High‐dose steroid therapy for acute respiratory distress syndrome lacking common risk factors: predictors of outcome

Kinoshita, Yoshiaki; Ishii, Hiroshi; Kushima, Hisako; Watanabe, Kentaro; Fujita, Masaki

doi:10.1002/ams2.321

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…In a clinical setting, MP is predominantly administered intravenously or orally ( Kinoshita et al, 2017 ; Meduri et al, 2018 ), while other corticosteroid drugs, such as budesonide and formoterol, have proven clinical benefits when inhaled ( Barnes, 2011 ). However, the aim of this study was not to evaluate the action of MP by itself but rather to show the responsiveness of the model to corticosteroid treatment in vitro .…”

Section: Discussionmentioning

confidence: 99%

An Inflamed Human Alveolar Model for Testing the Efficiency of Anti-inflammatory Drugs in vitro

Drašler

Karakoçak

Tankus

et al. 2020

Front. Bioeng. Biotechnol.

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A large number of prevalent lung diseases is associated with tissue inflammation. Clinically, corticosteroid therapies are applied systemically or via inhalation for the treatment of lung inflammation, and a number of novel therapies are being developed that require preclinical testing. In alveoli, macrophages and dendritic cells play a key role in initiating and diminishing pro-inflammatory reactions and, in particular, macrophage plasticity (M1 and M2 phenotypes shifts) has been reported to play a significant role in these reactions. Thus far, no studies with in vitro lung epithelial models have tested the comparison between systemic and direct pulmonary drug delivery. Therefore, the aim of this study was to develop an inflamed human alveolar epithelium model and to test the resolution of LPS-induced inflammation in vitro with a corticosteroid, methylprednisolone (MP). A specific focus of the study was the macrophage phenotype shifts in response to these stimuli. First, human monocyte-derived macrophages were examined for phenotype shifts upon exposure to lipopolysaccharide (LPS), followed by treatment with MP. A multicellular human alveolar model, composed of macrophages, dendritic cells, and epithelial cells, was then employed for the development of inflamed models. The models were used to test the anti-inflammatory potency of MP by monitoring the secretion of pro-inflammatory mediators (interleukin [IL]-8, tumor necrosis factorα [TNF-α], and IL-1β) through four different approaches, mimicking clinical scenarios of inflammation and treatment. In macrophage monocultures, LPS stimulation shifted the phenotype towards M1, as demonstrated by increased release of IL-8 and TNF-α and altered expression of phenotype-associated surface markers (CD86, CD206). MP treatment of inflamed macrophages reversed the phenotype towards M2. In multicellular models, increased pro-inflammatory reactions after LPS exposure were observed, as demonstrated by protein secretion and gene expression measurements. In all scenarios, among the tested mediators the most pronounced anti-inflammatory effect of MP was observed for IL-8. Our findings demonstrate that our inflamed multicellular human lung model is a promising tool for the evaluation of anti-inflammatory potency of drug candidates in vitro. With the presented setup, our model allows a meaningful comparison of the systemic vs. inhalation administration routes for the evaluation of the efficacy of a drug in vitro.

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Section: Discussionmentioning

confidence: 99%

An Inflamed Human Alveolar Model for Testing the Efficiency of Anti-inflammatory Drugs in vitro

Drašler

Karakoçak

Tankus

et al. 2020

Front. Bioeng. Biotechnol.

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“…Furthermore, intravenous high-dose methylprednisolone pulse therapy (IHDMPPT) at 1 g per person for 3 consecutive days, with or without subsequent tapered lower dose steroid therapy, is frequently prescribed for ARDS treatment by physicians in Japan [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study

Hirashima

Arai

Kitajima

et al. 2021

Journal of Infection and Chemotherapy

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Introduction The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. Methods All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients’ records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. Results Data from 61 patients (16 Pt–CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt–CSI were significantly older and had hypertension or diabetes than Pt-MMI ( P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt–CSI than in Pt-MMI ( P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt–CSI than in Pt-MMI ( P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt–CSI than in Pt-MMI ( P = 0.013). Among the 16 Pt–CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died. Conclusions The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.

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“…As cytokine storm is relatively common in severe cases and often leads to exacerbation [11], several anti-in ammation treatments are proposed, including non-steroidal anti-in ammatory drugs, and glucocorticoids, chloroquine/hydroxychloroquine, immunosuppressant, in ammatory cytokines antagonists [12]. Concerning the widespread use of corticosteroids as a therapy for ARDS [13]and proof of e cacy to treat SARS, which could signi cantly decrease the mortality of severe SARS patients, we aimed to evaluate the e cacy of methylprednisolone pulse on intermediate, and severe COVID-19 patients admitted to Intensive Care Unit (ICU).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Efficacy of Methylprednisolone Pulse Therapy in Treatment of Covid-19 Adult Patients with Severe Respiratory Failure: Randomized, Clinical Trial

Farahani

Mosaed

Nezami-Asl

et al. 2020

Preprint

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Background: Covid-19 is now global concern and widely spread to the world due to high mortality among the nations we tried to evaluate the efficacy of methylprednisolone pulse in COVID-19 patients with severe respiratory failure.Methods: This study was phase2, double-blind, randomized, clinical trial in adults with COVID-19 (aged ≥18 years old) admitted to the intensive care unit (ICU) of *. Patients with intermediate or severe COVID-19 with PaO2/FiO2 less than 300 and progressive disease unresponsive to standard treatments admitted to ICU. Patients were randomly allocated in either control or investigation group. The control group received recommended regimen for COVID-19. The investigation group received the recommended regimen plus Methylprednisolone (1000mg/day for three days) and oral prednisolone 1mg/kg with tapering of dose within ten days. Results: A total of 29 ICU patients with intermediate or severe COVID-19 pneumonia recruited in this study. Fourteen patients (4 female, ten male) allocated in the investigation group, and 15 patients (6 female, nine male) assigned to the control group. The participant’s average age was 64.03±13.545 (case: 61.07±12.83, control: 66.80±14.03). The patients with methylprednisolone pulse had significantly higher systolic (P=0.018) and diastolic (P=0.001) blood pressure, meanwhile, the Glasgow coma scale (GCS) of methylprednisolone group was considerably (P<0.001) higher, and by the improvement in SpO2 of methylprednisolone group none of these patients needed mechanical ventilation.Conclusion: This study demonstrated methylprednisolone pulse in COVID-19 severe respiratory failure dramatically improves the clinical condition of patients including, GCS, and SpO2 of patients.Clinical Trial Registration Number: IRCT20200406046963N1

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High‐dose steroid therapy for acute respiratory distress syndrome lacking common risk factors: predictors of outcome

Cited by 4 publications

References 25 publications

An Inflamed Human Alveolar Model for Testing the Efficiency of Anti-inflammatory Drugs in vitro

An Inflamed Human Alveolar Model for Testing the Efficiency of Anti-inflammatory Drugs in vitro

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study

Evaluation of the Efficacy of Methylprednisolone Pulse Therapy in Treatment of Covid-19 Adult Patients with Severe Respiratory Failure: Randomized, Clinical Trial

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