Objective: To evaluate the relation of clinical parameters and genotype with the serum phospholipid fatty acid (FA) composition in cystic fibrosis (CF) patients. Methods: A blood sample was taken from CF patients with stable pulmonary disease for the determination of phospholipid FA composition and vitamin E concentration who had been followed for at least 6 months at our Cystic Fibrosis Centre. Genotype, age, pancreatic function, nutritional status, caloric intake, pulmonary function and presence of Pseudomonas colonization, liver disease or diabetes mellitus were recorded. Patients were divided into two groups according to their genotype (group A: mutation class I, II, or III, group B: mutation class IV, V). Results: CF patients (group A and B together) have significantly lower docosahexaenoic acid (DHA) (p < 0.007) and linoleic acid (LA) (p < 0.0001) and higher dihomogammalinolenic acid (DHGLA) (p < 0.0001), oleic acid (OA) (p < 0.0001) and Mead acid (MA) (p < 0.0001), resulting in an increased ratio of arachidonic acid (AA)/DHA (p < 0.004), MA/AA (p < 0.0001) and OA/LA (p < 0.0001). Compared to group B, group A had a lower LA (p < 0.002) and a higher DHGLA (p < 0.002), 22:4ω–6 (p < 0.03), 22:5ω–6 (p < 0.03) and 20:3ω–9 (p < 0.04). There was however no significant difference between the groups for age, pulmonary function, nutritional status and vitamin E concentration. There was no relation of serum FA composition with nutritional status, caloric intake, pancreatic function, gender, pulmonary function, Pseudomonas colonization or diabetes mellitus. In CF with liver disease the DHA was lower than in the patients of the same genotype. Conclusion: FA disturbances are more pronounced in the severe CF genotypes and the presence of CF-related liver disease. Future studies on supplementation should take these parameters into account.

Aim: To study the effect of Zn supplements in cystic fibrosis (CF) on disease evolution. Methods: A retrospective study of all CF patients treated with Zn supplements (January 2002 to December 2004). Data from patient files for the year before and the first year of supplementation were compared. The controls were CF patients with normal serum Zn and without Zn supplementation. Results: 21 patients (7 females), median age 8.9 (interquartile range 13.1) years, received 5 mg/kg Zn sulfate/day (maximum 150 mg). The number of infections decreased from 3 (1.25) to 2 (2.0) (tied p < 0.02) and the forced expiratory volume in 1 s (FEV₁) increased from 72.0 (38.4) to 76.5 (52)% (p < 0.02). Energy intake improved (92.3 (14.5) to 117.0 (28.5)%; tied p < 0.02), as did weight for height (W/H; 90 (9.4) to 94 (8.5)%; tied p = 0.043). In the CF control patients the number of infections (2.0 (2.0)), energy intake (116 (43.3)%) and nutritional status remained stable (W/H 99 (17.2)%), but pulmonary function decreased significantly (ΔFEV₁ loss of 2.0 (8.0)%). There was a significantly different evolution for the change in forced vital capacity (p < 0.004) and ΔFEV₁ (p < 0.001) between supplemented and control patients. Conclusions: Analysis of the clinical data on Zn supplementation in CF showed beneficial effects in Zn-deficient CF patients. These results must be confirmed in a prospective double-blind randomized control trial.

IntroductionCystic fibrosis (CF) is a severe monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Several types of CFTR modulators (correctors/potentiators) have been developed to overcome protein dysfunction associated with these mutations. CFTR modulator therapy is now available for the major CF-causing mutations, however 10% of people with CF remain without causal treatments. By combining investigational and market approved CFTR modulators, we aimed to maximise functional rescue of iva-, luma- and tezacaftor refractory mutants G85E and N1303K.MethodsWe used the well-established forskolin induced swelling (FIS) in primary rectal organoids to assess responses to different CFTR corrector and potentiator types. The FIS analysis was performed with brightfield microscopy, allowing both 1 h and 24 h follow-up. Corrector and potentiator activity of elexacaftor was investigated.ResultsFor G85E, maximal rescue was observed by a combination of elexacaftor and corr4a. For N1303K, the quadruple combination teza-elexa-ivacaftor with apigenin was required to obtain a rescue similar to that of luma-ivacaftor rescued F508del. Elexacaftor rescued G85E and N1303K by different mechanisms, with chronic corrector effects on G85E and acute potentiation of N1303K only in the presence of ivacaftor. Synergy in N1303K rescue for iva-elexacaftor and apigenin suggests at least three potentiator mechanisms for this mutant. 24 h FIS identified ivacaftor as the main CFTR modulator for N1303K and elexacaftor and apigenin as co-potentiators.ConclusionsNovel combinations of CFTR modulators can further improve functional rescue of G85E and N1303K in rectal organoids, although for N1303K more effective CFTR modulators are still needed.

ABBREVIATION COSCore outcome set AIM To develop a core outcome set (COS) for evaluating gastrostomy/gastrojejunostomy tube impact in children with neurological impairment.METHOD Healthcare providers/researchers and caregivers rated the importance of candidate outcomes on a 5-point Likert scale. Outcomes rated 'somewhat important' or 'very important' by most (≥85%) respondents were voted on during a consensus meeting. Outcomes that reached consensus for inclusion were ratified and assigned to Outcome Measures in Rheumatology filter core areas. The COS was validated in a separate group of caregivers.RESULTS Twelve outcomes were selected from 120 candidate outcomes to form the COS.These included five 'Life Impact' outcomes, three 'Pathophysiological Manifestations' outcomes, two 'Resource Use' outcomes, one 'Growth and Development' outcome, and one 'Death' outcome.INTERPRETATION We developed an evidence-informed and consensus-based COS for use in studies of gastrostomy/gastrojejunostomy tube feeding in children with neurological impairment. Implementation of this COS will help reduce heterogeneity between studies and facilitate evidence-based decision-making.

Aim: Assess the risk of zinc (Zn) deficiency in the older cystic fibrosis (CF) population. Method:Cross sectional investigation of all CF patients above the age of 4 followed at the Ghent university centre between 2002 and 2003. Data on age, weight and height z-score, pancreatic and pulmonary functions, chronic pseudomonas infection and CF transmembrane conductance regulator (CFTR) mutations were collected. Serum Zn, vitamin A, E, retinol binding protein (RBP), albumin, sedimentation rate, total IgG and cholesterol were determined. Serum Zn was compared with a local healthy control group (1) and with literature data (3). Results: 101 patients (median age 16 years) were included. There was no difference in serum Zn concentration between CF patients and controls. In CF patients no difference in serum Zn concentration between pancreatic sufficient or insufficient patients was seen. Serum Zn was not associated to nutritional status or height Z-score. A significant association serum Zn to serum albumin (p< 0.0005) and to vitamin A (p< 0.01) was seen. No associations of serum Zn to serum vitamin E, RBP, cholesterol or CFTR were present. There is a significant association serum Zn -forced vital capacity (p<0.01). Serum Zn was not associated to inflammatory parameters or chronic pseudomonas infection. Conclusion: Comparison of CF patients with local controls revealed no significant differences. However, since persisting steatorrhoea increases Zn loss (2) and 12.6% of our population has a serum Zn below the P 2.5 value of the NHANES II study (3), there could remain an increased risk of Zn deficiency in some CF patients. Further on the association with pulmonary function needs more investigation.