The Hering-Breuer Reflex in Bilateral Lung Transplant Patients (HB-DLTX)

The goal of this clinical trial (non-pharmacologic, single-center) is to determine whether the Hering-Breuer inflation reflex is preserved-and how it is modulated by end-expiratory pressure-in adult intensive-care patients who have undergone bilateral lung transplantation.

The study will enroll men and women ≥ 18 years admitted to the ICU during the early weaning phase and will include a comparison group of intubated ICU patients after major non-thoracic surgery.

The main questions it aims to answer are:

• Is the Hering-Breuer reflex (measured as the ratio THBR/TSPONT) absent or attenuated in double-lung-transplant recipients?
• Does changing the level of positive end-expiratory pressure (PEEP 8 vs 12 cmH₂O) influence the reflex?

Comparison group: Researchers will compare the transplant arm (post-bilateral lung transplantation) with the control arm (post-operative, non-thoracic surgery patients) to see whether loss or blunting of the reflex-and its response to PEEP-differs between the two cohorts.

Participants will:

• Have a nasogastric catheter with embedded electrodes positioned to record the electrical activity of the diaphragm (EAdi).
• Be ventilated in pressure-support mode at two preset PEEP levels (8 cmH₂O and 12 cmH₂O) during the weaning phase.
• Receive one standardized high-volume insufflation at ~30 cmH₂O in each PEEP condition to elicit the reflex, while EAdi, airway pressures, inspiratory/expiratory times, and tidal volumes are recorded for 10 minutes per level.

Study Overview

• Status: Recruiting
• Conditions: Hering-Breuer Reflex
• Intervention / Treatment: Device: Nasogastric tube placement and elicitation of Hering-Breuer reflex

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Michigan
    • Milan, Michigan, Italy, 20122
      • Recruiting
      • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
      • Contact: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Phone Number: +39 0255033285; Email: alessio.caccioppola@policlinico.mi.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age >18 years;
• Both sexes;
• For group 1: patients admitted to the Intensive Care Unit after undergoing bilateral lung transplantation, during respiratory weaning;
• For group 2: patients admitted to the Intensive Care Unit for support or monitoring after non-thoracic surgery, who will arrive intubated.

Exclusion Criteria:

For group 1, patients meeting at least one of the following criteria will be excluded:

• Re-transplantation or single-lung transplantation;
• Urgent lung transplantation;
• Post-transplant respiratory system compliance < 30 mL/cmH₂O;
• Hemodynamic instability (defined as the presence of one or more of the following: plasma lactate > 4 mmol/L, need for vasoactive support with norepinephrine and/or epinephrine at a dose > 0.05 mcg/kg/min, systolic arterial pressure < 80 mmHg);
• Increased risk of bleeding related to the placement of a nasogastric tube due to coagulopathy or severe thrombocytopenia (INR > 2 and platelets < 70,000);
• Pregnancy

For group 2, patients presenting with one or more of the following criteria will be excluded:

• Postoperative respiratory system compliance < 30 mL/cmH₂O;
• Hemodynamic instability (defined as the presence of one or more of the following: plasma lactate > 4 mmol/L, need for vasoactive support with norepinephrine and/or epinephrine at a dose > 0.05 mcg/kg/min, systolic arterial pressure < 80 mmHg);
• Contraindications to nasogastric tube placement (gastroesophageal surgery within the last 3 months, gastroesophageal bleeding in the previous 30 days, esophageal varices, facial trauma);
• Increased risk of bleeding related to the placement of a nasogastric tube due to coagulopathy or severe thrombocytopenia (INR > 2 and platelets < 70,000);
• History of lung transplantation or major thoracic surgery;
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bilateral Lung Transplant patients; This group include patients admitted to the Intensive Care Unit for post-operative care following bilateral lung transplantation during the weaning phase from mechanical ventilation. The following patients will be excluded: minors, those undergoing retransplantation, single-lung transplantation or urgent lung transplantation; patients with respiratory system compliance < 30 mL/cmH2O; haemodynamically unstable patients and those at increased risk of bleeding due to nasogastric tube placement.	Device: Nasogastric tube placement and elicitation of Hering-Breuer reflex; Enrolled patients will have a nasogastric tube placed, through which diaphragmatic electrical activity will be measured. Patients will be ventilated in pressure support mode with an expansion breath delivered at a maximum pressure of approximately 30 cmH2O in order to elicit the Hering-Breuer Reflex. Diaphragmatic electrical activity, timing, volumes and pressures will then be analyzed before and after the expansion breath over a 10 minute period, testing two levels of PEEP (8 and 12 cmH2O).
Active Comparator: Non-thoracic surgery patients; This group include patients admitted to the Intensive Care Unit for post-operative care or monitoring after non-thoracic surgery. The following patients will be excluded: minors, those who had undergone previous lung transplant or thoracic surgery; patients with respiratory system compliance < 30 mL/cmH2O; haemodynamically unstable patients; those at increased risk of bleeding due to nasogastric tube placement and patients with contraindications to nasogastric tube placement.	Device: Nasogastric tube placement and elicitation of Hering-Breuer reflex; Enrolled patients will have a nasogastric tube placed, through which diaphragmatic electrical activity will be measured. Patients will be ventilated in pressure support mode with an expansion breath delivered at a maximum pressure of approximately 30 cmH2O in order to elicit the Hering-Breuer Reflex. Diaphragmatic electrical activity, timing, volumes and pressures will then be analyzed before and after the expansion breath over a 10 minute period, testing two levels of PEEP (8 and 12 cmH2O).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
THBR/TSPONT ratio	Comparison of the ratio between the diaphragm electrical activation time after a high-volume breath aimed at eliciting the HBR (THBR) and a spontaneous breath (TSPONT), i.e., the THBR/TSPONT ratio, between patients who underwent bilateral lung transplantation and those who underwent non-thoracic surgery.	At the enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The variation of the THBR/TSPONT ratio as a function of PEEP	Variation of the THBR/TSPONT ratio calculated at two different PEEP levels (8 and 12 cmH₂O) in patients who underwent bilateral lung transplantation and in those who underwent non-thoracic surgery.	At the enrollment

Collaborators and Investigators

• Sponsor: Policlinico Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Hering-Breuer reflex; Bilateral Lung Transplant
• Other Study ID Numbers: ID 5483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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