Pulmonary pharmacology & therapeutics最新文献

{"title":"Triple inhaled therapy in asthma: beliefs, behaviours and doubts.","authors":"Bagnasco D, Ansotegui I, Baiardini I, Benfante A, Bernstein Ja, Bikov A, Bondi B, Boulet Lp, Panaitescu C, Canonica Gw, H Chong-Neto, Dubuske L, R El-Owaidy, Ferraris M, Filipovic M, F J Gonzalez-Barcala, Guidos Fogelbach G, Ivancevich Jc, Jusufovic E, Kowal K, Lantieri F, Mahboub B, Mihaicuta S, Mincarini M, Nedeva D, Novakova P, Novakova S, Nunes C, Ricchiuto Fr, Santus P, Scichilone N, Steiropoulos P, Tiotiu Cepuc A, Tomasello A, Virchow Jc, Yadav R, Zunino S, Braido F","doi":"10.1016/j.pupt.2024.102333","DOIUrl":"https://doi.org/10.1016/j.pupt.2024.102333","url":null,"abstract":"<p><p>Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma. With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023. Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed. Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7% specialists consider ITT as a relevant therapeutic option, 61.8% that is second option after reaching high dose of ICS-LABA and 89.2% agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response. Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice.</p>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":" ","pages":"102333"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688597","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":"Prevalence and clinical significance of pre- and post-bronchodilator airflow obstruction in COPD patients","authors":"Hyun Woo Lee ,&nbsp;Jung-Kyu Lee ,&nbsp;Youlim Kim ,&nbsp;June Hong Ahn ,&nbsp;Chang Youl Lee ,&nbsp;Yong Bum Park ,&nbsp;Hyoung Kyu Yoon ,&nbsp;Ji Ye Jung ,&nbsp;Kwang Ha Yoo ,&nbsp;Deog Kyeom Kim","doi":"10.1016/j.pupt.2024.102332","DOIUrl":"10.1016/j.pupt.2024.102332","url":null,"abstract":"<div><h3>Background</h3><div>Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation. This study investigates the prevalence and clinical significance of pre-bronchodilator (PREO) and post-bronchodilator (POSTO) airflow obstruction in COPD.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analyzed data from 3252 COPD patients aged ≥40 years, registered from January 2012 to December 2019 at 54 medical centers in South Korea. Patients were categorized into three groups: PREO &amp; post-bronchodilator non-obstruction (POSTN), pre-bronchodilator non-obstruction (PREN) &amp; POSTO, and PREO &amp; POSTO. The primary outcome was moderate-to-severe exacerbation over 3 years. Secondary outcomes included GOLD group progression and rapid FEV₁ decline.</div></div><div><h3>Results</h3><div>The majority of patients (96.2 %) were in the PREO &amp; POSTO group, with smaller proportions in the PREO &amp; POSTN (2.8 %) and PREN &amp; POSTO (1.0 %) groups. During the 3-year observation, 21.6 % of patients experienced moderate-to-severe exacerbations, 6.2 % exhibited GOLD group progression, and 20.0 % showed rapid FEV₁ decline. The PREO &amp; POSTO group had a higher risk of exacerbations compared to the PREO &amp; POSTN group (odds ratio = 8.33 [95 % CI = 1.53–45.4], <u>P-value = 0.014</u>), but this was not statistically significant in multivariable analysis. Post-bronchodilator spirometry patterns did not significantly impact GOLD group progression or FEV₁ decline.</div></div><div><h3>Conclusion</h3><div><u>PREO &amp; POSTO was common among COPD patients, while isolated PREO &amp; POSTN was rare,</u> supporting<u>pre-bronchodilator spirometry as a screening tool.</u> Although patients with PREO &amp; POSTO showed higher exacerbation risks <u>in univariable analysis, statistical significance disappeared</u> after adjustment. GOLD group progression or FEV₁ decline did not significantly differ by post-bronchodilator spirometry patterns.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102332"},"PeriodicalIF":3.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648792","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":"Interaction between fluticasone furoate and umeclidinium in passively sensitized isolated human airways","authors":"Maria Gabriella Matera ,&nbsp;Luigino Calzetta ,&nbsp;Barbara Rinaldi ,&nbsp;Carmela Belardo ,&nbsp;Francesco Facciolo ,&nbsp;Filippo Tommaso Gallina ,&nbsp;Clive P. Page ,&nbsp;Mario Cazzola ,&nbsp;Paola Rogliani","doi":"10.1016/j.pupt.2024.102331","DOIUrl":"10.1016/j.pupt.2024.102331","url":null,"abstract":"<div><div>Asthma management often includes inhaled corticosteroids (ICSs), with additional controllers like long-acting muscarinic antagonists (LAMAs) for severe cases. The primary goal of this study was to investigate the pharmacological interaction between various concentrations of fluticasone furoate (FF) and umeclidinium (UME) in isolated human airways to determine the nature of their interaction, whether synergistic or additive. Medium bronchi and small airways obtained from patients undergoing lobectomy were passively sensitized to mimic asthmatic conditions. The effects of FF and UME, alone and in combination, on airway relaxation were evaluated using histamine-induced contraction and electrical field stimulation. Pharmacological interactions were analyzed using the Bliss Independence theory. Results indicated that FF induced a partial, concentration-dependent relaxation of sensitized airways, while UME induced a larger relaxation in medium bronchi but a weaker effect in small airways. The combination of FF and UME resulted in significantly greater relaxation than either drug alone, demonstrating synergism at high concentrations in medium bronchi but only additive effects in small airways. This study suggests that higher doses of FF might be necessary in a fixed dose combination to achieve optimal synergistic bronchodilation with UME. Future research should focus on clinical trials to confirm these findings and explore the molecular mechanisms underlying these interactions, potentially improving personalized asthma therapy.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102331"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406808","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":"Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial","authors":"Anders Kjellberg ,&nbsp;Allan Zhao ,&nbsp;Anna Lussier ,&nbsp;Adrian Hassler ,&nbsp;Sarah Al-Ezerjawi ,&nbsp;Emil Boström ,&nbsp;Sergiu-Bogdan Catrina ,&nbsp;Peter Bergman ,&nbsp;Kenny Alexandra Rodriguez-Wallberg ,&nbsp;Peter Lindholm","doi":"10.1016/j.pupt.2024.102330","DOIUrl":"10.1016/j.pupt.2024.102330","url":null,"abstract":"<div><div>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.</div><div>In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.</div><div>Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p &lt; 0.001) and PaO₂/FiO₂ was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p &lt; 0.01).</div><div>We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.</div></div><div><h3>Trial registration</h3><div>NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102330"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406807","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":"Chest CT assess the impact of omalizumab treatment on airway remodeling in refractory asthma","authors":"Honglei Shi ,&nbsp;Zehu Chen ,&nbsp;Qianqian Lei ,&nbsp;Donghai Ma ,&nbsp;Meizhu Chen ,&nbsp;Jing Liu","doi":"10.1016/j.pupt.2024.102329","DOIUrl":"10.1016/j.pupt.2024.102329","url":null,"abstract":"<div><h3>Background</h3><div>To evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT.</div></div><div><h3>Methods</h3><div>This is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT.</div></div><div><h3>Results</h3><div>This study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p &lt; 0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p &lt; 0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p &lt; 0.05). ④After medication, the expression of airway mucous plugs decreased.</div></div><div><h3>Conclusions</h3><div>Omalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment.</div></div><div><h3>Trial registration</h3><div>This study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102329"},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378215","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":"Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience","authors":"E. Fragoso ,&nbsp;R. Boaventura ,&nbsp;L. Almeida ,&nbsp;A. Amorim ,&nbsp;F. Gamboa ,&nbsp;A.S. Santos ,&nbsp;F. Gonçalves ,&nbsp;C.M. Cruz ,&nbsp;A. Carreiro ,&nbsp;A.S. Gonçalves ,&nbsp;V. Teixeira ,&nbsp;P. Azevedo","doi":"10.1016/j.pupt.2024.102328","DOIUrl":"10.1016/j.pupt.2024.102328","url":null,"abstract":"<div><h3>Background</h3><p>Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 <em>F508del-CFTR</em> allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.</p></div><div><h3>Methods</h3><p>Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.</p></div><div><h3>Results</h3><p>132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the <em>F508del</em> variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV₁ was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV₁ was +0.46L (95 % CI: 0.37, 0.55; p &lt; 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p &lt; 0.001). PEx episodes decreased by 78 % (p &lt; 0.001) and hospitalizations for PEx decreased by 91.4 % (p &lt; 0.001). Body mass index (BMI) increased 1.2 kg/m² (95 % CI: 0.9, 1.5; p &lt; 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p &lt; 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.</p></div><div><h3>Conclusions</h3><p>ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102328"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272570","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":"Lipid nanoparticles for pulmonary fibrosis: A comprehensive review","authors":"Tushar Kanti Dhara,&nbsp;Sayak Khawas,&nbsp;Neelima Sharma","doi":"10.1016/j.pupt.2024.102319","DOIUrl":"10.1016/j.pupt.2024.102319","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a fatal progressive and irreversible ailment associated with the proliferation of fibroblast and accumulation of extracellular matrix (ECM) with gradual scarring of lung tissue. Despite several research studies, the treatments available are not efficient enough for the reversal of the disease and are constantly in progress. No drugs other than Pirfenidone and Nintedanib have been approved for the treatment of IPF, necessitating the exploration of novel therapeutic strategies. Recently, lipid-based nanoparticles (LNPs) have drawn more attention because of their potential to enhance the solubility of drugs, cross biological barriers of the lungs and specifically target lung fibrotic tissues, overcoming various challenges in treating IPF. LNPs offer a versatile platform to encapsulate a wide range of drugs, both hydrophilic and lipophilic, improving their bioavailability, allowing sustained release and reducing toxicity, which radiates their significant role in addressing the complexities of IPF. This review summarizes the pathogenesis and conventional treatment of idiopathic pulmonary fibrosis, along with their drawbacks. The review focuses on different types of lipid-based nanoparticles that have been tested in the treatment of idiopathic pulmonary fibrosis, including nanoemulsions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, niosomes and lipid-polymer hybrid nanoparticles. The review also highlights the future prospects that can offer a potential approach for developing novel strategies to treat idiopathic pulmonary fibrosis.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102319"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111375","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":"Ensifentrine approval: A milestone in the treatment of COPD","authors":"Luigino Calzetta ,&nbsp;Paola Rogliani","doi":"10.1016/j.pupt.2024.102318","DOIUrl":"10.1016/j.pupt.2024.102318","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102318"},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018427","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":"FTO promotes gefitinib-resistance by enhancing PELI3 expression and autophagy in non-small cell lung cancer","authors":"Yu-Zheng He ,&nbsp;Xiao-Ning Li ,&nbsp;Hai-Tao Li ,&nbsp;Xian-Hua Bai ,&nbsp;Yan-Chao Liu ,&nbsp;Fan-Nian Li ,&nbsp;Bao-Lei Lv ,&nbsp;Tian-Jie Qi ,&nbsp;Xiu-Min Zhao ,&nbsp;Shuai Li","doi":"10.1016/j.pupt.2024.102317","DOIUrl":"10.1016/j.pupt.2024.102317","url":null,"abstract":"<div><p>The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated <em>in vitro</em> and <em>in vivo</em>. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102317"},"PeriodicalIF":3.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000600","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":"Applicability of mouse models for induction of severe acute lung injury","authors":"Ana Paula Ferreira Leal ,&nbsp;Valentina Nieto Marín ,&nbsp;Vinícius Varzim Cabistany ,&nbsp;Júlia Morales ,&nbsp;Danieli Fernanda Buccini ,&nbsp;Octávio Luiz Franco","doi":"10.1016/j.pupt.2024.102316","DOIUrl":"10.1016/j.pupt.2024.102316","url":null,"abstract":"<div><p>Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as <em>Pseudomonas aeruginosa</em>, <em>Mycobacterium tuberculosis</em>, and <em>Streptococcus pneumoniae</em>, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102316"},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788934","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}