BREATHE Study: Spontaneous Breathing-Preserved Anesthesia and Surgical Strategy for Hospital Recovery in Lung Transplantation

This is a prospective, multicenter, single-arm clinical study designed to evaluate a standardized perioperative pathway for adult lung transplantation that aims to preserve spontaneous breathing ("tubeless" strategy). The study will enroll approximately 110 participants across multiple hospitals in China. To reduce assessment bias in a single-arm design, key study endpoints will be evaluated by an independent team using prespecified definitions and adjudication rules.

The investigational perioperative pathway integrates anesthesia and surgical management with the goal of maintaining the participant's own breathing as much as possible during and after transplantation, while minimizing exposure to tracheal intubation, invasive mechanical ventilation (IMV), and deep sedation. The approach typically uses a laryngeal mask airway (LMA) for airway support, intravenous anesthesia with careful titration, and multimodal analgesia to achieve adequate comfort and cough control while allowing spontaneous respiration. Regional and/or local anesthetic techniques may be used to improve pain control and reduce airway stimulation. Intraoperative monitoring and ventilatory support are individualized, and lung recruitment or short periods of assisted ventilation may be used when clinically indicated.

Participant safety is prioritized throughout the procedure and postoperative period. The clinical team may convert to conventional tracheal intubation and IMV at any time if predefined clinical concerns arise, such as inadequate gas exchange, airway protection issues, hemodynamic instability, uncontrolled bleeding, or conditions that compromise surgical safety. Extracorporeal membrane oxygenation (ECMO) may be initiated or escalated when necessary according to institutional practice and prespecified clinical triggers. Postoperatively, participants receive standard transplant care per each center's routine protocols, including intensive monitoring and timely escalation of respiratory or circulatory support when required.

The study timeline includes a screening period prior to transplantation, comprehensive perioperative data capture, in-hospital follow-up through discharge, and structured follow-up after discharge to document early recovery and safety outcomes. Safety surveillance focuses on events occurring within 30 days after transplantation, and additional follow-up through 90 days captures short-term outcomes such as survival status and rehospitalization.

All study data are recorded in standardized case report forms and entered into a centralized database with built-in quality checks. The coordinating center oversees data completeness and consistency across sites, and the independent outcome review team adjudicates endpoints according to prespecified rules.

【1】Inclusion Criteria

• Age and informed consent: Aged 18-70 years; able to understand the study and provide written informed consent; willing and able to complete follow-up.
• Transplant candidacy: Listed in the CLuTR registry and/or the local center's lung transplant waiting list, and scheduled to undergo allogeneic lung transplantation.
• Preoperative support status: Not on ongoing invasive mechanical ventilation preoperatively (endotracheal intubation or tracheostomy), and not receiving ECMO or other extracorporeal life support.
• Minimum key organ function requirements: LVEF ≥40%; eGFR ≥40 mL/min/1.73 m²; no acute liver failure and no evidence of decompensated cirrhosis/portal hypertension; ASA Physical Status (American Society of Anesthesiologists classification) ≤ IV.
• Infection and transmissible diseases: No evidence of active infection; no active tuberculosis; HIV/HBV/HCV status meeting the center's transplant requirements (e.g., undetectable viral load, noticeability per center policy).
• Rehabilitation potential and support: Demonstrates postoperative rehabilitation potential (able to cooperate with training) and has reliable caregiving support (at least one primary caregiver).

【2】Exclusion Criteria

• Informed consent/adherence: Refusal of or withdrawal of informed consent; investigator judgment that the participant cannot complete follow-up or has recurrent severe non-adherence.
• Transplant type: Re-transplantation, multi-organ transplantation, or planned lobar lung transplantation.
• Recent major cardiovascular/cerebrovascular events: Acute coronary syndrome/myocardial infarction or stroke within the past 30 days.
• Severe organ dysfunction/acute failure: LVEF <40%; eGFR <40 mL/min/1.73 m²; acute liver failure or decompensated cirrhosis/portal hypertension; acute kidney failure requiring dialysis with low likelihood of recovery; significant preoperative neuropsychiatric disorders or altered consciousness.
• High risk of severe infection: Septic shock; active extrapulmonary or disseminated infection; active tuberculosis; detectable HIV viral load (or otherwise not meeting the center's transplant criteria).
• High bleeding risk: Severe bronchiectasis in which preoperative vascular intervention has not been performed or bleeding risk cannot be adequately mitigated.
• Malignancy: Active malignancy or malignancy associated with a high risk of recurrence or cancer-related mortality.
• Extreme body habitus: BMI ≥35 kg/m² or BMI <16 kg/m²; or a confirmed diagnosis of severe chest wall deformity or spinal deformity.
• Substance use/dependence: Current use of cigarettes, e-cigarettes/vaping, smoked cannabis, or intravenous drug use.
• Tubeless/spontaneous-breathing strategy not safely feasible: The anesthesia team determines that a difficult airway is anticipated or that laryngeal mask airway (LMA)/non-intubated airway management is unsafe (e.g., expected intraoperative airway difficulty, pharyngeal/laryngeal stenosis unsuitable for LMA), including but not limited to: Mallampati class >III, mouth opening <3 cm, thyromental distance <5 cm, or significant airway anatomical variation (e.g., anomalous right upper lobe bronchial takeoff in candidates for right lung transplantation) deemed difficult to manage safely with an LMA or single-lumen airway.
• Donor/donor-lung limitations: Donor age >60 years; donor mechanical ventilation >14 days; positive donor-lung airway culture deemed unacceptable by the transplant team.
• Protected populations: Pregnant or breastfeeding women.