Protein Intake and Physical Activity Levels as Determinants of Sarcopenia Risk in Community-Dwelling Older Adults.

Community screening for sarcopenia is complex, with barriers including access to specialized equipment and trained staff to conduct body composition, strength and function assessment. In the current study, self-reported dietary protein intake and physical activity (PA) in adults ≥65 years was assessed relative to sarcopenia risk, as determined by body composition, strength and physical function assessments, consistent with the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Of those screened (n = 632), 92 participants (77% female) were assessed as being at high risk of developing sarcopenia on the basis of dietary protein intake ≤1 g∙kg-1∙day-1 [0.9 (0.7-0.9) g∙kg-1∙day-1] and moderate intensity physical activity <150 min.week-1. A further 31 participants (65% female) were defined as being at low risk, with both protein intake [1.2 (1.1-1.5) g∙kg-1∙day-1] and PA greater than the cut-off values. High-risk participants had reduced % lean mass [53.5 (7.8)% versus 54.8 (6.1)%, p < 0.001] and impaired strength and physical function. Notably, high-risk females exhibited greater deficits in lean mass and strength, with minimal differences between groups for males. In community-dwelling older adults, self-reported low protein intake and low weekly PA is associated with heightened risk for sarcopenia, particularly in older women. Future research should determine whether early intervention in older adults with low protein intake and PA attenuates functional decline.

Medicinal Mushroom Extracts from Hericium coralloides and Trametes versicolor Exert Differential Immunomodulatory Effects on Immune Cells from Older Adults In Vitro.

Medicinal mushroom extracts (MMEs) exert immunomodulatory effects on innate immunity. The present study aimed to examine the effect of medicinal mushroom components on in vitro immune cell responses to inflammatory stimuli by peripheral blood mononuclear cells (PBMCs) isolated from older adults, where immune function is altered. PBMCs were treated with extracts from Hericium coralloides (HC) and Trametes versicolor (TV) prior to stimulation with rhinovirus A1 (RVA1), influenza A/H1N1pdm09 (H1N1), lipopolysaccharide (LPS), or house dust mite (HDM) for 48 h. In the presence of virus, type I and II IFN significantly (p < 0.05) decreased following treatment with at least one concentration of all extracts compared to the untreated cell controls, along with significant increases in pro-inflammatory cytokines (IL-1ß, IL-6, IL-8). In the presence of LPS, extracts from TV reduced IL-1ß compared to untreated cells. In the presence of HDM, the concentration of IL-5 and/or IL-13 was significantly decreased with at least one dose of all extracts. MMEs exert differential effects on the release of inflammatory and antiviral mediators in vitro. Reduced type 2 cytokine responses to HDM may be beneficial in conditions where allergic inflammation is present, including asthma, allergic rhinitis, and eczema. Further research is needed to examine extracts in vivo.

The Effects of Increasing Fruit and Vegetable Intake in Children with Asthma on the Modulation of Innate Immune Responses.

Children with asthma are at risk of acute exacerbations triggered mainly by viral infections. A diet high in fruit and vegetables (F&V), a rich source of carotenoids, may improve innate immune responses in children with asthma. Children with asthma (3−11 years) with a history of exacerbations and low F&V intake (≤3 serves/d) were randomly assigned to a high F&V diet or control (usual diet) for 6 months. Outcomes included respiratory-related adverse events and in-vitro cytokine production in peripheral blood mononuclear cells (PBMCs), treated with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS). During the trial, there were fewer subjects with ≥2 asthma exacerbations in the high F&V diet group (n = 22) compared to the control group (n = 25) (63.6% vs. 88.0%, p = 0.049). Duration and severity of exacerbations were similar between groups. LPS-induced interferon (IFN)-γ and IFN-λ production showed a small but significant increase in the high F&V group after 3 months compared to baseline (p < 0.05). Additionally, RV1B-induced IFN-λ production in PBMCs was positively associated with the change in plasma lycopene at 6 months (rs = 0.35, p = 0.015). A high F&V diet reduced asthma-related illness and modulated in vitro PBMC cytokine production in young children with asthma. Improving diet quality by increasing F&V intake could be an effective non-pharmacological strategy for preventing asthma-related illness by enhancing children's innate immune responses.

Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.

Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with antimicrobial and immune-modulating properties. This review aimed to examine the evidence for the effect of Lf supplementation on inflammation, immune function, and respiratory tract infections (RTIs) in humans. Online databases were searched up to December 2020 to identify relevant, English-language articles that examined the effect of Lf supplementation in human subjects of all ages, on either inflammation, immune cell populations or activity, or the incidence, duration, or severity of respiratory illness or RTIs. Twenty-five studies (n = 20 studies in adults) were included, of which 8 of 13 studies (61%) in adults reported a decrease in at least 1 systemic inflammatory biomarker. Immune function improved in 6 of 8 studies (75%) in adults, with changes in immune cell populations in 2 of 6 studies (33%), and changes in immune cell activity in 2 of 5 studies (40%). RTI outcomes were reduced in 6 of 10 studies (60%) (n = 5 in adults, n = 5 in children), with decreased incidence in 3 of 9 studies (33%), and either decreased frequency (2/4, 50%) or duration (3/6, 50%) in 50% of studies. In adults, Lf reduced IL-6 [mean difference (MD): -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL], but not C-reactive protein (CRP) [standardized mean difference: -0.09; 95% CI: -0.82, 0.65], or NK cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children (OR: 0.78; 95% CI: 0.61, 0.98) but not in adults (OR: 1.00; 95% CI: 0.76, 1.32). Clinical studies on Lf supplementation are limited, although findings show 200 mg Lf/d reduces systemic inflammation, while formulas containing 35-833 mg Lf/d may reduce RTI incidence in infants and children, suggesting improved immune function. Future research is required to determine optimal supplementation strategies and populations most likely to benefit from Lf supplementation. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232186) as CRD42021232186.

Sulforaphane reduces pro-inflammatory response to palmitic acid in monocytes and adipose tissue macrophages.

Chronic low-grade systemic inflammation (SI), including activation of the NLRP3 inflammasome, is a feature of obesity, associated with increased circulating saturated fatty acids, such as palmitic acid (PA), and bacterial endotoxin lipopolysaccharide (LPS). PA and LPS may contribute to SI observed in obesity, while the dietary antioxidant sulforaphane has been shown to reduce activation of the NLRP3 inflammasome. This study investigated immune cell responses from obese subjects to PA, and the effects of sulforaphane on NLRP3 activation/inflammation. Peripheral blood monocytes isolated from obese (n = 8) and non-obese (n = 8) subjects and adipose tissue macrophages (ATMs) isolated from visceral fat obtained from obese subjects (n = 10) during bariatric surgery were pre-treated with/without sulforaphane (40 µM) for 3 hours then stimulated with PA (500 µM) ± LPS (1 ng/mL monocytes; 100 ng/mL ATMs) for 15 hours. Culture supernatants were assessed for tumor necrosis factor-α and interleukin-ß (IL-1ß) by enzyme-linked immunosorbent assay, NLRP3 inflammasome gene expression was assessed by quantitative polymerase chain reaction, IL-1ß and NLRP3 expression were higher in both unstimulated and PA treated monocytes from obese compared to nonobese subjects. In ATMs neither PA alone or combined with LPS increased cytokine production or inflammasome gene expression. Sulforaphane reduced tumor necrosis factor-α and IL-1ß from monocytes in both groups, however inflammasome associated genes were only reduced in monocytes from obese subjects. Sulforaphane reduced cytokine production and inflammasome gene expression in ATMs. NLRP3 inflammasome activation by PA is higher in obesity, which maybe driven by baseline activation of the NLRP3 inflammasome. Sulforaphane modulates inflammatory responses in immune cells and may play a role in reducing SI in obesity.

Nutrition in Asthma.

An emerging body of evidence suggests that diet plays an important role in both the development and management of asthma. The relationship between dietary intake and asthma risk has been explored in epidemiological studies, though intervention trials examining the effects of nutrient intake and dietary patterns on asthma management are scarce. Evidence for diets high in fruits and vegetables, antioxidants, omega-3 fatty acids and soluble fiber such as the Mediterranean diet is conflicting. However, some studies suggest that these diets may reduce the risk of asthma, particularly in young children, and could have positive effects on disease management. In contrast, a Westernized dietary pattern, high in saturated fatty acids, refined grains, and sugars may promote an inflammatory environment resulting in the onset of disease and worsening of asthma outcomes. This review will summarize the state of the evidence for the impact of whole dietary patterns, as well as individual nutrients, on the prevalence and management of asthma.

Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects.

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). Monocytes 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 harvested after 15 h incubation. TNF-α 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-α and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α 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.

The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.

Prebiotics, synbiotics, and SCFAs have been shown to decrease systemic inflammation and play a protective role in chronic respiratory conditions. However, their effects on infection and immune function are unclear. The objective of this systematic review was to summarize the current evidence for prebiotic, synbiotic, and SCFA supplementation on respiratory tract infections (RTIs) and immune function. The protocol for this systematic review was registered with PROSPERO (National Institute for Health Research, University of York, UK), accessed online at https://www.crd.york.ac.uk/prospero (CRD42019118786). Relevant English-language articles up to May 2021 were identified via online databases: MEDLINE, EMBASE, CINAHL, and Cochrane Library. Included studies (n = 58) examined the effect of prebiotics, synbiotics, or SCFA, delivered orally, on the incidence, severity, or duration of RTIs and/or markers of immune function (e.g., peripheral blood immunophenotyping, NK cell activity). The majority of studies were randomized controlled trials reporting on RTIs in infants and children. The meta-analysis indicated that the numbers of subjects with ≥1 RTI were reduced with prebiotic (OR, 0.73; 95% CI: 0.62-0.86; P = 0.0002; n = 17) and synbiotic (OR, 0.75; 95% CI: 0.65-0.87; P = 0.0001; n = 9) supplementation compared to placebo. Further, NK cell activity was increased with synbiotic (standardized mean difference, 0.74; 95% CI: 0.42-1.06; P < 0.0001, n = 3) supplementation. This review provides evidence that prebiotic, specifically oligosaccharide, supplementation may play a protective role in RTIs in infants and children. There is less evidence for this effect in adults. Supplementation with prebiotic and synbiotic treatment may alter immune function by increasing NK cell activity, though effects on immunophenotype were less clear.

Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma.

BACKGROUND: Obesity is a risk factor for asthma, and obese asthmatic individuals are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type 2 immunity, and eosinophilic inflammation have been described. OBJECTIVE: We investigated how obesity affects the pathogenesis and severity of asthma and identified effective therapies for obesity-associated disease. METHODS: We assessed associations between body mass index and inflammasome responses with type 2 (T2) immune responses in the sputum of 25 subjects with asthma. Functional roles for NLR family, pyrin domain-containing (NLRP) 3 inflammasome and T2 cytokine responses in driving key features of disease were examined in experimental high-fat diet-induced obesity and asthma. RESULTS: Body mass index and inflammasome responses positively correlated with increased IL-5 and IL-13 expression as well as C-C chemokine receptor type 3 expression in the sputum of subjects with asthma. High-fat diet-induced obesity resulted in steroid-insensitive airway hyperresponsiveness in both the presence and absence of experimental asthma. High-fat diet-induced obesity was also associated with increased NLRP3 inflammasome responses and eosinophilic inflammation in airway tissue, but not lumen, in experimental asthma. Inhibition of NLRP3 inflammasome responses reduced steroid-insensitive airway hyperresponsiveness but had no effect on IL-5 or IL-13 responses in experimental asthma. Depletion of IL-5 and IL-13 reduced obesity-induced NLRP3 inflammasome responses and steroid-insensitive airway hyperresponsiveness in experimental asthma. CONCLUSION: We found a relationship between T2 cytokine and NLRP3 inflammasome responses in obesity-associated asthma, highlighting the potential utility of T2 cytokine-targeted biologics and inflammasome inhibitors.

Children With Asthma Have Impaired Innate Immunity and Increased Numbers of Type 2 Innate Lymphoid Cells Compared With Healthy Controls.

Background: Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children. Objective: The present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma. Methods: Using a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1ß, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout. Results: The frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (P<0.01). RV1B-induced IL-1ß response and HDM-stimulated IL-5 production was higher in asthmatics than controls (P<0.05). In contrast, IL-1ß and IL-6 were significantly reduced in response to HDM and LPS in asthmatics compared to controls (P<0.05). Children with asthma also had reduced pulmonary function, indicated by lower respiratory reactance as well as higher area of-reactance and lung clearance index values compared with controls (P<0.05). Conclusion: Our study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.

The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial.

BACKGROUND: A high fruit and vegetable (F&V) diet reduces asthma exacerbations in adults; this has not been examined in children to date. OBJECTIVE: To investigate the effect of a 6-month, high F&V diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial. METHODS: Children (aged 3-11 years) with asthma, history of exacerbations and usual low F&V intake (≤3 serves/day) were randomized to the intervention (high F&V diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression. RESULTS: 67 children were randomized between September 2015 and July 2018. F&V intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p < 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (X5 ∆: 0.76 [0.04, 1.48] p = 0.038, X20 ∆: 0.93 [0.23, 1.64] p = 0.009) and changes in faecal microbiota were observed though there was no difference between groups in systemic inflammation or molecular mechanisms. In the control group, CRP and HDAC enzyme activity increased, while GPR41 expression decreased. No adverse events attributable to the interventions were observed. CONCLUSION & CLINICAL RELEVANCE: A high F&V diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

Asthma medication use in obese and healthy weight asthma: systematic review/meta-analysis.

BACKGROUND: Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy. OBJECTIVE: This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m-2) versus healthy-weight (BMI <25 kg·m-2) subjects with asthma. DESIGN: Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671). RESULTS: Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting ß2-agonists (OR 1.75, 95% CI 1.17-2.60; p=0.006, I2=41%) and maintenance oral corticosteroids (OR 1.86, 95% CI 1.49-2.31; p<0.001, I2=0%) compared to healthy-weight subjects. Inhaled corticosteroid (ICS) dose (µg·day-1) was significantly higher in obese subjects (mean difference 208.14, 95% CI 107.01-309.27; p<0.001, I2=74%). Forced expiratory volume in 1 s (FEV1) % predicted was significantly lower in obese subjects (mean difference -5.32%, 95% CI -6.75--3.89; p<0.001, I2=42%); however, no significant differences were observed in FEV1/forced vital capacity (FVC) ratio between groups. CONCLUSIONS: We found that obese subjects with asthma have higher use of all included asthma medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV1 and a similar FEV1/FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics.

Weight loss in obese children with asthma - is it important?

Obesity is a significant public health problem worldwide, and it has been identified as an independent risk factor for asthma in both adults and children. Not only does obesity increase asthma risk, but it is also associated with decreased asthma-related quality of life, worsened symptoms and asthma control, increased frequency and severity of asthma exacerbations and reduced response to asthma medications. In this review we examine the epidemiology and implications of obesity in both children and adults with asthma, and how the obesogenic "western" diet contributes to asthma prevalence and progression. Finally, we summarise the current evidence on the impact of weight loss on asthma outcomes in both adults and children, highlighting the need for further research to be conducted in the paediatric population.

Soluble fibre supplementation with and without a probiotic in adults with asthma: A 7-day randomised, double blind, three way cross-over trial.

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 (Δmedian [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-ΔCt, 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.

Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients.

BACKGROUND: Both obesity and high dietary fat intake activate the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. OBJECTIVE: We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. METHODS: Study 1 was a cross-sectional observational study of nonobese (n = 51) and obese (n = 76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n = 12 nonobese and n = 11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4 hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1ß protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24 hours, and IL-1ß release was measured (ELISA). RESULTS: In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1ß protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4 hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1ß when challenged with a combination of palmitic acid and LPS or TNF-α. CONCLUSION: The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.

Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis.

BACKGROUND: Inflammation is associated with an increased risk of a range of chronic diseases. A diet high in fruit and vegetables may help to reduce inflammation, as fruit and vegetables are rich sources of antioxidants and other biologically active substances, which may improve immune function. OBJECTIVE: To summarize the evidence, we executed a systematic review and meta-analysis examining the effects of fruit and/or vegetable intake on inflammatory biomarkers and immune cells in humans with different diseases and conditions. Design: Electronic databases including PubMed, Cochrane, CINAHL, and EMBASE were systematically searched up to March 2018. RESULTS: Eighty-three studies were included. Of these, 71 (86%) were clinical trials, and 12 were observational studies (n = 10 cross-sectional and n = 2 cohort). Amongst the observational research, n = 10 studies found an inverse association between intakes of fruit or vegetables and inflammatory biomarkers. Similarly, the majority of the intervention studies (68%, n = 48) reported beneficial effects of fruit or vegetable intake on ≥1 biomarker of systemic or airway inflammation. A meta-analysis of included studies showed that fruit or vegetable intake decreased circulating levels of C-reactive protein and tumor necrosis factor-α (P < 0.05) and increased the γδ-T cell population (P < 0.05). Conclusions: In conclusion, this review suggests that higher intakes of fruit and vegetables lead to both a reduction in proinflammatory mediators and an enhanced immune cell profile.

Diet and Asthma: Is It Time to Adapt Our Message?

Asthma is a chronic respiratory disorder which is associated with airway inflammation. Environmental factors, in association with genetic susceptibility, play a critical role in asthma pathophysiology. Inhaled allergens, smoke exposure, indoor and outdoor air pollution are common triggers of asthma symptoms. Although the role of diet has clearly established mechanisms in diseases such as cardiovascular disease, type 2 diabetes, and cancer, it is not commonly identified as a causal factor in asthma. However, some dietary patterns, such as the Western diet, which includes a high intake of refined grains, processed and red meats, and desserts, have pro-inflammatory effects. On the contrary, the Mediterranean diet, with high intake of fruits and vegetables has anti-inflammatory properties. The influence of food on asthma outcomes is of growing interest, but dietary habits of asthma patients are not commonly investigated in clinical practice. In this review, we focus on the impact of diet on asthma risk and asthma control. We also detail the influence of diet on obese patients with asthma.

Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis.

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-α (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.

A sputum gene expression signature predicts oral corticosteroid response in asthma.

Biomarkers that predict responses to oral corticosteroids (OCS) facilitate patient selection for asthma treatment. We hypothesised that asthma patients would respond differently to OCS therapy, with biomarkers and inflammometry predicting response.Adults with stable asthma underwent a randomised controlled cross-over trial of 50 mg prednisolone daily for 10 days (n=55). A six-gene expression biomarker signature (CLC, CPA3, DNASE1L3, IL1B, ALPL and CXCR2) in induced sputum, and eosinophils in blood and sputum were assessed and predictors of response were investigated (changes in forced expiratory volume in 1 s (ΔFEV1), six-item Asthma Control Questionnaire score (ΔACQ6) or exhaled nitric oxide fraction (ΔFeNO)).At baseline, responders to OCS (n=25) had upregulated mast cell CPA3 gene expression, poorer lung function, and higher sputum and blood eosinophils. Following treatment, CLC and CPA3 gene expression was reduced, whereas DNASE1L3, IL1B, ALPL and CXCR2 expression remained unchanged. Receiver operating characteristic (ROC) analysis showed the six-gene expression biomarker signature as a better predictor of clinically significant responses to OCS than blood and sputum eosinophils.The six-gene expression signature including eosinophil and Th2 related mast cell biomarkers showed greater precision in predicting OCS response in stable asthma. Thus, a novel sputum gene expression signature highlights an additional role of mast cells in asthma, and could be a useful measurement to guide OCS therapy in asthma.

Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis.

Abstract: Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (n = 58). Studies used cross-sectional (n = 30), cohort (n = 13), case-control (n = 8) and experimental (n = 7) designs. Most of the studies (n = 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (n = 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (p < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (p < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with n = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.