Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study.

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.

Patient experience in cystic fibrosis care: Development of a disease-specific questionnaire.

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.

Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial.

RATIONALE: Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF). OBJECTIVES: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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).

Increased expression of Interleukin-13 but not Interleukin-4 in cystic fibrosis patients.

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 TNFalpha 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 TNFalpha 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 TNFalpha production.