Bronchoscopic Cytology and Metagenomic Sequencing to Differentiate Cancer Treatment-related and Infectious Lung...

Patients with cancer treatment-related lung injury (CTLI) frequently present with non-specific respiratory symptoms and radiological changes that closely mimic infectious pneumonia or tumor progression, presenting a significant challenge for a definitive diagnosis. Traditional diagnostic processes, mainly evaluated through blood biomarkers and standard microbial cultures, usually cannot make a clear diagnosis and take too much time. Here, we present a comprehensive protocol to diagnose CTLI by combining bronchoalveolar lavage fluid (BALF) cytological analysis with metagenomic next-generation sequencing (mNGS). The procedural workflow consists of three primary stages. First, standardized bronchoscopy is performed to obtain high-quality BALF samples. Second, conducting cytological analysis of the obtained BALF samples provides a snapshot of the lung microenvironment. This allows identification of inflammatory features and screening for malignant cells to exclude tumor progression. Finally, mNGS is utilized to identify or exclude active infectious etiologies. This advanced genomic technique achieves rapid, highly sensitive, and unbiased pathogen detection, successfully overcoming the limitations of traditional cultures. Representative results using this method demonstrate that this approach can effectively distinguish immune-related pneumonitis from active pulmonary infections or tumor progression. Compared with traditional diagnostic methods, this protocol has the advantage of quickly and accurately distinguishing CTLI from infectious etiologies and occult malignancies. Ultimately, this standardized workflow clarifies clinical diagnoses, guides critical treatment decisions, and improves patient outcomes.