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The European Respiratory Journal Apr 2024The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a...
BACKGROUND
The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics.
METHODS
An international expert group was convened to develop guidelines for managing ABPA (caused by spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively.
RESULTS
We recommend screening for sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal -IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response.
CONCLUSION
We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.
Topics: Adult; Child; Humans; Aspergillosis, Allergic Bronchopulmonary; Immunoglobulin E; Invasive Pulmonary Aspergillosis; Itraconazole; Mycology; Prednisolone
PubMed: 38423624
DOI: 10.1183/13993003.00061-2024 -
Journal of Hepatology Apr 2024Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH.
METHODS
In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability.
RESULTS
Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018).
CONCLUSIONS
In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF.
IMPACT AND IMPLICATIONS
This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis.
TRIAL REGISTRATION NUMBER
#NCT02900443.
Topics: Humans; Female; Male; Azathioprine; Mycophenolic Acid; Hepatitis, Autoimmune; Prospective Studies; Treatment Outcome; Immunosuppressive Agents; Prednisolone; Remission Induction
PubMed: 38101756
DOI: 10.1016/j.jhep.2023.11.032 -
Ugeskrift For Laeger Nov 2023Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes...
Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes on the face and extremities, muscle pain and weakness. This is a case report of a ten-year-old boy initially suspected of having lupus erythematosus. He was later diagnosed with JDM by dermatologists. Treatment with methotrexate and prednisolone proved to be effective.
Topics: Male; Child; Humans; Dermatomyositis; Methotrexate; Skin; Inflammation; Prednisolone
PubMed: 37987452
DOI: No ID Found -
Intensive Care Medicine Dec 2023Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients.
METHODS
The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up.
RESULTS
We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group.
CONCLUSION
Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Coma; Methylprednisolone; Interleukin-6; Inflammation; Emergency Medical Services; Biomarkers; Phosphopyruvate Hydratase
PubMed: 37943300
DOI: 10.1007/s00134-023-07247-w -
Ugeskrift For Laeger Dec 2023In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI...
In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI showed longitudinal extensive myelitis. Lymph node biopsy was compatible with sarcoidosis and a diagnosis of probable neurosarcoidosis (NS) was made. The patient benefited from prednisolone but relapsed during withdrawal. Infliximab resulted in almost complete remission. In conclusion, relapse is often seen when phasing out prednisolone, whereas infliximab appears to have a lasting effect and should be considered in the early stages of severe NS.
Topics: Male; Humans; Middle Aged; Infliximab; Central Nervous System Diseases; Sarcoidosis; Myelitis; Prednisolone; Magnetic Resonance Imaging
PubMed: 38078475
DOI: No ID Found -
The Lancet. Respiratory Medicine Jan 2024Systemic glucocorticoids are recommended for use in chronic obstructive pulmonary disease (COPD) exacerbations; however, there is increased harm associated with their... (Randomized Controlled Trial)
Randomized Controlled Trial
Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial.
BACKGROUND
Systemic glucocorticoids are recommended for use in chronic obstructive pulmonary disease (COPD) exacerbations; however, there is increased harm associated with their use. We hypothesised that the use of eosinophil biomarker-directed oral prednisolone therapy at the time of an exacerbation of COPD was effective at reducing prednisolone use without affecting adverse outcomes.
METHODS
The studying acute exacerbations and response (STARR2) study was a multicentre, randomised, double-blind, placebo-controlled trial conducted in 14 primary care practices in the UK. We included adults (aged ≥40 years), who were current or former smokers (with at least a 10 pack year smoking history) with a diagnosis of COPD, defined as a post-bronchodilator FEV/forced vital capacity ratio of less than 0·7 previously recorded by the primary care physician, and a history of at least one exacerbation in the previous 12 months requiring systemic corticosteroids with or without antibiotics. All study staff and participants were masked to study group allocation and to treatment allocation. Participants were randomly assigned (1:1) to blood eosinophil-directed treatment (BET; to receive oral prednisolone 30 mg once daily if eosinophil count was high [≥2%] or placebo if eosinophil count was low [<2%]) or to standard care treatment (ST; to receive prednisolone 30 mg once daily irrespective of the point-of-care eosinophil result). Treatment was prescribed for 14 days and all patients also received antibiotics. The primary outcome was the rate of treatment failure, defined as any need for re-treatment with antibiotics or steroids, hospitalisation for any cause, or death, assessed at 30 days after exacerbation in the modified intention-to-treat population. Participants were eligible for re-randomisation at further exacerbations (with a maximum of four exacerbations per participant). A safety analysis was conducted on all randomly assigned participants. Although designed as a superiority trial, after identification of an error in the randomisation code before data lock the study converted to show non-inferiority. An upper margin of 1·105 for the 95% CI was defined as the non-inferiority margin. This study was registered with EudraCT, 2017-001586-24, and is complete.
FINDINGS
Between Nov 6, 2017, and April 30, 2020, 308 participants were recruited from 14 general practices. 144 exacerbations (73 in the BET group and 71 in the ST group) from 93 participants (mean age 70 years [range 46-84] and mean percent predicted FEV 60·9% [SD 19·4]; 52 [56%] male and 41 [44%] female; ethnicity data was not collected]) were included in the modified intention-to-treat analysis. There were 14 (19%) treatment failures at 30 days post-exacerbation in the BET group and 23 (32%) in the ST group; we found a large non-significant estimated effect between BET and ST (RR 0·60 [95% CI 0·33-1·04]; p=0·070) in reducing treatment failures after a COPD exacerbation. The non-inferiority analysis supported that BET was non-inferior to ST. Frequency of adverse events were similar between the study groups; glycosuria (2/102 [2%] in BET group and 1/101 [1%] in the ST group) and hospital admission for COPD exacerbation (2/102 [2%] in BET group and 1/101 [1%] in the ST group) were the two most common adverse events in both groups. No deaths occurred in the study.
INTERPRETATION
Blood eosinophil-directed prednisolone therapy at the time of an acute exacerbation of COPD is non-inferior to standard care and can be used to safely reduce systemic glucocorticoid use in clinical practice.
FUNDING
National Institute for Health and Care Research.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Anti-Bacterial Agents; Disease Progression; Double-Blind Method; Eosinophils; Glucocorticoids; Prednisolone; Primary Health Care; Pulmonary Disease, Chronic Obstructive; United Kingdom; Adult
PubMed: 37924830
DOI: 10.1016/S2213-2600(23)00298-9