Dr Hayley Scott

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 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.

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 FEV 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 FEV in asthma, these adipokines may be contributing to the obese asthma phenotype, thus providing a potential therapeutic target for obese asthma. 1 1

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/m ) 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/m (4.6) at baseline and reduced by 2.4 kg/m ((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. 2 2 2

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 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 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 ((r = 0.398, P = 0.015) and (r = 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 (r = 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 (r = 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. s s s s

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.