Maintenance Oral Prednisolone Research Articles

Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma

Nonadherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management. The goal of this study was to evaluate the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma. Timeline serum levels of prednisolone, cortisol, and metabolites were measured by using a validated LC-MS/MS assay following observed intake of prednisolone in patients receiving maintenance oral prednisolone. Patterns of adherence and nonadherence were determined from analysis of peak blood levels. The performance of a spot test for adherence (detectable prednisolone and suppressed cortisol) was assessed in a second cohort of patients receiving maintenance prednisolone and a control group. In the prednisolone absorption test, 27 patients (mean age, 38.6 years; age range, 17-63 years; 83%female) were included. We identified adherence in 13 (48%), nonadherence in 13 (48%), and malabsorption in one (3.7%). The median [interquartile range] peak serum assays of the adherent group compared with the nonadherent group were: cortisol, 36 [39.5] vs295 [153] nmol/L; and prednisolone, 1,810 [590] vs1,730 [727] nmol/L. The spot test cohort included 111 patients (67 on maintenance prednisolone and 44 control subjects); the mean age was 42.4 years, and 79%were female. Nonadherence was detected in 40.3%of patients; comparison of the adherent vsnonadherent groups revealed median [interquartile range] levels for cortisol of 27 [48] nmol/L vs211 [130] nmol/L and for prednisolone of 259 [622] nmol/L vs< 20nmol/L, respectively. Adherent patients had higher mean BMI (38.4 ± 8.7 vs32 ± 7.5kg/m2; P= .03), lower median blood eosinophils (0.09 [0.31] vs 0.51 [0.53] ×109/L; P< .001), and a trend toward reduced mean annual severe exacerbations (3.0 ± 2.6 vs4.3 ± 2.4; P= .3) than nonadherent patients. Nonadherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic by using the LC-MS/MS assay.

SUN-448 BYWATERS' SYNDROME A RARE COMPLICATION OF EPILEPTIC SEIZURE: CASE REPORT

The syndrome was first described by British physician Eric Bywaters in patients during the 1941 London Blitz. It is a reperfusion injury that appears after the release of the crushing pressure. The mechanism is believed to be the release into the bloodstream of muscle breakdown products notably myoglobin, potassium and phosphorus that are the products of rhabdomyolysis. Recently, similar condition was described in epileptic patients either due to severe attack of fits or following a toxicity induced by anti-epileptic medications. The specific action on the kidneys is not understood completely, but may be due partly to nephrotoxic metabolites of myoglobin. These systemic effects are caused by a rhabdomyolysis. In addition to tissue directly suffering the crush mechanism, down stream tissue is subject to ischemia-reperfusion injury of the appendicular musculoskeletal system. Without proper preparation, the patient, with pain control, may be cheerful before extrication, but die shortly thereafter. This sudden decompensation is called the "smiling death". A case report 28 year old male with history of epilepsy. he suddenly felt down into ground with attack of seizure activity followed by myalgia and muscle weakness. On presentation he was breathlessness hypertensive, lung congestion with low urine output (10 ml of dark red urine/day). Investigations revealed normal sonographic kidneys, high serum creatinine 8.22 mg/dl, serum creatine kinase (CK total) of 420,700 u/l (normal 30-200u/l), hyponatremia 128 mmol/l, hyperkalemia of 5.7 mmol/l, hyperuricemia uric acid 9.0 mg/dl, metabolic acidosis; serum bicarbonate was 15 mmol/l, hyperphosphatemia 8 mg/dl, hypocalcemia 6.2 mg/dl and positive myoglobin in urine. Supportive hemodialysis session was indicated for normalization of metabolic profile, adjustment of fluid overload, removal of myoglobin toxic burden, sevelamer was added to control hyperphosphatemia. Daily, hemodialysis was done for 4 consecutive days.clinically improved with serum creatinine, BUN and creatine kinase dropped to normal levels with normalization of electrolyte and uric acid, So Hemodialysis stopped. However, after days of improvement of serum creatinine it start to increase again by around 200 mg/dl per day, with maintaining of normal renal function. Clinically, patient complained of severe right thigh pain, hypotonia related to right thigh muscles with oedema of whole right leg up to inguinal region, with difficulity of walking. Doppler u/s of arterial and venous system of the lower limbs was normal, normal nerve conduction. Muscle biopsy was done under anesthesia, methylprednisolone was initiated 60 mg iv per day. On next day, a dramatic improvement of the patient clinical condition, he was walking with no pain. The muscles of the right thigh regained its normal tone and the oedema disappeared. The biopsy results came later and showed multifocal necrotic muscle fibers, myophagocytosis, up regulation of MHC-I in absence of inflammatory infiltrates. In view of this, patient was discharged on maintenance oral prednisolone 40 mg daily with gradual tapering of the dose over 15 days. After two months, his serum creatinine 0.8 mg/dl, normal serum creatine kinase. we report a rare case of crush syndrome after combined trauma and possible toxic effect from antiepileptic medications with good outcome after careful stepwise management.

Severe asthma in children-a review of definitions, epidemiology, and treatment options in 2019.

Severe asthma is a relatively uncommon condition in children but one which causes morbidity, occasionally mortality, and is a challenging condition to manage. There are several definitions of severe asthma, which have a common theme of poor control despite high dose inhaled corticosteroid treatment. Depending on the definition chosen, the prevalence of severe childhood asthma may be up to 5% within populations with asthma. Collectively, there is some evidence that the treatments used in severe asthma are beneficial, but a solid evidence-base is lacking for many treatments and some treatments have recognized side effects. Evidence supporting the use of maintenance oral prednisolone and intramuscular triamcinolone is weak. Response to systemic corticosteroids is heterogeneous and recognizing phenotypes or endotypes may identify those most likely to gain maximal benefit from treatment. For children aged 6 to 11 years, the anti-IgE biologic omalizumab is effective and anti-IL-5 agent (mepolizumab) has recently been licenced in Europe (but not the US). Biologics, which are licenced for >11 year olds include omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab. There is plenty that the clinician can offer to the child and adolescent with severe asthma in 2019, including nontherapeutic and therapeutic interventions. To manage severe asthma, practitioners from broad specialities must establish and maintain a close therapeutic relationship with patients. Looking beyond 2019, more treatment options will emerge for severe childhood asthma, and clinical teams will need to continue weighing up benefits and harms.

A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis

ObjectiveWe evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect.MethodsEighteen patients with...

Bronchial thermoplasty in severe asthma in Australia.

Bronchial thermoplasty (BT) is an approved bronchoscopic intervention for the treatment of severe asthma. However, limited published experience exists outside of clinical trials regarding patient selection and outcomes achieved. To evaluate the effectiveness and safety of BT in patients with severe asthma encountered in clinical practice. This is a retrospective analysis of the first 'real world' data from Australia. The following outcomes were measured prior to, and 6 months following BT: spirometry, Asthma Control Questionnaire-5 (ACQ-5) score, reliever and preventer medication use and exacerbation history. Twenty patients were treated from June 2014 to December 2015 at three university teaching hospitals. All subjects met the European Respiratory Society/American Thoracic Society definition of severe asthma. Mean pre-bronchodilator forced expiratory volume in 1 s was 62.8 ± 16.6% predicted (range: 33-95%). All patients were being treated with high dose inhaled corticosteroids, long-acting beta2 agonists and long-acting muscarinic antagonists. Ten patients (50%) were taking maintenance oral prednisolone. Most subjects also required at least one of montelukast (65%), omalizumab (30%) and methotrexate (20%). ACQ-5 improved from 3.6 ± 1.1 at baseline to 1.6 ± 1.2 at 6 months, P < 0.001. Short-acting reliever use decreased from a median of 8.0-0.25 puffs/day, P < 0.001, and exacerbations requiring corticosteroids also significantly reduced. Five of 10 patients completely discontinued maintenance oral corticosteroids. Ten patients with a baseline forced expiratory volume in 1 s of <60% predicted significantly improved from 49.2 ± 9.6% to 61.8 ± 17.6%, P < 0.05. Only two procedures required hospitalisation beyond the planned overnight admission. BT is a safe procedure which can achieve clinical improvement in those with uncontrolled symptoms and severe airflow obstruction.

P85 Home and school directly observed therapy in a child with difficult and life threatening asthma

Background and aimWe report the case of a child with difficult and life- threatening asthma whose control improved with directly observed therapy (DOT). School based DOT improves adherence1 but to...

Elevated VGKC-complex antibodies in a boy with fever-induced refractory epileptic encephalopathy in school-age children (FIRES)

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and behavioural difficulties. We describe a case of FIRES in a 4-year-old boy that was associated with elevated voltage-gated potassium channel (VGKC) complex antibodies and a significant clinical and immunological response to immunomodulation. This case, therefore, potentially expands the clinical phenotype of VGKC antibody-associated disease to include that of FIRES. Prior to immunomodulation, neuropsychology assessment highlighted significant attention, memory, and word-finding difficulties. The UK version of the Wechsler Preschool and Primary Scale of Intelligence assessment indicated particular difficulties with verbal skills (9th centile). Immunomodulation was initially administered as intravenous methylprednisolone (followed by maintenance oral prednisolone) and later in the disease course as regular monthly intravenous immunoglobulin infusions and low-dose azathioprine. Now aged 6 years, the seizure burden in this child is much reduced, although increased seizure frequency is observed in the few days before his monthly immunoglobulin infusions. Formal IQ assessment has not been repeated but there is no clinical suggestion of further cognitive regression. VGKC complex antibodies have been reported in a range of central and peripheral neurological disorders (predominantly presenting in adulthood), and the identification of elevated VGKC complex antibodies, combined with the response to immunotherapies in this child, supports an autoimmune pathogenesis in FIRES with potential diagnostic and therapeutic implications.

P20 The eligibility of patients with difficult asthma for omalizumab since the change to the treatment criteria

Omalizumab is a humanised monoclonal anti-IgE agent which is useful as an add-on therapy for severe atopic asthma. We have previously shown that 13.5% of patients attending our adult difficult...

Eosinophilic gastroenteritis: clinical experience with 15 patients.

To evaluate the clinic features of eosinophilic gastroenteritis and to examine the diagnosis, treatment, long-term outcome of this disease. Charts with a diagnosis of eosinophilic gastroenteritis from 1984 to 2002 at Mackay Memorial Hospital were reviewed retrospectively. There were 15 patients diagnosed with eosinophilic gastroenteritis. The diagnosis was established in 13 by histologic evaluation of endoscopic biopsy or operative specimen and in 2 by radiologic imaging and the presence of eosinophilic ascites. All the patients had gastrointestinal symptoms and 12 (80%) had hypereosinophilia (absolute eosinophil count 1,008 to 31,360/cm3). The most common symptoms were abdominal pain and diarrhea. Five of the 15 patients had a history of allergy. Seven patients had involvement of the mucosa, 2 of muscularis, and 6 of subserosa. One with a history of seafood allergy was successfully treated with an elimination diet. Another patient improved spontaneously after fasted for several days. The remaining 13 patients were treated with oral prednisolone, 10 to 40 mg/day initially, which was then tapered. The symptoms in all the patients subsided within two weeks. Eleven of the 15 patients were followed up for more than 12 months (12 to 104 months, mean 48.7), of whom 5 had relapses after discontinuing steroids (13 episodes). Two of these patients required long-term maintenance oral prednisolone (5 to 10 mg/day). Eosinophilic gastroenteritis is a rare condition of unclear etiology characterized by relapses and remissions. Short courses of corticosteroids are the mainstay of treatment, although some patients with relapsing disease require long-term low-dose steroids.

Systemic Bioactivity Profiles of Oral Prednisolone and Nebulized Budesonide in Adult Asthmatics

Because nebulized budesonide may be used as an alternative to maintenance oral prednisolone in the treatment of severe chronic asthma, it is important to compare these two drugs to determine their relative systemic bioactivity profiles in terms of effects on adrenal, bone, and hematologic markers. Twelve asthmatic patients (mean age; 34.7 years; mean FEV1; 88.3% predicted; mean forced expiratory flow between 25% and 75% of FVC, 54.8% predicted) were studied in a double-blind, double-dummy, randomized crossover design to compare placebo, low, medium, and high doses of nebulized budesonide given bid (1, 2, and 4 mg/d, respectively), and oral prednisolone given qd (5, 10, and 20 mg/d). All treatments and both placebos were given for 4 days at each dose level with a 7-day washout period between each treatment block with budesonide or prednisolone. All measurements were made at 8 AM after the last dose of each dose increment for plasma cortisol, serum osteocalcin, and blood eosinophil count. Regression analysis showed significant dose-related suppression with prednisolone for 8 AM plasma cortisol (p<0.0001), osteocalcin (p<0.05), and blood eosinophil count (p<0.0005), but not with budesonide. Compared with placebo, there were significant differences only with prednisolone, at the medium- and high-dose levels for all three markers. For all three systemic bioactivity markers (8 AM plasma cortisol, serum osteocalcin, and blood eosinophils), there was significant dose-related suppression with prednisolone but not with budesonide. Further long-term studies are required in more severe asthmatics in order to evaluate the therapeutic index.