{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:46:24Z","timestamp":1785843984541,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Introduction: Permissive hypercapnia has become an integral component of lung-protective ventilation strategies during one-lung ventilation (OLV), particularly in thoracic surgery. Its potential immunomodulatory effects have attracted increasing interest; however, clinical evidence remains limited and inconsistent. The Aim: The primary objective was to evaluate the effects of permissive hypercapnia on inflammatory biomarkers in bronchoalveolar lavage fluid and serum during one-lung ventilation. The secondary objective was to assess the influence of different ventilation modes on these inflammatory responses. Methods: Forty patients undergoing elective lung surgery requiring OLV were prospectively enrolled and allocated to either a normocapnic (n = 20) or hypercapnic group (n = 20). BAL concentrations of TNF-\u03b1, IL-1\u03b2, IL-6, and IL-8 were measured before and after intervention. Serum IL-6, C-reactive protein (CRP), and leukocyte counts were also assessed. Outcome Measures: Primary outcome: Change in bronchoalveolar lavage (BAL) levels of preselected biomarkers for inflammation (TNF-\u03b1, IL-1\u03b2, IL-6, and IL-8) and in serum (IL-6, CRP, and WBC) between the normocapnic and hypercapnic groups during one-lung ventilation. Secondary outcome: Whether the inflammatory response differed according to the ventilation mode (pressure-controlled versus volume-controlled ventilation). Results: Baseline and post-intervention BAL concentrations of TNF-\u03b1, IL-1\u03b2, IL-6, and IL-8 were generally comparable between the hypercapnic and normocapnic groups. No significant differences were observed in post-intervention BAL concentrations of TNF-\u03b1, IL-1\u03b2, or IL-6 among the ventilated subgroups. However, post hoc analysis demonstrated significantly lower IL-8 concentrations in the hypercapnic-PC subgroup compared with the normocapnic-PC subgroup (p = 0.034). Within the normocapnic cohort, BAL IL-8 concentrations were significantly higher in the PC subgroup than in the VC subgroup (p = 0.012). In serum, postoperative IL-6 concentrations were significantly higher in the hypercapnic than in the normocapnic group (p = 0.003). Conclusions: Permissive hypercapnia was not associated with a reduction in BAL concentration of the pro-inflammatory cytokines TNF-\u03b1, IL-1\u03b2, IL-6, and IL-8. However, postoperative serum IL-6 concentrations were significantly higher in patients exposed to hypercapnia. As the duration of surgery, one-lung ventilation, and mechanical ventilation was longer in the hypercapnic group, the observed increase in serum IL-6 cannot be attributed solely to hypercapnia. Further large-scale randomized studies are required to clarify the immunological effects of permissive hypercapnia during thoracic surgery.<\/jats:p>","DOI":"10.3390\/metabo16080550","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:38:08Z","timestamp":1785839888000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-1937","authenticated-orcid":false,"given":"Milena","family":"Stojanovi\u0107","sequence":"first","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Vasilijic","sequence":"additional","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-6735","authenticated-orcid":false,"given":"Jelena","family":"Zivadinovic","sequence":"additional","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"},{"name":"School of Medicine, University of Nis, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Randjelovic","sequence":"additional","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"},{"name":"School of Medicine, University of Nis, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0600-5411","authenticated-orcid":false,"given":"Tatjana","family":"Jevtovic Stoimenov","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Nis, 18000 Ni\u0161, Serbia"},{"name":"Department for Biochemistry, School of Medicine, University of Nis, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radmilo","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Anaesthesia and Intensive Therapy, University Clinical Center Ni\u0161, 18000 Ni\u0161, Serbia"},{"name":"School of Medicine, University of Nis, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1213\/ANE.0000000000000808","article-title":"Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung","volume":"121","author":"Lohser","year":"2015","journal-title":"Anesth. 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