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https://www.readbyqxmd.com/read/28102546/ataluren-and-similar-compounds-specific-therapies-for-premature-termination-codon-class-i-mutations-for-cystic-fibrosis
#1
REVIEW
Aisha A Aslam, Colin Higgins, Ian P Sinha, Kevin W Southern
BACKGROUND: Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance...
January 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28039554/serum-level-of-dnase1l3-in-patients-with-dermatomyositis-polymyositis-systemic-lupus-erythematosus-and-rheumatoid-arthritis-and-its-association-with-disease-activity
#2
Qi Zhao, Chunshu Yang, Jianing Wang, Yujia Li, Pingting Yang
DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study...
December 30, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27943680/progression-of-lung-disease-in-preschool-patients-with-cystic-fibrosis
#3
Sanja Stanojevic, Stephanie D Davis, George Retsch-Bogart, Hailey Webster, Miriam Davis, Robin C Johnson, Renee Jensen, Maria Ester Pizarro, Mica Kane, Charles C Clem, Leah Schornick, Padmaja Subbarao, Felix A Ratjen
RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVE: To define the utility of the Lung Clearance Index (LCI), measured by Multiple Breath Washout (MBW), as a means to track disease progression in preschool children with CF. METHODS: CF children between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy controls were enrolled at three North American CF centers...
December 12, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27942431/biomarkers-for-the-phenotyping-and-monitoring-of-asthma-in-children
#4
REVIEW
Anna James, Gunilla Hedlin
An important issue in relation to the utility and reliability of biomarkers for asthma monitoring is how asthma is defined and characterized. What kind of asthma, or at what stage of the disease is a particular biomarker supposed to add information? Often, the purpose, or usefulness of a biomarker is not made clear. Diagnosis, severity evaluation, and monitoring are all different clinical uses for a biomarker, and confusion may arise when a biomarker is suitable for one of these but not another. When the utility of available biomarkers are discussed, these different roles need to be clarified...
2016: Current Treatment Options in Allergy
https://www.readbyqxmd.com/read/27931123/developments-in-multibreath-washout-testing-in-children-with-cystic-fibrosis
#5
Clare Saunders, Katie Bayfield, Samantha Irving, Christopher Short, Andrew Bush, Jane C Davies
Lung Clearance Index (LCI) is becoming recognized as an important addition in the monitoring of pediatric cystic fibrosis (CF). The non-invasive technique is easy to perform in all ages, reproducible and increasingly being used in clinical trials. There is interest to utilize it within the clinic setting but its current use is mostly as a research tool. The procedure is highly dependent on skilled operators and a relaxed testing environment is key to obtaining good quality measurements. Standardization of LCI is part of an ongoing collaborative, multicenter process...
December 9, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27927050/the-use-of-multiple-breath-washout-for-assessing-cystic-fibrosis-in-infants
#6
Gwyneth Davies, Paul Aurora
Lung Clearance Index, measured using the multiple breath washout (MBW) technique, may be a useful test in infants with Cystic Fibrosis (CF). However, the requirement for specialised equipment and a number of important technical and methodological considerations relevant to testing in infants have complicated matters, and to date prevented its widespread translatability in this age group. Areas covered: We review the current status of infant MBW testing in CF, focusing on Lung Clearance Index. This includes a review of recent developments in the field relevant to testing methodology in the infant population, use in evaluating lung disease in CF in infancy, and the associated challenges which remain...
January 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/27919570/agreement-between-multiple-breath-nitrogen-washout-systems-in-children-and-adults
#7
William Poncin, Florian Singer, Anne-Sophie Aubriot, Patrick Lebecque
BACKGROUND: Comparability of multiple breath washout (MBW) systems has been little explored. We assessed agreement in lung clearance index (LCI) from two similar, commercial nitrogen MBW setups in patients with Cystic Fibrosis (CF) and controls. METHODS: The EasyOne Pro (NDD) and Exhalyzer D (EM) were randomly applied in 85 adults (34 with CF) and 97 children (47 with CF and normal forced expiratory volume in one second). We assessed differences between setups in LCI, lung volumes and breathing pattern and diagnostic performance for detecting abnormal lung function...
December 2, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/27885143/intrapulmonary-percussive-ventilation-as-a-lung-recruitment-strategy-in-brain-dead-organ-donors
#8
Geralyn Lerg, Linda Shanta
OBJECTIVE: To determine the strength of the evidence evaluating the effectiveness of intrapulmonary percussive ventilation (IPV) as a safe alternative or adjunctive therapy to traditional chest physiotherapy (CPT) among potential organ donors. DATA SOURCES: Literature search conducted from February 2015 to November 2015 using PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and bibliographies of pertinent articles. SEARCH TERMS: Intrapulmonary percussive ventilation, chest physiotherapy, chest wall oscillation, organ donors, and ventilation...
November 24, 2016: Progress in Transplantation
https://www.readbyqxmd.com/read/27872075/pharmacokinetic-pharmacodynamic-evaluation-of-gepotidacin-against-gram-positive-organisms-using-data-from-murine-infection-models
#9
Catharine C Bulik, Ólanrewaju O Okusanya, Elizabeth A Lakota, Alan Forrest, Sujata M Bhavnani, Jennifer L Hoover, David R Andes, Paul G Ambrose
Gepotidacin (formerly GSK2140944) is a novel triazaacenaphthylene bacterial topoisomerase inhibitor with in vitro activity against conventional and biothreat pathogens, including Staphylococcus aureus and Streptococcus pneumoniae Using neutropenic murine thigh- and lung-infection models, the pharmacokinetics-pharmacodynamics (PK-PD) of gepotidacin against S. aureus and S. pneumoniae were characterized. Single dose PK data from uninfected mice (16-128 mg/kg SC) were fit with candidate models. Dose-fractionation studies (one isolate/organism; 2-512 mg/kg/day) and dose-ranging studies (5 isolates/organism; 2-2048 mg/kg/day; MIC ranges: S...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27856821/determinants-of-early-life-lung-function-in-african-infants
#10
Diane Gray, Lauren Willemse, Ane Visagie, Dorottya Czövek, Polite Nduru, Aneesa Vanker, Dan J Stein, Nastassja Koen, Peter D Sly, Zoltán Hantos, Graham L Hall, Heather J Zar
BACKGROUND: Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. AIM: To assess the determinants of early lung function in African infants. METHOD: Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6-10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique...
November 17, 2016: Thorax
https://www.readbyqxmd.com/read/27805836/lumacaftor-ivacaftor-in-patients-aged-6-11-years-with-cystic-fibrosis-homozygous-for-f508del-cftr
#11
Carlos E Milla, Felix Ratjen, Gautham Marigowda, Fang Liu, David Waltz, Margaret Rosenfeld
RATIONALE: Combination lumacaftor/ivacaftor has been shown to improve lung function and other endpoints in patients aged ≥12 years with cystic fibrosis homozygous for F508del-CFTR but has not been assessed in younger patients. OBJECTIVES: This open-label phase 3 trial evaluated the safety, tolerability, pharmacodynamics, and efficacy of lumacaftor/ivacaftor combination therapy in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR. METHODS: Patients (N = 58) received 200 mg lumacaftor/250 mg ivacaftor orally every 12 hours for 24 weeks in addition to their existing cystic fibrosis medications...
November 2, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27730167/closed-circuit-rebreathing-to-achieve-inert-gas-wash-in-for-multiple-breath-wash-out
#12
Alex R Horsley, Katherine O'Neill, Damian G Downey, J Stuart Elborn, Nicholas J Bell, Jaclyn Smith, John Owers-Bradley
Multiple breath wash-out (MBW) testing requires prior wash-in of inert tracer gas. Wash-in efficiency can be enhanced by a rebreathing tracer in a closed circuit. Previous attempts to deploy this did not account for the impact of CO2 accumulation on patients and were unsuccessful. We hypothesised that an effective rebreathe wash-in could be delivered and it would not alter wash-out parameters. Computer modelling was used to assess the impact of the rebreathe method on wash-in efficiency. Clinical testing of open and closed circuit wash-in-wash-out was performed in healthy controls and adult patients with cystic fibrosis (CF) using a circuit with an effective CO2 scrubber and a refined wash-in protocol...
January 2016: ERJ Open Research
https://www.readbyqxmd.com/read/27695990/functional-and-genetic-predisposition-to-rhinovirus-lower-respiratory-tract-infections-in-prematurely-born-infants
#13
Simon B Drysdale, Mireia Alcazar, Theresa Wilson, Melvyn Smith, Mark Zuckerman, Hennie M Hodemaekers, Riny Janssen, Louis Bont, Sebastian L Johnston, Anne Greenough
: Term born infants are predisposed to human rhinovirus (HRV) lower respiratory tract infections (LRTI) by reduced neonatal lung function and genetic susceptibility. Our aim was to investigate whether prematurely born infants were similarly predisposed to HRV LRTIs or any other viral LRTIs. Infants born less than 36 weeks of gestational age were recruited. Prior to neonatal/maternity unit discharge, lung function (functional residual capacity by helium gas dilution and multiple breath washout, lung clearance index and compliance (Crs), and resistance (Rrs) of the respiratory system) was assessed and DNA samples assessed for eight single nucleotide polymorphisms (SNPs) in seven genes: ADAM33, IL10, MMP16 NFκB1A,SFTPC, VDR, and NOS2A...
December 2016: European Journal of Pediatrics
https://www.readbyqxmd.com/read/27645685/lung-clearance-index-lci-in-patients-with-bronchiolitis-obliterans-a-preliminary-report-and-comparison-to-cystic-fibrosis-patients
#14
Michal Gur, Karin Yaacoby-Bianu, Anat Ilivitzki, Ronen Bar-Yoseph, Vered Nir, Fahed Hakim, Yazeed Toukan, Lea Bentur
INTRODUCTION: Bronchiolitis obliterans (BO) is a chronic airway disease following an insult to the lower respiratory tract. Lung clearance index (LCI) measures ventilation inhomogeneity and has been studied in cystic fibrosis (CF). We aimed to evaluate LCI in BO and to compare it to LCI in CF patients. METHODS: LCI was measured in BO patients, compared to CF patients, and correlated with spirometry and CT findings. RESULTS: Twenty BO patients and 26 CF patients (with similar mean age and BMI) underwent evaluation...
August 31, 2016: Lung
https://www.readbyqxmd.com/read/27575911/comparison-of-lung-clearance-index-and-magnetic-resonance-imaging-for-assessment-of-lung-disease-in-children-with-cystic-fibrosis
#15
Mirjam Stahl, Mark O Wielpütz, Simon Y Graeber, Cornelia Joachim, Olaf Sommerburg, Hans-Ulrich Kauczor, Michael Puderbach, Monika Eichinger, Marcus A Mall
RATIONALE: Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF, however, the relationship between the two measures remains unknown. OBJECTIVES: To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF...
August 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27509359/lung-function-in-african-infants-in-the-drakenstein-child-health-study-impact-of-lower-respiratory-tract-illness
#16
Diane M Gray, Lidija Turkovic, Lauren Willemse, Ane Visagie, Aneesa Vanker, Dan J Stein, Peter D Sly, Graham L Hall, Heather J Zar
Rationale Lower respiratory tract illness is a major cause of childhood morbidity and mortality. It is unknown whether infants are predisposed to illness due to impaired lung function or whether respiratory illness reduces lung function. We aimed to investigate the impact of early life exposures, including lower respiratory tract illness on lung function during infancy. Methods Infants enrolled in the Drakenstein child health study had lung function at six weeks and one year. Testing, during quiet natural sleep, included tidal breathing, exhaled nitric oxide and multiple breath washout measures...
August 10, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27492518/clinical-characteristics-of-adult-asthma-associated-with-small-airway-dysfunction
#17
S Kjellberg, B K Houltz, O Zetterström, P D Robinson, Per M Gustafsson
Suboptimal asthma control is common despite modern asthma therapy. The degree of peripheral airway involvement remains unclear and poor medication delivery to these regions might be a contributing reason for this failure in obtaining adequate symptom control. A cohort of 196 adults (median (range) age 44 (18-61) years, 109 females, 54 ex-smokers, six current smokers) with physician-diagnosed asthma were recruited from primary care. Subjects were characterized clinically by interviews, questionnaires, skin prick tests (SPT) and blood eosinophil counts...
August 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27450411/study-protocol-rationale-and-recruitment-in-a-european-multi-centre-randomized-controlled-trial-to-determine-the-efficacy-and-safety-of-azithromycin-maintenance-therapy-for-6%C3%A2-months-in-primary-ciliary-dyskinesia
#18
Helene E Kobbernagel, Frederik F Buchvald, Eric G Haarman, Carmen Casaulta, Samuel A Collins, Claire Hogg, Claudia E Kuehni, Jane S Lucas, Heymut Omran, Alexandra L Quittner, Claudius Werner, Kim G Nielsen
BACKGROUND: Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD...
2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27395423/lung-clearance-index-in-adults-and%C3%A2-children-with-cystic-fibrosis
#19
Katherine O'Neill, Michael M Tunney, Elinor Johnston, Stephen Rowan, Damian G Downey, Jacqueline Rendall, Alastair Reid, Ian Bradbury, J Stuart Elborn, Judy M Bradley
BACKGROUND: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate end point in cystic fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometric findings. Further study of LCI as an end point in adults with CF is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI across the age range of people with CF. METHODS: Clinically stable adults and children with CF and age-matched healthy control subjects were recruited...
December 2016: Chest
https://www.readbyqxmd.com/read/27392915/efficacy-of-delayed-treatment-of-china-made-peramivir-with-repeated-intravenous-injections-in-a-mouse-influenza-model-from-clinical-experience-to-basal-experiment
#20
Zhengtu Li, Runfeng Li, Jing Li, Hui Xie, Yanbing Hao, Qiuling Du, Tingting Chen, Yimin Li, Rongchang Chen, Zifeng Yang, Nanshan Zhong
BACKGROUND: China-made Peramivir, an anti-influenza neuraminidase inhibitor drug, is manufactured and widely used in China. Although effective if initiated within 48 h of the onset of symptoms, yet we observed that this drug shows an inconclusive efficacy if treatment is delayed in clinical. Thus we evaluated the efficacy of delayed treatment of China-made Peramivir in a mouse model. METHODS: The mouse model of influenza infection was made and Peramivir was administered intravenously for 5 days following infection, and weight loss, lung index, viral shedding and survival rates were monitored...
2016: BMC Infectious Diseases
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