Professor Lisa Wood

Background: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. Methods: Blood samples were collected from 43 obese subjects (BMI = 30 kg/m2) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12¿18 months post-surgery and 8 healthy weight subjects (BMI 18.5¿24.9 kg/m2). Mono-cytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were har-vested after 15 h incubation. TNF-a and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. Results: TNF-a and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-a and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. Conclusion: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.

Aim: To investigate associations between changes in vegetable and fruit (V&F) intakes and anthropometric indices (weight, BMI, % body fat, waist circumference), including differences by sex, during a dietary weight-loss intervention. Methods: Adults (18-45 years) with overweight/obesity (BMI 25-35 kg/m2) entered a 10-week pre-post study, receiving individualised consults with an Accredited Practising Dietitian targeting increased V&F intakes. Dietary intake was assessed using 24-hour recalls and food frequency questionnaires. Linear mixed models were used to examine how much of the changes in anthropometric indices were explained by changes in V&F intakes. Sex differences were assessed by Wilcoxon rank sum tests. Results: Of the 43 participants enrolled, 34 completed the study (53% female). Significant differences in energy intake and anthropometric indices were observed between males and females at baseline. After 10 weeks, females significantly reduced their weight (-2.9%, P <.01), BMI (-0.82 kg/m2, P <.01), waist circumference (-1.70 cm, P <.01), energy intake (-824 kJ/day, P =.01) and improved diet quality (-14.0% energy-dense, nutrient-poor foods, P <.01). Males significantly reduced weight (-2.5%, P =.04), BMI (-0.76 kg/m2, P =.03), waist circumference (-2.40 cm, P =.02), energy intake (-2875 kJ/day, P <.01), increased fruit intake (+0.89 serves/day, P =.02) and improved diet quality (-6% energy-dense, nutrient-poor foods, P <.01). Compared to the other sex, greater reductions were observed in energy intake in males and energy-dense, nutrient-poor foods in females. Linear mixed models identified that changes in V&F intakes did not explain the variation in anthropometric measures. Conclusion: Future interventions may benefit from trialling sex tailored messages to enhance effects on anthropometric changes.

Asthma is a complex disease with heterogeneous phenotypes and endotypes that are incompletely understood. Obesity, obstructive sleep apnea, and gastroesophageal reflux disease co-occur in patients with asthma at higher rates than in those without asthma. Although these diseases share risk factors, there are some data suggesting that these comorbidities have shared inflammatory pathways, drive the development of asthma, or worsen asthma control. This review discusses the epidemiology, pathophysiology, management recommendations, and key knowledge gaps of these common comorbidities.

Background and objective: Severe asthma is responsible for a disproportionate burden of illness and healthcare costs spent on asthma. This study analyses sputum transcriptomics to investigate the mechanisms and novel treatment targets of severe asthma. Methods: Induced sputum samples were collected in a cross-sectional study from participants with severe asthma (n = 12, defined as per GINA criteria), non-severe uncontrolled (n = 21) and controlled asthma (n = 21) and healthy controls (n = 15). Sputum RNA was extracted and transcriptomic profiles were generated (Illumina HumanRef-8 V2) and analysed (GeneSpring). Sputum protein lysates were analysed for p38 activation in a validation study (n = 24 asthma, n = 8 healthy) by western blotting. Results: There were 2166 genes differentially expressed between the four groups. In severe asthma, the expression of 1875, 1308 and 563 genes was altered compared to healthy controls, controlled and uncontrolled asthma, respectively. Of the 1875 genes significantly different to healthy controls, 123 were >2-fold change from which four networks were identified. Thirty genes (>2-fold change) were significantly different in severe asthma compared to both controlled asthma and healthy controls. There was enrichment of genes in the p38 signalling pathway that were associated with severe asthma. Phosphorylation of p38 was increased in a subset of severe asthma samples, correlating with neutrophilic airway inflammation. Conclusion: Severe asthma is associated with substantial differences in sputum gene expression that underlie unique cellular mechanisms. The p38 signalling pathway may be important in the pathogenesis of severe asthma, and future investigations into p38 inhibition are warranted as a ¿non-Th2¿ therapeutic option.

Background and aims: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. Methods and results: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50¿80 years, body mass index: 25¿40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. Conclusion: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. Clinical trial registration: ACTRN12616000732482p.

Background: Although studies have consistently linked obesity and asthma, the potential influence of visceral obesity on asthma has not been well investigated. Objective: To study the associations of visceral fat area (VFA) and clinical and inflammatory features of asthma and to further explore the effects of VFA on the future risk of asthma exacerbation. Methods: A 12-month prospective cohort study based on the Australasian Severe Asthma Network was designed to observe patients with stable asthma grouped by the median value of VFA. The clinical and inflammatory features of asthma were compared between the low VFA (VFAlow) and high VFA (VFAhigh) groups. Relationships between VFA and clinical and inflammatory features of asthma were analyzed by using correlation analysis. Univariate and multivariable negative binomial regression analyses were performed to investigate the association of VFA with exacerbations within a 12-month follow-up period. Results: The patients in the VFAhigh group were older and had a longer asthma duration. Interleukin (IL) 6 and IL-8 in sputum were higher, whereas fractional exhaled nitric oxide (FeNO) and blood eosinophils were lower in the VFAhigh group. Gender-differentiated correlations of VFA with clinical and inflammatory variables were observed in age, FeNO, immunoglobulin E, blood total white cells and neutrophils, and sputum IL-1b and IL-8. Furthermore, compared with the VFAlow group, the VFAhigh group was at significantly increased risk of moderate-to-severe exacerbations (adjusted incidence rate ratio [IRR] 1.55 [95% confidence interval {CI}, 1.06¿2.28; p = 0.025), severe exacerbations (adjusted IRR 2.25 [95% CI, 1.26¿4.04]; p = 0.007), and emergency visits (adjusted IRR 5.33 [95% CI, 1.78¿17.16]; p = 0.003). Conclusion: The level of VFA was associated with specific clinical and inflammatory characteristics of asthma. Furthermore, VFA, as an independent risk factor, was associated with an increased risk of exacerbations. It indicated that VFA would provide more potential clinical implications for asthma management.

Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF) a-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01¿25 mM) with or without TNFa, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFa-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10 ¿25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFa resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFa alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFa-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells.

Background & aims: A brief assessment tool on frequency and variety of fruit and vegetable intake could provide a cost-effective and sustainable approach to improving diet. The primary aim was to evaluate the comparative validity of a brief index of Fruit And Vegetable VAriety (FAVVA) relative to food and nutrient intakes derived from a comprehensive food frequency questionnaire (FFQ). The secondary aim was to evaluate the FAVVA index in relation to fasting plasma carotenoid concentrations. Methods: Dietary intakes and fasting plasma carotenoid concentrations of 99 overweight and obese adults (49.5% female; 44.6 ± 9.9 years) were assessed at baseline and 3-months. Food and nutrient intakes were assessed using the Australian Eating Survey (AES) FFQ. The FAVVA index was derived from a sub-set of 35 AES questions related to fruit and vegetable intake frequency and variety. Associations were assessed using Spearman's correlation coefficients and linear regression analysis, and agreement using weighted kappa (K w ). Results: Total FAVVA score demonstrated moderate to strong, significant (all p < 0.01) correlations with total daily intakes of vegetables (r = 0.75), vitamin C (r = 0.71), fruit (r = 0.66), vitamin A (r = 0.49), fibre (r = 0.49), potassium (r = 0.46), magnesium (r = 0.39), iron (r = 0.26), riboflavin (r = 0.24), calcium (r = 0.23), zinc (r = 0.20) and niacin equivalent (r = 0.20). These associations remained significant in the adjusted regression analyses and agreement testing. Total FAVVA was significantly correlated with plasma carotenoid concentrations (µg/dL) of a¿carotene (r = 0.22, p < 0.01), ß¿carotene (r = 0.26, p < 0.001), ß¿cryptoxanthin (r = 0.22, p < 0.01) and total carotenoids (r = 0.18, p < 0.05). The associations with a¿carotene (ß = 0.09, p < 0.001), ß¿carotene (ß = 0.42, p < 0.05) and total plasma carotenoids (ß = 0.85, p < 0.05) remained significant in the adjusted regression analyses and for agreement testing. Conclusions: FAVVA is suitable as a brief tool to rank frequency and variety of fruit and vegetable intake.

Background: Paediatric obesity-related asthma causes high disease burden, is associated with metabolic abnormalities, has few therapeutic options, and disproportionately affects urban minority children. Although poor diet quality is linked to asthma, the association of nutritional status with disease burden among children with obesity-related asthma is not well understood. Objective: To quantify nutritional status, defined as concentrations of serum carotenoids and n-3 fatty acids, and its association with pulmonary function and metabolic markers among obese asthmatic children. Methods: We quantified serum carotenoids and fatty acids in a study cohort of 158 urban minority adolescents including 39 obese asthmatics, 39 healthy weight asthmatics, 38 obese controls and 42 healthy weight controls and compared between the groups. We correlated carotenoid and fatty acid levels with pulmonary function indices and with insulin resistance and dyslipidemia. Results: Mean total carotenoids were lowest in obese asthmatic children (0.41¿µg/mL), lower than healthy weight asthmatics (0.52¿µg/mL, P¿<¿0.05) and healthy weight controls (0.60¿µg/mL, P¿<¿0.001). n-6/n-3 polyunsaturated fatty acid (PUFA) ratio also differed between the groups (P¿<¿0.05). Total carotenoids positively correlated with per cent-predicted FEV1 and inversely correlated with insulin resistance among obese asthmatics only. n-6/n-3 PUFA ratio inversely correlated with per cent-predicted FEV1 in obese asthmatics. Conclusions & Clinical Relevance: Our findings suggest that carotenoids, which are lowest in obese asthmatic children, may have protective effects on metabolic health and pulmonary function among obese asthmatic children. Similarly, n-3 PUFA appear to be protective for pulmonary function.

Background and Objectives: The need for updated competencies for nutrition scientists in Australia was identified. The aim of this paper is to describe the process of revising of these competencies for undergraduate nutrition science degrees in Australia. Methods and Study Design: An iterative multiple methods approach comprising three stages was undertaken: 1. Scoping study of existing competencies; 2. Exploratory survey; and, 3. Modified Delphi process (2 rounds) involving 128 nutrition experts from industry, community, government and academia. A =70% consensus rule was applied to Rounds 1 and 2 of the Delphi process in order to arrive at a final list of competencies. Results: Stage 1: Scoping study resulted in an initial list of 71 competency statements, categorised under six core areas. Stage 2: Exploratory survey-completed by 74 Nutrition Society of Australia (NSA) members; 76% agreed there was a need to update the current competencies. Standards were refined to six core areas and 36 statements. Stage 3: Modified Delphi process-revised competencies comprise five core competency areas, underpinned by fundamental knowledge, skills, attitudes and values: Nutrition Science; Food and the Food System; Nutrition Governance, Sociocultural and Behavioural Factors; Nutrition Research and Critical Analysis; and Communication and Professional Conduct; and three specialist competency areas: Food Science; Public Health Nutrition; and Animal Nutrition. Conclusions: The revised competencies provide an updated framework of nutrition science knowledge for graduates to effectively practice in Australia. They may be used to benchmark current and future nutrition science degrees and lead to improved employability skills of nutrition science graduates.

Background: Dysfunction of the bronchial epithelium plays an important role in asthma; however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies. Objective: We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum-based measures could provide a relatively non-invasive means through which to monitor airway epithelial activation status. Methods: We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products. Results: Multivariate analysis and generation of 90th centile cut-offs (=11% or =18.1¿×¿104/mL) to identify columnar epithelial cell ¿high¿ asthma revealed a significant relationship between elevated sputum columnar cells and male gender, severe asthma and non-neutrophilic airway inflammation. Flow cytometry showed viable columnar epithelial cells were present in all sputum samples tested. An epithelial gene signature (SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53) was detected in columnar epithelial cell-high sputum. CLCA1 mRNA and periostin protein, previously identified biomarkers of IL-13-mediated epithelial activation, were elevated in columnar epithelial cell-high sputum samples, but only when accompanied by eosinophilia. Conclusions & clinical relevance: Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum samples could allow non-invasive assessment of altered bronchial epithelium status in asthma.

Objectives:The objective of this systematic review was to evaluate the effectiveness of interventions that include a nutrition component aimed at improving gestational weight gain and/or postpartum weight retention.Introduction:Excessive gestational weight gain and postpartum weight retention increase the risk of adverse maternal and neonatal outcomes. Current evidence comprises many interventions targeting gestational weight gain and postpartum weight retention that incorporate a nutrition component. To date, no review has synthesized evidence from pregnancy through the postpartum period or described the intervention approaches in detail.Inclusion criteria:The review included women (=18 years) during pregnancy and/or up to 12 months postpartum. Studies were included if they involved a weight management intervention with a nutrition component and had the primary objective of determining the impact of gestational weight gain and/or postpartum weight change. Interventions were compared to usual care (i.e. control conditions with no intervention or wait-list control or standard pregnancy or postpartum care) or "other" (alternative intervention). The review considered randomized controlled trials published between 1980 and January 21, 2016. Studies that included a weight related primary outcome measured during pregnancy and/or postpartum were included.Methods:Seven databases were searched and the reference lists of included studies were searched for additional studies not previously identified. Two independent reviewers assessed the methodological quality of studies using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI SUMARI). The JBI SUMARI standardized data extraction tool was used to extract data. A narrative synthesis was undertaken to qualitatively synthesize included studies, with meta-analyses used to pool weight outcome data from studies conducted separately for pregnancy and postpartum. Effect sizes for meta-analyses have been expressed as weighted mean differences (95% confidence intervals).Results:The search yielded 4063 articles of which 48 articles from 39 studies were included. Eleven of 20 studies during pregnancy reported significant reductions in gestational weight gain with the intervention when compared to control groups. One of five studies where the intervention was conducted during both pregnancy and postpartum reported statistically significant reductions in gestational weight gain, and postpartum weight retention between intervention and control groups. Nine of 14 studies conducted after childbirth reported statistically significant intervention effects, indicating lesser postpartum weight retention. Random effects meta-analyses indicated that despite considerable heterogeneity, interventions conducted during pregnancy (-1.25 kg; 95% CI:-2.10 kg,-0.40 kg; p = 0.004), and postpartum (-3.25 kg; 95% CI:-4.69 kg,-1.82 kg; p < 0.001) were significantly more effective at improving weight outcomes compared to usual care or other interventions. Most studies were of moderate quality due to lack of clarity in describing study details required for appraising methodological quality. Few interventions were conducted from pregnancy through the postpartum period (n = 5). Limited interventions adopted online modalities in intervention delivery (n = 4). Intention-to-treat analysis was used in only 12 studies.Conclusions:The pregnancy and postpartum period presents a unique opportunity to engage women in interventions to help optimize lifestyle behaviors for weight management, however the optimal approach is unclear. Improving consistency in intervention implementation and reporting will improve future evidence synthesis.

Asthma is a chronic inflammatory airways disease, estimated to affect 300 million people worldwide. Asthma management plans focus on optimisation of asthma pharmacotherapy. Lifestyle interventions also hold great promise for asthma sufferers as they are accessible, low cost and have minimal side-effects, thus making adherence more likely. This review explores lifestyle interventions that have been tested in asthma, including improving nutrition, increasing physical activity and introduction of relaxation therapies such as yoga and massage therapy. Available evidence suggests a protective effect of increasing fruit, vegetable and wholegrain intake and increasing physical activity levels in asthma. Weight loss is recommended for obese asthmatic patients, as just 5¿10% weight loss has been found to improve quality of life and asthma control in most obese asthmatic patients. Other lifestyle interventions such as meditation, yoga and massage therapy show promise, with positive effects on asthma seen in some studies. However, the study protocols are highly variable and the results are inconsistent. Additional research is needed to further develop and refine recommendations regarding lifestyle modifications that can be implemented to improve asthma.

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 Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Objective Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Design Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (â 1/4200 g/d) of nitrate-rich vegetables [high-nitrate (HN); â 1/4150 mg nitrate/d], 2) increased intake (â 1/4200 g/d) of nitrate-poor vegetables [low-nitrate (LN); â 1/422 mg nitrate/d], and 3) no increase in vegetables (control; â 1/46 mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Results Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P < 0.001). Plasma carotenoids increased with the HN and LN treatments compared with the control (P < 0.01). HN treatment did not reduce systolic blood pressure [24-h ambulatory - HN: 127.4 ± 1.1 mm Hg; LN: 128.6 ± 1.1 mm Hg; control: 126.2 ± 1.1 mm Hg (P = 0.20); home - HN: 127.4 ± 0.7 mm Hg; LN: 128.7 ± 0.7 mm Hg; control: 128.3 ± 0.7 mm Hg (P = 0.36); clinic - HN: 128.4 ± 1.3 mm Hg; LN: 130.3 ± 1.3 mm Hg; control: 129.8 ± 1.3 mm Hg (P = 0.49)] or diastolic blood pressure compared with LN and control treatments (P > 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P > 0.05). Conclusion Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive individuals when compared with increased intake of nitrate-poor vegetables and no increase in vegetables.

Obesity is responsible for increased morbidity and mortality in endometrial cancer. Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of endometrial cancer by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of endometrial cancer cells compared with preadipocyte-conditioned medium (PACM). Comparative cytokine array analysis of ACM and PACM reveal upregulation of a group of cytokines belonging to the VEGF signaling pathway in ACM. VEGF protein expression is upregulated in visceral adipose tissue (VAT) in obese patients, which is correlated with increased tumor growth in an in vivo xenograft model. The increased tumor size is mechanistically associated with the activation of the PI3K/AKT/mTOR pathway, a downstream target of VEGF signaling, and its suppression decreased the growth-promoting effects of VAT on endometrial cancer cells. Similar to the human model systems, pathologic changes in endometrial cells in a hyperphagic obese mouse model are associated with increased body weight and hyperactive mTOR signaling. Analysis of human tissue specimens depicts increased in tumor vasculature and VEGF-mTOR activity in obese endometrial cancer patients compared with nonobese patients. Collectively, these results provide evidence that VEGF-mTOR signaling drives endometrial cell growth leading to hyperplasia and cancer. Implications: Adipocyte-derived VEGF¿mTOR signaling may be an attractive therapeutic target against endometrial cancer in obese women.

Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [¿-6 polyunsaturated fatty acids (PUFAs) and ¿-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-a, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ¿-6 PUFA arachidonic acid (AA), but not ¿-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-a challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-a alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-a challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-¿B) nor by hyperactivation of NF-¿B or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ¿-6 PUFAs might promote airway inflammation via multiple pathways, including COX-depen-dent and-independent pathways, and in an obese person, may lead to more severe airway inflammation.

Background: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. Objective: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. Methods: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of =30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis. Results: FM (12.73 ± 3.95 versus 18.59 ± 2.95 versus 27.82 ± 5.17 kg; p < 0.0001), VFA (65.99 ± 23.17 versus 93.96 ± 10.28 versus 123.10 ± 18.34 cm2; p < 0.0001), PBF (23.86 ± 7.46 versus 30.74 ± 5.08 versus 36.21 ± 6.28 %; p = 0.0003) and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different among lean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, and IFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated through IL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin. Conclusion: Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, and IL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future.

Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.

Background: Prebiotic soluble fibers are fermented by beneficial bacteria in the colon to produce short-chain fatty acids (SCFAs), which are proposed to have systemic anti-inflammatory effects. Objective: This review examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation. Design: Relevant English language studies from 1947 to May 2017 were identified with the use of online databases. Studies were considered eligible if they examined the effects of SCFAs, prebiotics, or synbiotics; were delivered orally, intravenously, or per rectum; were on biomarkers of systemic inflammation in humans; and performed meta-analysis where possible. Results: Sixty-eight studies were included. Fourteen of 29 prebiotic studies and 13 of 26 synbiotic studies reported a significant decrease in =1 marker of systemic inflammation. Eight studies compared prebiotic and synbiotic supplementation, 2 of which reported a decrease in inflammation with synbiotics only, with 1 reporting a greater anti-inflammatory effect with synbiotics than with prebiotics alone. Meta-analyses indicated that prebiotics reduce C-reactive protein (CRP) [standardized mean difference (SMD): -0.60; 95% CI: -0.98, -0.23], and synbiotics reduce CRP (SMD: -0.40; 95% CI: -0.73, -0.06) and tumor necrosis factor-a (SMD -0.90; 95% CI: -1.50, -0.30). Conclusions: There is significant heterogeneity of outcomes in studies examining the effect of prebiotics and synbiotics on systemic inflammation. Approximately 50% of included studies reported a decrease in =1 inflammatory biomarker. The inconsistency in reported outcomes may be due to heterogeneity in study design, supplement formulation, dosage, duration, and subject population. Nonetheless, meta-analyses provide evidence to support the systemic anti-inflammatory effects of prebiotic and synbiotic supplementation.

Obesity has reached epidemic proportions in many developed countries as Western dietary patterns have been widely adopted. These diets are characterized by excess energy intake as well as regular consumption of processed or "fast" foods and limited consumption of fruit, vegetables, and whole grains. The result is a high intake of saturated fat, refined carbohydrates, and sodium; and a low intake of fiber, vitamins, and other phytochemicals. This type of poor-quality diet has been associated with increased risk of chronic inflammatory diseases, including asthma. Of particular note, high intake of saturated fat stimulates proinflammatory pathways via activation of pattern recognition receptors, endoplasmic reticulum stress, and fatty acid-binding protein activity. Conversely, with a low intake of soluble fiber, beneficial antiinflammatory mechanisms, such as free fatty acid receptor activation and histone deacetylase inhibition, are suppressed. Similarly, with a low intake of antioxidants such as vitamin C, vitamin E, and carotenoids, nuclear factor k-light-chain-enhancer of activated B cells activity is enhanced, creating a proinflammatory environment. There is evidence derived from human and experimental models of asthma suggesting that these mechanisms contribute to the development of airway inflammation, loss of asthma control, and/or worse lung function. Obese individuals have increased asthmamorbidity and reduced quality of life, so strategies for better management of these patients are urgently needed. Evidence suggests that, in addition to reducing the quantity of food consumed, interventions should also target the quality of food consumed to improve both asthmamanagement and the overall health and well being of these patients.

Introduction Sputum colour is associated with neutrophilic inflammation in chronic bronchitis and chronic obstructive pulmonary disease (COPD). Neutrophilia and sputum expectoration is notable in asthma, but whether sputum colour is associated with and predicts the presence of neutrophilic inflammation in asthma is unknown. The objective of the study is to assess the ability of sputum colour in distinguishing asthma inflammatory phenotypes. Methods Induced sputum samples collected from 271 adults with stable asthma were retrospectively assessed. Sputum colour was determined using the BronkoTest sputum colour chart and correlated to differential cell counts and CXCL-8 concentration. Neutrophilic inflammation was defined as an age-corrected sputum neutrophil proportion (=61.6% for age 20¿40 years; =63.2% for age 40¿60 and =67.2% for age >60 years), whereas neutrophilic bronchitis (NB) was defined as high total cell count (=5.1×106 cells/mL) plus an increased age-corrected neutrophil proportion. The optimal cut-off for sputum colour to predict neutrophilic inflammation and NB was determined using receiver operator characteristic curve analysis. Results A sputum colour score of =3 represented and predicted neutrophilic inflammation with modest accuracy (area under the curve (AUC)=0.64; p<0.001, specificity=78.4%, sensitivity=49.2%). Participants with a sputum colour score of =3 had significantly (p<0.05) higher CXCL-8, total cells and neutrophil number and proportion. Sputum colour score was also positively correlated with these factors. Sputum colour score =3 predicted NB with reasonably good accuracy (AUC=0.79, p<0.001, specificity=79.3%, sensitivity=70.7%). Conclusions Visual gradation of sputum colour in asthma relates to high total cell count and neutrophilic inflammation. Assessment of sputum colour can identify adults with asthma who are likely to have NB without the need for sputum processing and differential cell count, which may facilitate asthma management.

Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1ß and release of the pro-inflammatory cytokine, IL-1ß, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases.

Background and Aims Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. Methods In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. Results The diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (-¿8%, p¿=¿0.013) and LDL cholesterol (LDL-C) level (-¿8%, p¿=¿0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. Conclusion Improvement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.

Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1ß responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1ß in severe, steroid-resistant asthma. Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.

Sex differences in weight loss are often seen despite using the same weight loss program. There has been relatively little investigation of physiological influences on weight loss success in males and females, such as energy homeostasis and appetite regulating hormones. The aims were to 1) characterise baseline plasma leptin, ghrelin and adiponectin concentrations in overweight and obese males and females, and 2) determine whether baseline concentrations of these hormones predict weight loss in males and females.Subjects were overweight or obese (BMI 25-40 kg/m2) adults aged 18-60 years. Weight was measured at baseline, and after three and six months participation in a weight loss program. Baseline concentrations of leptin, adiponectin and ghrelin were determined by enzyme-linked immunosorbent assay (ELISA). An independent t-test or non-parametric equivalent was used to determine any differences between sex. Linear regression determined whether baseline hormone concentrations were predictors of six-month weight change.Females had significantly higher baseline concentrations of leptin, adiponectin and unacylated ghrelin as well as ratios of leptin:adiponectin and leptin:ghrelin. The ratio of acylated:unacylated ghrelin was significantly higher in males. In males and females, a higher baseline concentration of unacylated ghrelin predicted greater weight loss at six months. Additionally in females, higher baseline total ghrelin predicted greater weight loss and a higher ratio of leptin:ghrelin predicted weight gain at six months.A higher pre-weight-loss plasma concentration of unacylated ghrelin is a modest predictor of weight loss success in males and females, while a higher leptin:ghrelin ratio is a predictor of weight loss failure in females. Further investigation is required into what combinations and concentrations of these hormones are optimal for weight loss success.

Background Consumption of dietary carotenoids from fruits and vegetables (F/V) leads to accumulations in human skin, altering skin yellowness. The influence of the quantity of F/V consumed on skin yellowness and plasma carotenoid concentrations has not been examined previously. Objective To compare the influence of consuming high-carotenoid-containing F/V (HCFV) (176,425 µg beta carotene/wk) vs low-carotenoid F/V (LCFV) (2,073 µg beta carotene/wk) on skin yellowness and plasma carotenoid concentrations, over 4 weeks. Design and intervention A single-blind randomized controlled crossover trial from October 2013 to March 2014. Thirty women were randomized to receive 7 daily servings of HCFV or LCFV for 4 weeks. Following a 2-week washout period they followed the alternate intervention. Main outcome measures Skin color (Commission Internationale de l'Eclairage L*a*b* color space, where L* represents skin lightness and positive values of a* and b* represent degrees of redness and yellowness, respectively) was assessed by reflectance spectroscopy in both sun-exposed and nonexposed skin areas. Fasting plasma carotenoids were determined by high-performance liquid chromatography, before and after each intervention period. Statistical analyses performed Linear mixed models were used to determine the HCFV and LCFV response on skin color and plasma carotenoids, adjusting for intervention order, time, and interaction between baseline differences and time. Results There were no significant differences in mean daily fruit (P=0.42) and vegetable (P=0.17) intakes between HCFV and LCFV groups. Dietary alpha carotene, beta carotene, lutein, and beta cryptoxanthin intakes were significantly different between the two groups (P<0.01). Following HCFV there was a significantly greater increase in skin yellowness (b*) in both sun-exposed (P<0.001) and unexposed areas, (P<0.001), with no change in skin lightness (L*) or redness (a*). Significantly higher plasma alpha carotene (P=0.004), beta carotene (P=0.001), and lutein (P=0.028) concentrations were found following the HCFV intervention. Skin yellowness correlated with alpha carotene and beta carotene. Conclusions Skin yellowness (b*) and fasting plasma carotenoid concentrations were significantly higher following HCFV than LCFV over 4 weeks.

Consumption of a high fat meal can increase neutrophilic airway inflammation in asthma subjects. This study investigates the molecular mechanisms driving airway neutrophilia following a high fat meal in asthmatics. Subjects with asthma (n = 11) and healthy controls (n = 8) consumed a high-fat/energy meal, containing total energy (TE) of 3846 kJ and 48 g of total fat (20.5 g saturated). Sputum was induced at 0 and 4 h, and gene expression was examined by microarray and quantitative real-time PCR (qPCR). Following the high fat dietary challenge, 168 entities were significantly differentially expressed greater than >1.5 fold in subjects with asthma, whereas, in healthy controls, only 14 entities were differentially expressed. Of the 168 genes that were changed in asthma, several biological processes were overrepresented, with 25 genes involved in "immune system processes". qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. We also observed a strong correlation and a moderate correlation between the change in NLRP12 and S100A16 gene expression at 4 h compared to baseline, and the change in total and saturated non-esterified plasma fatty acid levels at 2 h compared to baseline. In summary, our data identifies differences in inflammatory gene expression that may contribute to increased airway neutrophilia following a high fat meal in subjects with asthma and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear. Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50). MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment. Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

Objective To examine pre-conception dietary patterns in pregnant asthmatic women and to identify associations between maternal diet and asthma control during pregnancy. Design Cross-sectional study. Pre-conception food frequency data were collected retrospectively. Asthma control was assessed using the Global Initiative for Asthma guidelines. Dietary patterns were derived using factor analysis. Binary logistic regression analyses were used to test the association between uncontrolled asthma and each dietary pattern (Z-score), with values presented as odds ratio and 95 % confidence interval. Setting Antenatal clinic in a tertiary hospital, Adelaide, Australia, May 2009-July 2013. Subjects One hundred and fifty-eight asthmatic pregnant women. Results Three dietary patterns were identified: (i) 'high protein/fruit' (strong food group loadings for fish, meat, chicken, fruit); (ii) 'high fat/sugar/takeaway' (takeaway foods, crisps, refined grains); and (iii) 'vegetarian-type' (vegetables, fruit, soya milk, whole grains). A 1 sd increase in score on the high fat/sugar/takeaway pattern was associated with increased likelihood of uncontrolled asthma (adjusted OR=1·54; 95 % CI 1·07, 2·23; P=0·022). Women with uncontrolled asthma (n 115) had higher energy-adjusted intakes of saturated fat, monounsaturated fat, carbohydrate, sugar and fibre compared with women with controlled asthma (n 43, all P=0·05). Conclusions Pre-pregnancy dietary patterns may influence maternal asthma control. Our work highlights the importance of achieving a healthy diet before pregnancy that is low in saturated fat, sugar and takeaway foods, and therefore higher in lean meats, poultry and fish, as well as fruits, vegetables and whole grains. A healthy dietary pattern should be encouraged in all asthmatic women who are of childbearing age, and should additionally be promoted before pregnancy and beyond.

Background Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. Methods Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. Results Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). Conclusions This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation.

The study was designed to determine the effect of thirty days of pomegranate extract oral supplementation on plasma inflammatory and oxidative stress biomarkers as well as serum metabolic profiles, in overweight and obese individuals. In this randomized, double-blind, placebo-controlled study 48 obese and overweight participants were randomly assigned to receive either 1000 mg of pomegranate extract, or a placebo, daily for 30 days. At baseline, and after 30 days of treatment, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, interleukin-and hyper sensitive-reactive protein and levels of serum lipids, glucose and insulin were assessed. Thirty days of PE supplementation resulted in a significant decrease in mean serum levels of glucose, insulin, total cholesterol, LDL-C, and plasma MDA, IL-and hs-CRP. HDL-significantly increased following the PE versus the PL intervention. Our study suggests that pomegranate extract consumption may reduce complications linked with obesity.

A link between metabolic syndrome (MetS) and lung diseases has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms, greater lung function impairment, pulmonary hypertension, and asthma. This review will discuss several potential mechanisms to explain these associations, including dietary factors and the effect of adiposity and fat-induced inflammation on the lungs, and the role of other comorbidities that frequently coexist with MetS, such as OSA and obesity. In contrast to the well-known association between asthma and obesity, the recognition that MetS affects the lung is relatively new. Although some controversy remains as to whether MetS is a unique disease entity, its individual components have independently been associated with changes in pulmonary function or lung disease. There is, however, uncertainty as to the relative contribution that each metabolic factor has in adversely affecting the respiratory system; also, it is unclear how much of the MetS-related lung effects occur independently of obesity. In spite of these epidemiological limitations, the proposed mechanistic pathways strongly suggest that this association is likely to be causal. Given the wide prevalence of MetS in the general population, it is imperative that we continue to further understand how this metabolic disorder impacts the lung and how to prevent its complications.

Background: Adipokines, such as resistin and adiponectin, modify inflammation and may contribute to increased asthma risk and severity in obese people. Objective: To examine plasma resistin and resistin:adiponectin ratio (i) in asthmatics compared to healthy controls, (ii) according to asthma severity, obesity and gender (iii) following weight loss in obese asthmatics. Methods: In a cross-sectional observational study of asthmatic adults (n = 96) and healthy controls (n = 46), plasma resistin and adiponectin were measured. In a separate intervention study, obese asthmatic adults (n = 27) completed a 10-week weight loss intervention and plasma resistin and adiponectin concentrations were analysed. Results: Plasma resistin and resistin:adiponectin ratio were higher in asthma compared to controls and were higher again in subjects with a severe vs. mild-to-moderate asthma pattern. Amongst asthmatic subjects, resistin was not modified by gender or obesity, while adiponectin was lower in males and obese subjects. As a result, resistin:adiponectin ratio was higher in obese males, non-obese males and obese females, compared to non-obese females. In a logistic regression model, plasma resistin concentration was a predictor of asthma risk. In a multiple linear regression model, plasma resistin:adiponectin ratio was a negative predictor of FEV1 in asthma. Following weight loss, neither resistin, adiponectin nor resistin:adiponectin ratio was changed. However, the change (¿) in %body fat was associated with ¿ resistin:adiponectin ratio. Post-intervention ¿ resistin was negatively correlated with both ¿FRC and ¿RV. Conclusion and clinical relevance: This study demonstrates that resistin and resistin:adiponectin ratio are higher in asthma and are higher again in subjects who have more severe disease. Resistin:adiponectin ratio is highest in obese male asthmatics. As resistin is a predictor of asthma risk and resistin:adiponectin is a predictor of FEV1 in asthma, these adipokines may be contributing to the obese asthma phenotype, thus providing a potential therapeutic target for obese asthma.

Background and objective Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity. Methods Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, a-defensins1-3, NE, IL-1ß and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. Results Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1ß, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. Conclusion NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.

Background/Objectives:Limited dietary intake tools have been validated specifically for hyperlipidaemic adults. The Australian Eating Survey (AES) Food Frequency Questionnaire (FFQ) was adapted to include foods with cardio-protective properties (CVD-AES). The aims were to estimate dietary fatty acid (FA) intakes derived from the CVD-AES and AES and compare them with red blood cell (RBC) membrane FA content.Subjects/Methods:Dietary intake was measured using the semi-quantitative 120-item AES and 177-item CVD-AES. Nutrient intakes were calculated using AUSNUT 2011-2013. Fasting RBC membrane FAs were assessed using gas chromatography. Extent of agreement between intakes estimated by AES or CVD-AES and RBC membrane composition (% of total FAs) for linoleic acid (LA), alpha-linolenic acid (ALA), eicosapentanoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were assessed using Spearman's correlation coefficients, adjusted linear regressions and Kappa statistics.Results:Data from 39 participants (72% female, 59.3±11.1 years) indicate stronger positive correlations between RBC membrane FAs and CVD-AES dietary estimates compared with the AES. Significant (P<0.05) moderate-strong correlations were found between CVD-AES FAs and FA proportions in RBC membranes for EPA (r=0.62), DHA (r=0.53) and DPA (r=0.42), with a moderate correlation for LA (r=0.39) and no correlation with ALA. Significant moderate correlations were found with the AES for DHA (r=0.39), but not for LA, ALA, EPA or DPA.Conclusions:The CVD-AES provides a more accurate estimate of long chain FA intakes in hyperlipidaemic adults, compared with AES estimates. This indicates that a CVD-specific FFQ should be used when evaluating FA intakes in this population.

High levels of lean mass are important in collision-based sports for the development of strength and power, which may also assist during contact situations. While skinfold-based measures have been shown to be appropriate for cross-sectional assessments of body composition, their utility in tracking changes in lean mass is less clear. Purpose: To determine the most effective method of quantifying changes in lean mass in rugby league athletes. Methods: Body composition of 21 professional rugby league players was assessed on 2 or 3 occasions separated by = 6 wk, including bioelectrical impedance analysis (BIA), leanmass index (LMI), and a skinfold-based prediction equation (SkF). Dual-X-ray absorptiometry provided a criterion measure of fat-free mass (FFM). Correlation coefficients (r) and standard errors of the estimate (SEE) were used as measures of validity for the estimates. Results: All 3 practical estimates exhibited strong validity for cross-sectional assessments of FFM (r > .9, P < .001). The correlation between change scores was stronger for the LMI (r = .69, SEE 1.3 kg) and the SkF method (r = .66, SEE = 1.4 kg) than for BIA (r = .50, SEE = 1.6 kg). Conclusions: The LMI is probably as accurate in predicting changes in FFM as SkF and very likely to be more appropriate than BIA. The LMI offers an adequate, practical alternative for assessing in FFM among rugby league athletes.

Background and objective: Obesity is an established risk factor for poor health outcomes, but paradoxically in chronic obstructive pulmonary disease (COPD), it is associated with improved survival and lung function. A major evidence gap exisits to inform treatment recommendations for patients with COPD who are obese. We aimed to determine the effect of weight reduction involving a low-energy diet utilizing a partial meal replacement plan, coupled with resistance exercise training in obese COPD patients. Methods: In a proof of concept before¿after clinical trial, obese (body mass index =30 kg/m2) COPD patients received a 12 week weight reduction programme involving meal replacements, dietary counselling by a dietitian and resistance exercise training prescribed and supervised by a physiotherapist. Patients were reviewed face to face by the dietitian and physiotherapist every 2 weeks for counselling. Results: Twenty-eight participants completed the intervention. Mean (standard deviation) body mass index was 36.3 kg/m2 (4.6) at baseline and reduced by 2.4 kg/m2 ((1.1) P < 0.0001) after the intervention. Importantly, skeletal muscle mass was maintained. Clinical outcomes improved with weight loss including exercise capacity, health status, dyspnea, strength and functional outcomes. There was also a significant reduction in the body mass index, obstruction, dyspnea and exercise score (BODE). Systemic inflammation measured by C-reactive protein however did not change. Conclusion: In obese COPD patients, dietary energy restriction coupled with resistance exercise training results in clinically significant improvements in body mass index, exercise tolerance and health status, whilst preserving skeletal muscle mass. This novel study provides a framework for development of guidelines for the management of obese COPD patients and in guiding future research.

Background/Objectives: Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues. Subjects/Methods: In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides). Results: Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels. Conclusions: The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.

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.

Background/Objectives:Globally, fruit and vegetable intakes are well below recommendations despite ample evidence to link insufficient intake with increased risk of overweight and obesity. Intakes of fruits and vegetables in the general population differ between males and females, and although there is growing evidence of intakes in men and women during weight loss, evidence that directly compares intakes in men and women during weight loss is lacking. This study aimed to identify any differences between males and females in fruit and vegetable intakes and plasma carotenoid concentrations during weight loss, and determine whether there is a relationship between any changes in fruit and vegetable intakes and weight change in both males and females.Subjects/Methods:Men and women (n=100; body mass index 25-40 kg/m2) aged 18-60 years were selected for the study. Dietary intake of fruits and vegetables was assessed using the Australian Eating Survey and fasting blood was collected to assess plasma carotenoids, which were determined by high-performance liquid chromatography.Results:There was little change in fruit or vegetable intakes during weight loss, although men tended to increase fruit intakes. Changes in intakes were influenced by baseline intakes, with males and females with the highest intakes at baseline reducing intakes. Males had better correlations between fruit and vegetable intakes and plasma carotenoid concentrations than females, and fruit and vegetable intakes during weight loss appear to predict weight loss for males but not females.Conclusions:Fruit and vegetable intake during weight loss does not appear to differ largely between males and females.

Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma. Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines. Plasma CRP (p<0.01) and leptin (p<0.01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=-0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02). Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level.

Background: Oral corticosteroids (OCS) are an efficacious treatment for asthma exacerbations, yet risk of adverse effects may decrease patient adherence to therapy. In particular, changes in appetite and dietary intake, which lead to weight gain and changes in body composition, are considered undesirable. Objective: To determine whether 10-day OCS therapy in adults with asthma causes changes in leptin, appetite, dietary intake, body weight and body composition. Methods: Double-blinded, placebo-controlled randomized cross-over trial of 10 days prednisolone (50 mg) in adults with stable asthma (n = 55) (ACTRN12611000562976). Pre- and post-assessment included spirometry, body weight, body composition measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis, appetite measured using a validated visual analogue scale (VAS) and dietary intake assessed using 4-day food records. Leptin was measured as a biomarker of appetite and eosinophils as an adherence biomarker. Outcomes were analysed by generalized linear mixed models. Results: Subject adherence was confirmed by a significant decrease in blood eosinophils (× 109/L) following prednisolone compared to placebo [Coef. -0.29, 95% CI: (-0.39, -0.19) P < 0.001]. There was no difference in serum leptin (ng/mL) [Coef. 0.13, 95% CI: (-3.47, 3.72) P = 0.945] or appetite measured by VAS (mm) [Coef. -4.93, 95% CI: (-13.64, 3.79) P = 0.267] following prednisolone vs. placebo. There was no difference in dietary intake (kJ/day) [Coef. 255, 95% CI: (-380, 891) P = 0.431], body weight (kg) [Coef. -0.38, 95% CI: (-0.81, 0.05) P = 0.083] or body fat (%) [Coef. -0.31, 95% CI: (-0.81, 0.20) P = 0.230]. Symptoms including sleep and gastrointestinal disturbance were reported significantly more often during prednisolone vs. placebo. Conclusions and Clinical Relevance: Short-term OCS in stable asthma did not induce significant changes in appetite, dietary intake, body weight or composition, although other adverse effects may require medical management. This evidence may assist in increasing medication adherence of asthmatics prescribed OCS for exacerbations.

Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.

Background Irisin, a myokine, expressed by muscle and adipose tissue, has been reported to stimulate conversion of white into brown adipose tissue. The beneficial health effects of exercise are thought to be mediated in part, via increased production of irisin. Objective The primary aim of this study was to assess the association between plasma irisin levels glycaemic indices in healthy adults. Associations between irisin and lipid levels, CRP and body composition were explored as secondary outcomes. Methods A cross-sectional sample of forty nine (n = 49) free living healthy males (n = 28) and females (n = 21), between the ages of 18 and 65, with body mass index (BMI) within the healthy range, were recruited. Body weight, height, and body composition measurements were taken. Fasting blood samples were collected for the analysis of glucose, insulin and irisin levels. Insulin resistance score, HOMA-IR, was calculated using fasting blood glucose and insulin values. The relationship between plasma irisin levels and anthropometric measurements, glucose, insulin and HOMA-IR was determined using Spearman's bivariate correlation test. Results A significant inverse relationship was found between plasma irisin levels and insulin(r = -0.380; P = 0.007) and HOMA-IR(r = -0.362; P = 0.011). This relation was further strengthened in males when the data was stratified by gender. Circulating irisin levels were positively correlated with HDL-C (r = 0.39; P = 0.05) in male participants. Additionally, there was a significant negative correlation between percent body fat (r = -0.43, P < 0.05) and body fat mass (r = -0.47, P < 0.05) and circulating irisin levels in male participants. Conclusions This study reports a sex-dependent inverse relationship between plasma irisin levels and insulin resistance in healthy subjects.

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

Background Although exercise has multiple health benefits, relatively little attention has been paid to its potential therapeutic effects in those with asthma. Objective To examine the effects of acute exercise on inflammation in physically inactive and active adults with asthma. Methods Fourteen adults with asthma (n = 6 physically inactive, n = 8 physically active) completed (1) 30 minutes of moderate-intensity exercise on a treadmill and (2) 30 minutes of rest in random order, with 4 weeks between sessions. Exhaled nitric oxide (eNO) was measured before and after the intervention (0, 0.5, 1, 2, 4, and 24 hours). Blood inflammatory mediators were measured before and after the intervention (0, 2, and 24 hours). Results Physically inactive participants had a significant decrease in eNO 4 hours after exercise (-4.8 ppb, -6.4 to -0.5 ppb, P =.028), which was not observed in physically active participants (P =.362). Interluekin-1 receptor antagonist increased in the physically inactive group 2 hours after exercise, with this increase strongly correlated with the decrease in eNO at 4 hours (R = -0.685, P =.007) and 24 hours (R = -0.659, P =.014) after exercise. Interleukin-6 was increased significantly 2 hours after exercise in physically inactive participants. Blood neutrophils and nuclear factor erythroid 2-like 2 gene expression were increased 2 hours after exercise in the overall cohort. Conclusion This study demonstrates that acute moderate-intensity exercise is associated with decreased eNO in physically inactive adults with asthma and suggests that interluekin-1 receptor antagonist could have a role in mediating this effect. The attenuated response in physically active participants might be due to the sustained anti-inflammatory effects of exercise training. Future studies should investigate the impact of exercise intensity and exercise training on airway inflammation in those with asthma.

Background: Asthma prevalence has increased in recent years, and evidence suggests that diet may be a contributing factor. Increased use of processed foods has led to a decrease in diet quality, which may be creating a pro-inflammatory environment, thereby leading to the development and/or progression of various chronic inflammatory diseases and conditions. Recently, the dietary inflammatory index (DII) has been developed and validated to assess the inflammatory potential of individual diets. Objective: This study aimed to examine the DII in subjects with asthma compared to healthy controls and to relate the DII to asthma risk, lung function and systemic inflammation. Methods: Subjects with asthma (n = 99) and healthy controls (n = 61) were recruited. Blood was collected and spirometry was performed. The DII was calculated from food frequency questionnaires administered to study subjects. Results: The mean DII score for the asthmatics was higher than the mean DII score for healthy controls (- 1.40 vs. - 1.86, P = 0.04), indicating that their diets were more pro-inflammatory. For every 1 unit increase in DII score, the odds of having asthma increased by 70% (OR: 1.70, 95% CI: 1.03, 2.14; P = 0.040). FEV1 was significantly associated with DII score (ß = - 3.44, 95% CI: - 6.50, - 0.39; P = 0.020), indicating that for every 1 unit increase in DII score, FEV1 decreased by 3.44 times. Furthermore, plasma IL-6 concentrations were positively associated with DII score (ß = 0.13, 95% CI: 0.05, 0.21; P = 0.002). Conclusion and Clinical Relevance: As assessed using the DII score, the usual diet consumed by asthmatics in this study was pro-inflammatory relative to the diet consumed by the healthy controls. The DII score was associated with increased systemic inflammation and lower lung function. Hence, consumption of pro-inflammatory foods may contribute to worse asthma status, and targeting an improvement in DII in asthmatics, as an indicator of suitable dietary intake, might be a useful strategy for improving clinical outcomes in the disease.

Air pollution worldwide has been associated with cardiovascular and respiratory morbidity and mortality, particularly in urban settings with elevated concentrations of primary pollutants. Air pollution is a very complex mixture of primary and secondary gases and particles, and its potential to cause harm can depend on multiple factors¿including physical and chemical characteristics of pollutants, which varies with fine-scale location (e.g., by proximity to local emission sources)¿as well as local meteorology, topography, and population susceptibility. It has been hypothesized that the intake of anti-oxidant and anti-inflammatory nutrients may ameliorate various respiratory and cardiovascular effects of air pollution through reductions in oxidative stress and inflammation. To date, several studies have suggested that some harmful effects of air pollution may be modified by intake of essential micronutrients (such as B vitamins, and vitamins C, D, and E) and long-chain polyunsaturated fatty acids. Here, we review the existing literature related to the potential for nutrition to modify the health impacts of air pollution, and offer a framework for examining these interactions.

PURPOSE OF REVIEW: The aim of the present review was to summarize recent research developments relating omega-3 polyunsaturated fatty acids (PUFAs) and chronic obstructive pulmonary disease (COPD).

Effective strategies are required to reduce the prevalence of overweight and obesity; however, the effectiveness of current weight loss programmes is variable. One contributing factor may be the difference in weight loss success between men and women. A systematic review was conducted to determine whether the effectiveness of weight loss interventions differs between men and women. Randomized controlled trials published up until March 2014 were included. Effect sizes (Hedges' g) were used to examine the difference in weight outcomes between men and women. A total of 58 studies met the eligibility criteria with 49 studies of higher quality included in the final data synthesis. Eleven studies that directly compared weight loss in men and women reported a significant sex difference. Ten of these reported that men lost more weight than women; however, women also lost a significant amount of weight. Analysis of effect sizes found small differences in weight loss favouring men for both diet (g=0.489) and diet plus exercise (g=0.240) interventions. There is little evidence from this review to indicate that men and women should adopt different weight loss strategies. Current evidence supports moderate energy restriction in combination with exercise for weight loss in both men and women.

Background and objective While weight loss has been shown to reduce obesity-related comorbidity, many weight loss treatments fail. Factors that enhance weight loss success are unknown, particularly in those with asthma. The aim of the study was to identify patient characteristics that predict weight loss success in adults with asthma. Methods Baseline and change in asthma characteristics and eating behaviours were investigated for relationships with weight loss and fat loss using multiple linear regression, in 38 overweight and obese adults with asthma randomized to dietary, exercise or combined interventions targeting weight loss for 10 weeks. Results Mean ± standard deviation weight loss was 6.6 ± 5.1 kg. Greater %weight loss and %fat loss was achieved in those with poorer asthma-related quality of life at baseline ((rs = 0.398, P = 0.015) and (rs = 0.455, P = 0.005) respectively), with 1.7% greater absolute weight loss at week 10 corresponding to each one unit reduction in the asthma-related quality of life score at baseline. Furthermore, a lower baseline forced expiratory volume in 1 s/forced vital capacity correlated with greater weight loss (rs = 0.398, P = 0.015). Male sex was associated with a 3.6 kg greater weight loss (P = 0.087). Reducing emotional eating during the programme was associated with greater weight loss in women (rs = 0.576, P = 0.010). Conclusions This study demonstrates that individuals with more severe asthma at baseline are more successful in achieving weight loss, which could be a consequence of greater motivation and could be used as a motivational tool within the clinical setting. Gender tailoring of weight loss programmes may be useful to enhance weight loss success. Future studies are urgently needed to establish predictors of long-term weight loss maintenance in those with asthma. See Editorial, page 179 This study is the first to demonstrate that more severe asthma at baseline, male sex, and improvements in eating behaviours during weight loss are associated with greater weight loss success in overweight and obese adults with asthma. Our findings may inform the development of asthma-specific weight management guidelines.

Background Previous research has demonstrated that plasma carotenoids are a reliable biomarker of usual fruit and vegetable intake. The review aims were to synthesize (i) the mean dietary intake and (ii) plasma concentrations of carotenoids reported from validation studies (iii) compare the strength of the relationship between the two, measured using different dietary assessment methods. Methods Six databases were used to locate studies that included: adult populations, assessment of dietary intake, measurement of plasma carotenoids and reported the comparison between the two measures. Results One hundred and forty-two studies were included with 95,480 participants, the majority of studies were cross-sectional (n = 86), with randomized controlled trials (RCTs) (n = 18), 14 case-control studies and 13 cohorts. The most common reported dietary carotenoid and plasma carotenoid was lycopene: weighted dietary mean intake (4555.4 ug/day), and plasma concentration 0.62 umol/L (95% CI: 0.61, 0.63, n = 56studies. The strongest weighted correlation between the two measures was found for cryptoxanthin (r = 0.38, 95% CI 0.34, 0.42) followed by a-carotene (r = 0.34, 95% CI 0.31, 0.37). Conclusion This review summarizes typical dietary intakes and plasma concentrations and their expected associations based on validation studies conducted to date which provides a benchmark for future validation studies.

The impact of a polyunsaturated fatty acid, arachidonic acid (AA), on membrane fluidity of epithelial cells and subsequent modulation of the drug transport was investigated. Membrane fluidity was assessed using molecular force microscopy. Calu-3 human bronchial epithelial cells were cultured on Transwell® inserts and the cell stiffness was assessed in the absence of fatty acids or in the presence of 30 µM AA. The morphology of the epithelial cells was distinctly different when AA was present, with the cell monolayer becoming more uniform. Furthermore the cell stiffness and variation in stiffness was lower in the presence of AA. In the fat-free medium, the median cell stiffness was 9.1 kPa which dropped to 2.1 kPa following exposure to AA. To further study this, transport of a common ß2-agonist, salbutamol sulphate (SS) was measured in the presence of AA and in a fat free medium. The transport of SS was significantly higher when AA was present (0.61 ± 0.09 µg versus 0.11 ± 0.003 µg with and without AA respectively). It was evidenced that AA play a vital role in cell membrane fluidity and drug transport. This finding highlights the significance of the dietary fatty acids in transport and consequentially effectiveness of medications used to treat pulmonary diseases such as asthma. This journal is

Background: Recent studies have reported that asthma prevalence increases on migration to Australia. We hypothesised that changes in dietary intake contribute to this phenomenon. The aim of this study was to assess dietary intake in relation to migration status, length of stay in Australia and the association with self-reported wheeze. Methods: Students (n = 144) in a multicultural high school in Western Sydney completed the asthma symptoms ISAAC video questionnaire (AVQ3.0), spirometry and allergy skin prick tests. A dietitian administered a'Food Frequency' and 'Food Habits' questionnaire and a dietary history interview. Results: Students who spoke a language other than English, consumed a traditional or mixed dietary pattern, with lower consumption of saturated fat, compared to students who spoke English only. Saturated fat intake increased and fibre intake decreased with length of time in Australia. Intake of foods high in saturated or trans fatty acids were positively associated with length of stay in Australia. No associations between nutrient intake or whole food intake and self-reported wheeze were observed. Conclusion: As time progressed, dietary intake of immigrant children changed. While this was not associated with the development of wheeze in the students in this cohort, these changes are likely to have negative health consequences.

Objective: Absorption of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to be potentiated when consumed with a high fat meal. However, the effect of different dietary fats on n-3PUFA absorption and postprandial kinetics has not been previously studied. Method: In a randomized cross-over design intervention, postprandial incorporation of LCn-3PUFA into plasma lipids following consumption of a meal rich in either saturated fat or omega-6 polyunsaturated fatty acids (n-6PUFA) was investigated. Healthy adult male and female subjects (n = 26) were fed an isocaloric meal containing equivalent amount of either butter or sunflower seed oil supplemented with 1.8. grams of LCn-3PUFA (300. mg eicosapentaenoic acid, 20:5n-3 and 1500. mg docosahexaenoic acid, 22:6n-3). Results: Postprandial plasma lipids were enriched with saturated fatty acids and linoleic acid (18:2n-6) following consumption of the butter and the sunflower oil containing meals respectively. The increase in plasma 20:5n-3 and 22:6n-3 levels over the 6. hour study period was similar in both the saturated and the n-6 fat groups. Conclusion: These results suggest that the expected competition between LCn-3PUFA and n-6PUFA at the absorption level is unlikely; therefore competition at the enzymatic level should be primarily responsible for differences in their metabolic and clinical effects.Trial registered with the Australia New Zealand Trial registry as ACTRN12612000654853.

Background: Asthma is the most prevalent chronic disease to complicate pregnancies worldwide, affecting around 12% of pregnant women in Australia. Oxidative stress and inflammation manifest during pregnancy; however asthma in pregnancies further intensifies oxidative stress. Consumption of antioxidant-rich foods has been shown to be beneficial for asthma control in non-pregnant asthmatic adults. It has not been investigated whether antioxidant-rich foods can improve the elevated oxidative stress that occurs with asthma in pregnancy, thereby improving asthma control. The primary aim of this study is to determine whether increased consumption of antioxidant-rich foods for 12 weeks will improve maternal asthma control, compared to standard dietary intake during pregnancy.Methods/design: A 12 week, parallel randomized controlled trial will be conducted. One hundred and sixty eight pregnant women with mild, moderate, or severe asthma, currently using inhaled corticosteroids, and with poor diet quality, will be recruited at approximately12 weeks gestation. Following a 4 week run-in period, women will be randomized to either a 12 week antioxidant intervention (increased consumption of antioxidant-rich foods (=5 servings/day vegetables, =2 servings/day fruit, =8 1-Feb servings/day grains (mostly wholegrains), 3-4 serving/week lean meat) or standard pregnancy care. The primary outcome is asthma control score (decrease of 0.5, the minimally clinically significant change). Secondary outcomes include plasma antioxidants, markers of oxidative stress, and time to, and number of, exacerbations. With two-tailed t-tests at 80% power, a sample size of 52 completions per group is required. Allowing for a 78% retention including a 20% removal of women from the analysis due to non-compliance, we will recruit 168 women.Discussion: It is expected that this 12 week study will improve asthma control. This is significant because asthma is the most prevalent condition to complicate pregnancies and contributes to poor maternal, neonatal and infant health outcomes. Our research will provide the first evidence to show that, in pregnancy, consumption of antioxidant-rich foods is a key modifier of clinical asthma status. This research is crucial for contributing to the evidence base to inform future guidelines given existing clinical and research gaps.Trial registration: ACTRN12613000301763. © 2014 Grieger et al.; licensee BioMed Central Ltd.

Background:Whether body composition is associated with lung function in asthmatic children has not been investigated. This study aimed to primarily investigate whether BMI z-score and body composition were associated with respiratory function in asthmatic children.Methods:In a cross-sectional study, male (n = 27; mean age: 11.9 y (SD: 2.3)) and female (n = 21; mean age: 13.6 y (SD: 2.2)) asthmatic children underwent clinical assessment.Results:BMI z-score was associated with forced expiratory volume in 1 s (FEV 1; r = 0.458), forced vital capacity (FVC; r = 0.477), and total lung capacity (TLC; r = 0.451) in males only (P < 0.05). Total lean mass was associated with FEV 1 (r = 0.655), FVC (r = 0.562), and TLC (r = 0.635) in males, as was thoracic lean mass (FEV 1 (r = 0.573), FVC (r = 0.526), and TLC (r = 0.497); P < 0.05). TLC was associated with total (r = 0.522) and thoracic (r = 0.532) lean mass in females (P < 0.05). Fat mass was not associated with lung function in this group.Conclusion:Lean mass, not fat mass, is associated with lung function in children with asthma. The positive association between BMI z-score and respiratory function in male children is driven by lean mass. Although body weight can be easily monitored in the clinical setting, body composition can provide important information. Future research exploring lean mass and lung function associations could inform future interventions. Copyright © 2014 International Pediatric Research Foundation, Inc.

Consumption of foods rich in saturated fatty acids (SFA) has often been associated with elevated blood lipid levels and consequently with risk for chronic diseases, including coronary heart disease. However, epidemiological and interventional studies on this topic are contradictory. While some studies have established a positive link, other studies have failed to show a significant association between saturated fat consumption and blood lipid levels, and others have even found an inverse association. Moreover, studies using animal models have demonstrated that dietary saturated fats raise blood lipid (cholesterol and triglycerides) levels only when the diet is deficient in omega-3 polyunsaturated fatty acids (n-3PUFA). The n-3PUFA are known for their potential in the management of hyperlipidaemia for the prevention of coronary heart disease, as well as for their anti-arrhythmic, anti-aggregatory and anti-inflammatory potential. We believe that with an adequate consumption of n-3PUFA dietary saturated fat may not result in elevated blood lipid levels. Therefore, we critically evaluated the literature regarding saturated fat and blood lipid level, with an emphasis on the role of n-3PUFA on this relationship. Evidence from animal studies and few clinical trials lead to the hypothesis that there are beneficial or neutral effects of saturated fatty acids when combined with recommended levels of n-3PUFA in the diet. However, an intervention focusing on the background fat when the volunteers' diet is supplemented with n-3PUFA is yet to be done. Proving the authenticity of this hypothesis would mean a substantial change in public health messages regarding saturated fats and their health effects; and also a change in the strategies related to prevention of chronic cardiac and artery diseases. © 2013 Elsevier Ltd.

Background: Severe asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which the mechanisms are not fully understood. A disintegrin and metalloproteinase domain 8 (ADAM8) is an enzyme expressed on most leucocytes and may be important for facilitating leucocyte migration in respiratory disease. Objective: To investigate ADAM8 mRNA and protein expression in asthma and COPD and its relationship between asthma severity and inflammatory phenotypes. Methods: Induced sputum was collected from 113 subjects with asthma (severe n = 31, uncontrolled n = 39 and controlled n = 35), 20 subjects with COPD and 21 healthy controls. Sputum ADAM8 mRNA expression was measured by qPCR, and soluble ADAM8 (sADAM8) protein was measured in the sputum supernatant by validated ELISA. Results: ADAM8 mRNA correlated with ADAM8 protein levels (r = 0.27, P < 0.01). ADAM8 mRNA (P = 0.004) and sADAM8 protein (P = 0.014) levels were significantly higher in both asthma and COPD compared with healthy controls. ADAM8 mRNA (P = 0.035) and sADAM8 protein (P = 0.002) levels were significantly higher in severe asthma compared with controlled asthma. Total inflammatory cell count (P < 0.01) and neutrophils (P < 0.01) were also elevated in severe asthmatic sputum. Although ADAM8 mRNA was significantly higher in eosinophilic and neutrophilic asthma (P < 0.001), sADAM8 did not differ between asthma inflammatory phenotypes. ADAM8 expression positively correlated with sputum total cell count and sputum neutrophils. Conclusions and Clinical Relevance: ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD. © 2013 John Wiley & Sons Ltd.

Asthma is a chronic inflammatory disorder of the airways. The inflammatory response in asthma is heterogeneous. Allergen specific responses lead to activation of the acquired immune system, via a predominantly IL-5 mediated, eosinophilic pathway. Stimuli such as viruses and bacteria activate the innate immune system, via a predominantly IL-8 mediated, neutrophilic pathway. Asthma has also been demonstrated to involve a systemic inflammatory component. Glucocorticoids are the predominant pharmacological treatment used to control inflammation in asthma. However, compliance with medications can be compromised due to patient concerns about side effects. Hence dietary interventions that target the inflammatory response in asthma have great potential. Various aspects of dietary intake are known to modulate inflammation. Saturated fatty acids can induce an inflammatory response via activation of pattern recognition receptors. Omega-3 fatty acids can be anti-inflammatory, via mechanisms such as modification of eicosanoid production. Antioxidants can have anti-inflammatory effects as they scavenge free radicals, preventing activation of transcription factors including NF-¿B. Chronic excess energy intake can lead to obesity, which augments inflammation due to the release of inflammatory mediators by adipose tissue. Here we review the role of these dietary components in asthma. © 2014 Bentham Science Publishers.

Background Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. Objective This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes. Methods An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. Results From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3); deoxyribonuclease I-like 3 (DNASE1L3); IL-1ß (IL1B); alkaline phosphatase, tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P <.0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV1; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. Conclusions A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma. © 2013 American Academy of Allergy, Asthma & Immunology.

The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF) analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible contribution of mast cells to the unique metabolome of obese asthma. This review examines proposed multilevel interactions between metabolic and immune systems in obese asthmatics that underlie the negative effects of obesity and may offer significant therapeutic promise. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Tomatoes are the richest source of lycopene, a potent antioxidant. Tomato products improve antioxidant defences and reduce the risk of inflammatory diseases, at least partly, due to the presence of lycopene. Lycopene, as an anti-inflammatory agent, prevents the production of inflammatory cytokines. Obesity is a chronic inflammatory condition in which the increased level of body fat leads to an increase in circulating inflammatory mediators. We hypothesised that the consumption of a lycopene-rich food would reduce inflammation in people who are overweight or obese. A total of 106 overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to an intervention group (n 53) or a control group (n 53) consuming 330 ml/d of tomato juice or water, respectively, for 20 d. At baseline and day 20, serum concentrations of IL-6, IL-8, high-sensitivity C-reactive protein and TNF-a were analysed by ELISA and compared between the groups. Serum concentrations of IL-8 and TNF-a decreased significantly in the intervention group compared with the control group and with baseline. Subgroup analysis indicated that this effect was confined to subjects who were overweight. Among obese subjects, serum IL-6 concentration was decreased in the intervention group compared with the control group, with no differences in IL-8 and TNF-a observed. Tomato juice reduces inflammation in overweight and obese females. Thus, increasing tomato intake may provide a useful approach for reducing the risk of inflammatory diseases such as CVD and diabetes, which are associated with obesity. Copyright © 2012 The Authors.