pulmicort and Protein-Losing-Enteropathies

Recent studies have shown that oral budesonide can be used to improve albumin level in patients with protein-losing enteropathy (PLE) following Fontan procedure. However, there has never been a systematic review and meta-analysis to confirm this finding. We performed a systematic review and meta-analysis to explore the therapeutic effect of budesonide in patients with PLE post-Fontan procedure.. We searched the databases of MEDLINE and EMBASE from inception to January 2019. Included studies were published studies that evaluate albumin level before and after budesonide therapy in patients with PLE following Fontan procedure. Data from each study were combined using the random-effects model.. Five studies with 36 post-Fontan operation patients with PLE were included. In random-effects model, there was a statistically significant difference in albumin level between before and after budesonide treatment (weighted mean difference = 1.28, 95% confidence interval: 0.76-1.79). No publication bias was observed on a funnel plot and Egger test with a. The results of this systematic review and meta-analysis show that budesonide can be used to increase albumin level in patients with PLE following Fontan operation. Further studies may focus on the impact of outcome of budesonide in this population.

Topics: Anti-Inflammatory Agents; Budesonide; Databases, Factual; Fontan Procedure; Heart Defects, Congenital; Humans; Postoperative Complications; Protein-Losing Enteropathies; Treatment Outcome

Protein-losing enteropathy (PLE) is a chronic condition involving multiple organ systems that may develop any time following Fontan completion. The pathogenesis of PLE is complex and multifactorial. Chronic venous hypertension, low cardiac output, and abnormal lymphatics may all play a role in the pathogenesis of PLE. Common signs and symptoms include chronic diarrhea, abdominal pain, and ascites. Diagnosis is based on the presence of signs and symptoms in addition to hypoalbuminemia and elevated stool alpha 1 antitrypsin. Early identification and a comprehensive approach to evaluation and treatment are important, as they may affect survival. The initial evaluation should include cardiac catheterization for hemodynamic assessment. Although an evidence base for treatment is lacking, various medical, interventional, and surgical approaches have been described with variable degrees of success. Commonly used therapies include nutritional support, diuretics, subcutaneous unfractionated heparin, budesonide, and sildenafil. Limited data exist for Fontan conversion or takedown. Assessment for heart transplantation should be considered. PLE mortality is high-approximately 50%-but may be mitigated by aggressive investigation and management. The evolving understanding of the role of lymphatics in the pathophysiology of PLE and the emerging role of interventional lymphatic procedures may further improve outcomes in this patient population.

Topics: Abdominal Pain; Academic Medical Centers; Ascites; Budesonide; Chronic Disease; Combined Modality Therapy; Diagnosis, Differential; Diarrhea; Diuretics; Female; Fontan Procedure; Heart Defects, Congenital; Heparin; Humans; Male; Prognosis; Protein-Losing Enteropathies; Rare Diseases; Risk Assessment; Sildenafil Citrate; Treatment Outcome

To evaluate for evidence of systemic glucocorticoid absorption in cases of Fontan-associated protein-losing enteropathy (PLE) treated with enteral budesonide, we reviewed the charts of 27 patients with Fontan-associated PLE followed at Children's Hospital Colorado from 2005 to 2018. Cases were excluded for lack of budesonide thserapy or a treatment duration of less than 6 months. Charts were examined by two endocrinologists for review of prior biochemical endocrine evaluations, alterations in linear growth, and physical exam findings consistent with steroid excess. Twelve patients met inclusion criteria. Eight had prior documented cortisol screening. Three patients were tested while on treatment with a median fasting AM cortisol of 0.9 mcg/dL; two of these had a concomitantly measured ACTH, both below the detectable limit. Five patients were tested while weaning or having discontinued budesonide, with a median fasting AM cortisol of 9.1 mcg/dL. Eleven patients had decreases in height velocity associated with starting budesonide. Six patients had documentation of cushingoid features by an endocrinologist. In this cohort of children treated with budesonide for PLE following Fontan, clinical signs of systemic glucocorticoid absorption were frequent. Cortisol secretion was suppressed while on therapy, with adrenal recovery noted once budesonide was discontinued. Growth failure and cushingoid features were common findings. While these findings should be confirmed in larger cohorts, we recommend that the evaluation for systemic absorption of exogenous steroids be considered in patients treated with long-term enteral budesonide given the potential risk for adrenal crisis in times of physiologic stressors.

Topics: Budesonide; Child; Child, Preschool; Cohort Studies; Female; Fontan Procedure; Glucocorticoids; Humans; Male; Protein-Losing Enteropathies; Retrospective Studies

Protein-losing enteropathy is an infrequent but severe condition occurring after Fontan procedure. The multifactorial pathogenesis remains unclear and no single proposed treatment strategy has proven universally successful. Therefore, we sought to describe different treatment strategies and their effect on clinical outcome and mortality.. We performed a retrospective observational study. From the total cohort of 439 Fontan patients treated in our institution during the study period 1986-2019, 30 patients (6.8%) with protein-losing enteropathy were identified. Perioperative, clinical, echocardiographic, laboratory, and invasive haemodynamic findings and treatment details were analysed.. Median follow-up after disease onset was 13.1 years [interquartile range 10.6]. Twenty-five patients received surgical or interventional treatment for haemodynamic restrictions. Medical treatment, predominantly pulmonary vasodilator and/or systemic anti-inflammatory therapy with budesonide, was initiated in 28 patients. In 15 patients, a stable remission could be achieved by medical or surgical procedures (n = 3 each), by combined multimodal therapy (n = 8), or ultimately by cardiac transplantation (n = 1). Phrenic palsy, bradyarrhythmia, Fontan pathway stenosis, and absence of a fenestration were significantly associated with development of protein-losing enteropathy (p = 0.001-0.48). Ten patients (33.3%) died during follow-up; 5-year survival estimate was 96.1%. In unadjusted analysis, medical therapy with budesonide and pulmonary vasodilator therapy in combination was associated with improved survival.. Protein-losing enteropathy is a serious condition limiting survival after the Fontan procedure. Comprehensive assessment and individual treatment strategies are mandatory to achieve best possible outcome. Nevertheless, relapse is frequent and long-term mortality substantial. Cardiac transplantation should be considered early as treatment option.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Child; Combined Modality Therapy; Disease Management; Female; Fontan Procedure; Heart Transplantation; Hemodynamics; Humans; Male; Protein-Losing Enteropathies; Remission Induction; Retrospective Studies; Risk Factors; Survival Analysis; Vasodilator Agents; Young Adult

A 7-year-old male patient who had abdominal swelling and eyelid oedema was diagnosed with restrictive cardiomyopathy. His serum albumin level was 2.3 g/dl. Protein-losing enteropathy due to restrictive cardiomyopathy was diagnosed and oral budesonide was started. His serum albumin level began to rise and ascites and peripheric oedema disappeared. The patient underwent a successful cardiac transplantation and budesonide was stopped. After the heart transplantation, the albumin level decreased to 2.3 g/dl, and therefore it was restarted. When the serum albumin level increased, the budesonide dose was tapered and stopped in 1 month. Budesonide may be an effective drug in patients with protein-losing enteropathy due to heart failure.

Topics: Administration, Oral; Ascites; Budesonide; Cardiomyopathy, Restrictive; Child; Edema; Glucocorticoids; Heart Transplantation; Humans; Male; Protein-Losing Enteropathies; Serum Albumin; Treatment Outcome

Protein-losing enteropathy is a rare complication of the Fontan palliation surgery. Budesonide is an effective treatment option for protein-losing enteropathy. We reviewed our retrospective experience in four patients who were treated with oral budesonide.. Four patients with refractory protein-losing enteropathy after the Fontan operation were started on oral budesonide 9 mg/daily. After achieving normal serum albumin the dose was tapered to 3 mg. Response to oral budesonide, side effects, and serum albumin levels before the treatment and at first, fourth, and ninth months of the budesonide course were recorded. Efficacy was measured based on serum albumin levels and clinical symptoms.. Mean pretherapy albumin was 2.25 g/dL (range 1.7 to 2.5 g/dL) and nine months after therapy it was 4.15 g/dL (range 3.9 to 4.4 g/dL) (p < 0.05). All patients had at least a transient improvement in serum albumin levels and clinical findings. Systemic side effects included cushingoid features and oral moniliasis. All patients had improvement in side effects after tapering budesonide to 3 mg. The treatment was terminated in one case as soon as serum albumin level exceeded 3 g/dL. One death occurred from respiratory arrest six months after budesonide discontinuation.. Budesonide can be used to treat protein-losing enteropathy in selected patients with cardiac diseases.

Topics: Administration, Oral; Adolescent; Biomarkers; Budesonide; Child; Child, Preschool; Female; Fontan Procedure; Glucocorticoids; Humans; Male; Postoperative Complications; Protein-Losing Enteropathies; Retrospective Studies; Serum Albumin; Treatment Outcome

Protein-losing enteropathy (PLE) is a rare complication of Fontan palliation associated with significant morbidity and mortality. It is characterized by the loss of serum proteins into the intestinal lumen, and its pathophysiology likely involves enteral inflammation. Budesonide, an oral steroid, is an attractive treatment option because of its potent enteral activity and minimal systemic side effects. A single-center, retrospective review of Fontan-palliated PLE patients treated with oral budesonide for 6 months or longer was performed. The patient characteristics reviewed were demographics, anatomic diagnosis, budesonide treatment (dose and duration), other medications and therapeutic interventions, hospitalizations, serum albumin levels, medical complications, and patient status at the time of follow-up assessment. The study enrolled 10 patients representing 228 patient-months of on-therapy follow-up evaluation. Serum albumin levels increased after initiation of budesonide for 90% of the patients, and clinical evidence of fluid overload improved for 60% of them. Symptomatic improvement was reported in 80% of the cases. During the treatment period, 50% of the patients met the primary end point of death or cardiac transplantation. In this series of PLE patients, oral budesonide therapy was associated with significant symptomatic improvement and sustained increases in serum albumin. However, budesonide therapy may not alter the long-term outcome for patients with advanced PLE.

Topics: Administration, Oral; Budesonide; Child, Preschool; Female; Follow-Up Studies; Fontan Procedure; Glucocorticoids; Heart Defects, Congenital; Humans; Infant; Male; Postoperative Complications; Protein-Losing Enteropathies; Retrospective Studies; Time Factors; Treatment Outcome

Approximately 5% to 15% of patients develop protein-losing enteropathy (PLE) after the Fontan operation. Oral controlled release (CR) budesonide has been used as a treatment strategy, but its use in the older Fontan population has not been described.. Seven patients with refractory PLE after the Fontan operation were started on oral CR-budesonide at 9 mg. After 3 to 9 months, the dose was weaned to 3 mg. Response to treatment was assessed by clinical evaluation, serum albumin levels, and fecal α-1 antitrypsin clearance when available.. Median age at last evaluation was 20 years (range, 16 to 32 years). Six patients had increases in serum albumin levels but only 4 patients had symptomatic improvement. Systemic side effects included: cushingoid features (5), adrenal insufficiency (4), and new-onset type 2 diabetes mellitus (2). One patient had improvement in cushingoid features after weaning CR-budesonide to 3 mg. Older patients (ages 27 to 32 years) had the worst side effect profiles and were the most refractory to treatment. These patients had sonographic evidence of hepatic cirrhosis but normal serum liver function tests. Two deaths occurred: 1 from sepsis 1 month after CR-budesonide initiation and 1 from respiratory arrest 5 months after CR-budesonide discontinuation.. CR-budesonide can be used to treat PLE in certain patients, but careful assessment of hepatic function should be performed before initiation of therapy as systemic side effects can limit treatment. Normal serum liver function tests do not preclude hepatic dysfunction in the Fontan patient, and it is important to perform radiographic assessments as well.

Topics: Administration, Oral; Adolescent; Adult; alpha 1-Antitrypsin; Anti-Inflammatory Agents; Budesonide; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Feces; Female; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Humans; Male; Postoperative Care; Protein-Losing Enteropathies; Serum Albumin; Time Factors; Treatment Outcome; Young Adult

Topics: Budesonide; Female; Fontan Procedure; Humans; Male; Postoperative Care; Protein-Losing Enteropathies

Intestinal inflammation is a component of the pathophysiology of protein-losing enteropathy after the Fontan operation. Oral controlled-release budesonide is 90% metabolized at first pass through the liver, has high enteric anti-inflammatory activity and relatively low systemic effects, and may be an ideal agent for use in treating this disease.. Budesonide was administered to 9 patients (4 male) with protein-losing enteropathy after the Fontan operation. The median interval between the Fontan operation and diagnosis of protein-losing enteropathy was 4 years (range, 0.1 to 13.3). Prior interventional therapy included pulmonary artery stent (1), fenestration (3), pacemaker placement (3) and Fontan revision (2). Prior medical therapy included oral prednisone (5), heparin (4), sildenafil (2), infliximab (1), and octreotide (1), all without persistent success. The starting daily dose of budesonide was 9 mg for patients 4 years old or older, and 6 mg for patients less than 4 years of age.. Mean serum albumin level 3 months before starting budesonide was 1.9 g/dL (range, 1 to 2.4 g/dL). Serum albumin level improved in all patients within 6 months of starting budesonide (mean 2.9 g/dL; range, 2.2 to 3.8 g/dL). Albumin levels of 3 g/dL or more were achieved in 8 of 9 patients within a median of 4.3 months (range, 2 to 25). Side effects included Cushingoid features and osteoporosis (3), infection requiring antibiotic treatment (5), and acne exacerbation (1). Weaning from high initial dose to a lower dose was possible with sustained effect; however, discontinuation of budesonide resulted in recurrence of hypoalbuminemia.. Oral budesonide is an effective therapy for treating protein-losing enteropathy after the Fontan operation. To maintain response, low-dose therapy must be continued.

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Female; Fontan Procedure; Humans; Male; Protein-Losing Enteropathies; Serum Albumin; Young Adult

We report the clinical, laboratory, endoscopic and histopathological findings in a 40-year-old woman with watery diarrhoea and hypoproteinaemia. Elevated alpha(1)-antitrypsin clearance confirmed massive protein-losing enteropathy. Gastroscopic and colonoscopic biopsies showed abundant infiltration of the small bowel wall with eosinophils in proximal duodenum and terminal ileum, respectively. These findings established the diagnosis of eosinophilic gastroenteritis. Both the inflammatory alterations and the severe intestinal protein loss were successfully treated with budesonide, a topically active corticosteroid preparation with controlled small bowel release. The case report illustrates that remission of protein-losing enteropathy secondary to eosinophilic gastroenteritis can be achieved with budesonide, thus supporting its use for this uncommon disease characterised by inflammatory intestinal lesions.

Topics: Adult; Anti-Inflammatory Agents; Biopsy; Budesonide; Duodenum; Eosinophilia; Female; Gastroenteritis; Humans; Ileum; Protein-Losing Enteropathies