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Waters V, Ratjen F. Reply to: Oral corticosteroids for cystic fibrosis pulmonary exacerbation: seeking the future in the past. Eur Respir J 2024; 64:2401577. [PMID: 39362682 DOI: 10.1183/13993003.01577-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 10/05/2024]
Affiliation(s)
- Valerie Waters
- Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Felix Ratjen
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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Haan BJ, Blackmon SN, Cobb AM, Cohen HE, DeVier MT, Perez MM, Winslow SF. Corticosteroids in critically ill patients: A narrative review. Pharmacotherapy 2024; 44:581-602. [PMID: 38872437 DOI: 10.1002/phar.2944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/15/2024] [Accepted: 05/15/2024] [Indexed: 06/15/2024]
Abstract
Corticosteroids have been utilized in modern medicine for decades. Many indications have been investigated across various treatment settings with both benefit and harm observed. Given the instability of critically ill patients, the increased risk of corticosteroid-related complications, and the pervasive comorbidities, patients who receive corticosteroids must be carefully managed. Common critical care disease states in which corticosteroids have been studied and are routinely utilized include acute respiratory distress syndrome, adrenal insufficiency, angioedema, asthma, chronic obstructive pulmonary disease, community-acquired pneumonia, coronavirus disease 2019, septic shock, and spinal cord injury. Benefits of corticosteroids include an improvement in disease state-specific outcomes, decreased hospital length of stay, decreased mechanical ventilatory support, and decreased mortality. The harm of corticosteroids is well documented through adverse effects that include, but are not limited to, hyperglycemia, tachycardia, hypertension, agitation, delirium, anxiety, immunosuppression, gastrointestinal bleeding, fluid retention, and muscle weakness. Furthermore, corticosteroids are associated with increased health care costs through adverse effects as well as drug acquisition and administration costs. Given the assortment of agents, dosing, benefits, risks, and utilization in the critical care setting, there may be difficulty with identifying the appropriate places for use of corticosteroids in therapy. There currently exists no comprehensive report detailing the use of corticosteroids in the aforementioned disease states within the critical care setting. This narrative review sets out to describe these in detail.
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Affiliation(s)
- Bradley J Haan
- Department of Pharmacy, Ascension Genesys Hospital, Grand Blanc, Michigan, USA
| | - Samantha N Blackmon
- Department of Pharmacy, Ascension St Vincent's Birmingham Hospital, Birmingham, Alabama, USA
| | - Alex M Cobb
- Department of Pharmacy, Ascension St. John Medical Center, Tulsa, Oklahoma, USA
| | - Heather E Cohen
- Department of Pharmacy, Ascension Illinois Metro Region, Chicago, Illinois, USA
| | - Margaret T DeVier
- Department of Pharmacy, Ascension Saint Thomas Hospital Midtown, Nashville, Tennessee, USA
| | - Mary M Perez
- Department of Pharmacy, Ascension St Vincent's Birmingham Hospital, Birmingham, Alabama, USA
| | - Samuel F Winslow
- Department of Pharmacy, Ascension Providence Hospital, Southfield, Michigan, USA
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Waters V, Shaw M, Perrem L, Quon BS, Tullis E, Solomon M, Rayment JH, Lavoie A, Tse SM, Daigneault P, Bilodeau L, Price A, Nicholson M, Chin M, Parkins M, McKinney ML, Tam JS, Stanojevic S, Grasemann H, Ratjen F. A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment. Eur Respir J 2024; 63:2302278. [PMID: 38697648 DOI: 10.1183/13993003.02278-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 04/05/2024] [Indexed: 05/05/2024]
Abstract
BACKGROUND Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 s (FEV1) % pred in CF pulmonary exacerbations not responding to antibiotic therapy. METHODS This was a randomised, double-blind, placebo-controlled trial in pwCF treated with intravenous antibiotics for a pulmonary exacerbation. At day 7, those who had not returned to >90% baseline FEV1 % pred were randomised to adjuvant prednisone 1 mg·kg-1 twice daily (maximum 60 mg·day-1) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline FEV1 % pred at day 14 of i.v. antibiotic therapy. RESULTS 173 subjects were enrolled, with 76 randomised. 50% of subjects in the prednisone group recovered baseline FEV1 on day 14 compared with 39% of subjects in the placebo group (difference of 11%, 95% CI -11-34%; p=0.34). The mean±sd change in FEV1 % pred from day 7 to day 14 was 6.8±8.8% predicted in the prednisone group and 4.6±6.9% predicted in the placebo group (mean difference 2.2% predicted, 95% CI -1.5-5.9%; p=0.24). Time to subsequent exacerbation was not prolonged in prednisone-treated subjects (hazard ratio 0.83, 95% CI 0.45-1.53; p=0.54). CONCLUSIONS This study failed to detect a difference in FEV1 % pred recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of i.v. antibiotic therapy for pulmonary exacerbations.
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Affiliation(s)
- Valerie Waters
- Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Michelle Shaw
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Lucy Perrem
- Department of Respiratory Medicine, Children's Health Ireland, Dublin, Ireland
| | - Bradley S Quon
- Division of Respiratory Medicine, Department of Medicine, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Elizabeth Tullis
- Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | - Melinda Solomon
- Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Jonathan H Rayment
- Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Annick Lavoie
- Division of Respiratory Medicine and Critical Care, Department of Medicine, Hotel Dieu Hospital, Montreal, QC, Canada
| | - Sze Man Tse
- Division of Respiratory Medicine, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada
| | - Patrick Daigneault
- Division of Respiratory Medicine, Department of Pediatrics, Centre Hospitalier de l'Université de Quebec, Quebec, QC, Canada
| | - Lara Bilodeau
- Division of Respiratory Medicine, Department of Medicine, Institut de l'Université de Cardiologie et Pneumologie de Quebec, Quebec, QC, Canada
| | - April Price
- Division of Respiratory Medicine, Department of Pediatrics, London Health Sciences Centre, London, ON, Canada
| | - Michael Nicholson
- Division of Respiratory Medicine, Department of Medicine, London Health Sciences Centre, London, ON, Canada
| | - Melanie Chin
- Division of Respiratory Medicine, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Michael Parkins
- Division of Respiratory Medicine, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Martha L McKinney
- Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - Julian S Tam
- Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Sanja Stanojevic
- Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada
| | - Hartmut Grasemann
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Felix Ratjen
- Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
- Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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Diaz Caballero LA, Aijaz A, Saleem Paryani N, Mahmood S, Salman M, Omer Khan M, Ahluwalia D, Arham Siddiq M, Hameed I. Comparing the efficacy of corticosteroids among patients with community-acquired pneumonia in the ICU versus non-ICU settings: A systematic review and meta-analysis. Steroids 2024; 205:109389. [PMID: 38354995 DOI: 10.1016/j.steroids.2024.109389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 12/05/2023] [Accepted: 02/07/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND Despite the potential of corticosteroids in treating community-acquired pneumonia (CAP), conflicting evidence exists regarding their effect on mortality. To address this gap and provide new insights, we conducted a pre-specified subgroup meta-analysis of corticosteroid use in CAP patients, focusing on the ICU versus non-ICU subsets. METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to May 2023 for randomized controlled trials (RCTs). The primary outcomes of interest were mortality, need for mechanical ventilation, need for ICU admission, and treatment failure. Secondary outcomes analysed were the need for hospital readmission, length of hospital stay, length of ICU stay, gastrointestinal (GI) bleeding, secondary infections, and hyperglycaemic events. The results were analysed through the random-effects model. A p-value < 0.05 was considered significant. RESULTS Eighteen randomized controlled trials (n = 4472) analyzing patients withCAP were included. Our results suggest that corticosteroids significantly reduced the incidence of mortality (RR: 0.66; 95 % CI: 0.54, 0.81; P = <0.0001) and need for mechanical ventilation (RR: 0.57; 95 % CI: 0.44, 0.73; P = <0.00001). It was also observed that corticosteroids significantly decrease the lengths of ICU (MD: -1.67; 95 % CI: -2.97, -0.37; P = 0.01) and hospital stay (MD: -1.94; 95 % CI: -2.89, -0.98; P = 0.0001), while increasing the number of hyperglycemic events (RR: 1.68; 95 % CI: 1.32, 2.12; P = <0.0001) and hospital readmissions (RR: 1.19; 95 % CI: 1.04, 1.37; P = 0.01). CONCLUSIONS The results of this meta-analysis demonstrate that corticosteroids yield improved outcomes in CAP patients with regard to reduced mortality and the need for mechanical ventilation. It highlights the need for further large-scale RCTs with the proposed, specific stratifications.
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Affiliation(s)
- Luis A Diaz Caballero
- Department of Pulmonary and Critical Care Medicine, Einstein Medical Center Philadelphia 5501 Old York Road, Philadelphia, PA, USA
| | - Ashnah Aijaz
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Neha Saleem Paryani
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Samar Mahmood
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Madiha Salman
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Mohammad Omer Khan
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Dayal Ahluwalia
- Department of Medicine, Einstein Medical Center Philadelphia 5501 Old York Road, Philadelphia, PA, USA
| | | | - Ishaque Hameed
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
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See XY, Wang TH, Chang YC, Lo J, Liu W, Choo CYW, Lee YC, Ma KSK, Chiang CH, Hsia YP, Chiang CH, Chiang CH. Impact of different corticosteroids on severe community-acquired pneumonia: a systematic review and meta-analysis. BMJ Open Respir Res 2024; 11:e002141. [PMID: 38262670 PMCID: PMC10806634 DOI: 10.1136/bmjresp-2023-002141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/09/2024] [Indexed: 01/25/2024] Open
Abstract
OBJECTIVES Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP. METHODS We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model. RESULTS A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I2=0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I2=0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia. CONCLUSIONS The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360.
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Affiliation(s)
- Xin Ya See
- Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York, USA
| | - Tsu Hsien Wang
- Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Foundation, New Taipei City, Taiwan
| | - Yu-Cheng Chang
- Department of Medicine, Danbury Hospital, Danbury, Connecticut, USA
| | - Juien Lo
- Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Weitao Liu
- Department of Medicine, Yale New Haven Hospital, New Haven, Connecticut, USA
| | | | - Yu-Che Lee
- Division of Pulmonary, Critical Care and Sleep Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Kevin Sheng Kai Ma
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Cho-Hsien Chiang
- Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yuan Ping Hsia
- Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Foundation, New Taipei City, Taiwan
| | - Cho-Hung Chiang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Cho-Han Chiang
- Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, USA
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Zhao L, Liu H, Wang Y, Wang S, Xun D, Wang Y, Cheng Y, Zhang B. Multimodal Identification by Transcriptomics and Multiscale Bioassays of Active Components in Xuanfeibaidu Formula to Suppress Macrophage-Mediated Immune Response. ENGINEERING (BEIJING, CHINA) 2023; 20:63-76. [PMID: 34815890 PMCID: PMC8601788 DOI: 10.1016/j.eng.2021.09.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/23/2021] [Accepted: 09/21/2021] [Indexed: 05/22/2023]
Abstract
Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 104 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma, Phragmitis Rhizoma, and Citri grandis Exocarpium rubrum, were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide I, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.
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Affiliation(s)
- Lu Zhao
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Hao Liu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yingchao Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Shufang Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Dejin Xun
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yi Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yiyu Cheng
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Boli Zhang
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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Alagheband Bahrami A, Azargoonjahromi A, Sadraei S, Aarabi A, Payandeh Z, Rajabibazl M. An overview of current drugs and prophylactic vaccines for coronavirus disease 2019 (COVID-19). Cell Mol Biol Lett 2022; 27:38. [PMID: 35562685 PMCID: PMC9100302 DOI: 10.1186/s11658-022-00339-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Designing and producing an effective vaccine is the best possible way to reduce the burden and spread of a disease. During the coronavirus disease 2019 (COVID-19) pandemic, many large pharmaceutical and biotechnology companies invested a great deal of time and money in trying to control and combat the disease. In this regard, due to the urgent need, many vaccines are now available earlier than scheduled. Based on their manufacturing technology, the vaccines available for COVID-19 (severe acute respiratory syndrome coronavirus 2 (SAR-CoV2)) infection can be classified into four platforms: RNA vaccines, adenovirus vector vaccines, subunit (protein-based) vaccines, and inactivated virus vaccines. Moreover, various drugs have been deemed to negatively affect the progression of the infection via various actions. However, adaptive variants of the SARS-CoV-2 genome can alter the pathogenic potential of the virus and increase the difficulty of both drug and vaccine development. In this review, along with drugs used in COVID-19 treatment, currently authorized COVID-19 vaccines as well as variants of the virus are described and evaluated, considering all platforms.
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Affiliation(s)
- Armina Alagheband Bahrami
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Samin Sadraei
- Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Aryan Aarabi
- Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Payandeh
- Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden
| | - Masoumeh Rajabibazl
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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8
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Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS. Pharmaceutics 2021; 13:pharmaceutics13122092. [PMID: 34959373 PMCID: PMC8703685 DOI: 10.3390/pharmaceutics13122092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/02/2021] [Accepted: 12/02/2021] [Indexed: 12/13/2022] Open
Abstract
Acute respiratory distress syndrome (ARDS) is a common complication of critical illness and remains a major source of morbidity and mortality in the intensive care unit (ICU). ARDS is characterised by diffuse lung inflammation, epithelial and endothelial deterioration, alveolar–capillary leak and oedema formation, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory activity of nitric-oxide-releasing dexamethasone derivative NCX-1005 as a potential novel drug for ARDS. Adult rabbits with lavage-induced ARDS were treated with dexamethasone i.v. (0.5 mg/kg; DEX) and nitro-dexamethasone i.v. (0.5 mg/kg, NCX-1005) or were untreated (ARDS). Controls represented healthy ventilated animals. The animals were subsequently oxygen-ventilated for an additional 4 h and respiratory parameters were recorded. Lung oedema, inflammatory cell profile in blood and bronchoalveolar lavage, levels of the cytokines (IL-1β, IL-6, IL-8, TNF-α), and oxidative damage (TBARS, 3NT) in the plasma and lung were evaluated. Nitric oxide-releasing dexamethasone derivative NCX-1005 improved lung function, reduced levels of cytokines, oxidative modifications, and lung oedema formation to similar degrees as dexamethasone. Only NCX-1005 prevented the migration of neutrophils into the lungs compared to dexamethasone. In conclusion, the nitric oxide-releasing dexamethasone derivative NCX-1005 has the potential to be effective drug with anti-inflammatory effect in experimental ARDS.
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Vidaeff AC, Aagaard KM, Belfort MA. Antenatal corticosteroids in COVID-19 perspective. World J Exp Med 2021; 11:37-43. [PMID: 34616665 PMCID: PMC8462011 DOI: 10.5493/wjem.v11.i4.37] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/23/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
The aim of this manuscript is to discuss the practice of antenatal corticosteroids administration for fetal maturation in severe acute respiratory syndrome coronavirus 2 positive pregnant women. Recent high-quality evidence supports the use of dexamethasone in the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Randomized disease outcome data have identified an association between disease stage and treatment outcome. In contrast to patients with more severe forms who benefit from dexamethasone, patients with mild disease do not appear to improve and may even be harmed by this treatment. Therefore, indiscriminate usage of fluorinated corticosteroids for fetal maturation, regardless of disease trajectory, is unadvisable. Obstetrical care needs to be adjusted during the COVID-19 pandemic with careful attention paid to candidate selection and risk stratification.
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Affiliation(s)
- Alex C Vidaeff
- Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Texas Children’s Hospital, Baylor College Medicine, Houston, TX 77030, United States
| | - Kjersti M Aagaard
- Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Texas Children’s Hospital, Baylor College Medicine, Houston, TX 77030, United States
| | - Michael A Belfort
- Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Texas Children’s Hospital, Baylor College Medicine, Houston, TX 77030, United States
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10
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Lin Z, Phyu WH, Phyu ZH, Mon TZ. The Role of Steroids in the Management of COVID-19 Infection. Cureus 2021; 13:e16841. [PMID: 34522487 PMCID: PMC8425064 DOI: 10.7759/cureus.16841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 08/02/2021] [Indexed: 12/23/2022] Open
Abstract
Steroids are anti-inflammatory drugs that have been utilized in a wide range of clinical illnesses, including rheumatologic, autoimmune, inflammatory, and numerous lung diseases. Because of the inhibition of the inflammatory cascade, corticosteroids are beneficial in many pulmonary disorders, including asthma, chronic obstructive pulmonary disease (COPD), laryngotracheobronchitis, interstitial lung diseases, severe pneumonia, and acute respiratory distress syndrome. We will report a case of a COVID-19 patient treated with remdesivir, antibiotics, and steroids. We will also discuss the role of steroids in the management of COVID-19 patients.
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Affiliation(s)
- Zayar Lin
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Wai Hnin Phyu
- Internal Medicine, University of Medicine 1, Yangon, MMR
| | - Zin Hnin Phyu
- Internal Medicine, University of Medicine 1, Yangon, MMR
| | - Tin Zar Mon
- Internal Medicine, Sakura Hospital, Yangon, MMR
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11
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Dai W, Lund H, Chen Y, Zhang J, Osinski K, Jones SZ, Kreuziger LB, López JA, Benjamin IJ, Silverstein RL, Zheng Z. Hypertriglyceridemia during hospitalization independently associates with mortality in patients with COVID-19. J Clin Lipidol 2021; 15:724-731. [PMID: 34470719 PMCID: PMC8353976 DOI: 10.1016/j.jacl.2021.08.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 06/14/2021] [Accepted: 08/02/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown. OBJECTIVE To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients. METHODS We conducted a retrospective study of 600 hospitalized patients with COVID-19 diagnosis (ICD10CM:U07.1) and/or SARS-CoV-2 positive testing results between March 1, 2020 and December 21, 2020 at a tertiary academic medical center in Milwaukee, Wisconsin. De-identified data, including demographics, medical history, and blood triglyceride levels were collected and analyzed. Of the 600 patients, 109 patients died. The triglyceride value on admission was considered the baseline and the peak was defined as the highest level reported during the entire period of hospitalization. Hypertriglyceridemia was defined as greater than 150 mg/dl. Logistic regression analyses were performed to evaluate the association between hypertriglyceridemia and mortality. RESULTS There was no significant difference in baseline triglyceride levels between non-survivors (n = 109) and survivors (n = 491) [Median 127 vs. 113 mg/dl, p = 0.213]. However, the non-survivors had significantly higher peak triglyceride levels during hospitalization [Median 179 vs. 134 mg/dl, p < 0.001]. Importantly, hypertriglyceridemia independently associated with mortality [odds ratio=2.3 (95% CI: 1.4-3.7, p = 0.001)], after adjusting for age, gender, obesity, history of hypertension and diabetes, high CRP, high leukocyte count and glucocorticoid treatment in a multivariable logistic regression model. CONCLUSIONS Hypertriglyceridemia during hospitalization is independently associated with 2.3 times higher mortality in COVID-19 patients. Prospective studies are needed to independently validate this retrospective analysis.
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Affiliation(s)
- Wen Dai
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA
| | - Hayley Lund
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Yiliang Chen
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Jue Zhang
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA
| | - Kristen Osinski
- Clinical & Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Lisa Baumann Kreuziger
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - José A López
- Department of Medicine, University of Washington, Seattle, WA, USA; Bloodworks Research Institute, Seattle, WA, USA
| | - Ivor J Benjamin
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Roy L Silverstein
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ze Zheng
- Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
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12
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Kukhon FR, Festic E. Adjuvant Inhaled Corticosteroids in Community-Acquired Pneumonia: A Review Article. Med Sci (Basel) 2021; 9:34. [PMID: 34071031 PMCID: PMC8162532 DOI: 10.3390/medsci9020034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 12/15/2022] Open
Abstract
Community-acquired pneumonia is still a major cause of morbidity and mortality worldwide. Since the inflammatory response induced by the immune system is often a major contributor to the lung injury, it becomes reasonable to assess the potential benefit of anti-inflammatory agents in treating community-acquired pneumonia. The role of corticosteroids as adjunct anti-inflammatory agents in treating community-acquired pneumonia is still controversial. Several studies have assessed the benefit of their use in patients with community-acquired pneumonia. In most of those studies, the route of corticosteroids administration was systemic. The aim of this article is to provide a concise review of the role of corticosteroids in treating community-acquired pneumonia when administered via inhalational route, with the potential benefit of avoiding systemic side effects of corticosteroids while exerting the same anti-inflammatory effects on the lungs. Conclusion: the use of inhaled corticosteroids may be of benefit in certain patient subsets with community-acquired pneumonia. Further randomized controlled trials are needed for better determination of such patient subsets.
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Affiliation(s)
| | - Emir Festic
- Division of Pulmonary and Sleep Medicine, Mayo Clinic Florida, Jacksonville, FL 32224, USA;
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13
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Ali FEM, Mohammedsaleh ZM, Ali MM, Ghogar OM. Impact of cytokine storm and systemic inflammation on liver impairment patients infected by SARS-CoV-2: Prospective therapeutic challenges. World J Gastroenterol 2021; 27:1531-1552. [PMID: 33958841 PMCID: PMC8058655 DOI: 10.3748/wjg.v27.i15.1531] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 02/17/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2 (SARS-CoV-2) that is associated with a high spreading and mortality rate. On the date this review was written, SARS-CoV-2 infected about 96 million people and killed about 2 million people. Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2 (ACE2) receptor expression or cytokine storm strength production. In a similar pattern, hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming, which worsens the hepatic impairment and increases the mortality rate. In this review, the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed. Besides, we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.
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Affiliation(s)
- Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Zuhair M Mohammedsaleh
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Mahmoud M Ali
- Pre-graduated students, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Osama M Ghogar
- Pre-graduated students, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
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14
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The proportion and effect of corticosteroid therapy in patients with COVID-19 infection: A systematic review and meta-analysis. PLoS One 2021; 16:e0249481. [PMID: 33882090 PMCID: PMC8059814 DOI: 10.1371/journal.pone.0249481] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 03/19/2021] [Indexed: 01/08/2023] Open
Abstract
Objectives Coronavirus disease 2019 (COVID-19) remains a global challenge. Corticosteroids constitute a group of anti-inflammatory and immunosuppressive drugs that are widely used in the treatment of COVID-19. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19. Methods We conducted a comprehensive literature review and meta-analysis of research articles, including observational studies and clinical trials, by searching the PubMed, EMBASE, Cochrane Controlled Trials Registry, and China Academic Journal Network Publishing databases. Patients treated between December 1, 2019, and January 1, 2021, were included. The outcome measures were the proportion of patients treated with corticosteroids, viral clearance and mortality. The effect size with the associated 95% confidence interval is reported as the weighted mean difference for continuous outcomes and the odds ratio for dichotomous outcomes. Results Fifty-two trials involving 15710 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids (35.19% vs. 64.49%). In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere cases treated with corticosteroids (27.91% vs. 20.91%). We also performed subgroup analyses stratified by whether patients stayed in the intensive care unit (ICU) and found that the proportion of patients who received corticosteroids was significantly higher among those who stayed in the ICU than among those who did not. The results of our meta-analysis indicate that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference in the use of corticosteroids for COVID-19 between patients who died and those who survived. This result indicates that mortality is not correlated with corticosteroid therapy. Conclusion The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 infections delayed viral clearance and did not convincingly improve survival; therefore, corticosteroids should be used with extreme caution in the treatment of COVID-19.
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15
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Liu D, Zhang T, Wang Y, Xia L. The Centrality of Obesity in the Course of Severe COVID-19. Front Endocrinol (Lausanne) 2021; 12:620566. [PMID: 33776917 PMCID: PMC7992974 DOI: 10.3389/fendo.2021.620566] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 02/11/2021] [Indexed: 12/15/2022] Open
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global public health challenge. Most patients do not experience severe complications, but approximately 25% of patients progress to acute respiratory distress syndrome (ARDS), and the mortality rate is approximately 5-7%. Clinical findings have determined several risk factors for severe complications and mortality in COVID-19 patients, such as advanced age, smoking, obesity, and chronic diseases. Obesity is a common and serious health problem worldwide that initiates a cascade of disorders, including hypertension, cardiovascular disease (CVD), diabetes mellitus, and chronic kidney disease (CKD). The presence of these disorders is linked to a more severe course of COVID-19. Given the "epidemic" of obesity worldwide and the importance of obesity in the progression of COVID-19, we investigated the mechanisms through which obesity increases the susceptibility to and severity of COVID-19 to support the selection of more appropriate therapies for individuals with obesity.
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16
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Parveen RS, Hegde S, Nayak V. Investigational Drugs for the COVID 19 Pandemic – A Concise Review. PHARMACEUTICAL SCIENCES 2020. [DOI: 10.34172/ps.2020.80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Reena Sherin Parveen
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
| | - Sherya Hegde
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
| | - Veena Nayak
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
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17
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Ahmed MH, Hassan A. Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. ACTA ACUST UNITED AC 2020; 2:2637-2646. [PMID: 33163859 PMCID: PMC7599121 DOI: 10.1007/s42399-020-00610-8] [Citation(s) in RCA: 123] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2020] [Indexed: 12/15/2022]
Abstract
The World Health Organization (WHO) declared COVID-19 (novel coronavirus) as a global pandemic in the middle of March 2020, after the disease spread to more than 150 countries and territories leading to tens of thousands of cases within a couple of months. To date, there are no effective pharmaceutical treatments available. As well as that, the novel vaccines have not yet been approved as establishing their efficacy will take time. This study aims to summarize the evidence regarding corticosteroids such as dexamethasone for the treatment of COVID-19. Electronic searches were conducted on 7 September 2020 on Google Scholar database, MEDLINE and PubMed. A further search was conducted on the World Health Organization’s COVID-19 research article database. The findings of recent investigations that proved, both, the in vitro and in vivo activity of corticosteroids against COVID-19 and other coronavirus-related pneumonia were discussed. Low doses of corticosteroids (dexamethasone) could reduce the mortality in patients with severe COVID-19 disease; however, they had no effect on the mortality rate of those patients with a mild form of the condition. Moreover, the liberal use of corticosteroids was not advocated for, as high doses of the drug can cause more harm than good.
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Affiliation(s)
- Mukhtar H Ahmed
- SISAF Nanotechnology Drug Delivery, Ulster University, BT37 0QB Belfast, UK
| | - Arez Hassan
- School of Medicine, Queen's University, Belfast, BT9 7BL UK
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18
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Exposure to Porphyromonas gingivalis Induces Production of Proinflammatory Cytokine via TLR2 from Human Respiratory Epithelial Cells. J Clin Med 2020; 9:jcm9113433. [PMID: 33114582 PMCID: PMC7693763 DOI: 10.3390/jcm9113433] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/19/2020] [Accepted: 10/22/2020] [Indexed: 12/25/2022] Open
Abstract
Aspiration pneumonia is a major health problem owing to its high mortality rate in elderly people. The secretion of proinflammatory cytokines such as interleukin (IL)-8 and IL-6 by respiratory epithelial cells, which is induced by infection of respiratory bacteria such as Streptococcus pneumoniae, contributes to the onset of pneumonia. These cytokines thus play a key role in orchestrating inflammatory responses in the lower respiratory tract. In contrast, chronic periodontitis, a chronic inflammatory disease caused by the infection of periodontopathic bacteria, typically Porphyromonas gingivalis, is one of the most prevalent microbial diseases affecting humans globally. Although emerging evidence has revealed an association between aspiration pneumonia and chronic periodontitis, a causal relationship between periodontopathic bacteria and the onset of aspiration pneumonia has not been established. Most periodontopathic bacteria are anaerobic and are therefore unlikely to survive in the lower respiratory organs of humans. Therefore, in this study, we examined whether simple contact by heat-inactivated P. gingivalis induced proinflammatory cytokine production by several human respiratory epithelial cell lines. We found that P. gingivalis induced strong IL-8 and IL-6 secretion by BEAS-2B bronchial epithelial cells. P. gingivalis also induced strong IL-8 secretion by Detroit 562 pharyngeal epithelial cells but not by A549 alveolar epithelial cells. Additionally, Toll-like receptor (TLR) 2 but not TLR4 was involved in the P. gingivalis-induced proinflammatory cytokine production. Furthermore, P. gingivalis induced considerably higher IL-8 and IL-6 production than heat-inactivated S. pneumoniae. Our results suggest that P. gingivalis is a powerful inflammatory stimulant for human bronchial and pharyngeal epithelial cells and can stimulate TLR2-mediated cytokine production, thereby potentially contributing to the onset of aspiration pneumonia.
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19
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Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs 2020; 80:1267-1292. [PMID: 32696108 PMCID: PMC7372203 DOI: 10.1007/s40265-020-01367-z] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms ‘coronavirus’, ‘immunology’, ‘cytokine storm’, ‘immunomodulators’, ‘pharmacology’, ‘severe acute respiratory syndrome 2’, ‘SARS-CoV-2’, and ‘COVID-19’. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte–macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
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Affiliation(s)
- John G Rizk
- Edson College, Arizona State University, Phoenix, AZ, USA.
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine, School of Medicine, Irvine, CA, USA.,Department of Epidemiology, University of California, Los Angeles, UCLA Fielding School of Public Health, Los Angeles, CA, USA.,Tibor Rubin VA Long Beach Healthcare System, Long Beach, CA, USA
| | - Mandeep R Mehra
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA, USA
| | - Youssef Rizk
- Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Donald N Forthal
- Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USA.,Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine, Irvine, CA, USA
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20
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Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020; 81:e13-e20. [PMID: 32283144 PMCID: PMC7195158 DOI: 10.1016/j.jinf.2020.03.062] [Citation(s) in RCA: 234] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVES An outbreak of novel coronavirus in 2019 threatens the health of people, and there is no proven pharmacological treatment. Although corticosteroids were widely used during outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, their efficacy remainedhighly controversial. We aimed to further evaluate the influence of corticosteroids on patients with coronavirus infection. METHODS We conducted a comprehensive search of literature published in PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) from January 1, 2002 to March 15, 2020. All statistical analyses in this study were performed on stata14.0. RESULTS A total of 5270 patients from 15 studies were included in this meta-analysis. The result indicated that critical patients were more likely to require corticosteroids therapy (risk ratio [RR] = 1.56, 95% confidence interval [CI] = 1.28-1.90, P<0.001). However, corticosteroid treatment was associated with higher mortality (RR = 2.11, 95%CI = 1.13-3.94, P = 0.019), longer length of stay (weighted mean difference [WMD] = 6.31, 95%CI = 5.26-7.37, P<0.001), a higher rate of bacterial infection (RR = 2.08, 95%CI = 1.54-2.81, P<0.001), and hypokalemia (RR = 2.21, 95%CI = 1.07-4.55, P = 0.032) but not hyperglycemia (RR = 1.37, 95%CI=0.68-2.76, P = 0.376) or hypocalcemia (RR = 1.35, 95%CI = 0.77-2.37, P = 0.302). CONCLUSIONS Patients with severe conditions are more likely to require corticosteroids. Corticosteroid use is associated with increased mortality in patients with coronavirus pneumonia.
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Affiliation(s)
- Zhenwei Yang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China
| | - Jialong Liu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China
| | - Yunjiao Zhou
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China
| | - Xixian Zhao
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China
| | - Qiu Zhao
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China
| | - Jing Liu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China.
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21
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Nora D, Nedel W, Lisboa T, Salluh J, Póvoa P. The role of steroids in severe CAP. Hosp Pract (1995) 2020; 48:12-22. [PMID: 31977280 DOI: 10.1080/21548331.2020.1720215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 01/21/2020] [Indexed: 12/16/2022]
Abstract
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality despite adequate antibiotic therapy. It is the single most common cause of infection-related mortality in the United States. An exaggerated host inflammatory response can potentially be harmful to both the lung and host, and has been associated with treatment failure and mortality. Modulation of inflammatory response may, therefore, be theoretically beneficial. The anti-inflammatory and immunosuppressive effects of steroids seem an attractive therapeutic option in severe CAP patients. Available datapoint to overall shorter time to clinical stability and decreased length-of-stay in CAP patients, with a potential mortality benefit in severe CAP. The level of evidence is, however, low to moderate regarding mortality due to high heterogeneity and insufficient power of data. Furthermore, steroids were deleterious in influenza pneumonia and in patients with pneumococcal pneumonia data suggest a lack of efficacy and potential harm. Both European and American guidelines recommend not using corticosteroids in CAP. Patients who might benefit and those that can be harmed from steroids remain to be clearly identified, as does the ideal steroid for CAP patients, based on pharmacokinetic and pharmacodynamic properties. It is essential for future studies to avoid the same methodological bias present in the available data so that high-quality evidence on the true role of steroids in CAP can be provided.
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Affiliation(s)
- David Nora
- Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Centro Hospitalar De Lisboa Ocidental, Lisbon, Portugal
- NOVA Medical School, CHRC, New University of Lisbon, Lisbon, Portugal
| | - Wagner Nedel
- Intensive Care Unit, Hospital Nossa Senhora Da Conceição, Porto Alegre, Brazil
| | - Thiago Lisboa
- Critical Care Department, Hospital De Clínicas De Porto Alegre, Post-Graduation Program (PPG) Pneumology,Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil
| | - Jorge Salluh
- D'or Institute for Research and Education, Rio De Janeiro, Brazil
| | - Pedro Póvoa
- Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Centro Hospitalar De Lisboa Ocidental, Lisbon, Portugal
- NOVA Medical School, CHRC, New University of Lisbon, Lisbon, Portugal
- Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Denmark
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22
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Lee YJ, Ahn YM, Jang GC, Chung HL, Chung EH, Hwang YH, Shim JY. Real-world treatment pattern of mycoplasma pneumonia in hospitalized children: A multicenter retrospective study. ALLERGY ASTHMA & RESPIRATORY DISEASE 2020. [DOI: 10.4168/aard.2020.8.2.66] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- Young Ju Lee
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Min Ahn
- Department of Pediatrics, Eulji University Eulji General Hospital, Seoul, Korea
| | - Gwang Cheon Jang
- Department of Pediatrics, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
| | - Hai Lee Chung
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Hee Chung
- Department of Pediatrics, Chungnam National University Hospital, Daejeon, Korea
| | - Yoon Ha Hwang
- Department of Pediatrics, Busan St. Mary's Hospital, Busan, Korea
| | - Jung Yeon Shim
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Gavrilovic S, Andrijevic A, Mujakovic A, Odeyemi Y, Paralija B, Gajic O. Adjunct corticosteroid treatment in patients with pneumonia: A precision medicine approach. Bosn J Basic Med Sci 2019; 19:315-320. [PMID: 30640592 PMCID: PMC6868487 DOI: 10.17305/bjbms.2019.3977] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 12/18/2018] [Indexed: 01/29/2023] Open
Abstract
Pneumonia is the leading infectious cause of death worldwide. While inflammation is critically important in host response to microbial invasion, exaggerated inflammation can damage the lungs, contributing to respiratory failure and mortality. Corticosteroids are effective in reducing inflammation and can also cause immune suppression. Presently, clinicians are unable to reliably distinguish between exaggerated and appropriate immune response and thus cannot rapidly identify patients most likely to benefit from adjunctive corticosteroids. In this review, we propose a biomarker-guided, precision medicine approach to corticosteroid treatment, aimed to give these medications at appropriate dose and time and only to patients who have exaggerated inflammation.
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Affiliation(s)
- Srdjan Gavrilovic
- Intensive Care Unit, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
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24
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Hsu SC, Huang WC, Liu CT, Hsu YP, Chang JH, Huang SK, Hsu CW. Sphingosine-1-phosphate as an indicator for deciding the use of adjuvant corticosteroids therapy in community-acquired pneumonia (sphingosine-1-phosphate and pneumonia trial): Study protocol for a randomized, placebo-controlled trial. Medicine (Baltimore) 2019; 98:e17278. [PMID: 31568009 PMCID: PMC6756703 DOI: 10.1097/md.0000000000017278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
INTRODUCTION Pneumonia is one of the leading causes of death worldwide, represents a potentially life-threatening condition. In recent studies, adjuvant corticosteroids therapy has been shown to improve outcome in severe community-acquired pneumonia (CAP); however, the treatment response to corticosteroids vary. It is important to select patients likely to benefit from the treatment. Currently, the optimal patient selection of corticosteroids treatment is not yet clearly defined. METHODS Sphingosine-1-phosphate and pneumonia (SOPN) trial is a double-blinded, randomized, placebo-controlled trial that will investigate if sphingosine-1-phosphate (S1P) can be an indicator for initiating adjuvant corticosteroids therapy in patients with severe CAP. Participants will be recruited from the emergency department and randomized to receive 20 mg of methylprednisolone twice daily or placebo for 5 days. The primary outcome will be "in-hospital mortality." Secondary outcomes will include intensive care unit (ICU) admission, length of ICU stay, length of hospital stay, and clinical outcomes at Day 7 and Day 14. CONCLUSION SOPN trial is the first randomized placebo-controlled trial to investigate whether S1P can be a predictive biomarker for adjuvant corticosteroids therapy in patients with severe CAP. The trial will add additional data for the appropriate use of adjuvant corticosteroids therapy in patients with severe CAP. Results from this clinical trial will provide foundational information supporting that if the S1P is appropriate for guiding the patient selection for corticosteroids adjuvant therapy.
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Affiliation(s)
- Shih-Chang Hsu
- Emergency Department, Department of Emergency and Critical Medicine, Wan Fang Hospital
- Department of Emergency Medicine, School of Medicine
| | - Wen-Cheng Huang
- Emergency Department, Department of Emergency and Critical Medicine, Wan Fang Hospital
- Department of Emergency Medicine, School of Medicine
| | - Chung-Te Liu
- Graduate Institute of Clinical Medicine, College of Medicine
- Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital
- Department of Internal Medicine
| | - Yuan-Pin Hsu
- Emergency Department, Department of Emergency and Critical Medicine, Wan Fang Hospital
- Department of Emergency Medicine, School of Medicine
- Graduate Institute of Clinical Medicine, College of Medicine
| | - Jer-Hwa Chang
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
- Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei
| | - Shau-Ku Huang
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
- Lou-Hu Hospital, Shen-Zhen University, Shen-Zhen, China
- Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore
| | - Chin-Wang Hsu
- Emergency Department, Department of Emergency and Critical Medicine, Wan Fang Hospital
- Department of Emergency Medicine, School of Medicine
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Abstract
PURPOSE OF REVIEW Pleural infection remains an important pulmonary disease, causing significant morbidity and mortality. There is a resurgence of disease burden despite introduction of antibiotics and pneumococcal vaccines. A revisit of the pathogenesis and update on intervention may improve the care of pleural infection. RECENT FINDINGS Recent studies have uncovered the prognostic implication of the presence of a pleural effusion in patients with pneumonia. Identifying where the bacteria lives may have diagnostic and therapeutic implications. Over-exaggerated pleural inflammation may underlie development of parapneumonic effusion as indirect evidence and a randomized study in children raised a role of corticosteroids in parapneumonic pleural effusions, but data are lacking for adults. Optimization of the delivery regimen of intrapleural fibrinolytic and deoxyribonuclease therapy is ongoing. SUMMARY The review aims to review the current practice and explore new directions of treatment on pleural infection.
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Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care 2019; 23:99. [PMID: 30917856 PMCID: PMC6437920 DOI: 10.1186/s13054-019-2395-8] [Citation(s) in RCA: 264] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 03/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background The effect of corticosteroids on clinical outcomes in patients with influenza pneumonia remains controversial. We aimed to further evaluate the influence of corticosteroids on mortality in adult patients with influenza pneumonia by comparing corticosteroid-treated and placebo-treated patients. Methods The PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Information Sciences Institute (ISI) Web of Science databases were searched for all controlled studies that compared the effects of corticosteroids and placebo in adult patients with influenza pneumonia. The primary outcome was mortality, and the secondary outcomes were mechanical ventilation (MV) days, length of stay in the intensive care unit (ICU LOS), and the rate of secondary infection. Results Ten trials involving 6548 patients were pooled in our final analysis. Significant heterogeneity was found in all outcome measures except for ICU LOS (I2 = 38%, P = 0.21). Compared with placebo, corticosteroids were associated with higher mortality (risk ratio [RR] 1.75, 95% confidence interval [CI] 1.30 ~ 2.36, Z = 3.71, P = 0.0002), longer ICU LOS (mean difference [MD] 2.14, 95% CI 1.17 ~ 3.10, Z = 4.35, P < 0.0001), and a higher rate of secondary infection (RR 1.98, 95% CI 1.04 ~ 3.78, Z = 2.08, P = 0.04) but not MV days (MD 0.81, 95% CI − 1.23 ~ 2.84, Z = 0.78, P = 0.44) in patients with influenza pneumonia. Conclusions In patients with influenza pneumonia, corticosteroid use is associated with higher mortality. Trial registration PROSPERO (ID: CRD42018112384). Electronic supplementary material The online version of this article (10.1186/s13054-019-2395-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yue-Nan Ni
- Department of Respiratory and Critical Care Medicine, West China School of Medicine and West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Guo Chen
- Department of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Jiankui Sun
- State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, No. 14, Section 3 Renmin Nanlu, Chengdu, 610041, Sichuan, China
| | - Bin-Miao Liang
- Department of Respiratory and Critical Care Medicine, West China School of Medicine and West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
| | - Zong-An Liang
- Department of Respiratory and Critical Care Medicine, West China School of Medicine and West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
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Garnacho-Montero J, Barrero-García I, Gómez-Prieto MDG, Martín-Loeches I. Severe community-acquired pneumonia: current management and future therapeutic alternatives. Expert Rev Anti Infect Ther 2018; 16:667-677. [DOI: 10.1080/14787210.2018.1512403] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Jose Garnacho-Montero
- Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - Irene Barrero-García
- Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | | | - Ignacio Martín-Loeches
- Department of Anaesthesia and Critical Care, St James University Hospital, Trinity Centre for Health Sciences, Multidisciplinary Intensive Care Research Organization (MICRO), Dublin, Ireland
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Lee MS, Oh JY, Kang CI, Kim ES, Park S, Rhee CK, Jung JY, Jo KW, Heo EY, Park DA, Suh GY, Kiem S. Guideline for Antibiotic Use in Adults with Community-acquired Pneumonia. Infect Chemother 2018; 50:160-198. [PMID: 29968985 PMCID: PMC6031596 DOI: 10.3947/ic.2018.50.2.160] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Indexed: 01/07/2023] Open
Abstract
Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea.
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Affiliation(s)
- Mi Suk Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jee Youn Oh
- Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Cheol In Kang
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eu Suk Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sunghoon Park
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Chin Kook Rhee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Ye Jung
- Division of Pulmonology, The Institute of Chest Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Wook Jo
- Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Eun Young Heo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea
| | - Gee Young Suh
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Sungmin Kiem
- Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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Abstract
BACKGROUND Bronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000. OBJECTIVES To evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline. SEARCH METHODS We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Register of trials, MEDLINE and Embase databases. We ran the latest literature search in June 2017. SELECTION CRITERIA All randomised controlled trials (RCTs) comparing ICS with a placebo or no medication. We included children and adults with clinical or radiographic evidence of bronchiectasis, but excluded people with cystic fibrosis. DATA COLLECTION AND ANALYSIS We reviewed search results against predetermined criteria for inclusion. In this update, two independent review authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro forma. We analysed treatment as 'treatment received' and performed sensitivity analyses. MAIN RESULTS The review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies.Due to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months).During stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV1) at the end of the study (mean difference (MD) -0.09, 95% confidence interval (CI) -0.26 to 0.09) and forced vital capacity (FVC) (MD 0.01 L, 95% CI -0.16 to 0.17) in adults on ICS (compared to no ICS). Similarly, we did not find any significant difference in the average exacerbation frequency (MD 0.09, 95% CI -0.61 to 0.79) or health-related quality of life (HRQoL) total scores in adults on ICS when compared with no ICS, though data available were limited. Based on a single non-placebo controlled study from which we could not extract clinical data, there was marginal, though statistically significant improvement in sputum volume and dyspnoea scores on ICS.The single study on long-term outcomes (over 6 months) that examined lung function and other clinical outcomes, showed no significant effect of ICS on any of the outcomes. We could not draw any conclusion on adverse effects due to limited available data.Despite the authors of all seven studies stating they were double-blind, we judged one study (in the short duration ICS) as having a high risk of bias based on blinding, attrition and reporting of outcomes. The GRADE quality of evidence was low for all outcomes (due to non-placebo controlled trial, indirectness and imprecision with small numbers of participants and studies). AUTHORS' CONCLUSIONS This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.
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Affiliation(s)
- Nitin Kapur
- Children's Health Queensland, Lady Cilento Children's HospitalDepartment of Respiratory and Sleep MedicineBrisbaneQueenslandAustralia
- The University of QueenslandSchool of Clinical MedicineBrisbaneAustralia
| | - Helen L Petsky
- Griffith UniversitySchool of Nursing and Midwifery, Griffith University and Menzies Health Institute QueenslandBrisbaneQueenslandAustralia
| | - Scott Bell
- The Prince Charles HospitalRode RoadChermsideBrisbaneQueenslandAustralia4032
| | - John Kolbe
- The University of AucklandDepartment of Medicine, Faculty of Medical and Health SciencesPrivate Bag 92019AucklandNew Zealand1142
| | - Anne B Chang
- Menzies School of Health Research, Charles Darwin UniversityChild Health DivisionPO Box 41096DarwinNorthern TerritoriesAustralia0811
- Queensland University of TechnologyInstitute of Health and Biomedical InnovationBrisbaneAustralia
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Torres A, Ferrer M, Niederman MS. Adjuvant therapies in critical care: steroids in community-acquired pneumonia. Intensive Care Med 2018; 44:478-481. [PMID: 29071427 PMCID: PMC7095014 DOI: 10.1007/s00134-017-4967-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 10/11/2017] [Indexed: 12/15/2022]
Affiliation(s)
- Antoni Torres
- Department of Pneumology, Respiratory Institute, Hospital Clinic of Barcelona, University of Barcelona (UB), Villarroel 170, 08036, Barcelona, Spain.
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
- Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Barcelona, Spain.
| | - Miquel Ferrer
- Department of Pneumology, Respiratory Institute, Hospital Clinic of Barcelona, University of Barcelona (UB), Villarroel 170, 08036, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Barcelona, Spain
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Abstract
BACKGROUND Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011. OBJECTIVES To assess the efficacy and safety of corticosteroids in the treatment of pneumonia. SEARCH METHODS We searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible. MAIN RESULTS We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93). AUTHORS' CONCLUSIONS Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.
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Affiliation(s)
- Anat Stern
- Rambam Health Care CampusDivision of Infectious DiseasesHa‐aliya 8 StHaifaIsrael33705
| | - Keren Skalsky
- Beilinson Hospital, Rabin Medical CenterDepartment of Medicine E39 Jabotinski StreetPetah TikvaIsrael49100
| | - Tomer Avni
- Beilinson Hospital, Rabin Medical CenterDepartment of Medicine E39 Jabotinski StreetPetah TikvaIsrael49100
| | - Elena Carrara
- Policlinico San Matteo HospitalInfectious DiseasesUniversity of PaviaPaviaLombardyItaly27100
| | - Leonard Leibovici
- Beilinson Hospital, Rabin Medical CenterDepartment of Medicine E39 Jabotinski StreetPetah TikvaIsrael49100
| | - Mical Paul
- Rambam Health Care CampusDivision of Infectious DiseasesHa‐aliya 8 StHaifaIsrael33705
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McSorley ST, Dolan RD, Roxburgh CSD, McMillan DC, Horgan PG. How and why systemic inflammation worsens quality of life in patients with advanced cancer. ACTA ACUST UNITED AC 2017. [DOI: 10.1080/23809000.2017.1331705] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Stephen T. McSorley
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow, UK
| | - Ross D. Dolan
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow, UK
| | | | - Donald C. McMillan
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow, UK
| | - Paul G. Horgan
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow, UK
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Sibila O, Rodrigo-Troyano A, Torres A. Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them? Semin Respir Crit Care Med 2016; 37:913-922. [PMID: 27960215 PMCID: PMC7171709 DOI: 10.1055/s-0036-1593538] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality.
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Affiliation(s)
- Oriol Sibila
- Respiratory Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona (UAB), Barcelona, Spain
- Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Ana Rodrigo-Troyano
- Respiratory Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona (UAB), Barcelona, Spain
- Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Antoni Torres
- Pulmonolgy Department, Respiratory Institute (ICR), Hospital Clinic of Barcelona, Spain
- Centro de Investigación Biomedica En Red - Enfermedades Respiratorias, Barcelona, Spain
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34
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Villar J, Belda J, Añón JM, Blanco J, Pérez-Méndez L, Ferrando C, Martínez D, Soler JA, Ambrós A, Muñoz T, Rivas R, Corpas R, Díaz-Dominguez FJ, Soro M, García-Bello MA, Fernández RL, Kacmarek RM. Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial. Trials 2016; 17:342. [PMID: 27449641 PMCID: PMC4957909 DOI: 10.1186/s13063-016-1456-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 06/15/2016] [Indexed: 12/28/2022] Open
Abstract
Background Although much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality. Methods/design This is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment. Discussion This study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS. Trial registration Registered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website (NCT01731795). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1456-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jesús Villar
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. .,Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, 4th floor - South Wing, 35019, Las Palmas de Gran Canaria, Spain. .,Keenan Research Center for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
| | - Javier Belda
- Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | | | - Jesús Blanco
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.,Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Lina Pérez-Méndez
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.,Division of Clinical Epidemiology and Biostatistics, Research Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain
| | - Carlos Ferrando
- Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Domingo Martínez
- Intensive Care Unit, Hospital Virgen de la Arrixaca, Murcia, Spain
| | | | - Alfonso Ambrós
- Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain
| | - Tomás Muñoz
- Intensive Care Unit, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain
| | - Rosana Rivas
- Intensive care Unit, Hospital Galdakao-Usansolo, Usansolo, Vizcaya, Spain
| | - Ruth Corpas
- Intensive Care Unit, Hospital N.S. del Prado, Talavera de la Reina, Toledo, Spain
| | | | - Marina Soro
- Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | | | - Rosa Lidia Fernández
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.,Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, 4th floor - South Wing, 35019, Las Palmas de Gran Canaria, Spain
| | - Robert M Kacmarek
- Department of Respiratory Care, Massachusetts General Hospital, Boston, MA, USA.,Department of Anesthesiology, Harvard University, Boston, MA, USA
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Torres A. Corticosteroids for severe CAP: the pros. Rev Bras Ter Intensiva 2016; 27:202-4. [PMID: 26465242 PMCID: PMC4592112 DOI: 10.5935/0103-507x.20150041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 08/06/2015] [Indexed: 11/20/2022] Open
Affiliation(s)
- Antoni Torres
- Servei de Pneumologia, Hospital Clinic of Barcelona, Barcelona, ES
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36
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Rello J, Perez A. Precision medicine for the treatment of severe pneumonia in intensive care. Expert Rev Respir Med 2016; 10:297-316. [PMID: 26789703 DOI: 10.1586/17476348.2016.1144477] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Despite advances in its management, community-acquired pneumonia (CAP) remains the most important cause of sepsis-related mortality and the reason for many ICU admissions. Severity assessment is the cornerstone of CAP patient management and the attempts to ensure the best site of care and therapy. Survival depends on a combination of host factors (genetic, age, comorbidities, defenses), pathogens (virulence, serotypes) and drugs. To reduce CAP mortality, early adequate antibiotic therapy is fundamental. The use of combination therapy with a macrolide seems to improve the clinical outcome in the subset of patients with high inflammation due to immunomodulation. Guidelines on antibiotic therapy have been associated with beneficial effects, and studies of newer adjunctive drugs have produced promising results. This paper discusses the current state of knowledge regarding of precision medicine and the treatment of severe CAP patients.
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Affiliation(s)
- Jordi Rello
- a CIBERES , Barcelona , Spain.,b School of Medicine , Universitat Autonoma de Barcelona , Barcelona , Spain
| | - Antonio Perez
- a CIBERES , Barcelona , Spain.,b School of Medicine , Universitat Autonoma de Barcelona , Barcelona , Spain
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Bartko J, Stiebellehner L, Derhaschnig U, Schoergenhofer C, Schwameis M, Prosch H, Jilma B. Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans. Br J Clin Pharmacol 2016; 81:865-77. [PMID: 26647918 PMCID: PMC4834593 DOI: 10.1111/bcp.12857] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Revised: 11/23/2015] [Accepted: 12/01/2015] [Indexed: 12/14/2022] Open
Abstract
Aims The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. Methods In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Results Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. Conclusions The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other.
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Affiliation(s)
- Johann Bartko
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | | | - Ulla Derhaschnig
- Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Michael Schwameis
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Helmut Prosch
- Department of Radiology, Medical University of Vienna, Vienna, Austria
| | - Bernd Jilma
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
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Roxburgh CSD, McMillan DC. Therapeutics targeting innate immune/inflammatory responses through the interleukin-6/JAK/STAT signal transduction pathway in patients with cancer. Transl Res 2016; 167:61-6. [PMID: 26432924 DOI: 10.1016/j.trsl.2015.08.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 08/28/2015] [Accepted: 08/29/2015] [Indexed: 01/05/2023]
Abstract
Over the last 15 years, there has been an evolution in the thinking of how tumors grow and disseminate: from the earlier work where it was considered that the intrinsic characteristics of the tumor largely determined the process to more recent work where local and systemic inflammatory responses play a key role in disease progression and survival in patients with cancer. Although the immune/inflammatory responses to cancer are complex, it is clear that targeting the host immune/inflammatory responses (in particular, innate/humoral responses) has considerable potential to improve outcomes in patients with a variety of common solid tumors. There are a wide variety of agents from the nonselective glucocorticoids to the selective Janus Activated Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors that has considerable therapeutic potential. They may be considered to act through a main signal transduction mechanism, the interleukin-6/JAK/STAT pathway. This work heralds a new era in which it will be important not only to treat the tumor but also to treat the host, so called oncoimmunology.
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Affiliation(s)
- Campbell S D Roxburgh
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Donald C McMillan
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom.
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Corticosteroids as Adjunctive Therapy in Severe Community-Acquired Pneumonia. ANNUAL UPDATE IN INTENSIVE CARE AND EMERGENCY MEDICINE 2016. [PMCID: PMC7176164 DOI: 10.1007/978-3-319-27349-5_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Mortality in community acquired pneumonia (CAP) has not decreased in the intensive care unit (ICU), despite progress in antimicrobial therapy [1, 2]. Approximately 10% of patients hospitalized with CAP are admitted to the ICU [3]. In a multicenter study by Mongardon et al. in patients with severe pneumococcal CAP admitted to the ICU, the mortality rate was 29%, with high proportions of patients in septic shock and needing mechanical ventilation [4]. Severe CAP is a progressive disease and patients may die despite early and adequate antibiotic treatment. The host local and systemic inflammatory immune response in patients with severe CAP is exacerbated and disproportionate and this is probably the main cause for the high mortality in this specific population, as it contributes to impaired alveolar gas exchange, sepsis and end-organ dysfunction [5]. In this specific population of patients with severe CAP, adjuvant treatments, such as corticosteroids, may be beneficial.
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Restrepo MI, Anzueto A, Torres A. Corticosteroids for Severe Community-Acquired Pneumonia: Time to Change Clinical Practice. Ann Intern Med 2015; 163:560-1. [PMID: 26258646 DOI: 10.7326/m15-1805] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Marcos I. Restrepo
- From University of Texas Health Science Center at San Antonio, San Antonio, Texas, and Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain
| | - Antonio Anzueto
- From University of Texas Health Science Center at San Antonio, San Antonio, Texas, and Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain
| | - Antoni Torres
- From University of Texas Health Science Center at San Antonio, San Antonio, Texas, and Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain
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Siemieniuk RAC, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, Alexander PE, Fei Y, Vandvik PO, Loeb M, Guyatt GH. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med 2015; 163:519-28. [PMID: 26258555 DOI: 10.7326/m15-0715] [Citation(s) in RCA: 241] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Community-acquired pneumonia (CAP) is common and often severe. PURPOSE To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. DATA SOURCES MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. STUDY SELECTION Randomized trials of systemic corticosteroids in hospitalized adults with CAP. DATA EXTRACTION Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors. DATA SYNTHESIS The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. LIMITATIONS There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. CONCLUSION For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. PRIMARY FUNDING SOURCE None.
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Abstract
Despite remarkable progress in diagnosis and antibiotic therapy, mortality due to pneumonia has not changed significantly and ICU admissions are increasing. The management includes early evaluation of severity, collection of microbiological cultures, and appropriate antibiotic administration. The prognostic scores as the ATS/IDSA rule, the PIRO, or SCAP system are valuable in timely recognition of critically ill patients with community-acquired pneumonia (CAP) requiring admission to ICU. Implementation of guidelines for CAP treatment should be emphasized in order to increase survival. Guidelines for antibiotic management for severe CAP are based on illness severity, covering most likely bacterial and atypical pathogens and the level of ICU antibiotic resistance. Combination therapy suggested in patients with nonrefractory septic shock and severe sepsis pneumococcal bacteremia also. Recent studies suggest that steroid therapy may be valuable in nonrefractory septic shock from sCAP.
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What's new in severe community-acquired pneumonia? Corticosteroids as adjunctive treatment to antibiotics. Intensive Care Med 2015; 42:1276-8. [PMID: 26370691 PMCID: PMC7095221 DOI: 10.1007/s00134-015-4042-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 08/26/2015] [Indexed: 10/25/2022]
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Li M, Liu J, Tan R, Liu Z, Yin J, Qu H. Risk factors for slowly resolving pneumonia in the intensive care unit. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2014; 49:654-662. [PMID: 25553993 DOI: 10.1016/j.jmii.2014.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 06/02/2014] [Accepted: 11/06/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND Slowly resolving pneumonia (SRP) poses early challenges for identification and medical expense for clinicians in intensive care units (ICUs); to date, the literature has been very limited in this regard. METHODS This was a retrospective and cohort-based study in the ICU of a university-affiliated hospital in Shanghai. Medical records of pneumonia patients in the ICU between April 2008 and February 2011were reviewed retrospectively to evaluate the risk factors for SRP. RESULTS In all, 106 pneumonia patients in the ICU were identified as immune-competent with a diagnosis of bacterial pneumonia. There were 62 (58.49%) patients who showed SRP and their radiographic infiltrations were completely resolved between 5 weeks and 8 weeks. Multivariate logistic regression analysis demonstrated that initial treatment with an inappropriate antibiotic, multilobar infiltration, and a high CURB-65 score were independent risk factors for SRP, with odds ratio (OR) values of 8.338 [95% confidence interval (CI) 2.117-32.848], 11.184 (95% CI 2.526-49.514), and 2.329 (95% CI 1.172-4.626), respectively. The length of the ICU stay in the SRP group was twice as long as that of the normally resolving pneumonia (NRP) group (62.27 ± 73.73 vs. 32.25 ± 23, p = 0.002). The 28-day and 60-day mortality rates in the SRP group were 17.74% and 25.81%, respectively. In addition, the 60-day mortality rate was significantly higher in the SRP group than the NRP group (25.81% vs. 6.82%, respectively; p = 0.012). Moreover, SRP was an independent risk factor for 60-day mortality (OR 5.687, 95% CI 1.334-24.240). CONCLUSION Treatment with an inappropriate antibiotic, multilobar infiltration, and a high CURB-65 score were independent risk factors for SRP.
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Affiliation(s)
- Meiling Li
- Department of Critical Care Medicine and Respiratory Intensive Care Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialin Liu
- Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Ruoming Tan
- Department of Critical Care Medicine and Respiratory Intensive Care Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaojun Liu
- Department of Critical Care Medicine and Respiratory Intensive Care Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianyong Yin
- Department of Critical Care Medicine and Respiratory Intensive Care Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongping Qu
- Department of Critical Care Medicine and Respiratory Intensive Care Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial. Trials 2014; 15:257. [PMID: 24974155 PMCID: PMC4083867 DOI: 10.1186/1745-6215-15-257] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 06/16/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION 7 September 2009 on ClinicalTrials.gov: NCT00973154.
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Ferrer M, Torres A, Martínez R, Ramírez P, Polverino E, Montull B, Sialer S, Niederman MS, Agusti A, Menéndez R. Inhaled corticosteroids and systemic inflammatory response in community-acquired pneumonia: a prospective clinical study. Respirology 2014; 19:929-35. [PMID: 24909304 DOI: 10.1111/resp.12324] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 02/18/2014] [Accepted: 04/04/2014] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND OBJECTIVE The previous use of inhaled corticosteroids (ICS) may reduce the inflammatory response and mortality in patients with community-acquired pneumonia (CAP). METHODS We measured serum levels of several inflammatory biomarkers, as well as mortality at various time-points, in 663 consecutive patients hospitalized for CAP; 128 (19%) were receiving chronic outpatient treatment with ICS. Patients on previous oral corticosteroids were excluded from the analysis. RESULTS On admission, patients treated with ICS were older; had been diagnosed with chronic obstructive pulmonary disease (COPD), asthma and pneumonia in the previous year more often; and had higher CAP severity risk classes and lower tumour necrosis factor (TNF)-alpha (P < 0.001) and interleukin (IL)-6 (P = 0.015) serum levels. After adjusting for potential confounders, this association persisted for TNF-alpha (P < 0.001), but not for IL-6. Mortality at 30 and 90 days tended to be lower in patients treated with ICS (P = 0.062 and 0.050, respectively), but mortality was similar after 1 year in both groups (16, 13% vs 81, 15% for patients treated and not treated with ICS, respectively). Hospital readmission rate after 1 year was higher in patients treated with ICS (49, 38% vs 109, 20%, P < 0.001). The association of ICS treatment with a previous diagnosis of pneumonia, lower levels of TNF-alpha and IL-6 on admission and higher readmission rates during follow up persisted in the subpopulation of 210 patients with COPD. CONCLUSIONS Previous use of ICS in patients hospitalized for CAP is associated with a reduced systemic inflammatory response without any impact on long-term mortality.
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Affiliation(s)
- Miquel Ferrer
- Department of Pneumology, Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
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Lee SH, Teo J, Heng D, Zhao Y, Wai Kiong N, Chan HK, Tan RB. Steroid-Decorated Antibiotic Microparticles for Inhaled Anti-Infective Therapy. J Pharm Sci 2014; 103:1115-25. [DOI: 10.1002/jps.23874] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 12/23/2013] [Accepted: 01/03/2014] [Indexed: 11/06/2022]
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Liapikou A, Rosales-Mayor E, Torres A. Pharmacotherapy for hospital-acquired pneumonia. Expert Opin Pharmacother 2014; 15:775-86. [DOI: 10.1517/14656566.2014.889115] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Glucocorticosteroid in treatment of severe pneumonia. Mediators Inflamm 2013; 2013:865635. [PMID: 24363503 PMCID: PMC3865735 DOI: 10.1155/2013/865635] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 11/02/2013] [Indexed: 12/20/2022] Open
Abstract
Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage.
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Systemic inflammatory cytokine-mediated response after bronchoalveolar lavage in mechanically ventilated patients with suspected pneumonia. J Bronchology Interv Pulmonol 2013. [PMID: 23207351 DOI: 10.1097/lbr.0b013e318251d542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The aim of this study was to investigate systemic changes that can occur in critically ill patients shortly after flexible bronchoscopy and to determine plasma cytokine levels during this period as an expression of a systemic inflammatory response. METHODS A prospective and observational study was performed in a 17-bed medical-surgical intensive care unit. Patients with indications for bronchoscopic bronchoalveolar lavage (BAL) were prospectively and consecutively included during a time of study of 27 months, from October 2006 to December 2008. Heart rate, blood pressure, and temperature were recorded. Microbiological analysis of respiratory samples was carried out. The levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor α, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were determined 4 hours before flexible bronchoscopy, immediately after , 4 hours after, and 24 hours after the procedure; cytokine levels in BAL were also measured. RESULTS A total of 59 patients undergoing flexible bronchoscopy with BAL were included. A statistically significant, yet transient, decrease in blood pressure was observed 4 hours after the procedure, from 90.7±13.9 mm Hg to 80.7±14 mm Hg, which was correlated with a significant IL-6 concentration increase from 127±164.5 pg/mL to 196.4±238.2 pg/mL at the same time point. CONCLUSIONS BAL in mechanically ventilated patients causes a statistically significant blood pressure decrease 4 hours after the procedure in a high percentage of cases that correlates with a systemic inflammatory response resulting from increased IL-6 plasma levels.
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