Daily Respiratory Research Analysis
Three studies reshape respiratory care across prevention and perioperative risk. A NEJM RCT shows a single dose of clesrovimab prevents RSV lower respiratory illness and hospitalizations in healthy infants. Large multicenter cohorts identify intraoperative ventilation duration—not surgical approach—as the driver of postoperative pulmonary complications and establish persistent airflow limitation as a stable, high-risk trait across asthma/COPD.
Summary
Three studies reshape respiratory care across prevention and perioperative risk. A NEJM RCT shows a single dose of clesrovimab prevents RSV lower respiratory illness and hospitalizations in healthy infants. Large multicenter cohorts identify intraoperative ventilation duration—not surgical approach—as the driver of postoperative pulmonary complications and establish persistent airflow limitation as a stable, high-risk trait across asthma/COPD.
Research Themes
- RSV immunoprophylaxis in infants
- Perioperative ventilation and postoperative pulmonary complications
- Persistent airflow limitation as a cross-disease risk trait
Selected Articles
1. Clesrovimab for Prevention of RSV Disease in Healthy Infants.
In a randomized, placebo-controlled trial of 3614 infants, a single 105‑mg intramuscular dose of clesrovimab reduced RSV‑associated medically attended lower respiratory infection by 60.4% and hospitalizations by 84.2% through 150 days, with serious adverse events similar to placebo.
Impact: This large RCT provides robust evidence that a single-dose, long-acting monoclonal antibody can substantially prevent RSV disease and hospitalizations in healthy infants.
Clinical Implications: Clesrovimab may serve as an effective seasonal immunoprophylaxis option to reduce RSV-related clinical burden in infants, potentially complementing or offering an alternative to existing strategies like nirsevimab.
Key Findings
- Single 105 mg intramuscular dose reduced RSV medically attended lower respiratory infection by 60.4% (95% CI 44.1–71.9; P<0.001).
- RSV-associated hospitalizations were reduced by 84.2% (95% CI 66.6–92.6; P<0.001).
- Serious adverse events occurred at similar rates to placebo (11.5% vs 12.4%).
Methodological Strengths
- Large, multicenter randomized, placebo-controlled design with prespecified endpoints and trial registration (NCT04767373).
- Clinically meaningful outcomes (medically attended LRI and hospitalization) with precise effect estimates.
Limitations
- Head-to-head comparisons with existing long-acting antibodies (e.g., nirsevimab) were not performed.
- Efficacy and safety beyond 150 days and across multiple seasons remain to be established.
Future Directions: Head-to-head trials versus current standard prophylaxis, durability across seasons, cost-effectiveness analyses, and evaluation in special populations (preterm subgroups, comorbidities).
BACKGROUND: Clesrovimab is a long-acting investigational monoclonal antibody against site IV of the respiratory syncytial virus (RSV) fusion protein. Data regarding the safety and efficacy of clesrovimab in healthy infants are needed. METHODS: We randomly assigned healthy preterm and full-term infants entering their first RSV season in a 2:1 ratio to receive one intramuscular 105-mg dose of clesrovimab or placebo. The primary efficacy end point was RSV-associated medically attended lower respiratory infection (including at least one indicator of lower respiratory infection or disease severity) through 150 days after injection. A key secondary efficacy end point was RSV-associated hospitalization during the same period. RESULTS: A total of 3614 infants received an injection: 2412 infants received clesrovimab, and 1202 infants received placebo. Through day 150 after injection, RSV-associated medically attended lower respiratory infection occurred in 60 of 2398 infants in the clesrovimab group (incidence rate over 5-month period, 2.6%) and in 74 of 1201 infants in the placebo group (incidence rate over 5-month period, 6.5%), for an efficacy of 60.4% (95% confidence interval [CI], 44.1 to 71.9; P<0.001). RSV-associated hospitalization within 150 days was reported in 9 of 2398 infants in the clesrovimab group and in 28 of 1201 infants in the placebo group, for an efficacy of 84.2% (95% CI, 66.6 to 92.6; P<0.001). Serious adverse events were reported in 278 of 2409 infants (11.5%) in the clesrovimab group and 149 of 1202 infants (12.4%) in the placebo group. CONCLUSIONS: In healthy preterm and full-term infants, a single dose of clesrovimab reduced the incidence of RSV-associated medically attended lower respiratory infection and RSV-associated hospitalization, with a safety profile similar to that of placebo. (Funded by Merck Sharp and Dohme; CLEVER ClinicalTrials.gov number, NCT04767373.).
2. Postoperative Pulmonary Complications in Conventional Laparoscopic vs Robot-Assisted Abdominal Surgery.
Across 2738 abdominal surgery patients from 31 countries, PPCs were more frequent after robot-assisted than conventional laparoscopy, but mixed-effects modeling showed only intraoperative ventilation duration independently predicted PPCs, not surgical approach or ventilation intensity.
Impact: Identifies a modifiable, anesthesia-related driver (ventilation duration) of PPCs, reframing prevention strategies beyond surgical approach selection.
Clinical Implications: Perioperative teams should prioritize minimizing duration of mechanical ventilation (e.g., streamlining operative time, optimizing anesthesia plans, early extubation) to reduce PPCs, particularly in long robotic procedures.
Key Findings
- PPC incidence: 19.0% in RAS vs 9.5% in CLS (P<.001).
- RAS involved longer ventilation (median 219 vs 95 minutes) and higher 4DP+RR intensity.
- Only ventilation duration independently predicted PPCs (aOR 1.49; 95% CI 1.33–1.66); approach and intensity were not independent predictors.
Methodological Strengths
- Large, international pooled individual-patient dataset with mixed-effects modeling and multiple sensitivity analyses (mediation, matched cohorts).
- Prospective data sources (LAS VEGAS and AVATaR) with standardized perioperative variables.
Limitations
- Observational design with potential residual confounding and center-level practice variation.
- Data period up to 2019; contemporary robotic platforms and ERAS protocols may further affect ventilation duration.
Future Directions: Interventional studies targeting ventilation time reduction, anesthesia workflows, and surgical efficiency; incorporation into PPC risk calculators and ERAS pathways.
IMPORTANCE: Robot-assisted surgery (RAS) is increasingly used for abdominal procedures; however, postoperative pulmonary complications (PPCs) are more frequent in patients undergoing RAS compared with patients undergoing conventional laparoscopic surgery (CLS). OBJECTIVE: To compare the incidence of PPCs after CLS and RAS and to determine which patient-, surgery-, and anesthesia-related factors are associated with PPCs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Laparoscopic and Robot-Assisted Surgery (LapRAS) database, a pooled dataset containing individual patient data of 2 worldwide prospective cohort studies: the Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) study and the Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery and Its Effects on Postoperative Pulmonary Complications (AVATaR) study. Data were collected from adult patients requiring intraoperative ventilation during general anesthesia for CLS or RAS surgical procedures from 163 centers and 31 countries in the Americas, Europe, the Middle East, and North Africa from January 2013 to March 2019. Data were analyzed from December 2023 to October 2024. EXPOSURES: Type of surgical approach (CLS vs RAS), duration of intraoperative ventilation, and intensity of mechanical ventilation, assessed using the 4 times the driving pressure (DP) plus respiratory rate (RR) estimator (4DP + RR). MAIN OUTCOME AND MEASURES: The primary outcome was occurrence of 1 or more PPCs in the first 5 postoperative days. Mixed-effects logistic regression assessed associations with PPCs; mediation and matched cohort analyses served as sensitivity analyses. RESULTS: A total of 2738 patients (median [IQR] age, 56 [41-66] years; 1456 female [53.1%]) were included. PPCs occurred in 172 of 903 patients (19.0%) in the RAS group and 174 of 1835 patients (9.5%) in the CLS group (P < .001). Duration of intraoperative ventilation was longer in RAS compared with CLS (median [IQR] duration, 219 [180-270] vs 95 [68-145] minutes; P < .001) and the intensity of mechanical ventilation was higher (median [IQR] intensity, 84 [69-100] vs 72 [60-87] 4DP + RR; P < .001). PPCs were independently associated only with duration of ventilation (adjusted odds ratio [aOR], 1.49; 95% CI, 1.33-1.66; P < .001), not with the surgical approach (ie, RAS vs CLS; aOR, 1.35; 95% CI, 0.72-2.54; P = .35) nor the intensity of ventilation as measured by 4DP + RR (aOR, 1.01; 95% CI, 1.01-1.01; P = .21). A post hoc analysis showed a more pronounced association of intensity of ventilation in surgical procedures of shorter duration. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received RAS vs CLS had a higher incidence of PPCs and received longer and more intense mechanical ventilation; however, only the duration of ventilation rather than intensity of ventilation or type of surgical approach (ie, RAS vs CLS) was independently associated with the occurrence of PPCs, indicating that the longer duration of ventilation in RAS underlies the higher incidence of PPCs observed in those who undergo this type of surgery.
3. Prevalence and Clinical Characteristics of Persistent Airflow Limitation in the NOVELTY Cohort.
In 9,081 patients followed for 3 years, persistent airflow limitation was common, highly stable (84% persisted), and predicted worse symptoms and more frequent exacerbations across physician-diagnosed asthma and COPD. In asthma, PAL associated with higher blood eosinophils and FeNO, despite 60% never smoking.
Impact: Establishes PAL as a stable, cross-disease risk trait with prognostic value, informing stratified management beyond diagnostic labels.
Clinical Implications: PAL identification should trigger closer monitoring and exacerbation prevention strategies (optimized inhaled therapies, treatable traits), even in asthma patients—many of whom never smoked.
Key Findings
- Baseline PAL prevalence: asthma 24.2%/29.2% (ERS/ATS vs GOLD), asthma+COPD 63.3%/74.1%, COPD 65.4%/75.8%.
- 84% with PAL at baseline met PAL criteria at Year 3, indicating stability.
- PAL associated with higher symptom burden and more frequent moderate/severe exacerbations; in asthma, higher eosinophils and FeNO with 60% never-smokers.
Methodological Strengths
- Large, multinational prospective cohort across primary and secondary care with 3-year follow-up.
- Use of both ERS/ATS LLN and GOLD fixed-ratio definitions to assess robustness.
Limitations
- Physician-assigned diagnoses may introduce misclassification.
- Observational design limits causal inference and residual confounding is possible.
Future Directions: Integrate PAL into risk stratification algorithms and test targeted interventions (e.g., anti-inflammatory biologics, rehab) to reduce exacerbations in PAL-positive patients.
RATIONALE: The clinical characteristics of persistent airflow limitation (PAL) were explored in patients aged ≥12 years with physician-assigned diagnoses of asthma, asthma plus chronic obstructive pulmonary disease (COPD), or COPD in the NOVEL Observational longiTudinal studY (NOVELTY) cohort. The NOVELTY study is a prospective study conducted in primary and secondary care in 18 countries. OBJECTIVES: To determine the proportion of patients with PAL at baseline, their baseline characteristics, and the stability and prognostic utility of PAL during follow-up. METHODS: PAL was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio less than the lower limit of the normal range (European Respiratory Society [ERS]/American Thoracic Society [ATS]) or as <0.7 (Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria). RESULTS: We studied 9,081 patients over 3 years (asthma: 4,754; asthma+COPD; 1,147; COPD: 3,180). Baseline prevalence of PAL was 24.2% and 29.2% (asthma), 63.3% and 74.1% (asthma+COPD), and 65.4% and 75.8% (COPD) using ERS/ATS and GOLD criteria, respectively. Patients with PAL had markedly worse symptom burden and a history of more frequent moderate and severe exacerbations. In patients with asthma PAL was associated with higher blood eosinophils and fractional exhaled nitric oxide (FeNO) values; 60% had never smoked. Of patients with PAL at baseline 84% continued to meet PAL criteria at Year 3. Irrespective of physician diagnosis, PAL was a marker of increased risk of moderate and severe exacerbations and poor symptom control during the 3-year follow-up. CONCLUSIONS: PAL is a stable trait, associated with more severe disease and poor outcomes in adults with a physician-assigned diagnosis of asthma and/or COPD. Clinical Trial Registration (if any): NOVELTY: NCT02760329 This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).