Pulmonary pharmacology & therapeutics最新文献

{"title":"NEK-mediated barrier regulation","authors":"Nektarios Barabutis","doi":"10.1016/j.pupt.2024.102313","DOIUrl":"10.1016/j.pupt.2024.102313","url":null,"abstract":"<div><p>Endothelial dysfunction has been associated with devastating outcomes which can eventually lead to permanent disability and death. Elucidation of the meticulously devised network orchestrating endothelial responses, provides information to develop new therapies towards endothelial-related disorders. NEK kinases - which have been involved in the development of human disease – promote vascular leak; suggesting the possibility that their inhibition may ameliorate medical conditions related to barrier derangement.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443200","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":"Unveiling the protective role of sevoflurane in video-assisted thoracoscopic surgery associated-acute lung injury: Inhibition of ferroptosis","authors":"Yang Zhang ,&nbsp;Tianming Zha ,&nbsp;Guoxin Song ,&nbsp;Gulibositan Abudurousuli ,&nbsp;Jinxin Che ,&nbsp;Fei Zhao ,&nbsp;Lin Zhang ,&nbsp;Xing Zhang ,&nbsp;Bo Gui ,&nbsp;Linjia Zhu","doi":"10.1016/j.pupt.2024.102312","DOIUrl":"10.1016/j.pupt.2024.102312","url":null,"abstract":"<div><p>Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe²⁺, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe²⁺ concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437382","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 involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway","authors":"Tingting Ying ,&nbsp;Yulong Yu ,&nbsp;Qimin Yu,&nbsp;Gang Zhou,&nbsp;Lingyang Chen,&nbsp;Yixiao Gu,&nbsp;Lijun Zhu,&nbsp;Haifeng Ying,&nbsp;Minjuan Chen","doi":"10.1016/j.pupt.2024.102303","DOIUrl":"10.1016/j.pupt.2024.102303","url":null,"abstract":"<div><h3>Background</h3><p>Interferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated.</p></div><div><h3>Methods</h3><p>Using lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an <em>in vivo</em> and <em>in vitro</em> model was established. <em>In vivo</em>, Sting agonists and inhibitors were administered, while <em>in vitro</em>, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1β, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the <em>in vivo</em> mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both <em>in vivo</em> and <em>in vitro</em>.</p></div><div><h3>Results</h3><p><em>In vitro</em> experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1β), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, <em>in vitro</em> experiments using HUVEC cell lines validated these findings.</p></div><div><h3>Conclusions</h3><p>Our study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288513","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":"Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats","authors":"Janiana Raíza Jentsch Matias de Oliveira ,&nbsp;Mayara Alves Amorim ,&nbsp;Vitor Hélio de Souza Oliveira ,&nbsp;Daniela de Almeida Cabrini ,&nbsp;Michel Fleith Otuki ,&nbsp;Claudia Martins Galindo ,&nbsp;Bruna Barbosa da Luz ,&nbsp;Maria Fernanda de Paula Werner ,&nbsp;João Batista Calixto ,&nbsp;Eunice André","doi":"10.1016/j.pupt.2024.102302","DOIUrl":"10.1016/j.pupt.2024.102302","url":null,"abstract":"<div><p>Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B₂ antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186760","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":"Pharmacokinetic variability of CFTR modulators from standard and alternative regimens","authors":"Natalie R. Rose,&nbsp;Ashritha R. Chalamalla,&nbsp;Bryan A. Garcia,&nbsp;Stefanie Krick,&nbsp;Jonathan Bergeron,&nbsp;Hossein Sadeghi,&nbsp;Dennis E. Schellhase,&nbsp;Kevin J. Ryan,&nbsp;Alexander E. Dowell,&nbsp;Edward P. Acosta,&nbsp;Jennifer S. Guimbellot","doi":"10.1016/j.pupt.2024.102301","DOIUrl":"10.1016/j.pupt.2024.102301","url":null,"abstract":"<div><p>Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154719","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":"Shedding light on vitamin D in tuberculosis: A comprehensive review of clinical trials and discrepancies","authors":"Alan Santos-Mena ,&nbsp;Oscar E. González-Muñiz ,&nbsp;Yolanda M. Jacobo-Delgado,&nbsp;Bruno Rivas-Santiago","doi":"10.1016/j.pupt.2024.102300","DOIUrl":"10.1016/j.pupt.2024.102300","url":null,"abstract":"<div><p>Over the past few decades, there has been extensive research on the use of vitamin D as an adjunctive therapy in the treatment and prevention of tuberculosis. In vitro studies have provided valuable insights into the mechanisms by which vitamin D activates the immune response to combat <em>Mycobacterium tuberculosis</em>. These encouraging findings have spurred clinical investigations globally to assess the effectiveness of vitamin D as a preventive measure and as an adjunctive treatment for tuberculosis. However, the results from these clinical studies have been contradictory, with some demonstrating clear efficacy while others report only modest or no activity. In this review, we aim to analyze the clinical studies on vitamin D and examine the possible discrepancies observed in their outcomes.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899425","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":"Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant","authors":"François Rony ,&nbsp;Mauro Cortellini ,&nbsp;Alessandro Guasconi ,&nbsp;Kusum S. Mathews ,&nbsp;Annalisa Piccinno ,&nbsp;Gianluigi Poli ,&nbsp;Frédéric Vanhoutte ,&nbsp;Jelle Klein","doi":"10.1016/j.pupt.2024.102299","DOIUrl":"10.1016/j.pupt.2024.102299","url":null,"abstract":"<div><h3>Introduction</h3><p>Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential.</p><p>The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.</p></div><div><h3>Methods</h3><p>The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer.</p><p>All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (C_max) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC_0–t) for the analytes were between 80 and 125 %.</p></div><div><h3>Results</h3><p>In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB C_max in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for C_max and 127.34 % for AUC_0–t). In Study 1, GB AUC_0–t lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for C_max and 129.12 % for AUC_0–t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC_0–t, although not for C_max. Both formulations were similarly well tolerated in all three studies.</p></div><div><h3>Conclusions</h3><p>Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/<span>FF</span>/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000154/pdfft?md5=574f99472df77217cdeedb51aa0e81c2&pid=1-s2.0-S1094553924000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776001","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":"Suboptimal peak inspiratory flow rate in dry-powder inhaler users for chronic obstructive pulmonary disease in Korea","authors":"Ji-Yong Moon ,&nbsp;Sang Hyuk Kim ,&nbsp;Youlim Kim ,&nbsp;Hyun Lee ,&nbsp;Chin Kook Rhee ,&nbsp;Seung Won Ra ,&nbsp;Chang Youl Lee ,&nbsp;Joo Hun Park ,&nbsp;Yong Bum Park ,&nbsp;Kwang Ha Yoo","doi":"10.1016/j.pupt.2024.102298","DOIUrl":"https://doi.org/10.1016/j.pupt.2024.102298","url":null,"abstract":"<div><h3>Background</h3><p>A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available.</p></div><div><h3>Methods</h3><p>We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device. Suboptimal PIFR was defined as below the resistance-matched threshold. Multivariable logistic regression analysis was used to determine factors associated with suboptimal PIFR.</p></div><div><h3>Results</h3><p>Of 444 DPI users with COPD, the rate of suboptimal PIFR was 22.0 % (98/444). In a multivariable analysis, significant factors associated with suboptimal PIFR were age (adjusted odds ratio [aOR] = 1.06 by 1-year increase; 95 % confidence interval [CI] = 1.02–1.09), male sex (aOR = 0.28; 95 % CI = 0.11–0.73), body mass index (BMI) (aOR = 0.91 by 1 kg/m² increase; 95 % CI = 0.85–0.99), post-bronchodilator forced vital capacity (FVC) %pred (aOR = 0.97 by 1%pred increase; 95 % CI = 0.95–0.99), and In-Check DIAL R2-type inhaler [medium-low resistance] use (aOR = 3.70 compared with R1-type inhalers [low resistance]; 95 % CI = 2.03–7.03).</p></div><div><h3>Conclusions</h3><p>In Korea, more than one-fifth of DPI users with COPD had a suboptimal PIFR. The factors associated with suboptimal PIFR were age, female gender, low BMI, low FVC, and R2-type inhaler use. Therefore, clinicians should carefully evaluate the possibility of suboptimal PIFR when prescribing DPIs.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000142/pdfft?md5=b93e2894d7969eaf9d3d3e9beac1d9f6&pid=1-s2.0-S1094553924000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618137","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":"The incidence and prognosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of the lung related to methotrexate: A retrospective study","authors":"Atsushi Torii ,&nbsp;Masahide Oki ,&nbsp;Hiroatsu Iida ,&nbsp;Arisa Yamada ,&nbsp;Yoshihito Kogure ,&nbsp;Chiyoe Kitagawa ,&nbsp;Hideo Saka","doi":"10.1016/j.pupt.2024.102297","DOIUrl":"10.1016/j.pupt.2024.102297","url":null,"abstract":"<div><h3>Background and objective</h3><p>Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung.</p></div><div><h3>Methods</h3><p>Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed.</p></div><div><h3>Results</h3><p>Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63–82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3–84.2] months).</p></div><div><h3>Conclusion</h3><p>The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102340","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":"Association between pre-ICU aspirin administration and ARDS mortality in the MIMIC-IV database: A cohort study","authors":"Yi Yu ,&nbsp;Dengcan Yang ,&nbsp;Qianqian Wang ,&nbsp;Jian Li","doi":"10.1016/j.pupt.2024.102288","DOIUrl":"10.1016/j.pupt.2024.102288","url":null,"abstract":"<div><h3>Background</h3><p>Acute Respiratory Distress Syndrome (ARDS) is a severe condition with high mortality and morbidity rates. Evidence on the effectiveness of pharmacological interventions for ARDS treatment is limited. Recent studies suggest that aspirin may prevent ARDS development, but its efficacy in established ARDS is uncertain.</p></div><div><h3>Methods</h3><p>We enrolled patients with ARDS using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Primary outcomes were 30- and 90-day mortality rates and length of ICU stay. We employed multivariable Cox regression and linear regression models for statistical analysis and used propensity score matching (PSM) to ensure robust results.</p></div><div><h3>Results</h3><p>The study included 10,042 participants with an average age of 61.8 ± 15.3 years. Kaplan–Meier analysis showed significantly lower 30- and 90-day mortality rates in patients treated with pre-ICU admission aspirin compared with non-aspirin use (<em>p</em> &lt; 0.0001). Multivariable Cox regression models revealed a significant 63% reduction in 30-day mortality for pre-ICU aspirin users (HR = 0.37, 95% CI: 0.31–0.44, <em>p</em> &lt; 0.001). Aspirin use in the ICU was associated with a 59% reduction in ICU mortality and a 0.68-day reduction in length of ICU stay (<em>p</em> &lt; 0.05). These findings consistently indicate that aspirin may improve survival in patients with ARDS, even after further stratification of aspirin use and PSM analysis.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that aspirin treatment before ICU admission is associated with significantly reduced 30- and 90-day mortality rates and decreased length of ICU stay in patients with ARDS.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068659","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}