共查询到20条相似文献，搜索用时 562 毫秒
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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3.
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4.
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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6.
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7.
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8.
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9.
Kathryn A. Ramsey Caroline McGirr Stephen M. Stick Graham L. Hall Shannon J. Simpson 《Journal of cystic fibrosis》2017,16(6):713-718
Background
We assessed the effect of posture on ventilation distribution and the impact on associations with structural lung disease.Methods
Multiple breath washout (MBW) was performed in seated and supine postures in 25 healthy children and 21 children with CF. Children with CF also underwent a chest CT scan. Functional residual capacity (FRC), lung clearance index (LCI) and moment ratios were calculated from the MBW test. CT scans were evaluated for CF-related structural lung disease.Results
FRC was lower in the supine than in the seated posture, whereas LCI was higher in the supine than in the seated posture. In children with CF, associations between LCI and the extent of structural lung disease were stronger when performed in the supine posture.Conclusions
Body posture influences lung volumes and ventilation distribution in both healthy children and children with CF. MBW testing in the supine posture strengthened associations with structural lung damage. 相似文献10.
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11.
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12.
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13.
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14.
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15.
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16.
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17.
Dave P. Nichols Carrie L. Happoldt Preston E. Bratcher Silvia M. Caceres James F. Chmiel Kenneth C. Malcolm Milene T. Saavedra Lisa Saiman Jennifer L. Taylor-Cousar Jerry A. Nick 《Journal of cystic fibrosis》2017,16(3):358-366
Background
Concomitant use of oral azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic.Methods
Test the hypothesis that azithromycin reduces the clinical benefits of tobramycin by analyses of clinical trial data, in vitro modeling of P. aeruginosa antibiotic killing, and regulation of the MexXY efflux pump.Results
Ongoing administration of azithromycin associates with reduced ability of inhaled tobramycin, as compared with aztreonam, to improve lung function and quality of life in a completed clinical trial. In users of azithromycin FEV1 (L) increased 0.8% during a 4-week period of inhaled tobramycin and an additional 6.4% during a subsequent 4-week period of inhaled aztreonam (P < 0.005). CFQ-R respiratory symptom score decreased 1.8 points during inhaled tobramycin and increased 8.3 points during subsequent inhaled aztreonam (P < 0.001). A smaller number of trial participants not using azithromycin had similar improvement in lung function and quality of life scores during inhaled tobramycin and inhaled aztreonam. In vitro, azithromycin selectively reduced the bactericidal effects tobramycin in cultures of clinical strains of P. aeruginosa, while up regulating antibiotic resistance through MexXY efflux.Conclusions
Azithromycin appears capable of reducing the antimicrobial benefits of tobramycin by inducing adaptive bacterial stress responses in P. aeruginosa, suggesting that these medications together may not be optimal chronic therapy for at least some patients. 相似文献18.
Gina Hong Marissa White Noah Lechtzin Natalie E. West Robin Avery Heather Miller Richard Lee Robert J. Lovari Christian Massire Lawrence B. Blyn Xinglun Liang Deanna A. Sutton Jianmin Fu Brian L. Wickes Nathan P. Wiederhold Sean X. Zhang 《Journal of cystic fibrosis》2017,16(2):e3-e7
Background
Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies.Case summary
We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation.Discussion
We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host.Conclusion
Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. 相似文献19.
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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