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Cystic fibrosis ibuprofen

Sharon M Rymut, Binyu Lu, Aura Perez, Deborah A Corey, Kata Lamb, Calvin Utley Cotton, Thomas J Kelley
The use of high-dose ibuprofen as an anti-inflammatory therapy in cystic fibrosis has been shown to be an effective intervention though use is limited due to potential adverse events. Identifying the mechanism of ibuprofen efficacy would aid in the development of new therapies that avoid these adverse events. Previous findings demonstrated that ibuprofen treatment restores the regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells through a 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent mechanism...
March 20, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Zara I Kirkwood, Beverley C Millar, Damian G Downey, John E Moore
Background: Antimicrobial resistance (AMR) has rendered certain species of Mycobacterium difficult to treat clinically, particularly the nontuberculous Mycobacterium, Mycobacterium abscessus, in patients with cystic fibrosis (CF). Such patients are treated with several nonantibiotic medicines, which may have antimicrobial properties. Given the growing burden of AMR in M. abscessus, it is importtant to investigate the antimicrobial activity of all medicines used in the treatment of such patients...
October 2018: International Journal of Mycobacteriology
Adrián J Muñoz, Roxana V Alasino, Ariel G Garro, Valeria Heredia, Néstor H García, David C Cremonezzi, Dante M Beltramo
Ibuprofen (IBU-H), a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa , methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na) and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes...
May 17, 2018: Pharmaceuticals
Brittany A Bruch, Sachinkumar B Singh, Laura J Ramsey, Timothy D Starner
BACKGROUND: This study was undertaken to determine if a clinically relevant drug-drug interaction occurred between ibuprofen and lumacaftor/ivacaftor. METHODS: Peak ibuprofen plasma concentrations were measured prior to and after lumacaftor/ivacaftor initiation. A Wilcoxon signed rank sum test was used to compare the values. RESULTS: Nine patients were included in the final analysis. Peak ibuprofen plasma concentrations decreased an average of 36...
August 2018: Pediatric Pulmonology
Michael W Konstan, Donald R VanDevanter, Gregory S Sawicki, David J Pasta, Aimee J Foreman, Evgueni A Neiman, Wayne J Morgan
RATIONALE: Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade...
April 2018: Annals of the American Thoracic Society
Parth N Shah, Kimberly R Marshall-Batty, Justin A Smolen, Jasur A Tagaev, Qingquan Chen, Christopher A Rodesney, Henry H Le, Vernita D Gordon, David E Greenberg, Carolyn L Cannon
Clinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen's anti-inflammatory properties. Yet, a few previous reports demonstrated an antimicrobial activity of ibuprofen as well, although none investigated its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen's in vitro antimicrobial activity against Pseudomonas aeruginosa and Burkholderia species strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the tested strains in a dose-dependent fashion...
March 2018: Antimicrobial Agents and Chemotherapy
Mario H Vargas, Rosangela Del-Razo-Rodríguez, Amando López-García, José Luis Lezana-Fernández, Jaime Chávez, María E Y Furuya, Juan Carlos Marín-Santana
BACKGROUND: Patients with cystic fibrosis (CF) have airway inflammation that contributes to symptoms and to pulmonary function derangement. Current drugs used to diminish airway inflammation improve the clinical and spirometric status of patients with CF, but their use is limited due to their undesired side effects, for example, glucose intolerance, growth retardation, and cataracts with corticosteroids, gastrointestinal toxicity with ibuprofen, and macrolide resistance with azythromycin...
December 15, 2017: BMC Pulmonary Medicine
Jake Irvine, Afrina Afrose, Nazrul Islam
Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects...
February 2018: Drug Development and Industrial Pharmacy
Larry C Lands, Nurlan Dauletbaev
Cystic Fibrosis (CF) is the most common lethal genetic disorder in North America and Europe. Most patients succumb to progressive lung disease characterized by an exaggerated neutrophilic inflammation. In animal models of chronic infection, high-dose ibuprofen was demonstrated to reduce inflammation without hindering bacterial clearance. This led to two clinical trials, which demonstrated a benefit in slowing the progression of lung disease in CF. However, concerns about potential adverse effects have limited the use of high-dose ibuprofen in CF patients...
July 13, 2010: Pharmaceuticals
Sharon M Rymut, Claire M Kampman, Deborah A Corey, Tori Endres, Calvin U Cotton, Thomas J Kelley
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...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Larry C Lands, Sanja Stanojevic
BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. OBJECTIVES: To assess the effectiveness of treatment with non-steroidal anti-inflammatory drugs in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings...
April 7, 2016: Cochrane Database of Systematic Reviews
Jérémy Rocca, Sylvie Manin, Anne Hulin, Abdel Aissat, Wilfried Verbecq-Morlot, Virginie Prulière-Escabasse, Adeline Wohlhuter-Haddad, Ralph Epaud, Pascale Fanen, Agathe Tarze
BACKGROUND AND PURPOSE: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) patients due to exacerbated inflammation. To date, the only anti-inflammatory drug available to CF patients is high-dose ibuprofen, which can slow pulmonary disease progression, but whose cyclooxygenase-dependent digestive adverse effects limit its clinical use. Here we have tested sulindac, another non-steroidal anti-inflammatory drug with an undefined anti-inflammatory effect in CF airway epithelial cells...
June 2016: British Journal of Pharmacology
Emanuela Fabiola Craparo, Barbara Porsio, Carla Sardo, Gaetano Giammona, Gennara Cavallaro
Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide-polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells...
March 14, 2016: Biomacromolecules
James F Chmiel, Michael W Konstan, Frank J Accurso, James Lymp, Nicole Mayer-Hamblett, Donald R VanDevanter, Lynn M Rose, Bonnie W Ramsey
BACKGROUND: High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials. METHODS: We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessed IL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum...
November 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Donald R VanDevanter, David J Pasta, Michael W Konstan
BACKGROUND: Pulmonary exacerbations (PEx) are important CF clinical events. METHODS: We studied time to next PEx following intravenous (IV) antibiotic PEx treatment among Cleveland Ohio CF center patients occurring between January 2010 and September 2014. Patient demographics, clinical presentations, and treatments were modeled by Cox proportional hazards regression to identify covariates associated with time to next PEx. RESULTS: 193 patients were treated for PEx; 155 had a subsequent IV-treated PEx...
November 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Elena K Schneider, Johnny X Huang, Vincenzo Carbone, Mark Baker, Mohammad A K Azad, Matthew A Cooper, Jian Li, Tony Velkov
Ivacaftor is a novel cystic fibrosis (CF) transmembrane conductance regulator (CFTR) potentiator that improves the pulmonary function for patients with CF bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs may compete for the same plasma protein binding sites and impact the free drug concentration. This, in turn, could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes...
June 2015: Journal of Molecular Recognition: JMR
Graeme W Carlile, Renaud Robert, Julie Goepp, Elizabeth Matthes, Jie Liao, Bart Kus, Sean D Macknight, Daniela Rotin, John W Hanrahan, David Y Thomas
BACKGROUND: Small molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action. METHODS: CFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41o(-) and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes...
January 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Jonathan Liang, Thomas Higgins, Stacey L Ishman, Emily F Boss, James R Benke, Sandra Y Lin
OBJECTIVES/HYPOTHESIS: To systematically review existing literature on the effectiveness of medical management of chronic rhinosinusitis (CRS) in cystic fibrosis (CF) patients. STUDY DESIGN: Systematic review. METHODS: We performed a literature search of PubMed, Embase, and Cochrane CENTRAL from 1987 to 2012. Inclusion criteria included English language as containing original data, with five or more subjects, measurable clinical outcomes, and readily available interventions...
June 2014: Laryngoscope
James F Chmiel, Michael W Konstan, J Stuart Elborn
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s...
October 2013: Cold Spring Harbor Perspectives in Medicine
Larry C Lands, Sanja Stanojevic
BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis (CF). Non-steroidal anti-inflammatory drugs (NSAIDs) may prevent progressive pulmonary deterioration and morbidity in CF. OBJECTIVES: To assess the effectiveness of treatment with NSAIDs in CF. SEARCH METHODS: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings...
2013: Cochrane Database of Systematic Reviews
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