Pediatric population with cystic fibrosis in the centre of Portugal: Candidates for new therapies

Abstract Background: To carry out a complete clinical, pathological, genetic and microbiological characterization of pediatric patients with molecular confirmed cystic fibrosis (CF) attending the Carlos Andrade Marín Hospital (HCAM) within the study period. Methods: A cross-sectional analysis of the pediatric population with a confirmed diagnosis of CF disease who attended HCAM , one of the largest tertiary-level hospitals in Ecuador, between 2017 and 2018 was performed. All demographic, clinical and genetic variables were obtained from the electronic medical records (EMR) stored by the hospital. Results: 47 patients with CF were included in the study. Gender distribution was similar between male (48.9%, n = 23) and female patients (51.1%, n = 24). The Tiffeneau-Pinelli index (FEV 1 /FVC) changed significantly after nine months post-diagnosis (85.55 ± 13.26; p < 0.05). The most common pathogenic genetic variants were F508del, found in 52.78% of the cohort (n = 19); H609R, found in 36.11% (n = 13); g.204099A>C, found in 14.1% (n = 7), followed by G85E and the N1303K with 11.11% (n = 3) each. Conclusions: To our best knowledge, this is the first study exploring the clinical, genetic and bacteriological profile of CF’s patients in Ecuador. Within the cohort of patients, an important and unique genetic feature was characterized by the presence of the g.204099A> C and the c.206359C>A homozygous polymorphism as well as the presence of the H609R variant, a mutation only reported among Ecuadorians.

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Vancomycin Dosing and Monitoring in the Treatment of Cystic Fibrosis: Results of a National Practice Survey

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-22.6.406 ◽

2017 ◽

Vol 22 (6) ◽

pp. 406-411 ◽

Cited By ~ 1

Author(s):

Rebecca S. Pettit ◽

Stacy J. Peters ◽

Erin J. McDade ◽

Kaci Kreilein ◽

Radha Patel ◽

...

Keyword(s):

Cystic Fibrosis ◽

Trough Concentration ◽

Pediatric Population ◽

Area Under The Curve ◽

Monitoring Strategy ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Monitoring Strategies ◽

Cystic Fibrosis Foundation ◽

Initial Starting

OBJECTIVES Vancomycin is commonly used in patients with cystic fibrosis (CF) to treat acute pulmonary exacerbations, but few guidelines exist to help dose and monitor patients. The objective of this study was to assess vancomycin use and monitoring strategies at Cystic Fibrosis Foundation (CFF)–accredited centers in hopes of developing and implementing vancomycin dosing and monitoring standards. METHODS An anonymous national cross-sectional survey of pharmacists affiliated with CFF-accredited pediatric and/or adult centers was performed by using Surveymonkey.com. The survey consisted of 3 sections: (1) CF Center Demographic Information (10 questions); 2) vancomycin use in pediatric CF patients (31 questions); and 3) vancomycin use in adult CF patients (29 questions); it was administered from March 9, 2015, to April 13, 2015. RESULTS The survey was completed by 31/69 (45%) pharmacists and 28 (90.3%) reported using vancomycin in the pediatric population. The most common initial starting dose for pediatric patients was 15 mg/kg/dose (57.1%) and every 6 hours was the most common dosing frequency (67.9%). The most common monitoring strategy was collection of a trough concentration (92.9%) with 57.7% of pharmacist targeting a range of 15 to 20 mg/L. The most common initial starting vancomycin dose in adults with CF was 15 mg/kg/dose (61.5%), and initial frequency of every 8 hours (73.1%). The most common monitoring strategy was a trough concentration (96.2%) with 83.3% of pharmacists reporting a goal trough range of 15 to 20 mg/L. CONCLUSIONS The most common vancomycin dosing reported was 15 to 20 mg/kg/dose every 6 hours (pediatric) and 15 to 20 mg/kg/dose every 8 to 12 hours (adults). Serum concentrations measured to meet monitoring parameters of trough concentrations of 15 to 20 mg/L, or area under the curve to minimum inhibitory concentration ratio > 400, were the same in both pediatric and adult patients.

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Acute pancreatitis prevalence in children with cystic fibrosis and PIP score prediction applicability

Romanian Journal of Medical Practice ◽

10.37897/rjmp.2021.2.23 ◽

2021 ◽

Vol 16 (2) ◽

pp. 248-253

Author(s):

Valentina-Daniela COMĂNICI ◽

◽

Ioana Florentina CODREANU ◽

Anca BĂLĂNESCU ◽

Alina Angelica BELIVACĂ ◽

...

Keyword(s):

Cystic Fibrosis ◽

Acute Pancreatitis ◽

Abdominal Pain ◽

Retrospective Study ◽

Pediatric Population ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Substitution Therapy ◽

Imaging Evaluation ◽

Female Predominance

One of the affected organs in cystic fibrosis (CF) is the pancreas, mainly translated into exocrine pancreatic insufficiency. Although rare, acute pancreatitis (AP) has been described, mostly in pancreatic sufficient patients. Objectives. Estimating AP prevalence in CF pediatric population of the I.N.S.M.C. „AlessandrescuRusescu” CF centre. Material and methods. 5 year retrospective study (2011-2016) including INSMC CF centre pediatric population aged 3-18 years. PA diagnosis was established on the presence of minimum 2 criteria between: characteristic abdominal pain, x3 normal value for age elevation of amylase/lipase, medical imaging evaluation suggestive for AP. Patients were evaluated with different criteria including PIP score of predicting AP risk. Outcomes. 48 patients were included with a slight female predominance (54%). 3 of them presented diagnostic criteria for AP (6,25%), all heaving pancreatic insufficiency and high PIP score (low risk of developing AP); 2 of them have low compliance with pancreatic enzymes substitution therapy; one of them presented recurrent episodes of AP. Conclusions. AP is a rare CF complication. It can be easily missed due to a large number of abdominal pain and emesis causes in CF patients. Although it is usually associated with pancreatic sufficiency, all our patients were pancreatic insufficient.

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Editorial: The changing landscape of cystic fibrosis: new therapies, challenges and a global pandemic

Current Opinion in Pulmonary Medicine ◽

10.1097/mcp.0000000000000734 ◽

2020 ◽

Vol 26 (6) ◽

pp. 668-670

Author(s):

Peter J. Barry ◽

Barry J. Plant

Keyword(s):

Cystic Fibrosis ◽

New Therapies ◽

Global Pandemic

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MRSA Characteristics In A Cystic Fibrosis Pediatric Population

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1128 ◽

2011 ◽

Author(s):

Lisa Read ◽

John McNamara ◽

Mahrya Johnson ◽

Meixia Liu

Keyword(s):

Cystic Fibrosis ◽

Pediatric Population

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Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00126.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. L317-L327 ◽

Cited By ~ 12

Author(s):

Sharon M. Rymut ◽

Claire M. Kampman ◽

Deborah A. Corey ◽

Tori Endres ◽

Calvin U. Cotton ◽

...

Keyword(s):

Cystic Fibrosis ◽

Epithelial Cells ◽

Intracellular Transport ◽

Pediatric Population ◽

Microtubule Dynamics ◽

Cyclooxygenase Inhibitors ◽

High Dose ◽

Cell Periphery ◽

Wild Type ◽

Compound C

High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF.

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