Daily Respiratory Research Analysis
Analyzed 193 papers and selected 3 impactful papers.
Summary
A nationwide pragmatic randomized trial in older adults showed that RSVpreF vaccination reduced RSV-related and broader cardiorespiratory hospitalizations, including in people with chronic kidney disease. Complementing this, Chile’s universal nirsevimab rollout yielded large reductions in health-care utilization and net cost savings using augmented synthetic controls. A prospective pharmacokinetic study during ECMO revealed time-varying voriconazole clearance, supporting early and repeated therapeutic drug monitoring to maintain antifungal exposure.
Research Themes
- RSV immunization effectiveness and policy impact
- Causal inference with augmented synthetic controls in real-world health programs
- ECMO pharmacokinetics and therapeutic drug monitoring (TDM)
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 nationwide pragmatic randomized trial of 131,276 adults ≥60 years, RSVpreF vaccination significantly reduced RSV-related respiratory hospitalizations and broader cardiorespiratory hospitalizations, with similar benefit in participants with and without chronic kidney disease. Kidney-related hospitalizations were not reduced; mortality estimates in CKD were imprecise due to few events.
Impact: This large, pragmatic randomized study provides compelling real-world effectiveness evidence for RSVpreF in older adults, including those with CKD—a high-risk group—on clinically meaningful endpoints derived from national registries.
Clinical Implications: Support routine RSV vaccination in older adults, including those with CKD, to reduce respiratory and cardiorespiratory hospitalization risk. Monitor mortality and kidney outcomes as more data accrue; shared decision-making remains key in CKD subgroups.
Key Findings
- RSVpreF reduced RSV-related respiratory hospitalization with overall VE 83.3% (95% CI 42.9–96.9%).
- Benefits extended to cardiorespiratory hospitalization irrespective of CKD status (no significant interaction).
- No reduction in kidney-related hospitalizations; mortality estimates in CKD were imprecise due to few events.
Methodological Strengths
- Pragmatic, individually randomized design with nationwide registry linkage for outcome capture.
- Prespecified subgroup analysis by CKD status with large overall sample size (n=131,276).
Limitations
- Open-label design may introduce behavioral or ascertainment biases.
- CKD subgroup had fewer events, leading to imprecise mortality estimates.
Future Directions: Validate mortality and kidney outcome effects in larger CKD cohorts; assess durability across seasons and potential differential effects by CKD stage and dialysis status.
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. Health care utilization and cost implications of Chile's 2024 nirsevimab strategy for RSV prevention: a counterfactual analysis.
Using augmented synthetic controls on national data (2019–2024), Chile’s universal nirsevimab program reduced outpatient visits, hospital and ICU bed-days, and maternal medical leave during April–November 2024, generating a net economic benefit of USD 23.5M after program costs. Both seasonal and catch-up cohorts contributed substantially to savings.
Impact: This is among the first nationwide, real-world evaluations of universal infant RSV prophylaxis demonstrating large health-system gains and net savings using robust causal inference, directly informing policy decisions.
Clinical Implications: Health systems can expect meaningful reductions in RSV-related service use and costs with universal nirsevimab, including catch-up cohorts. Program design should consider broad eligibility to maximize population benefit.
Key Findings
- ASCM estimated reductions of ~25,620 outpatient visits, 59,072 basic/intermediate bed-days, and 25,632 ICU bed-days in April–November 2024.
- Net economic benefit of USD 23.5 million after immunization costs; public sector savings ~USD 15.5 million.
- Catch-up cohort contributed 53.41% of total cost savings; seasonal cohort 46.59%.
Methodological Strengths
- Nationwide registry linkage with Augmented Synthetic Control Method to construct a robust counterfactual.
- Multiple utilization endpoints and cost-benefit analysis grounded in national tariffs.
Limitations
- Observational design susceptible to residual confounding and model misspecification.
- Partial funding from manufacturers may introduce perceived conflicts; independent replication desirable.
Future Directions: Assess effectiveness across seasons and subregions, equity of reach, and integration with maternal RSV vaccination; evaluate downstream outcomes (e.g., long-term wheeze/asthma).
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.
3. Time-varying voriconazole clearance during extracorporeal membrane oxygenation.
In 31 ECMO patients receiving IV voriconazole, population PK modeling identified early circuit sequestration and a subsequent rise in intrinsic clearance, yielding time-varying clearance (6.2→22.3 L/h). Standard dosing achieved therapeutic levels in only ~50% at 48 h, declining by day 7; early and repeated TDM is recommended.
Impact: Provides mechanistic PK evidence explaining erratic voriconazole exposure during ECMO and offers actionable guidance (time-varying clearance, TDM need) relevant to antifungal stewardship in critical care.
Clinical Implications: Implement early and repeated TDM for voriconazole during ECMO; anticipate declining exposure after day 2 and adjust dosing dynamically. Consider potential CYP2C19 effects but recognize current uncertainty.
Key Findings
- Dual-pathway PK model with early circuit sequestration and rising intrinsic clearance (6.2→22.3 L/h) best fit the data.
- Subtherapeutic levels increased from 28% (days 1–5) to 47% (days 6–10).
- Standard dosing achieved therapeutic concentrations in only ~50% at 48 h, declining by day 7; TDM is essential.
Methodological Strengths
- Prospective design with serial sampling and population PK modeling.
- ClinicalTrials.gov-registered study with genotype data integration.
Limitations
- Single-center study with modest sample size; generalizability may be limited.
- CYP2C19 effects on late-phase clearance estimated with substantial uncertainty.
Future Directions: Validate dosing algorithms incorporating time-varying clearance in multicenter cohorts; evaluate extrapolation to other hepatically metabolized agents and different ECMO circuits.
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.