Characterising the nutritional status of children with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, heterogeneous genetic disorder where impaired mucociliary clearance is caused by dysfunctional motile cilia leading to bronchiectasis. There is limited evidence characterising the nutritional status of children with PCD, although lower body mass index (BMI) z-score has been associated with worse lung function (FEV1). METHODS: All children (n = 43) with PCD, aged <16 years, from a single tertiary centre were prospectively enrolled. Information on clinical phenotype and nutritional status including bioelectrical impedance spectroscopy (BIS) phase-angle was collected. RESULTS: There was a weak positive association between height-for-age z-score (HAZ) and FEV1 z-score (n = 28, r = 0.4, p = 0.049). Those with a low fat free mass index (<-2 z scores) had a lower BMI z score (-1.3 ± 1.2 vs. 0.8 ± 0.7, p = 0.0002). BIS phase angle identified more patients at nutritional risk than using moderate malnutrition cut-offs of either HAZ or BMI ≤ -2 z scores alone (21% vs. 4.6% vs. 6.9% respectively). PCD patients had a higher incidence of vitamin D insufficiency (<50 nmoL/L) (54%) and deficiency (<30 nmoL/L) (26%) than healthy children. CONCLUSIONS: We have characterised the nutritional phenotype of a cohort of children with PCD. Monitoring vitamin D levels is important in PCD patients. There is a weak association between lung function and nutritional status, and measures of BIS phase-angle. The use of BIS phase-angle may allow for early identification of at risk children and may therefore be of benefit for nutritional assessments in the clinical setting. These findings will help inform a future nutritional intervention strategy in children with PCD.

Upper and lower airway nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and asthma.

BACKGROUND: Patients with primary ciliary dyskinesia (PCD) have abnormal ciliary function and low nitric oxide levels. Nitric oxide (NO) biosynthesis is dependent on nitric oxide synthases (NOS). Cilia line the bronchial but not the alveolar epithelium. It has been hypothesised that NOS function relies on normal ciliary function and that in PCD bronchial but not alveolar NO might therefore be reduced. The aim of this study was to assess bronchial and alveolar NO levels primarily comparing healthy children to PCD and secondarily to cystic fibrosis (CF) and asthmatic children. METHODS: Multiple flow-rate fractional exhaled and nasal NO measurements were performed using a NIOX(®) Flex NO analyser (Aerocrine, Sweden) in children with PCD (n = 14), asthma (n = 18), CF (n = 12) and healthy controls (n = 18). Alveolar and bronchial NO levels were derived using a model of pulmonary NO exchange-dynamics. RESULTS: Both the bronchial and alveolar NO were significantly lower in PCD than healthy controls (mean (SD) 264 (209) picolitres/second (pl/s) vs. 720 (514) pl/s, p = 0.024 and 1.7 (0.8) parts per billion (ppb) vs. 3.5 (1.3) ppb, p = 0.001 respectively.) In asthmatics bronchial NO was found to be significantly higher than in healthy controls and in children with CF alveolar NO was significantly lower (2100 (1935) pl/s, p = 0.045 and 2.5 (1.2) ppb, p = 0.034 respectively.) CONCLUSION: Our findings do not support the hypothesis that NOS and ciliary function are coupled instead suggesting a more generalised mechanism for the low levels of NO seen in PCD. Our findings in CF and asthma corroborate evidence that these are diseases of the lung peripheries and bronchi respectively.

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study.

OBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.