Obese asthmatics are characterized by altered adipose tissue macrophage activation.

BACKGROUND: Adipose tissue-derived inflammation is linked to obesity-related comorbidities. This study aimed to quantify and immuno-phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non-asthmatics and to examine associations between adipose tissue, systemic and airway inflammation. METHODS: Visceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C-reactive protein (CRP) and CD163 were measured by ELISA. RESULTS: VAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non-asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV1 %. Sputum macrophage count was correlated positively with M1 ATMs and negatively with M2 ATMs in VAT. In obese asthmatics, CRP was positively associated with M1:M2 ratio in VAT. There were no associations with CD163. An elevated ratio of M1:M2 ATMs was observed in VAT of obese asthmatics with increased disease severity. CONCLUSIONS AND CLINICAL RELEVANCE: Visceral inflammation with increased pro-inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.

Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

Comparison of fatty acid intakes assessed by a cardiovascular-specific food frequency questionnaire with red blood cell membrane fatty acids in hyperlipidaemic Australian adults: a validation study.

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.

Resistin is a predictor of asthma risk and resistin:adiponectin ratio is a negative predictor of lung function in asthma.

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.

Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype.

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.

Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids.

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.

Comparison of fruit and vegetable intakes during weight loss in males and females.

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/m(2)) 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.

Effects of short-term oral corticosteroid intake on dietary intake, body weight and body composition in adults with asthma - a randomized controlled trial.

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 (× 10(9) /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.

Effectiveness of weight loss interventions--is there a difference between men and women: a systematic review.

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.

Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in 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.

Sputum ADAM8 expression is increased in severe asthma and COPD.

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.

Saturated fat consumption may not be the main cause of increased blood lipid levels.

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.

Diet-induced weight loss in obese children with asthma: a randomized controlled trial.

BACKGROUND: Obesity is highly prevalent in asthmatic children and associated with worse clinical outcomes. Energy restriction to induce weight loss in asthmatic children has not been investigated in a randomized controlled trial (RCT). OBJECTIVE: To assess if (1) weight loss can be achieved in obese asthmatic children using a dietary intervention; and (2) changes in asthma outcomes occur following diet-induced weight loss. METHODS: In a 10-week pilot RCT, obese asthmatic children, aged 8-17 years, were randomized to a wait-list control (WLC) (n = 15) or dietary-intervention group (DIG) (n = 13). Lung function, Asthma Control Questionnaire (ACQ) score, and sputum and systemic inflammation were assessed at baseline and post-intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000955011). RESULTS: Body mass index (BMI) z-score reduced significantly in the DIG vs. the WLC (-0.2 [-0.4, -0.1] vs. 0.0 [-0.1, 0.0], P = 0.014). Expiratory reserve volume (ERV) increased significantly within the DIG, but not compared to the WLC (0.7 [0.0, 1.0] L vs. 0.3 [0.0, 0.8] L, P = 0.355). ACQ improved significantly in the DIG, compared to the WLC (-0.4 [-0.7, 0.0] vs. 0.1 [0.0, 0.6], P = 0.004). Airway and systemic inflammation did not change within the DIG. In comparison, C-Reactive Protein (CRP) increased significantly in the WLC (-0.4 [-0.5, 0.4] vs. 0.7 [-0.1, 1.9], P = 0.037). Change (∆) in BMI z-score correlated with ∆CRP (r = 0.47, P = 0.012) and ∆exhaled nitric oxide (eNO) (r = 0.46, P = 0.034), and ∆ACQ was associated with ∆CRP (r = 0.43, P = 0.029). CONCLUSION AND CLINICAL RELEVANCE: Dietary intervention can induce acute weight loss in obese asthmatic children with subsequent improvements in static lung function and asthma control. Systemic and airway inflammation did not change following weight loss. However, changes in BMI z-score were associated with changes in airway and systemic inflammation and this requires further investigation in a larger RCT. This is the first weight loss RCT conducted in obese asthmatic children. Diet-induced weight loss can achieve significant improvements in clinical outcomes for obese children with asthma.

Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial.

BACKGROUND: Obesity and asthma are associated conditions; however, the mechanisms linking the two remain unclear. Few studies have examined the effects of weight loss on inflammation and clinical outcomes in obese-asthma. OBJECTIVE: To compare the effects of weight loss achieved by dietary restriction, exercise or combined dietary restriction and exercise on airway inflammation and clinical outcomes in overweight and obese adults with asthma. METHODS: Participants (n = 46; 54.3% female, body mass index (mean ± SD) 33.7 ± 3.5 kg/m(2) ) were randomized to complete a 10-week dietary, exercise or combined dietary and exercise intervention. Dual-energy x-ray absorptiometry was performed, the Juniper Asthma Control Questionnaire and Juniper Asthma Quality of Life Questionnaire completed and inflammatory markers, dietary intake and physical activity measured. The trial was registered with the Australian Clinical Trials Registry: ACTRN12611000235909. RESULTS: Retention was 82.6%. Mean ± SD weight loss was 8.5 ± 4.2%, 1.8 ± 2.6% and 8.3 ± 4.9% after the dietary, exercise and combined interventions respectively. Asthma control improved after the dietary (mean ± SD; -0.6 ± 0.5, P ≤ 0.001) and combined interventions (-0.5 ± 0.7, P = 0.040), whereas quality of life improved after the dietary [median (IQR); 0.9 (0.4, 1.3), P = 0.002], exercise [0.49 (0.03, 0.78), P = 0.037] and combined [0.5 (0.1, 1.0), P = 0.007] interventions. A 5-10% weight loss resulted in clinically important improvements to asthma control in 58%, and quality of life in 83%, of subjects. Gynoid adipose tissue reduction was associated with reduced neutrophilic airway inflammation in women [ß-coefficient (95% CI); 1.75 (0.02, 3.48), P = 0.047], whereas a reduction in dietary saturated fat was associated with reduced neutrophilic airway inflammation in males (r = 0.775, P = 0.041). The exercise intervention resulted in a significant reduction to sputum eosinophils [median (IQR); -1.3 (-2.0, -1.0)%, P = 0.028]. CONCLUSION AND CLINICAL RELEVANCE: This study suggests a weight-loss goal of 5-10% be recommended to assist in the clinical management of overweight and obese adults with asthma. The obese-asthma phenotype may involve both innate and allergic inflammatory pathways.

Soluble RAGE is deficient in neutrophilic asthma and COPD.

The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asthma and chronic obstructive pulmonary disease (COPD). Bronchial lavage fluid from subjects with moderate-to-severe persistent asthma (n = 16) or COPD (n = 37), or from healthy controls (n = 18), was analysed for neutrophils, total sRAGE, endogenous secretory RAGE (esRAGE), HMGB1 and SAA. We also determined systemic levels of sRAGE in a separate group of asthmatic (n = 101) and COPD (n = 34) subjects. Subjects with neutrophilic asthma or COPD had undetectable levels of lung sRAGE, while levels of sRAGE in asthma/COPD without neutrophilia were similar to those in controls. Systemic sRAGE was significantly decreased in subjects with neutrophilic asthma or COPD compared with those without airway neutrophilia. There was significant positive correlation between total sRAGE and esRAGE in the lung and systemically. HMGB1 levels were similar in all subject groups, while SAA was below detectable levels. Neutrophilic airway inflammation in asthma and COPD is associated with reduced sRAGE.

The obesity phenotype in children with asthma.

Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an 'obese asthma' phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients.

Airway inflammation is augmented by obesity and fatty acids in asthma.

Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma. Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood samples analysed for inflammatory markers. There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (ß=1.015, 95% CI 0.258-1.772; p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9% versus 16.2%; p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (ß=0.108, 95% CI 0.036-0.180; p=0.004) and negatively with monounsaturated fatty acids (ß= -0.068, 95% CI -0.131- -0.005; p=0.035). This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.

Characterization of innate immune signalling receptors in virus-induced acute asthma.

BACKGROUND: The role of toll-like receptors (TLRs) and innate immune activation in clinical asthma exacerbations and their relationship to virus infection are unclear. OBJECTIVE: This study aimed to characterize TLR expression and innate immune activity during virus infection in acute asthma. METHODS: Subjects with acute asthma, stable asthma and healthy controls were recruited and underwent spirometry and sputum induction with isotonic saline. Selected sputum was dispersed with dithiothreitol and total and differential leucocyte counts were performed. Selected sputum was also used for quantitative real-time PCR for TLR2, TLR3, TLR4, IL-10 and IP-10mRNA expression. Sputum supernatant was used for the measurement of innate immune markers, including IL-8, matrix metalloproteinase-9 and neutrophil elastase activity. Viruses were detected using real-time and gel-based PCR. RESULTS: Sputum TLR2 mRNA expression was up-regulated in both acute and stable asthma compared with healthy controls and decreased 4-6 weeks after acute exacerbation. Sputum TLR2 mRNA expression was elevated in viral, compared with non-viral, acute asthma. Sputum TLR3 mRNA expression was similar in controls, stable and acute asthma. However, in acute asthma, subjects with virus-induced acute asthma had significantly higher sputum TLR3 mRNA expression. Induced sputum gene expression for IP-10 and IL-10 were increased in viral, compared with non-viral, acute asthma. In virus-induced acute asthma, levels of IP-10 and IL-10 mRNA expression were correlated with the mRNA expression of TLR2 and TLR3. CONCLUSIONS AND CLINICAL RELEVANCE: Virus-induced acute asthma leads to specific induction of TLR2, TLR3, IP-10 and IL-10, suggesting that signalling via TLRs may play an important role in mediating airway inflammation, via both innate and adaptive pathways, in virus-induced exacerbations. These mediators may provide potential treatment targets for virus-induced asthma. They may also be useful in diagnosing the nature of acute asthma exacerbations and monitoring treatment responses, which would be useful in the clinical management of asthma exacerbations.

Assessment of dietary fat intake and innate immune activation as risk factors for impaired lung function.

BACKGROUND/OBJECTIVES: Preservation of lung health with aging is an important health issue in the general population, as loss of lung function with aging can lead to the development of obstructive lung disease and is a predictor of all-cause and cardiovascular mortality. Inflammation is increasingly linked to loss of lung function and evidence suggests that consumption of dietary fat exacerbates inflammation. We aimed to determine the association between dietary fat intake and lung function in older people. SUBJECTS/METHODS: Participants from the Hunter community study, a population-based cohort, were recruited during 2004 and 2005. Participants received a clinical assessment, including spirometry, and provided a blood sample. Diets were analyzed using food-frequency questionnaires. Plasma interleukin (IL)-6 and C-reactive protein was measured by Enzyme-Linked immunosorbent assay. RESULTS: Using backward stepwise linear regression, %energy from dietary fat, age and plasma IL-6 were considered as negative predictors of forced expiratory volume in one second (FEV(1)) in men. Also in men, % energy intake from dietary fat, age, body mass index and IL-6 were negative predictors of %predicted forced vital capacity (FVC). Smoking and age were negative predictors of FEV(1)/FVC. In women, plasma IL-6 and age were negative predictors of %FVC, whereas obesity was positively associated with FEV(1)/FVC. CONCLUSIONS: An increased proportion of fat in the diet is associated with the reduced lung function in older men. Dietary-fat induced innate immune activation and IL-6 release may contribute to this effect. Dietary interventions involving fat restriction should be further investigated as means of preserving lung function with aging.