Corticosteroid Response Research Articles

Sex Differences in Serotonin 5-HT 1A Receptor Responses to Repeated Restraint Stress in Adult Male and Female Rats.

Male and female rats were exposed to repeated restraint to determine how changes in serotonin (5-hydroxytryptamine; 5-HT) 1A receptors associate with stress hypothalamic-pituitary-adrenal (HPA) axis habituation. In response to 2-hour episodes of restraint, repeated daily for 5 consecutive days, males and females displayed reliable declines in HPA output, indicated by diminished adrenocorticotropin and corticosterone secretory responses. Using the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) as a pharmacological challenge for inducing hypothermia and elevations in plasma corticosterone, males displayed sensitized hypothermal responses after repeated restraint, whereas corticosterone responses to 8-OH-DPAT were enhanced in both sexes following single or repeated exposure. Only males showed elevations in 5-HT 1A receptor G-protein coupling responses in the dorsal raphe after repeated restraint, whereas only females showed an increase in 5-HT 1A receptor responses in the hippocampus following single or repeated exposure. G-protein coupling responses within both regions correlated positively with 5-HT 1A receptor binding capacity. Thus, despite expressing similar capacities for stress HPA axis habituation, males and females emerged from repeated restraint to show region-specific changes in 5-HT 1A receptor function that may be explained, at least in part, by changes in receptor availability. Based on the hypothermal and corticosteroid responses to 8-OH-DPAT, the present data suggest that stress habituation is met by an increase in the sensitivity of presynaptic 5-HT 1A receptors in males and by an increase in the sensitivity of a population of postsynaptic receptors in both sexes.

Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma—A Randomized, Placebo-Controlled Crossover Trial (MAPLE)

Mepolizumab inhibits IL-5 activity and reducesexacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma(SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms. To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment. A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo,-0.23; 95% CI,-0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI,-0.26 to 0.42), St. George's Respiratory Questionnaire (0.24; 95% CI,-3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI,-0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI,-4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%). OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.

Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection.

RationaleSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes long‐term pulmonary sequelae in adults, but little is known about pulmonary outcomes in pediatrics.Objective(s)The aim of this study was to describe long‐term subjective and objective pulmonary abnormalities after SARS‐CoV‐2 infection in pediatric populations.MethodsSingle‐center, retrospective cohort of patients seen in post‐coronavirus disease 2019 (COVID‐19) pulmonary clinic in 2021. Subjects evaluated had persistent pulmonary symptoms 4 weeks or more after initial infection. Clinical testing included a 6‐min walk test (6MWT), chest X‐ray, pre‐ and postbronchodilator spirometry, plethysmography, and diffusion capacity. Patients were followed 2‐to‐3‐months after the initial visit with repeat testing. The primary outcome was the presence of abnormal pulmonary function testing. Secondary measures included variables associated with pulmonary outcomes.ResultsEighty‐two adolescents were seen at a median of 3.5 months postinfection, with approximately 80% reporting two or more symptoms at clinic presentation (cough, chest pain, dyspnea at rest, and exertional dyspnea). At follow‐up (~6.5 months) exertional dyspnea persisted for most (67%). Spirometry was normal in 77% of patients, but 31% had a positive bronchodilator response. No abnormalities were noted on plethysmography or diffusion capacity. Clinical phenotypes identified included inhaled corticosteroid responsiveness, paradoxical vocal fold motion disorder, deconditioning, and dysautonomia. Multivariable modeling demonstrated that obesity, anxiety, and resting dyspnea were associated with reduced 6MWT, while female sex and resting dyspnea were associated with higher Borg Dyspnea and Fatigues scores.ConclusionsThis is the largest study to date of pediatric patients with long‐term pulmonary sequelae post‐COVID‐19. Identified clinical phenotypes and risk factors warrant further study and treatment.

Diagnostic accuracy of FeNO in asthma and predictive value for inhaled corticosteroid responsiveness: A prospective, multicentre study.

SummaryBackgroundFractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled corticosteroids (ICS).MethodsWe conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measurement. Reference standard was Tiffeneau ratio (FEV1/VC) or airway resistance as assessed by whole body plethysmography, with additional BP or bronchodilation test. Follow-up was performed after 12 weeks. Analyses of Receiver Operating Characteristics curves were conducted to determine the diagnostic accuracy and predictive value of FeNO.Findings308 patients with complete follow-up were recruited, 186 (60·4%) were female, average age was 44·7 years, 161 (52·3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0·718 (95% CI 0·661–0·775; p < 0·001). Sensitivity at FeNO >50 ppb was 0·24 (95% CI 0·18–0·32), specificity 0·99 (0·95–1·0), positive predictive value (PPV) 0·95 (0·84–0·99), negative predictive value (NPV) 0·54 (0·48–0·60). In 66 patients with ´wheezing´ and ´allergic rhinitis´, the sensitivity at FeNO >33 ppb was 0·49 (0·34–0·64), specificity 0·88 (0·64–0·99), PPV 0·92 (0·75–0·99), NPV 0·38 (0·23–0·54). In 68 patients with ICS medication, responsiveness was predicted at the cut-off >43 ppb, with a sensitivity of 0·55 (95%CI 0·36–0·74), specificity 0·82 (0·66–0·92), PPV 0·70 (0·47–0·87), NPV 0·71 (0·56–0·84).InterpretationFeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values.FundingCircassia Germany gave 25% discount on the purchase of three NIOX VERO devices.

Early Intestinal Ultrasound Predicts Intravenous Corticosteroid Response in Hospitalised Patients With Severe Ulcerative Colitis

Our aim was to determine if transabdominal intestinal ultrasound changes after 48 ± 24 h of intravenous corticosteroids can predict treatment outcomes in hospitalised patients with severe ulcerative colitis. We performed a blinded observational multicentre study. Ultrasound parameters were assessed before treatment initiation, after 48 ± 24 h, and 6 ± 1 days. Treatment response was determined within 7 days by two outcome measures: 1] partial Mayo score reduction; 2] no administration of rescue therapy. Out of 69 recruited patients, 56 were included in the final analysis, with 37 responders. The colon segment with the highest baseline bowel wall thickness was analysed, being the sigmoid in all patients. There was no difference in baseline bowel wall thickness between responders and non-responders in the partial Mayo score outcome. At 48 ± 24 h, a significant difference between responders and non-responders was identified in both absolute bowel wall thickness [median 3.1 mm vs 4.9 mm; p <0.0001], absolute reduction [-1.9 mm vs -0.2 mm; p <0.001], and relative reduction [-35.9% vs -4.1%; p <0.0001]. A ≤20% reduction had a sensitivity of 84.2% (95% confidence interval [CI] 60.4, 96.6%) and a specificity of 78.4% [61.8, 90.2%] for determining non-response [area under the curve 0.85]. In the multivariable analysis, a >20% reduction had the highest odds ratio (22.6 [4.2, 201.2]; p = 0.001) for determining response. Similar results were seen for the rescue therapy outcome. Changes in bowel wall thickness, after 48 ± 24 h following intravenous corticosteroid treatment in hospitalised patients with severe ulcerative colitis, identify responders with high accuracy and might be used as an early marker to guide accelerated rescue therapy.

Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GRβ) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GRiKO) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study.

A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD). To construct a measure of clinical response to dexamethasone that was well aligned with the incidence of severe BPD or death at 36 weeks' postmenstrual age. Retrospective cohort study. Level IV Neonatal Intensive Care Unit. Infants treated with dexamethasone for developing BPD between 2010 and 2020. Two models were built based on demographics, changes in ventilatory support, andpartial pressure of carbon dioxide (pCO2 ) after dexamethasone administration. An ordinal logistic regression and regularized binary logistic model for the composite outcome were used to associate response level to BPD outcomes defined by both the 2017 BPD Collaborative and 2018 Neonatal Research Network definitions. Ninety-fiveinfants were treated with dexamethasone before 36 weeks. Compared to the baseline support and demographic data at the time of treatment, changes in ventilatory support improved ordinal model sensitivity and specificity. For the binary classification, BPD incidence was well aligned with risk levels, increasing from 16% to 59%. Incorporation of response variables as measured by changes in ventilatory parameters and pCO2 following dexamethasone administration were associated with downstream outcomes. Incorporating drug response phenotype into a BPD model may enable more rapid development of future therapeutics.

Interaction Between CD34+ Fibrocytes and Airway Smooth Muscle Promotes IL-8 Production and Akt/PRAS40/mTOR Signaling in Asthma.

BackgroundThe circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs.MethodsCD34+ fibrocytes were purified from peripheral blood of asthmatic (Global Initiative for Asthma treatment step 4–5) and normal subjects and cultured for 5∼7 days. In a transwell plate, ASMCs were co-cultured with fibrocytes at a ratio of 2:1, ASMCs were cultured alone (control condition), and fibrocytes were cultured alone for 48 h. Measurements were obtained of interleukin-8 (IL-8), IL-6, IL-17, thymic stromal lymphopoietin, and IL-33 levels in the supernatant and IL-33 levels in the cell lysate of the co-culture. Screening for intracellular signaling in the ASMCs after stimulation was performed using condition medium from the patients’ co-culture (PtCM) or IL-8. mRNA and western blot analysis were used to analyze AKT/mTOR signaling in ASMCs stimulated via treatment with PtCM or IL-8.ResultsCompared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs.ConclusionThe interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma.

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study.

SummaryBackground and AimsTo assess whether corticosteroids improve prognosis in patients with AS‐AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids.MethodsThis was a retrospective cohort study including all patients with AS‐AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan–Meier and Cox regression methods were used for data analysis.ResultsOf 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90‐day transplant‐free survival was 61.6% (95% confidence interval [CI] 55.4–67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2–0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C‐index 0.82; [95% CI 0.8–0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non‐responders. MELD on day 7 with a cut‐off of 25 (sensitivity 62.5%[95% CI: 47.0–75.8]; specificity 95.2% [95% CI: 89.9–97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3–2.1).ConclusionOlder patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.

MOG autoimmunity mimicking CLIPPERS syndrome: Case report and literature review

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome characterized by the predominant involvement of the pons, the cerebellum and the spinal cord with a distinct corticosteroid responsiveness. To date, several cases of neurological disorders with a CLIPPERS-like phenotype have been described, including patients with Immunoglobulin G (IgG) antibodies binding to myelin oligodendrocyte glycoprotein (MOG). We herein report the case of a man with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) fulfilling the diagnostic criteria for probable CLIPPERS and a literature review of CLIPPERS-mimicking patients with MOG-IgG.

Implications of SARS-CoV-2 Infection in Systemic Juvenile Idiopathic Arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is a serious multifactorial autoinflammatory disease with a significant mortality rate due to macrophage activation syndrome (MAS). Recent research has deepened the knowledge about the pathophysiological mechanisms of sJIA-MAS, facilitating new targeted treatments, and biological disease-modifying antirheumatic drugs (bDMARDs), which significantly changed the course of the disease and prognosis. This review highlights that children are less likely to suffer severe COVID-19 infection, but at approximately 2–4 weeks, some cases of multisystem inflammatory syndrome in children (MIS-C) have been reported, with a fulminant course. Previous established treatments for cytokine storm syndrome (CSS) have guided COVID-19 therapeutics. sJIA-MAS is different from severe cases of COVID-19, a unique immune process in which a huge release of cytokines will especially flood the lungs. In this context, MIS-C should be reinterpreted as a special MAS, and long-term protection against SARS-CoV-2 infection can only be provided by the vaccine, but we do not yet have sufficient data. COVID-19 does not appear to have a substantial impact on rheumatic and musculoskeletal diseases (RMDs) activity in children treated with bDMARDs, but the clinical features, severity and outcome in these patients under various drugs are not yet easy to predict. Multicenter randomized controlled trials are still needed to determine when and by what means immunoregulatory products should be administered to patients with sJIA-MAS with a negative corticosteroid response or contraindications, to optimize their health and safety in the COVID era.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) among Patients with Refractory Shock at a Tertiary Hospital: A Look into Clinical Practices and Patient Outcomes

Introduction. A significant number of critically ill patients, as high as 60% among patients with septic shock, suffer from critical illness-related corticosteroid insufficiency (CIRCI), which refers to an inadequate corticosteroid response to the level of stress.&#x0D; Objectives. This study aimed to determine the strategies employed in managing patients with critical illness-related corticosteroid insufficiency and the outcomes of these patients at a tertiary hospital.&#x0D; Methods. This was a single-center, mixed-methods study which consisted of a review of charts of patients 19 years old and above admitted for shock or developed refractory hypotension from January 2017-December 2019, and key informant interviews and focus group discussion among clinicians who have experience in managing CIRCI.&#x0D; Results. A total number of 362 patient charts reviewed showed a relatively low rate of initiation of corticosteroids for patients with refractory shock, at just 28.57% of the entire population. After corticosteroids were initiated, patients were in shock for a median of just one day and the median blood pressure improved to 100/60 mm Hg. In this cohort, patients who were started on steroids had more severe illness, as measured by the Mortality Probability Model (MPM) score, which had a median of 43.65% for the group on steroids and just 25.0% for the non-steroid group (p ≤ 0.0001). Patients who were started on steroids had a statistically significant longer median days on a ventilator, 5 days vs. 3 days for the non-steroid group (p = 0.0297); longer median length of intensive care unit (ICU) stay, 8 days vs. 5 days for the non-steroid group (p = 0.0410), and a higher morbidity and mortality rate. The need for steroids, the presence of septic shock, and a higher MPM score were significant predictors of mortality.&#x0D; Discussions among clinicians revealed significant variability in practices in the management of CIRCI.&#x0D; Conclusion. The presence of clinical features of CIRCI is a poor prognostic factor. Timely recognition, work-up, and interventions to address CIRCI are paramount in critical care.

Transcriptome profiling reveals stress-responsive gene networks in cattle muscles.

In meat-producing animals, preslaughter operations (e.g., transportation, mixing unfamiliar animals, food and water deprivation) may be a source of stress with detrimental effects on meat quality. The objective of this work was to study the effect of emotional and physical stress by comparing the transcriptomes of two muscles (M. longissimus thoracis, LT and M. semitendinosus, ST) in Normand cows exposed to stress (n = 16) vs. cows handled with limited stress (n = 16). Using a microarray, we showed that exposure to stress resulted in differentially expressed genes (DEGs) in both muscles (62 DEGs in LT and 32 DEGs in ST, of which eight were common transcription factors (TFs)). Promoter analysis of the DEGs showed that 25 cis transcriptional modules were overrepresented, of which nine were detected in both muscles. Molecular interaction networks of the DEGs targeted by the most represented cis modules helped identify common regulators and common targets involved in the response to stress. They provided elements showing that the transcriptional response to stress is likely to (i) be controlled by regulators of energy metabolism, factors involved in the response to hypoxia, and inflammatory cytokines; and (ii) initiate metabolic processes, angiogenesis, corticosteroid response, immune system processes, and satellite cell activation/quiescence. The results of this study demonstrate that exposure to stress induced a core response to stress in both muscles, including changes in the expression of TFs. These factors could relay the physiological adaptive response of cattle muscles to cope with emotional and physical stress. The study provides information to further understand the consequences of these molecular processes on meat quality and find strategies to attenuate them.

Predictors of Response to Oral Medications and Low-Histamine Diet in Patients with Chronic Urticaria.

Background Chronic urticaria (CU) is comprised of diverse phenotypes, and thus, a shift towards a precision medical approach is warranted in its management. Methods This study enrolled 78 patients with CU. Serum erythrocyte sedimentation rate, hemoglobin, hematocrit, eosinophil count, IgE, antinuclear antibody (ANA), and serum diamine oxidase (DAO) levels of the patients were measured and were compared according to the patient's response to second-generation antihistamines (sgAH), corticosteroids, leukotriene receptor antagonist (LTRA), H2 blockers, and low-histamine diet. Results Age- and sex-adjusted logistic regression analysis showed that patients with duration of CU > 3 years (adjusted odd ratio [aOR] = 4.39) and a DAO level < 10 U/mL (aOR = 3.90) were significantly associated with a good sgAH response. Age > 50 years (aOR = 0.02), duration of chronic urticaria > 3 years (aOR =0.06), and an ANA titer ≥ 1 : 80 (aOR = 0.03) were significantly and inversely associated with corticosteroid response. A low-histamine diet response was significantly associated with LTRA response (aOR = 67.29). In addition, a DAO level < 5.4 U/mL (aOR = 71.95) was significantly associated with H2 blocker response. Furthermore, concomitant angioedema (aOR = 10.56), multiple food triggers (aOR = 11.69), and a DAO level < 5.4 U/mL (aOR = 3.78) were significantly associated with a low-histamine diet response. Conversely, dermatographic urticaria and a hematocrit level < 36% were significantly and inversely associated with low-histamine diet response. Conclusions Several promising biomarkers were identified in this study to predict the efficacy of chronic urticaria treatment. DAO could be a novel biomarker for predicting the efficacy not only of dietary intervention but also for antagonists of H1 and H2 receptors.

Lung Microbiota Signature and Corticosteroid Responses in Pneumonia-Associated Acute Respiratory Distress Syndrome in Hematological Patients.

ObjectiveIn this study, we aim to classify hematological patients with the pneumonia-associated acute respiratory syndrome (ARDS) into different groups that were characterized by distinct early responsiveness to corticosteroids, describe the microbiota signatures of the non-responders and responders, and compare the prognosis of the two groups.MethodsHematological patients with ARDS were included and treated with mechanical ventilation and corticosteroid. According to the early improvement to the corticosteroid therapy, patients were classified as non-responders and responders. The lung microbiota signatures and the outcomes of the non-responders and responders were compared.ResultsFifty patients were included in this study. Twenty-eight patients were classed as non-responders and 22 as responders. Compared to the non-responders, responders had higher serum levels of IL-6, IL-8, TNF-α and CRP, their lung microbiota was with lower alpha diversity and enriched with virus species. The responders had an overall higher ventilator free days than the non-responders [4 (0–6) vs 6 (0–10), p=0.034], for survivors the difference was more significant [5 (3–6) vs 8 (3–10), p=0.012]. Survival analysis showed that there was no difference in survival rate between the two groups over time (Log-rank p=0.073). When non-responders were stratified into subgroups of patients with infection or co-infection, those non-responders with co-infection had significantly lower survival rate than other patients (Log-rank p= 0.028).ConclusionFor hematological patients with pneumonia-associated ARDS, the responders of corticosteroids had higher ventilator free days at day 28 than the non-responders. The microbiota signatures were distinct in the two groups. The non-responders with coinfections had the lowest survival rate when compared to the non-responders with no coinfections and the responders.

POS-224 The ratio of neutrophils to lymphocytes effectively predicts glucocorticoid response in idiopathic membranous nephropathy

Several systemic inflammatory indicators, such as neutrophil to lymphocyte ratio (NLR), play important roles in the prognosis of various diseases. Due to its strong anti-inflammatory effects, corticosteroids are recommended as the basic treatment for patients with idiopathic membranous nephropathy (IMN). However, a key issue is how to objectively determine the factors related with corticosteroid treatment. Therefore, this study aimed to evaluate the value of NLR in predicting corticosteroid response in IMN.

Presence of multilobular necrosis on liver biopsy identifies corticosteroid responsiveness in acute indeterminate hepatitis.

Treatment of patients with severe indeterminate hepatitis (IAH) is an unmet need. Corticosteroids are often used in the management of these patients but criteria for the selection of patients for this intervention are arbitrary. The aims of this study were to analyse the clinical and pathological features of patients with IAH to define predictors of corticosteroid responsiveness. This study included consecutive patients with acute indeterminate hepatitis admitted to a single hospital and underwent a liver biopsy. The clinical manifestation and histopathological features of steroid and non-steroid groups were compared and their relationship with corticosteroids response was evaluated. Forty-eight patients were included, 24 (50%) recovered and the other half underwent liver transplantation or died within 3-months. Of the 48 cases, 24 received corticosteroids (initial dose of 45±12mg prednisolone). Corticosteroids were initiated 2.7±3.8days after admission. Liver biopsy was performed 2-days (median, IQR 1-3) after admission. Fifteen (62.5%) patients receiving corticosteroids survived without transplantation compared with 9 (37.5%) that did not receive steroids (P=.149). In those with multilobular necrosis, 50% reduction in the death/transplantation rate was observed after steroid treatment (P=.018). In patients without multilobular necrosis and with or without perivenulitis, corticosteroids did not impact the outcome. Response to corticosteroids was independent of the MELD score. The presence of multilobular necrosis on liver biopsy helps identify a subgroup of IAH cases who may benefit from the administration of corticosteroids.

Ambulatory care management of 69 patients with acute severe ulcerative colitis in comparison to 695 inpatients: insights from a multicentre UK cohort study

IntroductionAcute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.AimsWe used data from PROTECT,...

Predictors of High Sputum Eosinophils in Chronic Obstructive Pulmonary Disease.

Eosinophils are involved in the development of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroid responsiveness. We evaluated clinical predictors of high sputum eosinophil levels in a COPD cohort in China. We conducted an observational, prospective, population-based, cross-sectional study. Participants were tested for COPD and underwent spirometry, computed tomography scans, and a blood test. Participants also produced induced sputum and responded to an information-gathering questionnaire. High sputum eosinophils were defined as ≥3.0%. Multivariate logistic regression was used to identify predictors of high sputum eosinophil levels. We recruited 895 patients with complete and quality control data. The median percentage of sputum eosinophil abundance was 2.00% (interquartile range: 0.75-5.00) and the prevalence of COPD with high sputum eosinophils was 38.0%. Covariance analysis indicated that the high sputum eosinophil group had lower lung function, more severe emphysema, and air trapping. Multivariate logistic regression indicated that high blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases were associated with high sputum eosinophil levels. High blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases may be predictors of high sputum eosinophil levels in Chinese COPD patients. High sputum eosinophils were associated with lower lung function, more emphysema, and gas trapping.