{"doi":"10.1093/toxsci/kfae162","title":"Inhaled ozone induces distinct alterations in pulmonary function in models of acute and episodic exposure in female mice","abstract":"Ozone is an urban air pollutant known to cause lung injury and altered function. Using established models of acute (0.8 ppm, 3 h) and episodic (1.5 ppm, 2 h, 2 times/wk, 6 wk) inhalation exposure, we observed distinct structural changes in the lung; whereas acutely, ozone primarily disrupts the bronchiolar epithelial barrier, episodic exposure causes airway remodeling. Herein we examined how these responses altered pulmonary function. A SCIREQ small animal ventilator was used to assess lung function; impedance was used to conditionally model resistance and elastance. Episodic, but not acute ozone exposure reduced the inherent and frequency-dependent tissue recoil (elastance) of the lung. Episodic ozone also increased central and high-frequency resistance relative to air control after methacholine challenge, indicating airway hyperresponsiveness. Pressure-volume (PV)-loops showed that episodic ozone increased maximum lung volume, whereas acute ozone decreased lung volume. Episodic ozone-induced functional changes were accompanied by increases in alveolar circularization; conversely, minimal histopathology was observed after acute exposure. However, acute ozone exposure caused increases in total phospholipids, total surfactant protein D (SP-D), and low-molecular weight SP-D in bronchoalveolar lavage fluid. Episodic ozone exposure only increased total SP-D. These findings demonstrate that acute and episodic ozone exposure caused distinct alterations in surfactant composition and pulmonary function. Whereas loss in PV-loop area following acute ozone exposure is likely driven by increases in SP-D and inflammation, emphysematous pathology and airway hyperresponsiveness after episodic ozone appear to be the result of alterations in lung structure.","journal":"Toxicological Sciences","year":2025,"id":549970,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1115301,"name":"J. Meshanni","orcid":"0000-0002-1491-3594","position":1,"is_corresponding":false},{"id":928349,"name":"K. Vayas","orcid":null,"position":2,"is_corresponding":false},{"id":751487,"name":"Vasanthi R. Sunil","orcid":"0000-0003-1159-0926","position":3,"is_corresponding":false},{"id":329177,"name":"Jared Radbel","orcid":"0000-0002-3013-6270","position":4,"is_corresponding":false},{"id":304789,"name":"Jeffrey D. Laskin","orcid":"0000-0003-1603-7388","position":5,"is_corresponding":false},{"id":304790,"name":"Debra L. Laskin","orcid":"0000-0003-1832-7311","position":6,"is_corresponding":false},{"id":492158,"name":"Andrew J. Gow","orcid":"0000-0003-0876-5158","position":7,"is_corresponding":false},{"id":1445352,"name":"Jordan M. Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"39798125","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}