{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:06:58Z","timestamp":1775797618790,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 (\u226565 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1788532","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:25:45Z","timestamp":1775795145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Respiratory adverse events associated with PD-1\/PD-L1 inhibitors: an analysis based on the FDA adverse event reporting system"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhenyu","family":"Wang","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuting","family":"Cui","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guimei","family":"Wang","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanting","family":"Qiu","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianan","family":"Jin","sequence":"additional","affiliation":[{"name":"Graduate School, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanliang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29050247","article-title":"Immune checkpoint inhibitors in cancer therapy","volume":"29","author":"Shiravand","year":"2022","journal-title":"Curr Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0488-6","article-title":"The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications","volume":"17","author":"Zhang","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00561","article-title":"PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front Pharmacol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13045-019-0779-5","article-title":"Immune checkpoint inhibitors of PD-L1 as cancer therapeutics","volume":"12","author":"Akinleye","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"101967","DOI":"10.1016\/j.eclinm.2023.101967","article-title":"Psychiatric disorders associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database","volume":"59","author":"Zhou","year":"2023","journal-title":"EClinicalMedicine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.3390\/cancers16101896","article-title":"Uncommon adverse events of immune checkpoint inhibitors in small cell lung cancer: a systematic review of case reports","volume":"16","author":"Lee","year":"2024","journal-title":"Cancers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13541","article-title":"Meta-analysis of immune-related adverse events of immune checkpoint inhibitor therapy in cancer patients","volume":"11","author":"Song","year":"2020","journal-title":"Thorac Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1631273","article-title":"Evaluating the toxicity profile of combination immune checkpoint inhibitors: a disproportionality analysis of real-world adverse events from the FDA adverse event reporting system for tremelimumab, durvalumab, ipilimumab, and nivolumab","volume":"16","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13045-024-01581-2","article-title":"Dual blockade immunotherapy targeting PD-1\/PD-L1 and CTLA-4 in lung cancer","volume":"17","author":"Cheng","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1398667","article-title":"Immune-related adverse events in small-cell lung cancer patients treated with immune checkpoint inhibitors: a comprehensive analysis from the FDA adverse event reporting system","volume":"15","author":"Bai","year":"2024","journal-title":"Front Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.21037\/jtd-23-588","article-title":"Efficacy and safety of durvalumab + chemotherapy vs. atezolizumab + chemotherapy in the treatment of small-cell lung cancer: a retrospective comparative cohort study","volume":"15","author":"Zou","year":"2023","journal-title":"J Thorac Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"160026","DOI":"10.1038\/sdata.2016.26","article-title":"A curated and standardized adverse drug event resource to accelerate drug safety research","volume":"3","author":"Banda","year":"2016","journal-title":"Sci Data"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.941079","article-title":"Respiratory system toxicity induced by immune checkpoint inhibitors: A real-world study based on the FDA adverse event reporting system database","volume":"12","author":"Cui","year":"2022","journal-title":"Front Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00408-021-00425-x","article-title":"Lessons from pharmacovigilance: pulmonary immune-related adverse events after immune checkpoint inhibitor therapy","volume":"199","author":"Reese","year":"2021","journal-title":"Lung"},{"key":"B15","unstructured":"FDA AEs reporting system (FAERS) public dashboard"},{"key":"B16","volume-title":"Postmarketing safety reporting for human drug and biological products: guidance for industry","year":"2001"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3701","article-title":"FDA adverse event reporting system (FAERS) essentials: A guide to understanding, applying, and interpreting adverse event data reported to FAERS","volume":"118","author":"Potter","year":"2025","journal-title":"Clin Pharmacol Ther"},{"key":"B18","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA Adverse Event Reporting System","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int J Med Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.09.050","article-title":"Pneumonitis after chemoradiotherapy and adjuvant durvalumab in stage III non-small cell lung cancer","volume":"118","author":"Edwards","year":"2024","journal-title":"Int J Radiat. Oncol Biol Phys"},{"key":"B20","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ijrobp.2024.07.2333","article-title":"Concerning safety and efficacy of concurrent and consolidative durvalumab with thoracic radiation therapy in PDL1-unselected stage III non-small cell lung cancer: brief report","volume":"121","author":"Zhang","year":"2025","journal-title":"Int J Radiat. Oncol Biol Phys"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2024.01.217","article-title":"Pneumonitis risk after chemoradiotherapy with and without immunotherapy in patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis","volume":"119","author":"Han","year":"2024","journal-title":"Int J Radiat. Oncol Biol Phys"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2021.02.002","article-title":"Increased incidence of venous thromboembolism with cancer immunotherapy","volume":"2","author":"Roopkumar","year":"2021","journal-title":"Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1159\/000512633","article-title":"The risk factors associated with immune checkpoint inhibitor-related pneumonitis","volume":"99","author":"Asada","year":"2021","journal-title":"Oncology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"178156","DOI":"10.1016\/j.ejphar.2025.178156","article-title":"Analysis of pulmonary adverse events associated with immune checkpoint inhibitors based on FAERS and VigiBase database","volume":"1006","author":"Li","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.03.204","article-title":"Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma","volume":"32","author":"Owen","year":"2021","journal-title":"Ann Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004670","article-title":"Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study","volume":"10","author":"Tiu","year":"2022","journal-title":"J Immunother. Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.944342","article-title":"Pulmonary adverse events associated with hypertension in non-small cell lung cancer patients receiving PD-1\/PD-L1 inhibitors","volume":"13","author":"Chen","year":"2022","journal-title":"Front Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s12931-024-02890-3","article-title":"Correlation between immune-related adverse events and efficacy of PD-(L)1 inhibitors in small cell lung cancer: a multi-center retrospective study","volume":"25","author":"Zhang","year":"2024","journal-title":"Respir Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000895","article-title":"Pulmonary adverse events following immune checkpoint inhibitors","volume":"28","author":"Spagnolo","year":"2022","journal-title":"Curr Opin Pulm. Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"afaf008","DOI":"10.1093\/ageing\/afaf008","article-title":"Immune-related adverse events in older adults receiving immune checkpoint inhibitors: a comprehensive analysis of the food and drug administration adverse event reporting system","volume":"54","author":"Esen","year":"2025","journal-title":"Age Ageing"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1607170","article-title":"Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"16","author":"Zhou","year":"2025","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.186483","article-title":"ICOS+CD4+ T cells define a high susceptibility to anti-PD-1 therapy-induced lung pathogenesis","volume":"10","author":"Yokoi","year":"2025","journal-title":"JCI Insight"},{"key":"B33","doi-asserted-by":"publisher","first-page":"100744","DOI":"10.1016\/j.jtocrr.2024.100744","article-title":"First-line chemo-immunotherapy in SCLC: outcomes of a binational real-world study","volume":"6","author":"Moliner","year":"2024","journal-title":"JTO Clin Res Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"115056","DOI":"10.1016\/j.ejca.2024.115056","article-title":"Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry","volume":"212","author":"\u00d6zkan","year":"2025","journal-title":"Eur J Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-025-03848-7","article-title":"Impact of comorbidity on survival in cancer patients receiving immune checkpoint inhibitors","volume":"27","author":"Yal\u00e7\u0131ner","year":"2025","journal-title":"Clin Transl Oncol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ejca.2021.09.010","article-title":"Immune checkpoint inhibitors for cancer and venous thromboembolic events","volume":"158","author":"Gong","year":"2021","journal-title":"Eur J Cancer"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-006072","article-title":"Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer","volume":"11","author":"Khorana","year":"2023","journal-title":"J Immunother. Cancer"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010761","article-title":"Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis","volume":"13","author":"Sussman","year":"2025","journal-title":"J Immunother. Cancer"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404873","article-title":"Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer","volume":"391","author":"Cheng","year":"2024","journal-title":"N Engl J Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1016\/j.ijrobp.2021.07.1250","article-title":"Risk of pneumonitis in patients with stage III non-small cell lung cancer treated with definitive chemo-RT and durvalumab consolidation","volume":"111","author":"Koffer","year":"2021","journal-title":"Int J Radiat. Oncol Biol Phys"},{"key":"B41","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s00262-024-03869-1","article-title":"Differences in immune-related toxicity between PD-1 and PD-L1 inhibitors: a retrospective cohort study in patients with advanced cancer","volume":"74","author":"Ladjevardi","year":"2024","journal-title":"Cancer Immunol Immunother"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3718","article-title":"Safety and efficacy of PD-1\/PD-L1 inhibitors combined with radiotherapy in patients with non-small-cell lung cancer: a systematic review and meta-analysis","volume":"10","author":"Geng","year":"2021","journal-title":"Cancer Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"109243","DOI":"10.1016\/j.thromres.2024.109243","article-title":"Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: a Bayesian network meta-analysis","volume":"246","author":"Lin","year":"2025","journal-title":"Thromb Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.2668","article-title":"Late-onset immune-related adverse events after immune checkpoint inhibitor therapy","volume":"8","author":"Durbin","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1186\/s12885-024-13220-7","article-title":"Immune-related adverse events correlate with the clinical efficacy in advanced Non-Small-Cell Lung Cancer patients treated with PD-1 inhibitors combination therapy","volume":"24","author":"Xie","year":"2024","journal-title":"BMC Cancer"},{"key":"B46","doi-asserted-by":"publisher","first-page":"101220","DOI":"10.1016\/j.blre.2024.101220","article-title":"Thrombotic events associated with immune checkpoint inhibitors and novel antithrombotic strategies to mitigate bleeding risk","volume":"67","author":"Chen","year":"2024","journal-title":"Blood Rev"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1788532\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:25:46Z","timestamp":1775795146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1788532\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":46,"alternative-id":["10.3389\/fonc.2026.1788532"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1788532","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"article-number":"1788532"}}