Dr Evan Williams

Background: Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma. Methods: A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured. Findings: There was no difference in change in total plasma SCFA levels (µmol/L) in the placebo versus soluble fibre (¿median [95% CI] 16·3 [-16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [-14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (¿median (IQR) -0·35 (-0·5, -0·13), p = 0·006), sputum %eosinophils decreased (-1.0 (-2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (-0.49 (-0.83, -0.27) 2-¿Ct, p =.008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms. Interpretation: Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. Fund: John Hunter Hospital Charitable Trust.

Background/Aims Chronic Obstructive Pulmonary Disease (COPD) is characterized by airway inflammation, in which contributes to loss of lung function. Systemic inflammation is also a feature of COPD contributing to many associated co-morbidities. Statins, omega-3 fatty acids (docosahexanoic acid, DHA and eicosapentanoic acid, EPA) and lycopene have been shown to decrease systemic inflammation; however their combined effects have not been investigated. This study aims to identify changes in systemic and airway inflammation induced by statins alone or in combination with DHA, EPA and lycopene in COPD. Methods COPD patients (n¿=¿11) received rosuvastatin (20¿mg/day) for 4 weeks, then a combination of rosuvastatin (20¿mg/day), DHA and EPA (1.5¿g/day) and lycopene (45¿mg/day) for 8 weeks. Blood and sputum were collected and lung function measured by spirometry at baseline, week 4 and 12. Plasma fatty acids were measured using gas chromatography, while plasma carotenoids were analysed using high-performance liquid chromatography. Plasma CRP and IL-6 concentrations were measured using ELISA; and peripheral blood gene expression was measured using the nCounter¿ GX Human Inflammation Kit 2. Results Following the interventions, clinical characteristics and plasma IL-6 and CRP were unchanged. Sputum neutrophil proportion and absolute count was increased and macrophage proportion decreased by rosuvastatin (P¿=¿0.020 and P¿=¿0.015; respectively). Rosuvastatin increased LTB4R and decreased CXCL10 and AGER gene expression in white blood cells. The addition of lycopene and omega-3 fatty acids decreased LTB4R and increased CXCL10 to basal levels, whilst combined use of interventions increased ALOX15 blood gene expression. Conclusion This study shows that rosuvastatin, omega-3 fatty acids and lycopene have some anti-inflammatory effects systemically, but rosuvastatin may increase airway neutrophils, which would be undesirable in COPD patients, warranting further investigation.