3
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mitogen-activated protein kinase-guided drug discovery for post-viral and related types of lung disease

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Respiratory viral infections are a major public health problem, with much of their morbidity and mortality due to post-viral lung diseases that progress and persist after the active infection is cleared. This paradigm is implicated in the most common forms of chronic lung disease, such as asthma and COPD, as well as other virus-linked diseases including progressive and long-term coronavirus disease 2019. Despite the impact of these diseases, there is a lack of small-molecule drugs available that can precisely modify this type of disease process. Here we will review current progress in understanding the pathogenesis of post-viral and related lung disease with characteristic remodelling phenotypes. We will also develop how this data leads to mitogen-activated protein kinase (MAPK) in general and MAPK13 in particular as key druggable targets in this pathway. We will also explore recent advances and predict the future breakthroughs in structure-based drug design that will provide new MAPK inhibitors as drug candidates for clinical applications. Each of these developments point to a more effective approach to treating the distinct epithelial and immune cell based mechanisms, which better account for the morbidity and mortality of post-viral and related types of lung disease. This progress is vital given the growing prevalence of respiratory viruses and other inhaled agents that trigger stereotyped progression to acute illness and chronic disease.

          Shareable abstract

          This review covers progress on pathogenesis and consequent MAPK-guided treatment for post-viral and related types of lung disease, including asthma, COPD, and COVID-19. The advances refine a paradigm that features MAPK13 to control the disease process. https://bit.ly/49nzgRl

          Related collections

          Most cited references93

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

          Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            Persistent Symptoms in Patients After Acute COVID-19

            This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Susceptibility to exacerbation in chronic obstructive pulmonary disease.

              Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
                Bookmark

                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                31 January 2024
                28 February 2024
                : 33
                : 171
                : 230220
                Affiliations
                [1 ]Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
                [2 ]Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
                [3 ]NuPeak Therapeutics Inc., St. Louis, MO, USA
                Author notes
                Corresponding author: Michael J. Holtzman ( mjholtzman@ 123456wustl.edu )
                Article
                ERR-0220-2023
                10.1183/16000617.0220-2023
                10900067
                38417971
                17920a45-817b-490a-85e5-6056003843b2
                Copyright ©The authors 2024

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ 123456ersnet.org

                History
                : 27 October 2023
                : 18 January 2024
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases, doi 10.13039/100000060;
                Award ID: R01 AI130591
                Funded by: National Heart, Lung, and Blood Institute, doi 10.13039/100000050;
                Award ID: R35-HL145242
                Award ID: STTR R41-HL149523
                Award ID: UH2-HL123429
                Funded by: Hardy Research Fund
                Funded by: Harrington Discovery Institute, University Hospitals, doi 10.13039/100018576;
                Funded by: U.S. Department of Defense, doi 10.13039/100000005;
                Award ID: W81XWH2010603
                Award ID: W81XWH2210281
                Categories
                Lung Science Conference Reviews
                12

                Comments

                Comment on this article