic, time-varying PK model for voriconazole on ECMO with direct dosing implications and registered protocol, addressing a high-mortality setting with inconsistent prior data.
Clinical Implications: Implement early and repeated TDM for voriconazole during ECMO; consider higher or adaptive dosing and circuit-related sequestration early, with genotype-aware adjustments as clearance increases later.
Key Findings
- Voriconazole exposure on ECMO is time-varying: early circuit sequestration and later rise in intrinsic clearance (6.2→22.3 L/h).
- Standard dosing yielded therapeutic levels in ~50% at 48 h, falling to 53% subtherapeutic by days 6–10.
- CYP2C19 intermediate/poor metabolizers had 36% lower late-phase clearance (with uncertainty), supporting genotype-aware dosing and TDM.
Methodological Strengths
- Prospective design with serial intensive sampling and population PK modeling
- ClinicalTrials.gov registration and simulation of dosing scenarios
Limitations
- Single-center study with modest sample size limits generalizability
- Genotype effects estimated with substantial uncertainty
Future Directions: Validate the time-varying model across ECMO circuits and centers; evaluate adaptive Bayesian dosing algorithms integrating real-time TDM and genotype.
Invasive aspergillosis causes high mortality in critically ill patients, particularly those with viral pneumonitis receiving extracorporeal membrane oxygenation. Achieving effective voriconazole exposure in this setting is difficult, and existing data on drug concentrations during extracorporeal support are inconsistent. To characterize voriconazole pharmacokinetics in adults receiving extracorporeal membrane oxygenation and evaluate the influence of CYP2C19 genotype on drug exposure. This single-center prospective observational study included adults treated with intravenous voriconazole for suspected or confirmed aspergillosis during extracorporeal support. Serial plasma samples were analyzed using population pharmacokinetic modeling to describe drug disposition and simulate dosing regimens. Thirty-one patients (median age 40 years, mean weight 87 kilograms) provided 131 plasma samples; 61% carried reduced-function CYP2C19 variants. Voriconazole concentrations varied widely, with subtherapeutic levels increasing from 28% on days 1-5 to 47% by days 6-10. A dual-pathway model incorporating an early, rapidly decaying circuit sequestration process followed by a logistic rise in intrinsic clearance from 6.2 to 22.3 liters per h best described the data. Intermediate or poor metabolizers had 36% lower late-phase clearance, though genotype effects were estimated with substantial uncertainty. Simulations indicated that standard dosing achieved therapeutic concentrations in only half of patients at 48 h, declining sharply by day 7. Voriconazole clearance during extracorporeal membrane oxygenation is time-varying, with evidence of early circuit sequestration and later metabolic recovery influenced by CYP2C19 genotype. Early and repeated monitoring is required to maintain effective antifungal exposure. Time-varying clearance should inform dosing of voriconazole and other hepatically metabolized agents during extracorporeal support.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04868188.
3. Health care utilization and cost implications of Chile's 2024 nirsevimab strategy for RSV prevention: a counterfactual analysis.
Using nationwide registry data and Augmented Synthetic Control, Chile’s universal infant nirsevimab program reduced outpatient visits, bed-days (basic/intermediate and ICU), and maternal leave days, yielding a net economic benefit of USD 23.5M after immunization costs. Catch-up and seasonal cohorts both contributed substantially to savings.
Impact: Provides rigorous, real-world, population-level causal inference of a national RSV prevention strategy with simultaneous health service and economic endpoints, informing policy and financing.
Clinical Implications: Supports inclusion of universal and catch‑up infant nirsevimab in RSV prevention programs to reduce hospitalizations and ICU burden; cost-benefit data facilitate health system planning and payer decisions.
Key Findings
- ASCM estimated substantial reductions: 25,620 outpatient visits, 59,072 basic/intermediate bed-days, and 25,632 ICU bed-days.
- Net economic benefit of USD 23.5 million after accounting for immunization costs.
- Catch-up cohort generated 53.41% of savings; seasonal cohort 46.59%.
Methodological Strengths
- Nationwide registries with Augmented Synthetic Control for counterfactual construction
- Multiple system-level outcomes and cost-benefit analysis
Limitations
- Observational design susceptible to unmeasured confounding despite ASCM
- Program costs and utilization patterns may vary across seasons and regions
Future Directions: Assess multi-season durability, equity of impact across regions and socioeconomic strata, and integration with maternal vaccination; evaluate indirect effects on health system resilience.
BACKGROUND: In 2024, Chile became the first Southern Hemisphere country to implement a universal nirsevimab immunization strategy against respiratory syncytial virus (RSV). This study evaluates the real-world health impact and cost-effectiveness of the program, specifically comparing seasonal (born April-September 2024) and catch-up (born October 2023-March 2024) cohorts. METHODS: We performed a retrospective analysis using Chilean nationwide health registry data. The Augmented Synthetic Control Method (ASCM) utilized 2019-2024 data to estimate a counterfactual scenario for April-November 2024. Outcomes included outpatient medical attentions, basic/intermediate hospital bed-days, intensive care unit (ICU) bed-days, and days of maternal medical leave, identified through diagnoses for lower respiratory tract infections (LRTIs) and related viral agents. Differences between observed and predicted events were used to calculate treatment effects and cost-benefit ratios based on national healthcare costs. FINDINGS: Nirsevimab was associated with substantial reductions across all metrics: approximately 20,430 days of medical leave, 25,620 medical attentions, 59,072 basic/medium bed-days, and 25,632 ICU bed-days. These reductions translated into a net economic benefit after subtracting the cost of immunization, of USD 23.50 million, including USD 15.50 million in the public healthcare sector. The catch-up cohort accounted for 53.41% of total cost savings, and the seasonal cohort for 46.59%. INTERPRETATION: Chile's nationwide nirsevimab rollout substantially reduced infant RSV morbidity and healthcare utilization. These real-world findings demonstrate that universal immunization with long-acting monoclonal antibodies can significantly decrease hospitalizations and health system burden, supporting broad prevention strategies that include infants born prior to the RSV season. FUNDING: This research was partially funded by Instituto Sistemas Complejos de Ingeniería (ISCI) and by an independent research grant from Sanofi-AstraZeneca received by the ISCI team.