Safety Profile of Ultrasound-guided Transparietal Lung Biopsy in Patients With Diffuse Interstitial Lung Disease

The TOUCANS study is a prospective, interventional, single-center protocol designed to evaluate the feasibility and safety of transthoracic ultrasound-guided lung biopsy (BPTE) for the histopathological assessment of patients with interstitial lung disease (ILD). Surgical lung biopsy (SLB) remains the reference diagnostic standard when high-resolution CT and multidisciplinary evaluation are inconclusive; however, SLB requires general anesthesia and thoracoscopy and is associated with non-negligible morbidity. Cryobiopsy offers a less invasive option but still relies on general anesthesia and does not provide real-time guidance during tissue acquisition. BPTE, routinely used in oncology, may provide a safer and more accessible alternative by combining real-time thoracic ultrasound guidance with local anesthesia and outpatient feasibility. Its use in ILD has been limited due to a lack of prospective safety and diagnostic performance data.

Scientific Background ILDs often involve peripheral and subpleural abnormalities that can be visualized using thoracic ultrasound. Real-time ultrasound allows operators to identify pleural irregularities, increased B-lines, or localized reductions in aeration that may correspond to accessible sampling sites. These features form the basis for selecting BPTE target zones. BPTE has shown low complication rates in other clinical contexts, including pneumothorax and hemorrhage, but its applicability to ILD requires systematic evaluation given the underlying fragility of this patient population.

Study Rationale By performing both BPTE and SLB in each participant, the study aims to document the safety profile of BPTE relative to the current gold standard and compare tissue quality. This within-subject design allows direct assessment of histological adequacy and potential concordance between techniques, while limiting inter-individual variability. The protocol also aims to document patient-reported outcomes such as pain and dyspnea and to characterize local tissue effects at the BPTE site during subsequent thoracoscopy.

Study Procedures After standard diagnostic workup and confirmation of biopsy indication by multidisciplinary discussion, participants undergo baseline clinical assessment and high-resolution CT imaging. BPTE is performed 2-4 weeks before SLB to ensure procedural independence and adequate healing time. Under local anesthesia and spontaneous ventilation, the operator identifies an appropriate intercostal window using thoracic ultrasound. A target region is selected based on pleural surface abnormalities or an increased number of B-lines. One or two core biopsies measuring at least 1 cm are obtained using a dedicated cutting needle during a brief apnea. Post-procedure monitoring includes lung ultrasound and chest radiography to detect pneumothorax. Patients are discharged after a four-hour observation period unless complications occur.

SLB is performed under general anesthesia via video-assisted thoracoscopy. The thoracic surgeon documents the BPTE site, enabling evaluation of hematoma or other local effects. Standard postoperative care includes pleural drainage and scheduled follow-up visits. Histological samples obtained through BPTE are stored and analyzed at the end of the follow-up period to ensure blinded comparison with surgical specimens.

Data Collection and Management Clinical assessments include evaluation of procedural tolerance, pain, dyspnea, and healing. Thoracoscopic imaging of the BPTE site provides additional information on local changes. All data are entered into electronic case report forms (eCRFs) with access restricted to authorized study personnel. Data management follows GDPR and CNIL requirements, with predefined monitoring procedures to ensure accuracy, completeness, and consistency.

Statistical Approach Given the exploratory nature of the study, the sample size of 15 participants is based on feasibility considerations. Analyses will primarily rely on descriptive statistics to summarize safety outcomes, histological adequacy, and patient-reported measures. No formal hypothesis testing is planned, but the dataset is expected to support the design of future multicenter studies.

Safety Oversight Adverse events and serious adverse events will be documented throughout the study period. Investigators are responsible for evaluating severity and causality and reporting events to the sponsor. An independent safety monitoring committee will review safety data periodically. Regulatory and ethical compliance includes approval from national authorities and ethics committees, informed consent procedures, and insurance coverage for participants.

Expected Contribution The TOUCANS study will provide the first prospective evidence on BPTE in ILD. The findings may clarify whether BPTE can serve as a safe and technically reliable method for obtaining diagnostic tissue in selected ILD patients, potentially reducing the need for surgical biopsy and improving access to histological diagnosis in those with contraindications to invasive procedures.