Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mepolizumab is an anti-interleukin-5 monoclonal antibody that is in clinical trials with GlaxoSmithKline (GSK) for the treatment of severe asthma, nasal polyposis and hypereosinophilic syndrome and eosinophilic oesophagitis (the latter two indications are classed as eosinophilia in the phase table). Interleukin-5 stimulates the production, activation and maturation of eosinophils. Since mepolizumab inhibits interleukin-5 and has a long terminal half-life, treatment with mepolizumab causes a sustained reduction in the numbers of circulating eosinophils. Thus, mepolizumab may be a useful therapeutic agent for the treatment of conditions characterized by increased levels of eosinophils. Hypereosinophilic syndrome is a rare idiopathic disease with broad clinical signs and symptoms that is diagnosed based on a persistent blood eosinophil count of >1500 cells, various end-organ damages (including skin, heart, lung, nervous system and digestive system), and with exclusion of known secondary causes of hypereosinophilia. Mepolizumab is in clinical trials for the treatment of hypereosinophilic syndrome, eosinophilc oesophagitis, severe asthma (in patients with airway eosinophilia) and nasal polyposis. GlaxoSmithKline (GSK) has completed enrolment in a phase II study of mepolizumab in 20 patients with symptomatic eosinophilic bronchitis with or without asthma in Canada. The randomized, double-blind, placebo-controlled study is evaluating the effects of intravenous mepolizumab on asthma control, airway eosinophilia and the degree to which concomitant corticosteroid treatment can be reduced (NCT00292877). In previous clinical studies, including trials in the EU and US, mepolizumab has shown a lack of effect on allergen-induced airway responses and inflammation despite a significant reduction in blood and sputum eosinophil levels.A randomized, double-blind, placebo-controlled, multicentre, phase III study of mepolizumab over 9 months in 85 patients with hypereosinophilic syndrome was completed in 2006. All patients have been offered, and continued in, a phase III, open-label, long-term extension study of mepolizumab. Enrolment in this study was completed in September 2006.A phase III, compassionate use trial of mepalizumab (NCT00244686) in patients with hypereosinophilic syndrome was ongoing in October 2007 in the US. Patients who have significant clinical disease but are unresponsive to traditional treatment and those who have demonstrated clinical benefit from previous anti-IL-5 treatment are eligible to take part in the trial. Mepolizumab received orphan drug status for first-line treatment in patients with hypereosinophilic syndrome in the US and the EU in 2004. Mepolizumab is also in phase I/II clinical development for the treatment of eosinophilic oesophagitis. A phase I/II trial (NCT00358449) began in August 2006 in the US, Australia, the UK and Canada, and will enrol approximately 72 paediatric patients with eosinophilic oesophagitis. The randomized, parallel-group clinical trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous mepolizumab for 12 weeks. In September 2006, GSK completed enrolment in a phase I/II study of mepolizumab for the treatment of eosinophilic oesophagitis in ten adult patients in Switzerland (NCT00274703). The randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of IV mepolizumab.A phase I/II trial of mepolizumab in four patients with eosinophilic oesophagitis conducted by Cincinnati Children's hospital found the monoclonal antibody was safe and effective. Brigham and Women's Hospital in association with GSK is conducting a phase I/II trial of mepolizumab in patients with Churg-Strauss Syndrome (CSS) in the US. The trial, which started in September 2007, will evaluate the potential of mepolizumab to reduce the need for corticosteroid therapy in patients with CSS (NCT00527566). CSS, otherwise known as allergic granulomatosis, is defined by patients with asthma, eosinophilia and vasculitis.
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PMID:Mepolizumab: 240563, anti-IL-5 monoclonal antibody - GlaxoSmithKline, anti-interleukin-5 monoclonal antibody - GlaxoSmithKline, SB 240563. 1829 30

BACKGROUND Hypereosinophilic syndrome (HES) is defined as hypereosinophilia with eosinophil mediated organ damage or dysfunction, provided that other causes of organ damage have been excluded. CASE REPORT An 83-year-old female presented with worsening dyspnea for 3 weeks. She was initially diagnosed with bronchitis and prescribed oral antibiotics along with prednisone taper. However, her dyspnea continued to worsen requiring hospitalization. Physical examination was significant for signs of volume overload. Laboratory investigations were notable for leukocytosis with eosinophilia, elevated BNP (brain natriuretic peptide) and troponin. Electrocardiogram (ECG) showed normal sinus rhythm with non-specific ST-T wave changes. Computed tomography (CT) scan of the chest showed pulmonary edema, bilateral peripheral ground glass opacities, and pleural effusions. Transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 45%. She was diagnosed with NSTEMI (non-ST-elevation myocardial infarction) with new onset heart failure; appropriate management was initiated. Left heart catheterization did not show any significant obstructive lesions. Presence of peripheral ground glass opacities on the CT chest scan and eosinophilia raised suspicion for HES. Thorough HES workup was done, all tests came back negative except for elevated serum IgE level. Cardiac biopsy returned positive for eosinophilic myocarditis. Bone marrow biopsy showed 20% eosinophils. Positron emission tomography (PET) scan did not show any hypermetabolic lesions to suggest malignancy. The patient was managed for idiopathic HES with high dose steroids resulting in significant clinical improvement. CONCLUSIONS About 40% of patient with HES manifest cardiac involvement, and one quarter of patients with HES have pulmonary involvement with variable radiologic findings. Steroids remain the mainstay treatment for idiopathic HES.
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PMID:Idiopathic Hypereosinophilic Syndrome in an Elderly Female: A Case Report. 3090 63