This title slide highlights the key finding that early mucoactive agents reduce mortality. It specifies ventilated pneumonia patients in the Sasaki et al. 2025 nationwide cohort study.

Early Mucoactive Agents Reduce Mortality

in Ventilated Pneumonia Patients: Sasaki et al., 2025 Nationwide Cohort Study

Source: Association between early administration of mucoactive agents and in-hospital mortality in patients with pneumonia requiring mechanical ventilation: a nationwide cohort study

This agenda slide outlines a presentation on mucoactive agents for pneumonia patients on mechanical ventilation, with sections on Background and Context (3 slides), Study Objectives, Methods and Design (4 slides), Results and Findings (7 slides), and Discussion and Conclusion (4 slides). It highlights challenges, aims, nationwide cohort analysis, mortality reduction data, interpretations, implications, and limitations.

Presentation Agenda

1. Background and Context

Overview of pneumonia challenges and mechanical ventilation needs (3 slides)

2. Study Objectives

Aims focusing on mucoactive agents and patient outcomes

3. Methods and Design

Details of nationwide cohort study and analysis (4 slides)

4. Results and Findings

Mortality reduction data with charts and tables (7 slides)

5. Discussion and Conclusion

Interpretation, implications, limitations, and final takeaways (4 slides) Source: Association between early administration of mucoactive agents and in-hospital mortality in patients with pneumonia requiring mechanical ventilation: a nationwide cohort study (Sasaki et al., 2025)

This slide serves as the section header for "Background" (Section 02). It addresses challenges in pneumonia and mechanical ventilation, plus the role of mucoactive agents in mucus clearance.

Background

02

Background

Pneumonia and mechanical ventilation challenges; mucoactive agents' role in mucus clearance.

Source: Sasaki et al., 2025

The Pneumonia Burden slide highlights high mortality rates in mechanically ventilated pneumonia patients. It notes that mucoactives like ambroxol and carbocysteine aid mucus secretion, but identifies a key gap in optimal administration timing.

Pneumonia Burden

• High mortality in mechanically ventilated pneumonia patients
• Mucoactives (ambroxol, carbocysteine) aid mucus secretion
• Key gap: optimal timing of administration

Source: Sasaki et al., 2025

The slide "Ventilation Challenges" addresses rising in-hospital deaths from pneumonia, requiring urgent interventions amid mechanical ventilation complications. It highlights difficulties managing secretions and lung function, stressing the need for early mucoactive agents.

Ventilation Challenges

!Image

• Rising in-hospital deaths necessitate interventions.
• Mechanical ventilation complications in pneumonia.
• Challenges managing secretions and lung function.
• Urgent need for early mucoactive agents.

Source: Sasaki et al., 2025

The slide's rationale notes that early versus late mucoactives in ventilated pneumonia are unstudied, with limited data on timing's impact on mortality. It calls for a nationwide cohort to generate robust evidence and fill key gaps in clinical guidelines.

Rationale

• Early vs. late mucoactives unstudied in ventilated pneumonia
• Limited data on timing's impact on mortality
• Nationwide cohort needed for robust evidence
• Addresses key gap in clinical guidelines

Source: Sasaki et al., 2025

The slide outlines study objectives for a nationwide cohort analysis of ventilated pneumonia patients. It assesses early mucoactive use (<48h) versus in-hospital mortality and evaluates its impact on ventilator-free days (VFD).

Study Objectives

• Assess early mucoactive use (<48h) vs. in-hospital mortality
• Evaluate impact on ventilator-free days (VFD)
• Conduct nationwide cohort analysis of ventilated pneumonia patients

Source: Sasaki et al., 2025

This slide serves as a section header titled "Methods." Its subtitle describes a Japanese nationwide database cohort study design.

Methods

Methods

Japanese nationwide database cohort study design.

Source: Sasaki et al., 2025

The "Study Population" slide specifies inclusion criteria as patients with pneumonia requiring mechanical ventilation for ≥96 hours. Exclusion criteria include inter-hospital transfers, age <18 years, and other conditions, yielding a final cohort of N=12,853.

Study Population

Source: Sasaki et al., 2025

The study timeline begins in 2014 with nationwide data collection on pneumonia patients requiring mechanical ventilation, followed by continuous patient data accrual through 2020. It defines early mucoactive agent exposure within 48 hours of ventilation start and assesses primary outcomes of in-hospital mortality and ventilator-free days at day 28.

Study Timeline

2014: Study Period Begins Nationwide cohort data collection initiates for pneumonia patients requiring mechanical ventilation. 2014-2020: Patient Data Accrual Comprehensive records of treatments, exposures, and outcomes continuously gathered across hospitals. Within 48h: Early Mucoactive Exposure Administration of mucoactive agents within 48 hours of mechanical ventilation start defined. Day 28: Primary Outcomes Assessed In-hospital mortality and ventilator-free days at day 28 systematically evaluated.

Source: Sasaki et al., 2025

The Statistical Analysis slide highlights propensity score matching to balance baseline covariates between groups and Cox proportional hazards regression to model in-hospital mortality. Multiple sensitivity analyses confirmed the robustness of the primary findings.

Statistical Analysis

• Propensity score matching balanced baseline covariates between groups.
• Cox proportional hazards regression modeled in-hospital mortality.
• Multiple sensitivity analyses validated primary findings' robustness.

Source: Sasaki et al., 2025

The Baseline Characteristics slide shows a mean age of 70.2 years, 42% hypertension prevalence, and 28% diabetes mellitus across matched cohorts. These metrics indicate good balance, with similar rates pre- and post-matching and a maximum standardized mean difference (SMD) of ≤0.1 for covariates.

Baseline Characteristics

• 70.2: Mean Age (years)

Balanced pre/post-matching

• 42%: Hypertension Prevalence

Similar in matched cohorts

• 28%: Diabetes Mellitus

No significant differences

• ≤0.1: Max SMD Covariates

Indicating good balance Source: Sasaki et al., 2025

This section header slide is titled "Key Results." Its subtitle states that early mucoactive agents reduce in-hospital mortality without improving ventilator-free days.

Key Results

Key Results

Early mucoactive agents reduce in-hospital mortality without improving ventilator-free days.

Source: Sasaki et al., 2025

The slide presents a hazard ratio of 0.85 (95% CI 0.78-0.93) for mortality, favoring the early group over the late group. Mortality rates were 22.5% in the early group and 25.8% in the late group.

Mortality Outcomes

• 0.85: Hazard Ratio

95% CI 0.78-0.93 (early vs late)

• 22.5%: Early Group Mortality
• 25.8%: Late Group Mortality

Source: Sasaki et al., 2025

The Kaplan-Meier survival slide shows early mucoactive agents provide a clear survival benefit in ventilated pneumonia patients. Curves diverge significantly early, with reduced in-hospital mortality and a hazard ratio favoring early administration.

Kaplan-Meier Survival

!Image

• Early mucoactive agents show survival benefit
• Kaplan-Meier curves diverge significantly early
• Reduced in-hospital mortality in ventilated pneumonia patients
• Hazard ratio favors early administration

Source: Image from Wikipedia article "Kaplan–Meier estimator"

The Early Group mean ventilator-free days was 12.5, compared to 12.3 for the Late Group. No significant difference existed between groups (P=0.72).

Ventilator-Free Days

• 12.5: Early Group Mean

Ventilator-free days

• 12.3: Late Group Mean

Ventilator-free days

• P=0.72: No Significant Difference

Between groups in VFD Source: Sasaki et al., 2025

The Subgroup Findings slide shows mortality benefits consistent across disease severities and uniform across mucoactive agents. Ambroxol demonstrates the strongest mortality reduction.

Subgroup Findings

• Mortality benefit consistent across severities
• Benefit uniform across mucoactive agents
• Ambroxol shows strongest mortality reduction

Source: Sasaki et al., 2025

IPTW sensitivity analysis confirms early mucoactive agent use reduces in-hospital mortality (adjusted HR 0.85, 95% CI 0.78-0.93, p<0.001), robust to unmeasured confounding. No significant interaction exists with ventilator-free days (p=0.72), with benefits consistent across VFD tertiles.

Sensitivity Results

Source: Sasaki et al., 2025

This slide serves as a section header titled "Discussion & Conclusion." Its subtitle highlights implications for clinical practice in managing pneumonia patients on mechanical ventilation.

Discussion & Conclusion

Discussion & Conclusion

Implications for clinical practice in managing pneumonia patients requiring mechanical ventilation

Source: Sasaki et al., 2025

This slide, titled "Key Takeaway," features a quote highlighting that early mucoactive agents in mechanically ventilated pneumonia patients significantly reduce in-hospital mortality without affecting ventilator-free days. The quote is attributed to Sasaki et al., MD, PhD et al.

Key Takeaway

> In patients with pneumonia requiring mechanical ventilation, early administration of mucoactive agents significantly reduces in-hospital mortality, without impacting ventilator-free days.

— Sasaki et al., MD, PhD et al.

Source: Sasaki et al., Association between early administration of mucoactive agents and in-hospital mortality in patients with pneumonia requiring mechanical ventilation: a nationwide cohort study (2025)