Timing of dornase alfa inhalation for cystic fibrosis
CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that ...
Source: Cochrane Database of Systematic Reviews - March 9, 2021 Category: General Medicine Authors: Ruth Dentice Mark Elkins Source Type: research
Timing of dornase alfa inhalation for cystic fibrosis
CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that ...
Source: Cochrane Database of Systematic Reviews - March 9, 2021 Category: General Medicine Authors: Ruth Dentice Mark Elkins Source Type: research
Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis
The lung clearance index (LCI) measured by multiple breath washout (MBW) is a sensitive marker of lung disease even early in life in patients with cystic fibrosis (CF) [1 –3]. Conventionally, pulmonary function in patients with CF is monitored by spirometry from school-age, using the forced expired volume in 1 second (FEV1) as primary outcome [4]. Due to advancements in clinical care, an increasing proportion of school-age children with CF have retained FEV1 withi n the normal or near-normal range over the last decades [5]. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - February 19, 2021 Category: Respiratory Medicine Authors: Christian Voldby, Kent Green, Lue Philipsen, Rikke Mulvad Sandvik, Marianne Skov, Frederik Buchvald, Tacjana Pressler, Kim Gjerum Nielsen Tags: Original Article Source Type: research
Inspiration and Exasperation: The Challenges of Inhaled Biologics.
Abstract
The delivery of biotherapeutic molecules (antibodies, proteins, peptides) and nucleic acids via the respiratory route has presented challenges for regulatory approval, due in part to a lack of understanding of the expected pathology, mechanisms of toxicity, and immunogenicity induced by the inhalation route. Although the first inhaled biotherapeutic was approved some time ago (Dornase Alfa, Pulmozyme; Genetech, 1993), no other inhaled biotherapeutics have been marketed for the treatment of human disease other than the inhaled insulins (Exubera; Pfizer, 2006 and Afrezza; Mannkind Corporation, 2014)...
Source: Toxicologic Pathology - January 5, 2021 Category: Pathology Authors: Hall P, Vahle JL, Colman K Tags: Toxicol Pathol Source Type: research
Polysulfated Hyaluronan GM-1111 Inhibits Elastase and Improves Rheology in CF Sputum.
Abstract
Cystic fibrosis (CF) lung disease is marked by high concentrations of neutrophil elastase (NE) and DNA polymers; both factors contribute to airway disease. Although inhaled recombinant human dornase alfa reduces the frequency of CF pulmonary exacerbations, it also increases free NE activity in the sputum. There are no approved anti-NE therapies for patients with CF. We investigated whether synthetic, low molecular weight polysulfated hyaluronan (GM-1111) would be effective as an anti-NE drug using ex vivo CF sputum. Anti-NE activity of GM-1111 was tested in CF sputum in the presence or absence of ...
Source: Am J Respir Cell Mol... - December 2, 2020 Category: Respiratory Medicine Authors: Kummarapurugu AB, Zheng S, Pulsipher A, Savage JR, Ma J, Rubin BK, Kennedy TP, Voynow JA Tags: Am J Respir Cell Mol Biol Source Type: research
Launch of a novel intrapleural fibrinolytic service for empyema at a district general hospital in London
This study has led to the development of a procedure checklist to further enhance patient safety. Small sample size warrants further audit once our service has been expanded. (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Mackay, E., Sasikumar, S. Tags: Respiratory infections Source Type: research
Neutrophil Extracellular Traps (NETs) increase mucus viscoelasticity
Conclusion: We show that exposing airway mucus to NETs increases the viscoelasticity of airway mucus and that this may be due, in part, to oxidative stress. This implicates a role for NETs formation in the airways as an underlying mechanism in airway mucus obstruction. (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Linssen, R. S. N., Chai, G., Ma, J., Kummarapurugu, A., Van Woensel, J. B. M., Bem, R. A., Kaler, L., Duncan, G., Zhou, L., Rubin, B. K., Xu, Q. Tags: Paediatric respiratory infection and immun. Source Type: research
Predictors of eradication failure at first isolation of MRSA in cystic fibrosis patients
Conclusions: There is limited data investigating morbidity and mortality of chronic MRSA infection. This study has shown that pancreatic insufficiency is one of the predictors of eradication failure. Further prospective studies should be done to determine the best treatment option and impact of MRSA on disease progress. (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Mursaloglu, H. H., Akin, C., Yilmaz, C., Ergenekon, P., Gokdemir, Y., Erdem Eralp, E., Karakoc, F., Karahasan, A., Karadag, B. Tags: Cystic fibrosis Source Type: research
A review of treatment regimens at first isolation of PA in a single cystic fibrosis center
Conclusions: This retrospective review of PA eradication protocols revealed a lower success rate compared to other studies. Although oral ciprofloxacin + inhaled tobramycin regimen seems to be more effective, due to the limited number of patients it did not reach statistical significance. Randomized controlled studies are needed to determine an optimal treatment regimen. (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Mursaloglu, H. H., Akin, C., Yilmaz, C., Ergenekon, P., Gokdemir, Y., Erdem Eralp, E., Karakoc, F., Karahasan, A., Karadag, B. Tags: Cystic fibrosis Source Type: research
Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.
Abstract
Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress e.g. by the release of reactive oxygen species (ROS) and myeloperoxidase (MPO) during NETs formation in the airways would increase mucus viscoelasticity. We collected human mucus from endotracheal tubes of healthy patients adm...
Source: Am J Respir Cell Mol... - October 23, 2020 Category: Respiratory Medicine Authors: Linssen RS, Chai G, Ma J, Kummarapurugu AB, van Woensel JBM, Bem RA, Kaler L, Duncan GA, Zhou L, Rubin BK, Xu Q Tags: Am J Respir Cell Mol Biol Source Type: research
Dornase alfa and rate of lung function decline in European patients with cystic fibrosis: A retrospective registry cohort study
Dornase alfa, a treatment that hydrolyses DNA, is approved as a therapy for patients with Cystic Fibrosis (CF). This mucolytic effect was shown in a pivotal clinical trial to improve lung function and reduce the frequency of CF pulmonary exacerbations [1]. Subsequent longitudinal studies of the impact of dornase alfa on lung function in United States ’ and United Kingdom cohorts have shown additional long-term benefits including reductions in lung function decline, although these findings vary owing to differences in study design [2–4]. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 20, 2020 Category: Respiratory Medicine Authors: Edward F. McKone, Abaigeal D. Jackson, Godfrey Fletcher, Laura Kirwan Tags: Letter to the Editor Source Type: research
Short-course modified regimen intrapleural alteplase and pulmozyme (DNase) in pleural infection
Publication date: Available online 17 July 2020Source: Respiratory Medicine Case ReportsAuthor(s): M. Faisal, R. Farhan, X.K. Cheong, B.H. Ng, N. Nuratiqah, Ban Andrea YL (Source: Respiratory Medicine Case Reports)
Source: Respiratory Medicine Case Reports - July 18, 2020 Category: Respiratory Medicine Source Type: research
Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may trigger severe pneumonia in coronavirus disease of 2019 (COVID-19) patients through release of damage-associated molecular patterns (DAMPs) and ... (Source: Trials)
Source: Trials - June 19, 2020 Category: General Medicine Authors: J. P. Desilles, C. Gregoire, C. Le Cossec, J. Lambert, O. Mophawe, M. R. Losser, F. Lambiotte, S. Le Tacon, M. Cantier, N. Engrand, P. Trouiller and J. Pottecher Tags: Letter Source Type: research
Treatment adherence among children and adolescents in a cystic fibrosis reference center
Conclusions: The TAI was high particularly among children younger than 14 years. There was a positive correlation between the self-referenced TA and the one presumed by the Psychology (p=0.032) and the nutrition (p=0.012) professionals.RESUMO Objetivo: Avaliar o grau de ades ão ao tratamento (AT) autorreferida e pesquisar sua associação com variáveis clínicas e sociodemográficas em pacientes com fibrose cística (FC) de um centro de referência e comparar o grau de AT autorreferida com o presumido pela equipe multidisciplinar. Métodos: Estudo transversal, inclu indo crianças e adolescentes com FC entre zero e ...
Source: Revista Paulista de Pediatria - June 5, 2020 Category: Pediatrics Source Type: research
Low dose intrapleural alteplase and pulmozyme (DNase) in two post-surgical patients with pleural sepsis
Publication date: Available online 29 May 2020Source: Respiratory Medicine Case ReportsAuthor(s): M. Faisal, M. Fazlin, B.H. Ng, N. Nuratiqah, YL. Ban Andrea (Source: Respiratory Medicine Case Reports)
Source: Respiratory Medicine Case Reports - May 29, 2020 Category: Respiratory Medicine Source Type: research
