The Genotype List (GL) String grammar for reporting HLA and Killer‐cell Immunoglobulin‐like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings ...have been used to describe HLA and KIR genotypes for more than 40 million subjects, allowing these data to be recorded, stored and transmitted in an easily parsed, text‐based format. After a decade of working with HLA and KIR data in GL String format, with advances in HLA and KIR genotyping technologies that have fostered the generation of full‐gene sequence data, the need for an extension of the GL String system has become clear. Here, we introduce the new GL String delimiter “?,” which addresses the need to describe ambiguity in assigning a gene sequence to gene paralogs. GL Strings that do not include a “?” delimiter continue to be interpreted as originally described. This extension represents version 1.1 of the GL String grammar.
Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF).
We aimed to assess glutathione delivered by inhalation as a ...potential treatment for CF lung disease.
This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted. Subjects were randomized to receive 646 mg glutathione in 4 ml (n = 73) or placebo (n = 80) via an investigational eFlow nebulizer every 12 hours for 6 months.
FEV1 (absolute values), both as pre-post differences (P = 0.180) and as area under the curves (P = 0.205), were the primary efficacy endpoints, and were not different between the glutathione group and the placebo group over the 6-month treatment period. Exploratory analysis showed an increase of FEV1 from baseline over placebo of 100 ml or 2.2% predicted; this was significant at 3 months, but not later. Subjects receiving glutathione had neither fewer pulmonary exacerbations, nor better scores for quality of life. Whereas increased glutathione and metabolites in sputum demonstrated significant delivery to the lungs, there was no indication of diminished oxidative stress to proteins or lipids, and no evidence for anti-inflammatory or antiproteolytic actions of glutathione supplemented to the airways. The adverse event incidence was similar between glutathione and placebo.
Inhaled glutathione in the dose administered did not demonstrate clinically relevant improvements in lung function, pulmonary exacerbation frequency, or patient-reported outcomes. Glutathione delivery to the airways was not associated with changes in markers of oxidation, proteolysis, or inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT00506688) and https://eudract.ema.europa.eu/index.html (EudraCT 2005-003870-88).
As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. ...The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs.
We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had newly diagnosed diabetes. We used a central randomisation schedule derived from a Geigy random number table to assign patients 1:1 to receive insulin or repaglinide, stratified by sex and age (10-15 years or >15 years). The primary outcome was glycaemic control assessed by mean change in HbA
concentration from baseline after 24 months of treatment. Differences between groups were assessed by linear models. The primary and safety analyses were done in the modified intention-to-treat population (including patients who stopped treatment early because of lack of efficacy). This trial is registered with ClinicalTrials.gov, number NCT00662714.
We enrolled 34 patients in the repaglinide group and 41 in the insulin group, of whom 30 and 37, respectively, were included in the analyses. At 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA
concentration from baseline 0·2% SD 0·7%, 1·7 mmol/mol 8·1 mmol/mol with repaglinide vs -0·2% 1·3%, -2·7 mmol/mol, 14·5 mmol/mol with insulin; mean difference between groups -0·4%, (95% CI -1·1 to 0·2 -4·4 mmol/mol, -11·5 to 2·7, p=0·15). The most frequent adverse events were pulmonary events (43 40% of 107 in the repaglinide group and 60 45% of 133 in the insulin group), and the most frequent serious adverse events were pulmonary events leading to hospital admission (five 50% of ten and seven 54% of 13, respectively).
Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin.
Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association, and Novo Nordisk.
Background/Aims: In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality. Methods: In a multicentre, open-label, exploratory, ...non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U. twice daily) were sequentially combined with the aim to investigate the effect on 41 CF patients with chronic P. aeruginosa infections for six months (mean age 24 ± 10.8y). Results: Six patients had adverse events that were assessed as being related to treatment. Mucus production and coughing both decreased in 39%, whereas FEV1 absolute and relative to baseline increased by 4.9% and 9.1%, respectively (p = 0.004) in 29 patients, who were definitely treated sequentially. Efficacy of the therapy was rated ‘excellent' or ‘good' by the physicians in 80.5% of the patients. Conclusions: The results indicate that treatment with inhaled antibiotics, sequentially combined, was very well tolerated by most patients and may have a beneficial effect, even if transitory on lung function and respiratory symptoms.
Purpose is to investigate and compare professional quality of life (ProQoL) among health care providers (HCPs) in cystic fibrosis (CF) ambulances and inpatient clinic for child and adolescent ...psychiatry.
The ProQoL R-IV Inventory was administered to 96 HCPs to investigate: compassion satisfaction, burnout, and secondary traumatic stress (STS).
HCPs in CF centers and inpatient psychiatry did not differ in their ProQoL. However, the occupational groups differed regarding STS (F(3,92)=3.726, p=.01). Physicians reported more STS than other groups. Longer work experience was associated with more STS (r=-0.21, p=.04). Regular screening should be put in place to identify HCPs at risk of decreased ProQoL.
Objectives
The aim of this study was to develop valid and reliable disease-specific questionnaires for adult patients with cystic fibrosis and for parents of minors with cystic fibrosis for assessing ...patient experience with cystic fibrosis care.
Methods
The pilot versions of the questionnaires were developed based on a literature review, interviews with health professionals and focus groups. A postal survey with two reminders was conducted in 56 German cystic fibrosis centres recruiting 2874 participants. Psychometric evaluation was done via exploratory factor analysis and reliability and regression analysis. The questionnaires’ ability to differentiate between subgroups and between cystic fibrosis centres was evaluated.
Results
Response rates were 74% for both adult patients and parents. Ten factors were extracted for both the adult and the parents’ models (Cronbach’s alpha between 0.6 and 0.9), explaining 50% and 48% of the variance, respectively. The factors organisation & access and the doctor–patient/parent-interaction had the highest relevance for a good overall care experience. The questionnaires were able to distinguish between different cystic fibrosis centres.
Discussion
The questionnaires are well suited for use in internal and external quality management of cystic fibrosis care due to their good psychometric properties, the ability to differentiate between centres and its practicability.
Abstract Background Chronic rhinosinusitis is a hallmark of Cystic fibrosis (CF) impairing the patients' quality of life and overall health. However, therapeutic options have not been sufficiently ...evaluated. Bronchial inhalation of mucolytic substances is a gold standard in CF therapy. Previously, we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9% (net treatment benefit: − 5.87 ± 2.3 points, p = 0.017; SNOT-20 total score). This multicenter study compares the effect of NaCl 6.0% vs. NaCl 0.9% following the protocol from our preceding study with dornase alfa. Methods Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were randomized to receive sinonasal vibrating inhalation of either NaCl 6.0% or NaCl 0.9% for 28 days. After 28 days of wash-out, patients crossed over to the alternative treatment. The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test-20 (SNOT-20). Additionally, pulmonary function was assessed, as well as rhinomanometry and inflammatory markers in nasal lavage (neutrophil elastase, interleukin (IL)-1β, IL-6, and IL-8) in a subgroup. Results Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores (NaCl 6.0%: − 3.1 ± 6.5 points, NaCl 0.9%: − 5.1 ± 8.3 points, ns). In both treatment groups, changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant. We suppose that the irritating properties of NaCl 6.0% reduced the suitability of the SNOT-20 scores as an outcome parameter. Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were, however, not feasible. Conclusion Sinonasal inhalation with NaCl 6.0% did not lead to superior results vs. NaCl 0.9%, whereas dornase alfa had been significantly more effective than NaCl 0.9%.
Background: Many patients with cystic fibrosis (CF) suffer from allergic disease, which can complicate treatment of CF lung disease. Interleukin (IL)-4 and IL-13 have been shown to be important ...mediators in allergic disease.
Objective: To investigate the role of IL-4 and IL-13 in allergic and non-allergic CF patients.
Methods: Expression of IL-4 and IL-13 mRNA was investigated in peripheral blood mononuclear cells (PBM) of seven CF patients with allergy, of six patients without allergy and of nine healthy subjects as well as in BAL cells of four patients and of all controls. PBM from six patients were incubated with recombinant human IL-13 or human antiIL-13 antibody without and with LPS stimulation and TNFα levels were measured by ELISA.
Results: IL-13 mRNA expression was increased in allergic and non-allergic patients compared to controls. No significant difference in IL-4 expression could be found between patients and controls. Addition of IL-13 decreased TNFα in PBM culture supernatants.
Conclusion: Our data suggest that IL-13 rather than IL-4 might play an important role in both allergic and non-allergic CF patients. IL-13 might also compromise host defence by decreasing TNFα production.
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