Diet, Obesity, and Asthma Wood, Lisa G
Annals of the American Thoracic Society
14, Številka:
Supplement_5
Journal Article
Recenzirano
Obesity has reached epidemic proportions in many developed countries as Western dietary patterns have been widely adopted. These diets are characterized by excess energy intake as well as regular ...consumption of processed or "fast" foods and limited consumption of fruit, vegetables, and whole grains. The result is a high intake of saturated fat, refined carbohydrates, and sodium; and a low intake of fiber, vitamins, and other phytochemicals. This type of poor-quality diet has been associated with increased risk of chronic inflammatory diseases, including asthma. Of particular note, high intake of saturated fat stimulates proinflammatory pathways via activation of pattern recognition receptors, endoplasmic reticulum stress, and fatty acid-binding protein activity. Conversely, with a low intake of soluble fiber, beneficial antiinflammatory mechanisms, such as free fatty acid receptor activation and histone deacetylase inhibition, are suppressed. Similarly, with a low intake of antioxidants such as vitamin C, vitamin E, and carotenoids, nuclear factor κ-light-chain-enhancer of activated B cells activity is enhanced, creating a proinflammatory environment. There is evidence derived from human and experimental models of asthma suggesting that these mechanisms contribute to the development of airway inflammation, loss of asthma control, and/or worse lung function. Obese individuals have increased asthma morbidity and reduced quality of life, so strategies for better management of these patients are urgently needed. Evidence suggests that, in addition to reducing the quantity of food consumed, interventions should also target the quality of food consumed to improve both asthma management and the overall health and well being of these patients.
Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome ...contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.
Background Dietary fat activates systemic innate immune responses, but the effect on airway responses is unknown. Objective To examine effects of a high-fat versus low-fat meal on systemic and airway ...inflammation in asthma. Methods Nonobese subjects with asthma were randomized to consume a high-fat (n = 19; 48% 49 g fat) or low-fat (n = 18; 15% 3 g fat) meal. Fourteen obese patients with asthma and 21 healthy controls also consumed a high-fat meal. Another group of patients with asthma consumed a high-trans (n = 5; 5.2 g trans fat) or nontrans (n = 5, <0.3 g trans fat) fatty acid meal. Lung function was measured at baseline (prebronchodilator) and 2, 3, and 4 hours after bronchodilator. Airway inflammation was assessed by using induced sputum cell counts and Toll-like receptor 4 mRNA expression by real-time PCR. Systemic inflammation was measured by ELISA quantification of plasma TNF-α, high-sensitivity C-reactive protein, and IL-6 concentrations. Results In patients with asthma, at 4 hours postmeal, increases in sputum % neutrophils and Toll-like receptor 4 mRNA expression were higher and increases in FEV1 /forced vital capacity (FVC) were lower in the high-fat versus low-fat groups. Changes in plasma fatty acids correlated with changes in sputum % neutrophils and were negatively associated with changes in % FEV1 , % FVC, and FEV1 /FVC. After the high-trans fatty acid meal, sputum % neutrophils were significantly higher than after the nontrans meal. Conclusion A high-fat meal augments neutrophilic airway inflammation, with the effect dependent on the type of fat consumed. A high-fat meal also suppresses bronchodilator recovery in asthma. Modifying dietary fat intake may be useful in asthma.
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.
This review ...examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation.
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.
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).
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.
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.
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.
Electronic databases including PubMed, Cochrane, CINAHL, and EMBASE were systematically searched up to March 2018.
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).
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.
Background Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts; however, few studies have defined ...transcriptional phenotypes of asthma. Objective To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum. Methods Induced sputum samples were collected from 59 people with asthma with a mean age of 58 years and an FEV1 % predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11. Results Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV1 % predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV1 % predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation. Conclusion Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
Background Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. Objective This study aimed to identify and validate a sputum gene expression ...signature that discriminates asthma inflammatory phenotypes. Methods An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. Results From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC) ; carboxypeptidase A3 (CPA3) ; deoxyribonuclease I-like 3 (DNASE1L3) ; IL-1β (IL1B) ; alkaline phosphatase, tissue-nonspecific isozyme (ALPL) ; and chemokine (C-X-C motif) receptor 2 (CXCR2) , was reproducible and could significantly ( P < .0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV1 ; AUC, 91.5%). ICS treatment reduced the expression of CLC , CPA3 , and DNASE1L3 in patients with eosinophilic asthma. Conclusions A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.
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 (
= 58). Studies used cross-sectional (
= 30), cohort (
= 13), case-control (
= 8) and experimental (
= 7) designs. Most of the studies (
= 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 (
= 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 (
< 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (
< 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with
= 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.
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 (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects ...via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation-including changes in gene expression of free fatty acid receptors-in asthma. Adults with stable asthma consumed a soluble fibre meal (
= 17) containing 3.5 g inulin and probiotics, or a control meal (
= 12) of simple carbohydrates. Exhaled nitric oxide (eNO) was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8) protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation.
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