Hayley A. Scott

The Neutrophilic Inflammatory Phenotype Is Associated With Systemic Inflammation in Asthma

BACKGROUND The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects. METHODS Adults with stable asthma (n = 152) and healthy control subjects (n = 83) underwent hypertonic saline challenge and sputum induction. Differential leukocyte counts were performed on selected sputum. Plasma high-sensitivity C-reactive protein (CRP), IL-6, and tumor necrosis factor-α levels and sputum IL-8 and neutrophil elastase levels were determined by enzyme-linked immunosorbent assay. Sputum IL-8 receptor α (IL-8RA) and IL-8 receptor β (IL-8RB) messenger RNA expression were determined by real-time polymerase chain reaction. RESULTS Subjects with asthma were classified as having nonneutrophilic asthma or neutrophilic asthma. The asthma (neutrophilic) group had increased systemic inflammation compared with the asthma (nonneutrophilic) and healthy control groups, with median (interquartile range) CRP levels of 5.0 (1.6-9.2), 1.8 (0.9-5.3), and 1.8 (0.8-4.1) mg/L (P = .011), respectively, and IL-6 levels of 2.1 (1.5-3.1), 1.4 (1.0-2.1), and 1.1 (0.8-1.5) pg/mL (P < .001), respectively. The proportion of subjects with elevated CRP and IL-6 levels was also higher in the asthma (neutrophilic) group. Sputum IL-8 and neutrophil elastase protein and IL-8RA and IL-8RB gene expression were significantly increased in the asthma (neutrophilic) group. In multiple regression analysis of subjects with asthma, sex, BMI, statin use, and percent sputum neutrophils were significant predictors of log(10)CRP. Sex, BMI, and %FEV(1) were significant predictors of log(10)IL-6. CONCLUSIONS Systemic inflammation is increased in patients with asthma with neutrophilic airway inflammation and associated with worse clinical outcomes. Systemic inflammation may contribute to the pathophysiology of neutrophilic asthma.

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 (&bgr;=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 (&bgr;=0.108, 95% CI 0.036–0.180; p=0.004) and negatively with monounsaturated fatty acids (&bgr;= -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.

Fundamental movement skill interventions in youth: A systematic review and meta-analysis

BACKGROUND: Fundamental movement skill (FMS) proficiency is positively associated with physical activity and fitness levels. The objective of this study was to systematically review evidence for the benefits of FMS interventions targeting youth. METHODS: A search with no date restrictions was conducted across 7 databases. Studies included any school-, home-, or community-based intervention for typically developing youth with clear intent to improve FMS proficiency and that reported statistical analysis of FMS competence at both preintervention and at least 1 other postintervention time point. Study designs included randomized controlled trials (RCTs) using experimental and quasi-experimental designs and single group pre-post trials. Risk of bias was independently assessed by 2 reviewers. RESULTS: Twenty-two articles (6 RCTs, 13 quasi-experimental trials, 3 pre-post trials) describing 19 interventions were included. All but 1 intervention were evaluated in primary/elementary schools. All studies reported significant intervention effects for ≥1 FMS. Meta-analyses revealed large effect sizes for overall gross motor proficiency (standardized mean difference [SMD] = 1.42, 95% confidence interval [CI] 0.68–2.16, Z = 3.77, P < .0002) and locomotor skill competency (SMD = 1.42, 95% CI 0.56–2.27, Z = 3.25, P = .001). A medium effect size for object control skill competency was observed (SMD = 0.63, 95% CI 0.28–0.98, Z = 3.53, P = .0004). Many studies scored poorly for risk of bias items. CONCLUSIONS: School- and community-based programs that include developmentally appropriate FMS learning experiences delivered by physical education specialists or highly trained classroom teachers significantly improve FMS proficiency in youth.

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

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.

Manipulating antioxidant intake in asthma: a randomized controlled trial

BACKGROUND Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.

Innate immune mechanisms linking non-esterified fatty acids and respiratory disease.

Local airway inflammation in chronic respiratory disease is well described. Recently it has been recognised that chronic obstructive respiratory disease, asthma and obstructive sleep apnoea, all involve a systemic inflammatory component. Overspill of airway inflammation, as well as direct metabolic effects, are potential contributors to systemic inflammation. This review will discuss the role of certain types of fatty acids in promoting systemic inflammation, via the innate immune response. Fatty acids are necessary as the key energy source in the body. However, they can be detrimental if present in excess. Various features of respiratory disease lead to altered lipid metabolism, and notably an increase in circulating levels of non-esterified fatty acids (NEFA). Dietary intake, obesity, hypoxia and smoking, will be discussed as factors promoting an increase in circulating NEFA. While n-3 polyunsaturated and monounsaturated fatty acids may be non-(or anti-)inflammatory, saturated and n-6 polyunsaturated fatty acids have been shown to stimulate the innate immune response. Thus, increased circulating NEFA may be directly contributing to systemic inflammation, thereby increasing susceptibility of individuals to chronic inflammatory diseases, including respiratory disease, cardiovascular disease and diabetes. Finally, the review will discuss how the recognition of NEFA as important inflammatory stimulants in respiratory disease, leads to the possibility that pathways involved in lipid metabolism may provide therapeutic targets.

Relationship between body composition, inflammation and lung function in overweight and obese asthma

BackgroundThe obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma.MethodsOverweight and obese (BMI 28-40 kg/m2) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers.ResultsIn females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males.ConclusionsThis study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.

Macrophage activation, age and sex effects of immunometabolism in obese asthma

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. Macrophage activation is a determinant of pro-inflammatory effects of immunometabolism in childhood obese asthma http://ow.ly/ArCAH

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

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.

Should we treat obesity in COPD? The effects of diet and resistance exercise training

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.