Aspergillosis Detection Via EBC-GM in Ventilated Patients

Non-Invasive Detection of Aspergillosis in Ventilated Patients: Galactomannan Analysis in Exhaled Breath

Brief Research Proposal: Non-Invasive Detection of Invasive Pulmonary Aspergillosis in ICU Patients Background: Invasive Pulmonary Aspergillosis (IPA) is a critical threat to patients in ICUs, especially those undergoing mechanical ventilation. Traditional diagnostic methods are invasive and carry risks. This study proposes a non-invasive, innovative approach utilizing galactomannan (GM) analysis in Exhaled Breath Condensate (EBC) for early IPA detection.

Objective: To evaluate the diagnostic accuracy of measuring GM levels in EBC for detecting IPA in mechanically ventilated patients, comparing it against the conventional Bronchoalveolar Lavage Fluid (BALF)-GM measurements.

Methods: A clinical trial will be conducted with 75 mechanically ventilated patients suspected of having IPA. The study will compare the effectiveness of EBC-GM levels against BALF-GM levels in diagnosing IPA, focusing on sensitivity, specificity, and diagnostic accuracy. The novel, self-designed EBC collection device will facilitate the safe and efficient collection of EBC from patients.

Expected Outcomes:

Validation of EBC-GM Diagnostic Accuracy: Anticipate demonstrating that EBC-GM levels provide a comparable diagnostic accuracy to BALF-GM, establishing a non-invasive, safer alternative for IPA detection.

Implementation of a Non-Invasive Diagnostic Tool: The study aims to introduce a non-invasive diagnostic approach that can potentially replace more risky, invasive methods, improving patient care in ICUs.

Contribution to Clinical Practice: By providing a new method for early and safer detection of IPA, the study is expected to influence clinical guidelines and practices in the management of critically ill, ventilated patients.

Significance: This research has the potential to revolutionize the diagnosis of fungal infections in critically ill patients by offering a non-invasive, accurate, and safer diagnostic tool, thereby improving patient outcomes and reducing the risks associated with invasive diagnostic procedures.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Aspergillosis, Invasive Pulmonary; Exhaled Breath Condensate; Bronchoalveolar Lavage Fluid; Respiration Failure; Sensitivity and Specificity; Respiratory Fungal Infection
• Intervention / Treatment: Other: Compare the levels of Galactomannan (GM) levels in exhaled breath condensate (EBC) and BALF

Detailed Description

Research Proposal: Advancing the Diagnosis of Invasive Pulmonary Aspergillosis through Exhaled Breath Condensate Analysis in Ventilated Patients Background: Invasive Pulmonary Aspergillosis (IPA) remains a formidable challenge in the management of critically ill, immunocompromised patients, especially those requiring mechanical ventilation in Intensive Care Units (ICUs). The high morbidity and mortality rates associated with IPA underscore the urgent need for early and accurate diagnostic methods. Traditional diagnostic approaches, though effective, are invasive and pose significant risks to already vulnerable patients. This study introduces a novel, non-invasive diagnostic methodology by measuring galactomannan (GM) levels in Exhaled Breath Condensate (EBC), potentially revolutionizing the early detection of IPA.

Objective: To evaluate the effectiveness of a non-invasive diagnostic approach by analyzing galactomannan levels in exhaled breath condensate (EBC) for detecting Invasive Pulmonary Aspergillosis (IPA) in mechanically ventilated ICU patients.

Methods:

Study Design: A prospective clinical trial involving 75 mechanically ventilated patients suspected of having IPA within the Medical Intensive Care Unit (MICU) of a tertiary hospital.

Data Collection: Utilizing a self-designed EBC collection device, EBC samples will be collected from participants and analyzed for GM levels. These will be compared to Bronchoalveolar Lavage Fluid (BALF) GM levels, considered the current gold standard in IPA diagnostics.

Analytical Approach: The study will focus on assessing the diagnostic accuracy of EBC-GM measurements by determining sensitivity, specificity, and overall concordance with BALF-GM levels. The potential enhancement of diagnostic precision with the inclusion of cytokine measurements will also be explored.

Innovation: By leveraging a cutting-edge EBC collection device, this research aims to bypass the complications associated with invasive diagnostic procedures, offering a safer, more patient-friendly alternative. This innovative approach has the potential to significantly impact clinical practices in ICU settings by facilitating early and accurate IPA diagnosis without the need for bronchoscopy.

Expected Outcomes:

Diagnostic Performance: Investigators anticipate demonstrating that EBC-GM levels provide a reliable, non-invasive marker for IPA, with diagnostic accuracy comparable to BALF-GM measurements.

Clinical Impact: The successful validation of EBC-GM as a diagnostic tool for IPA will offer a significant advancement in the management of critically ill patients, reducing the need for invasive procedures and associated risks.

Guideline Integration: Findings from this study are expected to support the integration of EBC-GM analysis into clinical guidelines as a recommended diagnostic approach for IPA in mechanically ventilated patients.

Significance: This research has the potential to transform IPA diagnostics in ICU settings, promoting a shift towards non-invasive, risk-free methods that can lead to earlier detection and improved patient outcomes. By minimizing invasive diagnostic interventions, the study aims to enhance the safety and efficacy of IPA management in critically ill populations.

Ethics and Dissemination: The study adheres to the highest ethical standards, with approval from the institutional review board ensuring the protection and well-being of participants. Results will be actively disseminated through peer-reviewed journals and conference presentations, contributing to global efforts in improving ICU patient care in the context of fungal infections.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 86610072
      • Sichuan Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Investigators at Sichuan Provincial Hospital study mechanically ventilated adults for Invasive Pulmonary Aspergillosis (IPA) risks. They classify participants into IPA and control groups. IPA patients meet EORTC/MSG criteria, showing new lung lesions, positive Aspergillus cultures in LRT, positive galactomannan in BALF, and supporting BALF NGS evidence. The control group includes ventilated patients without Aspergillus, confirmed by negative cultures and NGS in BALF. The study aims to assess EBC-GM's diagnostic accuracy for IPA, comparing it with BALF-GM for early, non-invasive detection.

Description

Inclusion Criteria:

- Age: Between 18 and 85 years old. Antifungal Medication Use: Participants who have not used any antifungal medications within the three months prior to enrollment.

Mechanical Ventilation Status: Patients who have been undergoing mechanical ventilation treatment for more than three days.

Exclusion Criteria:

- Inadequate Clinical Data: Inability to provide reliable diagnostic measurements or insufficient clinical information.

Early Mortality: Patients who die within the first three days of ICU (Intensive Care Unit) admission or during the initial phase of the study.

Pregnancy: To avoid potential confounding effects on immune function and the composition of EBC (Exhaled Breath Condensate), pregnant women are excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IPA group; Investigators enrolled patients who meet diagnostic criteria for IPA according to EORTC/MSG: new exudative lung lesions unresponsive to antimicrobial therapy; positive Aspergillus on LRT and/or BALF microscopy cultures, positive BALF GM and positive BALF NGS results for Aspergillus. Investigators will test and compare the EBC-GM and BALF-GM levels in these patients.	Other: Compare the levels of Galactomannan (GM) levels in exhaled breath condensate (EBC) and BALF; Investigators tested EBC-GM levels and BALF-GM levels in patients with confirmed IPA to compare the diagnostic value of EBC-GM versus BALF-GM.
control group; Investigators enrolled patients who were mechanically ventilated patients without Aspergillus infection or colonization. BALF and EBC samples from the same patients were collected less than 4 hours apart, and BALF samples were used for NGS and microbiological cultures. Investigators will test and compare the EBC-GM and BALF-GM levels in these patients.	Other: Compare the levels of Galactomannan (GM) levels in exhaled breath condensate (EBC) and BALF; Investigators tested EBC-GM levels and BALF-GM levels in patients with confirmed IPA to compare the diagnostic value of EBC-GM versus BALF-GM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of EBC-GM vs. BALF-GM	The diagnostic accuracy of Galactomannan (EBC-GM) levels in Exhaled Breath Condensate vs. Bronchoalveolar Lavage Fluid (BALF-GM) levels was measured by Receiver Operating Characteristic (ROC) area under the curve (AUC) assessment. Accuracy of Galactomannan (BALF-GM) levels in the diagnosis of Invasive Pulmonary Aspergillosis (IPA).	EBC and BALF samples were collected simultaneously on the day of patient admission.
EBC-GM levels:	Evaluate sensitivity and specificity in differentiating patients with IPA from mechanically ventilated patients with non-aspergillosis infections, and determining the critical value of EBC-GM in the diagnosis of IPA.	The stability of the patients' vital signs was observed within 72 hours to assess the diagnostic accuracy of EBC-GM and BALF-GM.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between EBC-GM and BALF-GM levels	To assess the correlation between EBC-GM levels and BALF-GM levels in mechanically ventilated IPA patients.	Based on samples collected on the same day, followed by 72 hours of observation.

Collaborators and Investigators

• Sponsor: Lin Chen
• Investigators: Principal Investigator: Lin Chen, doctoral, Sichuan Provincial People's Hospita

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Invasive Pulmonary Aspergillosis; Galactomannan; Exhaled breath condensation; Bronchoalvelar lavage fluid; Non-invasive diagosis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease Attributes; Bacterial Infections and Mycoses; Invasive Fungal Infections; Lung Diseases, Fungal; Pulmonary Aspergillosis; Respiratory Insufficiency; Mycoses; Critical Illness; Aspergillosis; Invasive Pulmonary Aspergillosis
• Other Study ID Numbers: SichuanPPHLC04; 2020LY01 (Other Grant/Funding Number: Sichuan Provincial People's Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This study tests a non-invasive method for detecting Invasive Aspergillosis (IPA) in ICU patients using ventilators. By analyzing galactomannan in exhaled breath, we aim to identify IPA without invasive procedures. Phase 1 involves testing a new breath collection device on rats. Phase 2 applies this device to 75 ICU patients, comparing results with traditional lung fluid tests. Approval from an ethics committee ensures patient safety. Successful outcomes could lead to safer IPA diagnosis, enhancing treatment and reducing risks associated with current methods.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No