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1.
William Poncin Florian Singer Anne-Sophie Aubriot Patrick Lebecque 《Journal of cystic fibrosis》2017,16(2):258-266
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.Results
Compared to NDD, EM measured higher LCI, functional residual capacity and cumulative expired volume while respiratory rate was lower. Mean difference (limits of agreement) in LCI was 1.30 (? 2.34 to 4.94). In CF, prevalence of abnormal LCI was greater in children and similar in adults using EM compared to NDD.Conclusions
Agreement of MBW outcomes between setups is poor and explained by nitrogen measurement techniques and breathing pattern. 相似文献2.
Lasantha Gunasekara Mustafa Al-Saiedy Francis Green Ryan Pratt Candice Bjornson Ailian Yang W. Michael Schoel Ian Mitchell Mary Brindle Mark Montgomery Elizabeth Keys John Dennis Grishma Shrestha Matthias Amrein 《Journal of cystic fibrosis》2017,16(5):565-572
Background
Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation.Methods
Surfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD).Results
CF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products.Conclusion
We confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF. 相似文献3.
Stephanie S. Filigno Shannon M. Robson Rhonda D. Szczesniak Leigh A. Chamberlin Meredith A. Baker Stephanie M. Sullivan John Kroner Scott W. Powers 《Journal of cystic fibrosis》2017,16(4):519-524
Background
Adequate nutrition is essential for growth in children with cystic fibrosis (CF). The new CF Foundation Clinical Practice Guidelines bring attention to monitoring macronutrient intake as well as total energy.Methods
Dietary intake of 75 preschool children with CF and pancreatic insufficiency was examined and compared to the Clinical Practice Guidelines. Regression analyses examined relationships between macronutrient intake and growth.Results
Approximately 45% of children met the 110% minimum recommended dietary allowance (RDA) recommendation. Children consumed 35.3% (6.1) of total daily energy intake from fat, 12.7% (1.7) from protein, and 52.0% (6.1) from carbohydrates. Percent energy from protein was associated with height growth.Conclusions
Many preschoolers with CF are not meeting nutrition benchmarks for total energy and fat. To optimize nutrition early, dietary monitoring with frequent individualized feedback is needed. Optimizing intake of macronutrients that promote growth, especially fat and protein, should be a primary clinical target. 相似文献4.
Zoé Cavalli Quitterie Reynaud Romain Bricca Raphaële Nove-Josserand Stéphane Durupt Philippe Reix Marie Perceval Michèle Pérouse de Montclos Gérard Lina Isabelle Durieu 《Journal of cystic fibrosis》2017,16(5):579-584
Background
We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution.Methods
From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls).Results
48 CF patients with NTM-positive isolates were matched to 96 controls. The age group for whom incident NTM was higher was young adolescents aged 13 to 17. A significant association for NTM positivity was found with Staphylococcusaureus in multivariate analysis and with allergic bronchopulmonary aspergillosis, corticosteroid and itraconazole in univariate analysis. Mean annual FEV1 decline was faster for NTM-positive patients compared to controls.Conclusion
These data highlight the high incidence of NTM-positive cultures among young adolescents with CF. 相似文献5.
Lily Paemka Brian N. McCullagh Mahmoud H. Abou Alaiwa David A. Stoltz Qian Dong Christoph O. Randak Robert D. Gray Paul B. McCray 《Journal of cystic fibrosis》2017,16(4):471-474
Background
We sought to address whether CF macrophages have a primary functional defect as a consequence of CFTR loss and thus contribute to the onset of infection and inflammation observed in CF lung disease.Methods
Monocyte derived macrophages (MDMs) were prepared from newborn CF and non-CF pigs. CFTR mRNA expression was quantified by rtPCR and anion channel function was determined using whole cell patch clamp analysis. IL8 and TNFα release from MDMs in response to lipopolysaccharide stimulation was measured by ELISA.Results
CFTR was expressed in MDMs by Q-rtPCR at a lower level than in epithelial cells. MDMs exhibited functional CFTR current at the cell membrane and this current was absent in CF MDMs. CF MDMs demonstrated an exaggerated response to lipopolysaccharide stimulation.Conclusions
In the absence of CFTR function, macrophages from newborn CF pigs exhibit an increased inflammatory response to a lipopolysaccharide challenge. This may contribute to the onset and progression of CF lung disease. 相似文献6.
7.
Jeff R. Crosby Chenguang Zhao Chong Jiang Dong Bai Melanie Katz Sarah Greenlee Hiroshi Kawabe Michael McCaleb Daniela Rotin Shuling Guo Brett P. Monia 《Journal of cystic fibrosis》2017,16(6):671-680
Background
Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease.Methods
We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease.Results
The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach.Conclusions
Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. 相似文献8.
Background
Cystic fibrosis (CF, mucoviscidosis) is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), which is a chloride and bicarbonate channel necessary for fluid secretion and extracellular alkalization. For a long time, research concentrated on abnormal Cl- and Na+ transport, but neglected bicarbonate as a crucial factor in CF.Methods
The present short review reports early findings as well as recent insights into the role of CFTR for bicarbonate transport and its defects in CF.Results
The available data indicate impaired bicarbonate transport not only in pancreas, intestine, airways, and reproductive organs, but also in salivary glands, sweat duct and renal tubular epithelial cells. Defective bicarbonate transport is closely related to the impaired mucus properties and mucus blocking in secretory organs of CF patients, causing the life threatening lung disease.Conclusions
Apart from the devastating lung disease, abrogated bicarbonate transport also leads to many other organ dysfunctions, which are outlined in the present review. 相似文献9.
L. Nkam J. Lambert A. Latouche G. Bellis PR. Burgel M.N. Hocine 《Journal of cystic fibrosis》2017,16(6):702-708
Background
Therapeutic progress in patients with cystic fibrosis (CF) has resulted in improved prognosis over the past decades. We aim to reevaluate prognostic factors of CF and provide a prognostic score to predict the risk of death or lung transplantation (LT) within a 3-year period in adult patients.Methods
We developed a logistic model using data from the French CF Registry and combined the coefficients into a prognostic score. The discriminative abilities of the model and the prognostic score were assessed by c-statistic. The prognostic score was validated using a 10-fold cross-validation.Results
The risk of death or LT within 3 years was related to eight characteristics. The development and the validation provided excellent results for the prognostic score; the c-statistic was 0.91 and 0.90 respectively.Conclusion
The score developed to predict 3-year death or LT in adults with CF might be useful for clinicians to identify patients requiring specialized evaluation for LT. 相似文献10.
Isobel E.R. MacKenzie Valerie Paquette Frances Gosse Sheenagh George Frederic Chappe Valerie Chappe 《Journal of cystic fibrosis》2017,16(3):335-341
Background
The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation.Methods
Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada.Results
Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients.Conclusion
The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. 相似文献11.
12.
Alison DaCosta Cameron L. Jordan Olivia Giddings Feng-Chang Lin Peter Gilligan Charles R. Esther 《Journal of cystic fibrosis》2017,16(4):483-487
Background
Mycobacterium abscessus infection is associated with declining lung function in cystic fibrosis (CF), but there is little evidence on clinical efficacy to guide treatment.Methods
Retrospective review of 37 CF patients treated for M. abscessus respiratory infection at a single center from 2006 to 2014. Outcomes included change in FEV1 at 30, 60, 90, 180, and 365 days after treatment and clearance of M. abscessus from sputum cultures.Results
Lung function was significantly improved after 30 and 60 days of treatment, but not at later time points. Gains were inversely related to starting lung function. Antibiotic choices did not influence outcomes except for greater clearance with clarithromycin.Conclusions
Treatment of M. abscessus resulted in short term improvement in lung function that is inversely related to pre-treatment FEV1. 相似文献13.
Aaron J. Buckland Subaraman Ramchandran Louis Day Shay Bess Themistocles Protopsaltis Peter G. Passias Bassel G. Diebo Renaud Lafage Virginie Lafage Akhila Sure Thomas J. Errico 《The spine journal》2017,17(11):1601-1610
Background Context
Patients with degenerative lumbar stenosis (DLS) adopt a forward flexed posture in an attempt to decompress neural elements. The relationship between sagittal alignment and severity of lumbar stenosis has not previously been studied.Purpose
We hypothesized that patients with increasing radiological severity of lumbar stenosis will exhibit worsening sagittal alignment.Study Design
This is a cross-sectional study.Patient Sample
Our sample consists of patients who have DLS.Outcome Measures
Standing pelvic, regional, lower extremity and global sagittal alignment, and health-related quality of life (HRQoL) were the outcome measures.Methods
Patients with DLS were identified from a retrospective clinical database with corresponding full-body stereoradiographs. Exclusion criteria included coronal malalignment, prior spine surgery, spondylolisthesis>Grade 1, non-degenerative spinal pathology, or skeletal immaturity. Central stenosis severity was graded on axial T2-weighted magnetic resonance imaging (MRI) from L1–S1. Foraminal stenosis and supine lordosis was graded on sagittal T1-weighted images. Standing pelvic, regional, lower extremity, and global sagittal alignment were measured using validated software. The HRQoL measures were also analyzed in relation to severity of stenosis.Results
A total of 125 patients were identified with DLS on appropriate imaging. As central stenosis grade increased, patients displayed significantly increasing standing T1 pelvic angle, pelvic tilt, sagittal vertical axis, and pelvic incidence-lumbar lordosis (p<.05). No significant difference wasfound in pelvic incidence, supine lordosis, thoracic kyphosis, or T1 spinopelvic inclination between central stenosis groups. Despite similar supine lordosis between stenosis groups, patients with Grades 2 and 3 stenosis had less standing lordosis, suggesting antalgic posturing. Upper lumbar (L1–L3) stenosis predicted worse alignment than lower lumbar (L4–S1) stenosis.Increasing severity of foraminal stenosis was associated with reduced lumbar lordosis; however, no significant postural difference in lordosis, thoracolumbar, or lower extremity compensatory mechanisms were noted between foraminal stenosis groups. Stenosis grading did not predict worsening HRQoLs in central or foraminal stenosis.Conclusions
Severity of central lumbar stenosis as graded on MRI correlates with severity of sagittal malalignment. These findings support theories of sagittal malalignment as a compensatory mechanism for central lumbar stenosis. 相似文献14.
Fábio A. Araújo Ana Martins Nuno Alegrete Laura D. Howe Raquel Lucas 《The spine journal》2017,17(10):1426-1434
Background Context
In each specific habitual standing posture, gravitational forces determine the mechanical setting provided to skeletal structures. Bone quality and resistance to physical stress is highly determined by habitual mechanical stimulation. However, the relationship between bone properties and sagittal posture has never been studied in children.Purpose
This study aimed to investigate the association between bone physical properties and sagittal standing postural patterns in 7-year-old children. We also analyzed the relationship between fat or fat-free mass and postural patterns.Study Design
Cross-sectional evaluation.Patient Sample
This study was performed in a sample of 1,138 girls and 1,260 boys at 7 years of age participating in the Generation XXI study, a population-based cohort of children followed since birth (2005–2006) and recruited in Porto, Portugal.Outcome Measures
Sagittal standing posture was measured through photographs of the sagittal right view of children in the standing position. Three angles were considered to quantify the magnitude of major curves of the spine and an overall balance measure (trunk, lumbar, and sway angles). Postural patterns were identified using latent profile analysis in Mplus.Methods
Weight and height were measured. Total body less head fat or fat-free mass and bone properties were estimated from whole-body dual-energy X-ray absorptiometry scans. The associations of fat or fat-free mass and bone physical properties with postural patterns were jointly estimated in latent profile analysis using multinomial logistic regressions.Results
The identified patterns were labeled as Sway, Flat, and “Neutral to Hyperlordotic” (in girls), and “Sway to Neutral,” Flat, and Hyperlordotic (in boys). In both genders, children in the Flat pattern showed the lowest body mass index, and children with a rounded posture presented the highest: mean differences varying from ?0.86?kg/m2 to 0.60?kg/m2 in girls and from ?0.70?kg/m2 to 0.62?kg/m2 in boys (vs. Sway or “Sway to Neutral”). Fat and fat-free mass were inversely associated with a Flat pattern and positively associated with a rounded posture: odds ratio (OR) of 0.23 per standard deviation (SD) fat and 0.70 per SD fat-free mass for the Flat pattern, and 1.85 (fat) and 1.43 (fat-free) for the Hyperlordotic pattern in boys, with similar findings in girls. The same direction of relationships was observed between bone physical properties and postural patterns. A positive association between bone (especially bone mineral density) and a rounded posture was robust to adjustment for age, height, and body composition (girls: OR=1.79, p=.006 fat-adjusted, OR=2.00, p=.014 fat-free mass adjusted; boys: OR=2.02, p=.002 fat-adjusted, OR=2.42, p<.001 fat-free mass adjusted).Conclusions
In this population-based pediatric setting, there was an inverse association between bone physical properties and a Flat posture. Bone and posture were more strongly positively linked in a rounded posture. Our results support that both bone properties and posture mature in a shared and interrelated mechanical environment, probably modulated by pattern-specific anthropometrics and body composition. 相似文献15.
Michelle N. Eakin Shang-En Chung Jessica Hoehn Belinda Borrelli Devin Rand-Giovannetti Kristin A. Riekert 《Journal of cystic fibrosis》2017,16(5):637-644
Background
Beliefs about medication have been associated with adherence in other diseases but there are no existing disease-specific medication beliefs questionnaires for CF. This mixed-methods validated the Cystic Fibrosis Medication Belief Questionnaire (CF-MBQ), based on social cognitive theory.Methods
Based on previous research, items were developed for five domains: motivation, self-efficacy, perceived importance, and decisional balance to take or miss medications. Cognitive interviews were conducted with 15 adult patients with CF to refine item development. 128 patients with CF completed an online survey and objective medication adherence was measured using pharmacy refill data.Results
The five subscales demonstrated strong psychometric properties, with adequate-to-good internal consistency scores. More importantly, each domain demonstrated construct validity with adherence.Conclusions
These theoretically-derived measures may be important for clinical purposes to provide guidance on appropriate interventions to improve adherence and for research to provide enhanced understanding on patient determinants of medication adherence. 相似文献16.
Rhonda Szczesniak Lidija Turkovic Eleni-Rosalina Andrinopoulou Harm A.W.M. Tiddens 《Journal of cystic fibrosis》2017,16(2):175-185
Background
The dawn of precision medicine and CFTR modulators require more detailed assessment of lung structure in cystic fibrosis (CF) clinical studies. Various imaging markers have emerged and are measurable, but clarity is needed to identify what markers should count for clinical studies. High-resolution chest computed tomography (CT) scoring has yielded sensitive markers for the study of CF disease progression. Once completed, CT scores from ongoing randomized controlled trials can be used to examine relationships between imaging endpoints and therapeutic effectiveness. Similarly, Magnetic Resonance Imaging (MRI) is in development to generate structural as well as functional markers.Results
The aim of this review is to characterize the role of currently available CT and MRI markers in clinical studies, and to discuss study design, data processing and statistical challenges unique to these endpoints in CF studies. Suggestions to overcome these challenges in CF studies are included.Conclusions
To maximize the potential of CT and MRI markers in clinical studies and advance treatment of CF disease progression, efforts should be made to conduct longitudinal randomized controlled trials including these modalities, develop data repositories, promote standardization and conduct reproducible research. 相似文献17.
Jacqueline L. Anderson Caitlin Miles Audrey C. Tierney 《Journal of cystic fibrosis》2017,16(2):186-197
Background
An increasing body of research investigating the use of probiotics to improve health outcomes in patients with cystic fibrosis (CF) prompted the need to systematically assess and summarise the relevant literature.Methods
An electronic search of five databases and three trial databases was conducted. Studies describing the administration of probiotics to patients with CF older than 2 years, with a comparator group on respiratory, gastrointestinal and nutritional outcomes were included.Results
Three pre–post studies and six randomised controlled trials met the inclusion criteria. Overall studies showed a positive effect of probiotics on reducing the number of pulmonary exacerbations and decreasing gastrointestinal inflammation. There was limited effect of probiotics on other outcomes and inadequate evidence for the effects of specific probiotic species and strains.Conclusion
The findings suggest that probiotics may improve respiratory and gastrointestinal outcomes in a stable CF clinic population with no reported evidence of harm. There is inadequate evidence at this time to recommend a specific species, strain or dose of probiotic as likely to be of significant benefit. 相似文献18.
Nina Dickerhof Rufus Turner Irada Khalilova Emmanuelle Fantino Peter D Sly Anthony J Kettle 《Journal of cystic fibrosis》2017,16(2):214-221
Background
In cystic fibrosis (CF) there is an urgent need for earlier diagnosis of pulmonary infections and inflammation using blood- and urine-based biomarkers.Methods
Using mass spectrometry, oxidation products of glutathione and uric acid were measured in matched samples of bronchoalveolar lavage (BAL), serum and urine from 36 infants and children with CF, and related to markers of neutrophilic inflammation and infection in BAL.Results
Oxidation products of glutathione (glutathione sulfonamide, GSA) and uric acid (allantoin), were elevated in BAL of children with pulmonary infections with Pseudomonas aeruginosa (PsA) compared to those without (p < 0.05) and correlated with other markers of neutrophilic inflammation. Serum GSA was significantly elevated in children with PsA infections (p < 0.01). Urinary GSA correlated with pulmonary GSA (r = 0.42, p < 0.05) and markers of neutrophilic inflammation.Conclusions
This proof-of-concept study demonstrates that urinary GSA but not allantoin shows promise as a non-invasive marker of neutrophilic inflammation in early CF lung disease. 相似文献19.
Dominique Hubert Raphaël Chiron Boubou Camara Dominique Grenet Anne Prévotat Laurence Bassinet Stéphane Dominique Gilles Rault Julie Macey Isabelle Honoré Reem Kanaan Sylvie Leroy Nadine Desmazes Dufeu Pierre-Régis Burgel 《Journal of cystic fibrosis》2017,16(3):388-391
Objective
To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting.Methods
A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted.Results
Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was + 2.06% after one month of treatment (P = 0.086) and + 3.19% after 3 months (P = 0.009). BMI was unchanged.Conclusions
Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials. 相似文献20.
Sebastian Fischer Leonie Greipel Jens Klockgether Marie Dorda Lutz Wiehlmann Nina Cramer Burkhard Tümmler 《Journal of cystic fibrosis》2017,16(3):346-352