Pulmonary pharmacology & therapeutics最新文献

{"title":"A retrospective review of concurrent versus sequential administration of intrapleural tissue plasminogen activator and dornase alfa for empyemas","authors":"Katharine B. Strickland ,&nbsp;Jaclyn M. Hawn ,&nbsp;Shawn Leverett ,&nbsp;Carolyn Magee Bell","doi":"10.1016/j.pupt.2025.102359","DOIUrl":"10.1016/j.pupt.2025.102359","url":null,"abstract":"<div><h3>Background</h3><div>Intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) administered sequentially, separated by a one to 2 h interval, is a mainstay of pleural infection treatment. Recent literature supports similar efficacy and safety of concurrent therapy (administered immediately after one another). Insufficient evidence are available to utilize concurrent therapy routinely.</div></div><div><h3>Objective</h3><div>The primary objective of this study was to assess the safety and effectiveness of concurrent versus sequential intrapleural tPA and DNase in pleural infections.</div></div><div><h3>Methods</h3><div>This was a single-center, retrospective study of patients ≥18 years old admitted to the inpatient setting who received either concurrent or sequential intrapleural tPA or DNase between July 1, 2014, and January 1, 2023. The primary outcome was treatment failure, a composite of 30-day mortality and requirement for a video-assisted thoracoscopic surgery (VATS). Secondary outcomes included cumulative pleural fluid drainage, bleeding adverse events, and pain requiring analgesia dose escalation.</div></div><div><h3>Results</h3><div>A total of 184 patients were included: 158 patients in the concurrent group and 26 patients in the sequential group. Treatment failure was similar between groups (18.4 % vs 19.2 %, P &gt; 0.99). Increased pleural fluid drainage occurred in the concurrent versus sequential therapy group (1453 mL vs 836 mL, P = 0.05) with no differences in bleeding (23.4 % vs 19.2 %, P = 0.64) or analgesia dose escalation between groups (41.1 % vs 23.1 %, P = 0.09).</div></div><div><h3>Conclusion and Relevance</h3><div>Concurrent intrapleural fibrinolytics have similar effectiveness and safety compared to sequential administration however, further investigation into the compatibility and stability of the medications is warranted to optimize future pleural infection management.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102359"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The low global warming potential propellant HFA-152a does not induce bronchoconstriction or impair mucociliary clearance","authors":"Michela Salvadori ,&nbsp;Dave Singh ,&nbsp;Kusum Mathews ,&nbsp;Luca Girardello ,&nbsp;Mauro Cortellini ,&nbsp;Aida Emirova ,&nbsp;Ilaria Pacchetti ,&nbsp;Martina Foti ,&nbsp;Veronica Puviani ,&nbsp;Gianluigi Poli ,&nbsp;François Rony","doi":"10.1016/j.pupt.2025.102358","DOIUrl":"10.1016/j.pupt.2025.102358","url":null,"abstract":"<div><h3>Introduction</h3><div>Use of propellants with high global warming potential (e.g., HFA-134a) for pressurised metered-dose inhalers is being phased down. An alternative is reformulation using propellants with low global warming potential (e.g., HFA-152a), which requires evaluation of the propellant's safety, in particular whether it induces bronchoconstriction or impairs mucociliary clearance (MCC). In this manuscript, we describe two studies, the first comparing the bronchoconstriction potential of HFA-152a vs HFA-134a, the second comparing their effect on MCC.</div></div><div><h3>Methods</h3><div>The bronchoconstriction study was single-dose, randomised, double-blind, controlled, crossover, in adults with asthma. The primary endpoint was relative change from baseline in forced expiratory volume in 1 s (FEV₁) at 15 min post-dose.</div><div>The MCC study was multiple-dose (8 days), randomised, open-label, controlled, crossover, in healthy volunteers. The primary endpoint was percent particle retention in the right whole lung at 2 and 4 h after inhalation of radiolabelled particles (PPR₂ and PPR₄).</div></div><div><h3>Results</h3><div>For the bronchoconstriction study (N = 25), the 95 % CI of the adjusted mean FEV₁ difference between HFA-152a vs HFA-134a at 15 min post-dose was within the −10 % to +10 % equivalence limit (1.86 % [95 % CI –0.48 %, 4.20 %]; p = 0.113). Treatment-emergent adverse events were reported by 4.0 % (HFA-152a) and 12.0 % (HFA-134a) patients, all mild or moderate in intensity, and none serious.</div><div>For the MCC study (N = 20), the 95 % CIs for the adjusted mean differences between HFA-152a vs HFA-134a at Day 8 contained 0 for both PPR₂ (1.36 [–2.28, 4.99]%; p = 0.442) and PPR₄ (0.70 [–1.73, 3.12]%; p = 0.553). A similar proportion of subjects had treatment-emergent adverse events (25.0 % vs 35.0 %), all mild in intensity, and none serious.</div></div><div><h3>Conclusions</h3><div>These two studies suggest a switch in propellant from HFA-134a to HFA-152a is unlikely to induce post-dose bronchoconstriction in asthma or impact lung MCC, and is not accompanied by any safety concerns.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102358"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled vs. intravenous vasodilators in perioperative pulmonary hypertension during chest surgery using cardiopulmonary bypass: A systematic review and meta-analysis","authors":"Yasuhiro Ogura ,&nbsp;Eriya Imai ,&nbsp;Shunsuke Taito ,&nbsp;Tatsuya Tsuji ,&nbsp;Yuji Kamimura ,&nbsp;Takahiro Tsuge ,&nbsp;Kenichi Amano","doi":"10.1016/j.pupt.2025.102357","DOIUrl":"10.1016/j.pupt.2025.102357","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102357"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact on beclometasone dipropionate pharmacokinetics when switching to a low global warming potential propellant in a pressurised metered-dose inhaler","authors":"François Rony ,&nbsp;Maria Gloria Pittelli ,&nbsp;Cristina Contursi ,&nbsp;Ilaria Pacchetti ,&nbsp;Emanuele Rocco Calabrò ,&nbsp;Luca Vittorio Viganò ,&nbsp;Kusum S. Mathews ,&nbsp;Gianluigi Poli ,&nbsp;Katrin Van Leuven ,&nbsp;Matteo Martini","doi":"10.1016/j.pupt.2025.102356","DOIUrl":"10.1016/j.pupt.2025.102356","url":null,"abstract":"<div><h3>Introduction</h3><div>Use of high global warming potential propellants (e.g., HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Beclometasone dipropionate (BDP) is approved for the treatment of asthma in several countries via an HFA-134a propellant pMDI. This is being reformulated using the low global warming potential propellant HFA-152a. Two studies compared BDP pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.</div></div><div><h3>Methods</h3><div>Both studies (N = 71/study) were single-dose (four inhalations of BDP), randomised, double-blind, crossover (Study 1, four-way; Study 2, two-way), in healthy volunteers. In Study 1, subjects inhaled BDP via HFA-134a pMDI in two periods (200 μg/actuation in one period, 100 μg/actuation in the other) and HFA-152a pMDI in the other two (200 or 100 μg/actuation). In Study 2, subjects inhaled BDP 200 μg/actuation via HFA-134a or HFA-152a pMDI using a spacer device.</div><div>pMDIs containing HFA-152a and HFA-134a were compared in terms of lung availability (BDP comparisons) and total systemic exposure (beclometasone-17-monopropionate comparisons [B17MP; active metabolite of BDP]), with bioequivalence concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios of maximum plasma concentration (C_max) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC_0–t) were between 80 and 125 %.</div></div><div><h3>Results</h3><div>BDP C_max and AUC_0-t were equivalent for the two BDP 200 μg formulations, without (Study 1) and with spacer (Study 2). BDP 100 μg AUC_0-t met the bioequivalence criteria, but the C_max lower 90 % CI was marginally below the bioequivalence limit (79.46 %). B17MP C_max and AUC_0-t were bioequivalent with both propellants in all three comparisons.</div></div><div><h3>Conclusions</h3><div>Overall, bioequivalence was confirmed of HFA-152a and HFA-134a for BDP 200 μg/actuation, with and without a spacer. Although bioequivalence of the two formulations cannot be formally concluded for BDP 100 μg, the minimal difference suggests the two formulations can be considered therapeutically equivalent.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102356"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel synergistic therapeutic approach in idiopathic pulmonary fibrosis: Combining the antifibrotic nintedanib with the anti-inflammatory baricitinib","authors":"Qin Wan ,&nbsp;Dongdong Li ,&nbsp;Shu Shang ,&nbsp;Haifeng Wu ,&nbsp;Faxiu Chen ,&nbsp;Qiugen Li","doi":"10.1016/j.pupt.2025.102346","DOIUrl":"10.1016/j.pupt.2025.102346","url":null,"abstract":"<div><h3>Background</h3><div>Baricitinib and nintedanib can target inflammation and fibrosis respectively, which are the two most important processes in idiopathic pulmonary fibrosis (IPF). However, it is still unknown whether targeting these two processes simultaneously can synergistically improve the therapeutic effect of IPF. Therefore, it is necessary to predict the possible translational potential through preclinical studies.</div></div><div><h3>Methods</h3><div>We evaluated both the <em>in vitro</em> and <em>in vivo</em> efficacy of a drug combination, nintedanib with baricitinb, a JAK1/JAK2 inhibitor. We first examined the fibroblast proliferation and myofibroblast differentiation of single agents or combinations by the MTT assay. Then we determined the migration of the fibroblasts by a wound healing assay. Meanwhile, we quantified the protein level of related growth factor or cytokines in the cell supernatant by ELISA. Finally, we investigated the therapeutic potential and mechanism in a bleomycin-induced mouse model.</div></div><div><h3>Results</h3><div>Our results showed that the combination of nintedanib and baricitinib was more effective in suppressing fibroblast proliferation, myofibroblast transformation and fibroblast migration compared to either agent alone. In a bleomycin-induced IPF mouse model, the combination therapy resulted in a higher survival rate, increased body weight, and a lower lung/body weight ratio compared to the individual drugs. Moreover, both drugs improved lung functions in mice, but their combined administration led to superior outcomes. Histopathological analysis also revealed that the combination therapy mitigated pulmonary inflammation and fibrosis to a greater extent than the individual compounds. Mechanistically, baricitinib appears to orchestrate the effects of nintedanib in IPF by modulating the expression of genes such as <em>il-6</em>, <em>tgf-β</em>, <em>col1α1</em> and <em>fibronectin</em>.</div></div><div><h3>Conclusion</h3><div>The synergistic targeting of inflammation by baricitinib and fibrosis by nintedanib preclinically improves IPF outcomes, thus suggesting their potential as a novel combination therapy for this condition.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102346"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat","authors":"Elena Pistocchini ,&nbsp;Alicia Maria Carrillo Heredero ,&nbsp;Melissa Mazan ,&nbsp;Laurent Couetil ,&nbsp;Simone Bertini ,&nbsp;Luigino Calzetta","doi":"10.1016/j.pupt.2024.102342","DOIUrl":"10.1016/j.pupt.2024.102342","url":null,"abstract":"<div><div>Equine asthma, a prevalent chronic inflammatory condition affecting the equine population, significantly compromises the performance and quality of life in affected horses. Inhaled corticosteroids (ICS) are often the first-line pharmacological intervention due to their potent anti-inflammatory properties. This meta-analysis investigates the clinical efficacy of ICS in treating equine asthma, emphasizing the number needed to treat (NNT) and the likelihood of achieving a clinical response. A comprehensive literature search identified relevant studies comparing ICS with placebo (PCB) controlled treatments. Data were synthesized from four clinical trials involving 252 asthmatic horses. Results indicate an overall NNT of 3.2 (95 % CI 2.3–4.7), meaning that approximately three horses must be treated with ICS for one to achieve a significant clinical response. Additionally, the relative risk of achieving clinical improvement with ICS versus PCB was 1.73 (95 % CI 1.47–2.02), demonstrating a marked increase in therapeutic effectiveness. Subgroup analysis revealed an NNT of 3.0 for severe cases, underscoring the efficacy of ICS across different severity levels. Despite potential biases noted in some studies, sensitivity analyses confirmed the robustness of these findings. The GRADE assessment rated the quality of evidence as high. These results highlight the therapeutic value of ICS in managing equine asthma, providing evidence-based recommendations for their clinical use. Future research should explore long-term outcomes and potential synergistic effects of ICS combined with other treatments to enhance clinical efficacy in managing equine asthma.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102342"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat” [Pulm. Pharmacol. Therapeut. (88), March 2025, 102342]","authors":"Elena Pistocchini ,&nbsp;Alicia Maria Carrillo Heredero ,&nbsp;Melissa Mazan ,&nbsp;Laurent Couetil ,&nbsp;Simone Bertini ,&nbsp;Luigino Calzetta","doi":"10.1016/j.pupt.2024.102343","DOIUrl":"10.1016/j.pupt.2024.102343","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102343"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-life impact of genotype and severity of lung disease on efficacy of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis","authors":"Shahid Sheikh ,&nbsp;Melissa Holtzlander ,&nbsp;Mariah Eisner ,&nbsp;Courtney Gushue ,&nbsp;Sabrina Palacios ,&nbsp;Kavitha Kotha ,&nbsp;Sehyr Imran ,&nbsp;Karen S. McCoy","doi":"10.1016/j.pupt.2025.102345","DOIUrl":"10.1016/j.pupt.2025.102345","url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor-tezacaftor-ivacaftor (ETI) therapy has shown improvement in lung function, BMI and reduction in pulmonary exacerbations but the impact of genotype and severity of lung disease on heterogeneity of ETI efficacy in real life is not known.</div></div><div><h3>Methods</h3><div>This is a prospective observational study. Clinical data at baseline and at one-year of therapy were compared for the total cohort and for two subgroups; genotype [homozygous vs. heterozygous for F508del], and severity of lung disease at ETI initiation (ppFEV₁ &lt;80 % vs. ≥80 %).</div></div><div><h3>Results</h3><div>Among the total cohort of 115 pwCF, median age of 23 (17, 32) years, 66 (58 %) were homozygous, 76 (66 %) had ppFEV₁ &lt;80 %. Significant increases in mean ppFEV₁ and mean BMI and decrease in MRSA and Pa culture positivity on sputum/throat swab were observed at one year of ETI therapy in the total cohort, and in groups based on either genotype or disease severity (p &lt; 0.05 in all). Comparing one-year prior to one-year on ETI therapy, significant improvements were noted in pulmonary exacerbations, hospital admissions, antibiotic courses, number of pwCF receiving daily chest therapy, dornase alfa and hypertonic saline in the total cohort and in all four subgroups (p &lt; 0.05 for all). Though improvements were not dependent on genotype, we noted larger mean differences in ppFEV₁, BMI, pulmonary exacerbations and antibiotic use in the group with more severe lung disease (ppFEV₁ &lt;80 %) after one year of ETI therapy.</div></div><div><h3>Conclusion</h3><div>ETI therapy improved clinical outcomes in pwCF which were impacted by severity of underlying lung disease.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102345"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-10RA promotes lung cancer cell proliferation by increasing fatty acid oxidation via STAT3 signaling pathway","authors":"Wei Du ,&nbsp;Yuqing Ouyang ,&nbsp;Xiaofan Feng ,&nbsp;Chunyan Yu,&nbsp;Haoke Zhang,&nbsp;Siqi Chen,&nbsp;Zixuan Liu,&nbsp;Bo Wang,&nbsp;Xueying Li,&nbsp;Zihe Liu,&nbsp;Weimin Deng","doi":"10.1016/j.pupt.2025.102344","DOIUrl":"10.1016/j.pupt.2025.102344","url":null,"abstract":"<div><div>Metabolic reprogramming in tumor cells plays a crucial role in promoting cell proliferation and metastasis, and is currently recognized as a significant marker of tumor progression. Interleukin-10 receptor subunit alpha (IL-10RA), a member of the type II cytokine receptor family, is predominantly expressed on macrophages and T cells and plays a crucial role in regulating immune cell metabolism and immune response. However, its role in the energy metabolic pathways of tumor cells remains unclear. In this study, we found increased expression of IL-10RA in human non-small cell lung cancer (NSCLC), and a correlation between increased IL-10RA expression and tumor stage, tumor size, and short overall survival of patients with NSCLC. IL-10RA overexpression significantly promoted the proliferation of NSCLC cell lines and enhanced glycolysis and fatty acid oxidation (FAO), thereby boosting energy production. Correspondingly, the downregulation of IL-10RA inhibited proliferation, glycolysis, and FAO in NSCLC cell lines. Bioinformatic analyses indicated that IL-10RA upregulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. STAT3 inhibitor effectively blocked the increase in FAO levels and cell proliferation induced by IL-10RA overexpression. These findings suggest that IL-10RA accelerates NSCLC cell proliferation by increasing FAO levels via the STAT3 pathway, highlighting IL-10RA as a potential therapeutic target for NSCLC.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102344"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific domain antibody attenuates airway hyperresponsiveness and pulmonary inflammation in ovalbumin-lipopolysaccharide induced asthma model by inhibiting IL-23 and TNF-α","authors":"Chirag Ketan Gala ,&nbsp;Sandeep ,&nbsp;Abhay H. Pande ,&nbsp;Shyam Sunder Sharma","doi":"10.1016/j.pupt.2025.102347","DOIUrl":"10.1016/j.pupt.2025.102347","url":null,"abstract":"<div><div>Asthma, a chronic multi-factorial pulmonary inflammatory condition with a high morbidity rate, is characterized by airway hyperresponsiveness and persistent pulmonary inflammation. There is a need to develop more effective treatment(s) for the management of asthma. In this study, we have investigated the therapeutic potential of BiSpekDAb (an engineered bispecific antibody comprising an anti-IL-23 domain antibody and an anti-TNF-α domain antibody fused together via flexible linkers to a half-life extension partner) in asthma. Asthma was established by sensitization and challenge of female Wistar rats with the combination of ovalbumin and lipopolysaccharide and the efficacy of BiSpekDAb was investigated by its subcutaneous administration for 11 days on each alternative day (6 doses) during the challenge phase. Significant deterioration of pulmonary functions, enhanced airway hyperresponsiveness, increase in the number of immune cells such as lymphocytes, eosinophils, neutrophils in blood circulation as well as in lungs, enhanced production of inflammatory cytokines (IL-23, TNF-α, IL-1β, IL-6, IL-22), allergic IgE antibodies, oxidative stress markers, and histopathological changes (thickening of epithelial lining, infiltration of immune cells, mast cell degranulation, and overproduction of mucus) were observed in asthma animals, and administration of BiSpekDAb attenuated airway hyperresponsiveness (AHR), pulmonary inflammation and other pathological changes. BiSpekDAb significantly inhibited IL-23 and TNF-α levels in the lungs of asthmatic rats. Our results suggest that targeting IL-23 and TNF-α simultaneously opens a new therapeutic window for biologics development aimed at mitigating pulmonary inflammation such as asthma.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102347"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}