Christin Arnold

Macular Xanthophylls and ω-3 Long-Chain Polyunsaturated Fatty Acids in Age-Related Macular Degeneration: A Randomized Trial

IMPORTANCE It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration (AMD). Additionally, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may also be protective. OBJECTIVE To investigate the effect of a 12-month intervention with macular xanthophylls and ω-3 LC-PUFAs on xanthophylls and fatty acids in plasma, antioxidant capacity, and optical density of the macular pigment of patients with nonexudative AMD. DESIGN The LUTEGA study was a randomized, double-blind, placebo-controlled, parallel clinical trial that was conducted for 12 months. SETTING University Eye Hospital and Institute of Nutrition, Friedrich Schiller University Jena, Germany. PARTICIPANTS A total of 172 individuals with nonexudative AMD. INTERVENTION Individuals were enrolled and randomly divided as follows: placebo group, group 1 (a capsule containing 10 mg of lutein, 1 mg of zeaxanthin, 100 mg of docosahexaenoic acid, and 30 mg of eicosapentaenoic acid administered each day), and group 2 (same substances but twice the dose used in group 1). One hundred forty-five participants completed the study successfully. MAIN OUTCOME MEASURES Plasma xanthophyll concentrations and fatty acid profiles, optical density of the macular pigment, and antioxidant capacity in plasma (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent antioxidant capacity and photochemiluminescence). RESULTS The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups randomized to receive supplementary macular xanthophylls and ω-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study. Use of the double dose resulted in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1. The lipophilic antioxidant capacity in plasma was significantly elevated with the intervention. CONCLUSIONS AND RELEVANCE A supplement containing a fixed combination of lutein, zeaxanthin, and ω-3 LC-PUFAs during 12 months significantly improved plasma antioxidant capacity, circulating macular xanthophyll levels, and the optical density of the macular pigment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00763659.

Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings

Background & aims Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history. Methods A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status. Results AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status. Conclusion As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Increased cytokines in cystic fibrosis patients’ upper airways during a new P. aeruginosa colonization

Previously, we found linkages of inflammatory mediator levels in CF upper airways (UAW) sampled by nasal lavage (NL) to disease severity and to chronic pathogen colonization such as Pseudomonas aeruginosa (PsA). Here, we assess UAW cytokine dynamics in CF patients with a new PsA colonization.

Relation of Ultrasound Findings and Abdominal Symptoms obtained with the CFAbd-Score in Cystic Fibrosis Patients

Abdominal symptoms are a hallmark of Cystic fibrosis (CF). Yet, their association with morphological abnormalities of different abdominal organs is still poorly understood. Aim was therefore to relate these symptoms, assessed with a questionnaire, to findings in abdominal ultrasound (US). In 114 CF patients of all ages, findings in US considering seventeen specific parameters were related to abdominal symptoms compiled with our novel CF-specific 26-modal symptom score (CFAbd-Score). US abnormalities were detected in 95% of the patients. Most frequent findings were pancreatic lipomatosis (88%), liver steatosis (37%), hepatomegaly (31%), and thickened bowel walls (23%). Highest burden of GI-symptoms was clearly associated with pancreatic lipomatosis (p = 0.036). In detail, patients revealing this pathology reported higher rates of abdominal pain (p = 0.018), flatulence (p = 0.006), heartburn (p = 0.04), and reflux of stomach content (p = 0.006). Patients with pancreatic sufficiency had less US-findings (p = 0.033), which in turn was associated with lower rates of abdominal symptoms. The majority of them were carriers of class IV-VI or G551D mutations. Our approach gives new insights regarding the underestimated multi-organ abdominal involvement in CF. The new score can be of high interest e.g. as a complementary tool to assess the gastrointestinal effects of promising novel CF therapeutics.

Effects of Ivacaftor in Three Pediatric Siblings With Cystic Fibrosis Carrying the Mutations G551D And F508del

Cystic fibrosis (CF) is the most frequent life-shortening inherited disease in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.1 Loss or altered CFTR-function results in impaired transport of chloride and sodium, bicarbonate and water to the lumen of exocrine glands in different organ systems. Consequently, viscous secretions impair mucociliary clearance, and facilitate pathogen colonization, leading to pulmonary destruction and premature death in almost 90% of CF-patients. Furthermore, the majority of CF-patients reveal abdominal involvement with pancreatic insufficiency (PI), intestinal and hepatic manifestations. The recent discovery of small molecules modulating CFTR-dysfunction brought a major breakthrough in therapy of CF in the CFTR-gating mutation G551D, which worldwide concerns only 2%–4% of patients.2–4 The small molecule VX-770 (ivacaftor/IVA) increases Cl-secretion in human CF bronchial epithelia carrying G551D to almost 50% of the potential without CF.5 Consequently, VX-770 prompted the highest clinical effects hitherto achieved with a CF-drug, improving pulmonary function (FEV1) for 10%–12%, stabilizing weight and reducing sweat chloride from about 100 mmol/l to about 50 mmol/l.6–8 The drug was approved for adult and pediatric CF patients carrying a G551D mutation, and only recently down to the age of 2 years.2,3,9 To the best of our knowledge, this is the first report on three siblings with CF carrying the rare G551D-mutation and receiving the novel drug. The siblings reveal different symptoms and severity of disease manifestation, with intermittent Pseudomonas aeruginosa (PSA) colonization of the second child’s airways and diverging grades of pancreatic insufficiency (PI). However, until now they all present normal pulmonary function before and during the newly introduced CFTR-modulating therapy. Nevertheless, we show how the potent CFTR-modulator for gating mutations effectively improves involvement of the different organ systems.

161 Elaboration and first evaluation of a new questionnaire on abdominal symptoms in cystic fibrosis

Aim: To evaluate the prevalence of obesity among children with CF and its relationship with age, sex, pancreatic insufficiency, pseudomonas colonization, lung function and genotype. Methods: 56 children/adolescents (30 male) were evaluated. Body mass index (BMI), BMI z-score and nutritional status was assessed and classified according to the WHO BMI criteria. Lung function was assessed with Forced Expiratory Volume in 1 sec (FEV1) % predicted and Lung Clearance Index (LCI). Pancreatic insufficiency (PI), pseudomonas colonization and genotype were also recorded. Results: 56 patients with CF (mean age 9.5±4.6 years) were evaluated. 33 (58.9%) patients had normal nutritional status according to BMI z-score, 10 (17.9%) were underweight and 13 (23.2%) were overweight/obese. FEV1 % was higher among overweight/obese patients (112.6%±13.5 vs. 100.73%±22.7 in normal individuals and 96%±16.5 in malnourished children, p = 0.07). LCI was significantly different across the weight categories (p = 0.02). Nutritional status was significantly associated with PI, pseudomonas colonization and genotype (p < 0.05). 7/13(52.8%) of the overweight/obese patients were pancreatic insufficient, 1/13(7.7%) was DF508 homozygote, 7/13(53.8%) were DF508 heterozygote. Conclusions: The prevalence of overweight and obesity in our CF center is high, although a significant number of the patients were pancreatic insufficient. Overweight and obesity were associated with better lung function. However, the benefit of increased lung function among this patient group needs to be balanced against the known health risks of obesity.

ePS06.4 Upper airway infection and inflammation in CF and healthy controls during exacerbation and stable phases

Objectives Upper airway (UAW) infections are common in CF patients with nasal congestion, impaired climate function and reduced quality of life. Moreover, by postnasal drip, infections can descend to the lungs. Actually, there are no data comparing UAW infection and inflammation in CF and healthy controls in stable phases and during exacerbation. Methods We collected epithelial lining fluid from 49 CF patients and 38 healthy controls by nasal lavage in stable phases and during UAW infection. Microbiological (only CF cohort), cytological and immunological analyses (NE/IL-6/IL-8/IL-1β/MMP-9/TIMP-1) were performed. Results During UAW infection all measured inflammatory mediators increased in both, CF patients and the control cohort. Whereas levels of IL-6 and IL-8 were significantly higher in CF under stable conditions compared to healthy controls, the levels of the control cohort exceeded those of CF patients during infection. Age-stratified analyses showed higher releases of mediators during acute UAW infection in CF patients ≤12 years, especially for MMP-9, IL-8 and TIMP-1. These findings were not present in controls. Conclusion In CF patients, chronic inflammation with higher values of inflammatory mediators compared to healthy controls was observed. However, the increase of inflammation during UAW infection is not higher in CF compared to healthy controls. In contrast, for all measured parameters except TIMP-1 a weaker increase was observed in CF, suggesting a deregulation of the immune system in CF with a decreased ability of mediator release. This hypothesis is also supported by the observation of higher releases of MMP-9, TIMP-1 and IL-8 in younger CF patients.

Regarding Macular Xanthophylls and ω-3 Long-Chain Polyunsaturated Fatty Acids in Age-Related Macular Degeneration—Reply

Author Contributions: Dr Haines had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Haines. Acquisition of data: Haines, Longmuir. Analysis and interpretation of data: Haines, Longmuir. Drafting of the manuscript: Haines. Critical revision of the manuscript for important intellectual content: Longmuir. Administrative, technical, and material support: Longmuir. Study supervision: Longmuir.