Endotyping pediatric obesity-related asthma: Contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes to pulmonary function.

BACKGROUND: Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma. OBJECTIVE: We sought to endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. METHODS: Multiomics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and TH-cell transcriptome and DNA methylome data sets. RESULTS: Two clusters (n = 28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio [WHR], and body mass index [BMI] z score), metabolic, nutrient, and TH-cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different data set combinations. Metabolic measures attenuated the association of neck, WHR, and BMI z score with FEV1/forced vital capacity (FVC) ratio and expiratory reserve volume (ERV), of neck, midarm, and BMI z score with functional residual capacity, but only of WHR with inspiratory capacity. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z score with functional residual capacity, and of WHR with FEV1/FVC ratio, ERV, and inspiratory capacity. TH-cell transcriptome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio, but only of WHR with ERV and inspiratory capacity. The DNA methylome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio and ERV, but only of WHR with inspiratory capacity. CONCLUSIONS: Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity-related asthma.

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.

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.

Effects of Moderate- Versus Vigorous-Intensity Exercise Training on Asthma Outcomes in Adults.

BACKGROUND: The therapeutic effects of exercise have prompted calls for it to be embedded into standard asthma care, but evidence informing the optimal exercise intensity is lacking. OBJECTIVE: This study aimed to compare the effects of moderate- and vigorous-intensity aerobic exercise training on asthma outcomes and inflammation. METHODS: This was a 12-week randomized controlled trial in 46 adults with asthma randomized to either (1) 45-minute moderate-intensity exercise training 3 times/wk, (2) 30-minute vigorous-intensity exercise training 3 times/wk, or (3) the control group. Asthma-related quality of life (AQLQ), asthma control (ACQ), cardiorespiratory fitness, body composition, and airway and systemic inflammation were assessed before and after the intervention. RESULTS: Forty-one participants completed the study (89% retention). The moderate-intensity group had a statistically and clinically significant improvement in AQLQ (0.63 [0.33-0.93], P < .001) and ACQ (-0.51 [-0.83 to -0.19], P = .003) relative to control. The vigorous-intensity group had a statistically, but not clinically, significant improvement in AQLQ (0.46 [0.14-0.80], P = .007) and ACQ (-0.36 [-0.69 to -0.02], P = .040) relative to control. After moderate-intensity training, there was a reduction in sputum macrophage (-1341 [-2491 to -191] × 104/mL, P = .024) and lymphocyte (-114 [-220 to -8] × 104/mL, P = .036) counts relative to control. A reduction in android fat mass, but not a change in fitness, was associated with improved AQLQ (rs = -0.341, P = .030) and reduced sputum IL-6 (rs = 0.422, P = .013). CONCLUSIONS: Our findings suggest that both moderate-intensity and vigorous-intensity aerobic exercise training are associated with improvements in clinical asthma outcomes and, therefore, both intensities could be recommended as an adjuvant asthma therapy.

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.

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.

Comparing the Effect of Acute Moderate and Vigorous Exercise on Inflammation in Adults with Asthma: A Randomized Controlled Trial.

Rationale: Exercise is associated with improvements in asthma; however, the mechanisms responsible are not clear. Exercise induces changes in systemic inflammation, and it is possible that these inflammatory effects extend to the airways of people with asthma. Studies in healthy adults suggest inflammatory responses are dependent on exercise intensity: Although acute moderate exercise is antiinflammatory, acute vigorous exercise appears to be neutral or proinflammatory. The effect of exercise intensity on inflammation has not been investigated in people with asthma. Objectives: To compare acute changes in airway and systemic inflammation after a bout of moderate or vigorous exercise in physically inactive adults with asthma and to establish whether these effects differ according to asthma phenotype. Methods: Participants were randomized to either 1) control (no intervention), 2) 45 minutes of moderate exercise, or 3) 30 minutes of vigorous exercise. Induced sputum and blood samples were collected at baseline and 4 hours after intervention. Results: Fifty-six participants (75% female; mean age, 33.4 [9.9] yr) completed the trial. Moderate exercise induced a significant reduction in sputum eosinophil count (-173 [-337 to -10]; P = 0.032) and sputum percentage eosinophils (-2.2 [-4.9 to 0.5]; P = 0.049) relative to control. Vigorous exercise had no effect on airway inflammation. The antiinflammatory effects of moderate exercise were greatest in participants with eosinophilic asthma, with larger reductions in sputum eosinophils and larger increases in plasma interleukin (IL)-1ra than seen in participants with noneosinophilic asthma. Vigorous exercise induced a systemic proinflammatory response in participants with eosinophilic asthma, indicated by an increase in serum IL-5 and IL-1ß; however, this had no effect on airway inflammation. Conclusions: Exercise intensity modifies the acute inflammatory response to exercise in adults with asthma. Although a bout of moderate exercise is associated with a reduction in eosinophilic airway inflammation, vigorous exercise has no effect on airway inflammation. Interestingly, the effects of moderate exercise vary by asthma phenotype, with greater antiinflammatory effects in participants with eosinophilic asthma. Future studies should examine the impact of exercise training at different intensities on inflammation and clinical asthma outcomes. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12615000294550).

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.

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 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.

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.

Characterisation of histone variant distribution in human embryonic stem cells by transfection of in vitro transcribed mRNA.

Recent studies, primarily in mouse embryonic stem cells, have highlighted the unique chromatin state of pluripotent stem cells, including the incorporation of histone variants into specific genomic locations, and its role in facilitating faithful expression of genes during development. However, there is little information available on the expression and subcellular localisation of histone variants in human embryonic stem cells (hESCs). In this study, we confirmed the expression of a panel of histone variant genes in several hESC lines and demonstrated the utility of transfection of in vitro transcribed, epitope-tagged mRNAs to characterise the subcellular localisation of these proteins. The subcellular localisations of variant histone H3 (CENP-A, H3.3), H2A (MACROH2A, H2AX, H2AZ, H2ABBD) and H1 (H1A, HB, H1C, H1D) were examined, revealing distinct nuclear localisation profiles for each protein. These data highlight the differences between murine (m) ESCs and hESCs, including the presence of a MACROH2A-enriched inactive X chromosome in undifferentiated XX hESC lines. We also provide the first evidence for MACROH2A accumulation on the Y-chromosome in XY hESCs.

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.

Effects of an Encapsulated Fruit and Vegetable Juice Concentrate on Obesity-Induced Systemic Inflammation: A Randomised Controlled Trial.

Phytochemicals from fruit and vegetables reduce systemic inflammation. This study examined the effects of an encapsulated fruit and vegetable (F&V) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults. A double-blinded, parallel, randomized placebo-controlled trial was conducted in 56 adults aged ≥40 years with a body mass index (BMI) ≥28 kg/m². Before and after eight weeks daily treatment with six capsules of F&V juice concentrate or placebo, peripheral blood gene expression (microarray, quantitative polymerase chain reaction (qPCR)), plasma tumour necrosis factor (TNF)α (enzyme-linked immunosorbent assay (ELISA)), body composition (Dual-energy X-ray absorptiometry (DEXA)) and lipid profiles were assessed. Following consumption of juice concentrate, total cholesterol, low-density lipoprotein (LDL) cholesterol and plasma TNFα decreased and total lean mass increased, while there was no change in the placebo group. In subjects with high systemic inflammation at baseline (serum C-reactive protein (CRP) ≥3.0 mg/mL) who were supplemented with the F&V juice concentrate (n = 16), these effects were greater, with decreased total cholesterol, LDL cholesterol and plasma TNFα and increased total lean mass; plasma CRP was unchanged by the F&V juice concentrate following both analyses. The expression of several genes involved in lipogenesis, the nuclear factor-κB (NF-κB) and 5' adenosine monophosphate-activated protein kinase (AMPK) signalling pathways was altered, including phosphomevalonate kinase (PMVK), zinc finger AN1-type containing 5 (ZFAND5) and calcium binding protein 39 (CAB39), respectively. Therefore, F&V juice concentrate improves the metabolic profile, by reducing systemic inflammation and blood lipid profiles and, thus, may be useful in reducing the risk of obesity-induced chronic disease.

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.

Impact of multiple low-level anticholinergic medications on anticholinergic load of community-dwelling elderly with and without dementia.

BACKGROUND: Elderly people, particularly those with dementia, are sensitive to adverse anticholinergic drug effects. This study examines the prevalence of anticholinergic medication, and anticholinergic load and its predictors, in community-dwelling elderly patients (aged 75 years and older) in Australia. METHODS: A research nurse visited the home of each participant (n = 1,044), compiled a list of current medications, and assessed participants' cognitive status using a subsection of the revised Cambridge Examination for Mental Disorders of the Elderly (CAMCOG-R). Anticholinergic load was determined for each patient using the Anticholinergic Drug Scale (ADS). RESULTS: Multivariate analysis identified several patient factors that were associated with higher anticholinergic burden, including polypharmacy (i.e. taking five or more medications) (p < 0.001), increasing age (p = 0.018), CAMCOG-R dementia (p = 0.003), depression (p = 0.003), and lower physical quality of life (p < 0.001). The dementia group (n = 86) took a significantly higher number of medications (4.6 vs. 3.9; p = 0.04), and had a significantly higher anticholinergic load (1.5 vs. 0.8; p = 0.002) than those without dementia (n = 958). Approximately 60% of the dementia group and 40% of the non-dementia group were receiving at least one anticholinergic drug. This difference was due to the higher proportion of dementia patients taking level 1 (potentially anticholinergic) (p = 0.002) and level 3 (markedly anticholinergic) (p = 0.005) drugs. CONCLUSIONS: There is considerable scope for the improvement of prescribing practices in the elderly, and particularly those with dementia. Importantly, level 1 anticholinergics have been identified as major contributors to the anticholinergic load in people with dementia. Longitudinal studies are required to determine the effects of increased and decreased anticholinergic load on cognitive function and other clinical outcomes for people with dementia.