Respiratory adverse events associated with PD-1/PD-L1 inhibitors: an analysis based on the FDA adverse event reporting system

Background: Respiratory adverse events associated with programmed cell death protein 1 and programmed death-ligand 1 (PD-1/PD-L1) inhibitors have emerged as an important safety concern in clinical oncology. With the expanding use of immune checkpoint inhibitors (ICIs), a comprehensive evaluation of real-world respiratory toxicity is essential to optimize clinical risk management. This study aimed to systematically characterize the occurrence patterns and pharmacovigilance signals of respiratory adverse events related to PD-1/PD-L1 inhibitors using the FDA Adverse Event Reporting System (FAERS). Methods: Reports of suspected adverse events associated with PD-1/PD-L1 inhibitors were extracted from the FAERS database, covering the period from the first quarter of 2004 to the second quarter of 2025. Respiratory, thoracic, and mediastinal disorders were identified according to the System Organ Class (SOCs) and Preferred Terms (PTs) of MedDRA version 27.0. Disproportionality analyses were performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC025), and empirical Bayesian geometric mean (EBGM). Univariable and multivariable logistic regression analyses were further conducted to explore factors associated with respiratory adverse event reporting. Results: A total of 163,193 reports identified PD-1/PD-L1 inhibitors as the primary suspected drugs. Pneumonia-related signals were consistently detected across most ICIs, indicating a shared pattern of pulmonary toxicity encompassing both infectious pneumonia and immune-related pneumonitis. Respiratory adverse events predominantly occurred during the early treatment phase, particularly within the first 60 days, with a secondary increase observed after prolonged exposure exceeding six months. Elderly patients (≥65 years) accounted for a substantial proportion of cases and exhibited a higher frequency of fatal outcomes. Regression analyses demonstrated that sex, reporting region, and drug class were significantly associated with respiratory adverse event reporting. Conclusions: PD-1/PD-L1 inhibitors are associated with a significant risk of respiratory adverse events in real-world clinical practice. Early and targeted respiratory monitoring is warranted, particularly during the initial treatment phase and among elderly patients. These findings highlight the need for optimized risk stratification and proactive management strategies to improve the safety of PD-1/PD-L1 inhibitor therapy.