共查询到20条相似文献，搜索用时 835 毫秒
1.
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2.
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.
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.
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6.
Background
Outcome data for UK cystic fibrosis centres are publicly available in an annual report, which ranks centres by median FEV1% predicted. We wished to assess whether there are differences in lung function outcomes between adult centres that might imply differing standards of care.Methods
UK Registry data from 4761 subjects at 34 anonymised adult centres were used to calculate mean FEV1% and rate of change of lung function for 2007–13. These measures were used to rank centres and compare outcomes.Results
There are minor differences between centres for mean FEV1% for some years of the study and for rate of change of lung function over the study period. However, rankings are critically dependent on the outcome measure chosen and centre variation becomes negligible once patient population characteristics are taken into account.Conclusions
We have demonstrated that the ranking of centres is biased and any apparent difference in respiratory outcomes is unlikely to be related to differing standards of care between centres. 相似文献7.
Sebastian Fischer Leonie Greipel Jens Klockgether Marie Dorda Lutz Wiehlmann Nina Cramer Burkhard Tümmler 《Journal of cystic fibrosis》2017,16(3):346-352
Background
Early antimicrobial chemotherapy can prevent or at least delay chronic cystic fibrosis (CF) airways infections with Pseudomonas aeruginosa.Methods
During a 10-year study period P. aeruginosa was detected for the first time in 54 CF patients regularly seen at the CF centre Hannover. Amplicon sequencing of 34 loci of the P. aeruginosa core genome was performed in baseline and post-treatment isolates of the 15 CF patients who had remained P. aeruginosa – positive after the first round of antipseudomonal chemotherapy.Results
Deep sequencing uncovered coexisting alternative nucleotides at in total 33 of 55,284 examined genome positions including six non-synonymous polymorphisms in the lasR gene, a key regulator of quorum sensing. After early treatment 42 of 50 novel nucleotide substitutions had emerged in exopolysaccharide biosynthesis, efflux pump and porin genes.Conclusions
Early treatment selects pathoadaptive mutations in P. aeruginosa that are typical for chronic infections of CF lungs. 相似文献8.
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9.
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10.
C. Lehoux Dubois V. Boudreau F. Tremblay A. Lavoie Y. Berthiaume R. Rabasa-Lhoret A. Coriati 《Journal of cystic fibrosis》2017,16(3):418-424
Background
Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF.Methods
Cross-sectional and prospective analysis of CF patients (N = 260) who underwent a 2 h-oral glucose tolerance test. Clinical data was collected.Results
Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P = 0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P = 0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up.Conclusion
Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF. 相似文献11.
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12.
13.
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14.
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15.
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16.
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17.
18.
19.
Catrin Pedder Jones Chris Papadopoulos Gurch Randhawa 《Transplantation reviews (Orlando, Fla.)》2017,31(4):268-275
Background
Previous research has proposed that primary care interventions to increase organ donation rates can help address the discrepancy between organ donation rates and the number of patients awaiting transplant. However, no systematic review has been conducted to examine interventions in this setting.Objective
To synthesise evidence from previous organ donation interventions conducted in a primary care setting.Methods
Six databases and grey literature were systematically searched between November 2016 and July 2017. Inclusion criteria included English language, studies published after the year 2000 and unpublished studies. A quality assessment and narrative synthesis was conducted.Results
Ten studies met the inclusion criteria, nine of which examined actual organ donor registration as their primary outcome. Eight interventions increased registration to be an organ donor. Successful interventions utilised active methods of participant engagement that encouraged donation at the point of patient contact.Discussion
Despite the small pool of studies that met the inclusion criteria, the results suggest that primary care interventions could produce promising results for increasing organ donation registration. However, additional higher quality studies are required before firm conclusions can be made. Barriers to implementation were also found and suggest that the feasibility of a primary care environment for organ donation intervention should be investigated. 相似文献20.
Isobel E.R. MacKenzie Valerie Paquette Frances Gosse Sheenagh George Frederic Chappe Valerie Chappe 《Journal of cystic fibrosis》2017,16(3):335-341