Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation.

Innate lymphoid cells (ILCs) play an important role in the control and maintenance of barrier immunity. However, chronic activation of ILCs results in immune-mediated pathology. Here, we show that tissue-resident type 2 ILCs (ILC2s) display a distinct metabolic signature upon chronic activation. In the context of allergen-driven airway inflammation, ILC2s increase their uptake of both external lipids and glucose. Externally acquired fatty acids are transiently stored in lipid droplets and converted into phospholipids to promote the proliferation of ILC2s. This metabolic program is imprinted by interleukin-33 (IL-33) and regulated by the genes Pparg and Dgat1, which are both controlled by glucose availability and mTOR signaling. Restricting dietary glucose by feeding mice a ketogenic diet largely ablated ILC2-mediated airway inflammation by impairing fatty acid metabolism and the formation of lipid droplets. Together, these results reveal that pathogenic ILC2 responses require lipid metabolism and identify ketogenic diet as a potent intervention strategy to treat airway inflammation.

Intranasal curcumin and sodium butyrate modulates airway inflammation and fibrosis via HDAC inhibition in allergic asthma.

Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before. MATERIALS AND METHODS: In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections. RESULTS: Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups. CONCLUSION: This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.

Severe asthma and COVID-19: lessons from the first wave.

OBJECTIVE: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. METHODS: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. RESULTS: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. CONCLUSIONS: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

Effect of early and late prenatal vitamin D and maternal asthma status on offspring asthma or recurrent wheeze.

BACKGROUND: Childhood asthma developmental programming is complex. Maternal asthma is a strong risk factor for childhood asthma, whereas vitamin D (VD) has emerged as a modifiable prenatal exposure. OBJECTIVE: Our aim was to examine the combined effect of early and late prenatal VD status in during pregnancies in women with and without asthma on childhood asthma or recurrent wheeze development. METHODS: We conducted a cohort study using prospectively collected data from the Vitamin D Antenatal Asthma Reduction Trial, a randomized, double-blinded, placebo-controlled VD supplementation trial in pregnant women at high risk of offspring asthma (N = 806 mother-offspring pairs). 25-Hydroxyvitamin-D (25(OH)D) level was measured in early and late pregnancy. Our main exposure was an ordered variable representing early and late prenatal VD sufficiency (25(OH)D level ≥ 30 ng/mL) status during pregnancy in women with and without asthma. The primary outcome was offspring with asthma or recurrent wheeze by age 3 years. We also examined the effect of prenatal VD level on early life asthma or recurrent wheeze progression to active asthma at age 6 years. RESULTS: Among mothers with asthma versus among mothers with early and late prenatal VD insufficiency, those with early or late VD sufficiency (adjusted odds ratio = 0.56; 95% CI = 0.31-1.00) or early and late VD sufficiency (adjusted odds ratio = 0.36; 95% CI = 0.15-0.81) had a lower risk of offspring with asthma or recurrent wheeze by age 3 years (Pfor trend = .008). This protective trend was reiterated in asthma or recurrent wheeze progression to active asthma from age 3 to 6 years (Pfor trend = .04). CONCLUSION: This study implies a protective role for VD sufficiency throughout pregnancy, particularly in attenuating the risk conferred by maternal asthma on childhood asthma or recurrent wheeze development.

Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention.

Asthma is a complex disease that often starts in childhood. Genomic and environmental factors as well as aberrant immune maturation early in life can contribute to the onset of disease, with great disparity over time and geographical regions. Epidemiological studies have scrutinised environmental exposures and attempted to translate these exposures into prevention strategies. Some approaches for patients with asthma have been successful (eg, smoking ban, the Finnish Asthma Programme), and primary prevention of wheeze in pre-school children (age 0-5 years) by the supplementation of vitamin D or fish oil, or both, to pregnant women seems promising. Several recent prevention initiatives are based on strong asthma-protective environmental microbial exposures associated with traditional rural lifestyles. Preclinical studies with various bacterial lysates, bacterial and dietary metabolites, or helminthic compounds have yielded promising results that await translation into clinical practice. Given the immense societal and individual burden of asthma, there is an urgent need to further develop novel strategies to eradicate the disease.

Protocatechuic acid supplement alleviates allergic airway inflammation by inhibiting the IL-4Rα-STAT6 and Jagged 1/Jagged2-Notch1/Notch2 pathways in allergic asthmatic mice.

OBJECTIVE AND DESIGN: To clarify the effects of dietary supplementation of protocatechuic acid (PCA) and in-depth mechanisms on allergic asthma in ovalbumin (OVA)-induced mice. MATERIALS: Female BALB/c mice were randomly divided into three groups (n = 10 in each group): control group, OVA-induced allergic asthma group, and OVA plus PCA group. TREATMENT: Dietary supplementation of PCA was achieved by adding 50 mg/kg PCA to AIN 93G diet for 25 days. METHODS: Peripheral blood cells, pulmonary inflammatory cell infiltration, the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), the mRNA levels of Th2-related genes in the lungs, and the protein expressions of the IL-4Rα-STAT6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways were measured. RESULTS: Significantly reduced inflammatory cells infiltration and mucosal hypersecretion in the lung tissues, repaired levels of interleukin IL-4, IL-5, and IL-13 in the BALF, and decreased mRNA expression of IL-4, IL-5, and GATA3 were observed in OVA plus PCA group. Moreover, PCA treatment down-regulated the protein levels of IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways. CONCLUSIONS: Dietary supplement of PCA alleviated allergic asthma partly through suppressing the IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice. Our study provided the theoretic basis of PCA used as functional food in preventing allergic asthma.

Omega-3 and Omega-6 Intake Modifies Asthma Severity and Response to Indoor Air Pollution in Children.

Rationale: Higher indoor particulate matter (PM) concentrations are linked with increased asthma morbidity. Dietary intake of fatty acids, also linked with asthma outcomes, may influence this relationship. Objectives: To determine the relationship between omega-3 and omega-6 fatty acid intake and pediatric asthma morbidity, and the association between fatty acid intake and strength of indoor, PM-related asthma symptoms, albuterol use, and systemic inflammation. Methods: Analyses included 135 children with asthma enrolled in the AsthmaDIET Study. At baseline, 3 months, and 6 months, data included: week-long average home indoor concentration of PM ≤2.5 µm in aerodynamic diameter and PM ≤10 µm in aerodynamic diameter, dietary intake of omega-3 and omega-6 fatty acids, daily symptoms, and peripheral blood leukocytes. Asthma severity and lung function were assessed at baseline. Multivariable regression models, adjusted for known confounders, were used to determine associations between each fatty acid and outcomes of interest, with interaction terms (fatty acids × PM) in longitudinal analyses. Measurements and Main Results: Higher omega-6 intake associated with increased odds of increased asthma severity (P = 0.02), and lower FEV1/FVC ratio (P = 0.01). Higher omega-3 intake associated with reduced effect of indoor PM ≤2.5 µm in aerodynamic diameter on symptoms (P < 0.01), whereas higher omega-6 intake associated with amplified effect of indoor PM ≤2.5 µm in aerodynamic diameter on symptoms and circulating neutrophil percentage (P < 0.01). Conclusions: Omega-3 and omega-6 intake are associated with pediatric asthma morbidity and may modify the asthmatic response to indoor PM.

Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice.

BACKGROUND: Amylase-trypsin inhibitors (ATIs) in wheat and related cereals are potent activators of myeloid innate immune cells via engagement of TLR4. Furthermore, ATIs have been shown to serve as adjuvants in experimental intestinal inflammatory diseases. OBJECTIVE: The aim of this study was to analyze whether ATIs are also modifiers of allergic inflammation. METHODS: Therefore, CD4+ T cells from donors sensitized to grass or birch pollen were stimulated with autologous allergen-pulsed dendritic cells in the presence or absence of ATIs or the control storage protein zein from corn. To analyze allergen-induced gut and lung inflammation, immunodeficient mice were engrafted with PBMCs from these allergic donors plus the respective allergen, and fed with selected diets. Three weeks later, inflammation was induced by rectal or intranasal allergen challenge and monitored by mini endoscopy or airway hyperreactivity, respectively. RESULTS: Allergen-specific T-cell proliferation and cytokine production was significantly exacerbated by ATIs and not by zein. In vivo, allergen-specific human IgE level was strongly elevated in sera of mice receiving an ATI-containing diet compared with mice that were fed gluten-free and thus ATI-free diet. Importantly, allergen-induced IgE-dependent colitis and airway hyperreactivity were also enhanced in ATI-fed mice. Gut inflammation was further increased in mice receiving an additional ATI injection and even detectable in the absence of the aeroallergen, whereas zein had no such effect. Injection of anti-human TLR4 mAbs or the anti-human IgE mAb omalizumab completely abolished ATI-induced allergic inflammation. CONCLUSIONS: These results underline that wheat ATIs are important nutritional activators and adjuvants of allergy, which might be exploited for nutritional therapeutic strategies.

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.

The Role of Short-Chain Fatty Acids in the Interplay between a Very Low-Calorie Ketogenic Diet and the Infant Gut Microbiota and Its Therapeutic Implications for Reducing Asthma.

Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. The VLCKD appears to be more effective than caloric/energy restriction diets for the treatment of several diseases, such as obesity and diabetes. However, whether adherence to VLCKD affects the infant gut microbiota and the protective effects thereof on asthma remains uncertain. The exact mechanisms underlying this process, and in particular the potential role of short chain fatty acids (SCFAs), are still to be unravelled. Thus, the aim of this review is to identify the potential role of SCFAs that underlie the effects of VLCKD during pregnancy and lactation on the infant gut microbiota, and explore whether it incurs significant implications for reducing asthma.

How does high DHA fish oil affect health? A systematic review of evidence.

The health benefits of fish oil, and its omega-3 long chain polyunsaturated fatty acid content, have attracted much scientific attention in the last four decades. Fish oils that contain higher amounts of eicosapentaenoic acid (EPA; 20:5n-3) than docosahexaenoic acid (DHA; 22:6n-3), in a distinctive ratio of 18/12, are typically the most abundantly available and are commonly studied. Although the two fatty acids have traditionally been considered together, as though they were one entity, different physiological effects of EPA and DHA have recently been reported. New oils containing a higher quantity of DHA compared with EPA, such as fractionated and concentrated fish oil, tuna oil, calamari oil and microalgae oil, are increasingly becoming available on the market, and other oils, including those extracted from genetically modified oilseed crops, soon to come. This systematic review focuses on the effects of high DHA fish oils on various human health conditions, such as the heart and cardiovascular system, the brain and visual function, inflammation and immune function and growth/Body Mass Index. Although inconclusive results were reported in several instances, and inconsistent outcomes observed in others, current data provides substantiated evidence in support of DHA being a beneficial bioactive compound for heart, cardiovascular and brain function, with different, and at times complementary, effects compared with EPA. DHA has also been reported to be effective in slowing the rate of cognitive decline, while its possible effects on depression disorders are still unclear. Interestingly, gender- and age- specific divergent roles for DHA have also been reported. This review provides a comprehensive collection of evidence and a critical summary of the documented physiological effects of high DHA fish oils for human health.

Efficacy of probiotic supplementary therapy for asthma, allergic rhinitis, and wheeze: a meta-analysis of randomized controlled trials.

Background: Probiotic supplementary therapy to prevent allergic diseases, including asthma in children, has been widely explored in many randomized controlled trials. However, there is conflicting evidence on the effect of probiotic supplementation during pregnancy and infancy to the incidence of asthma and allergic rhinitis. Method: This study was designed to systematically explore the potential effects of probiotic supplementation on the occurrence and development of asthma, wheeze, and allergic rhinitis. Randomized controlled trials were searched in several medical literature data bases. A meta-analysis was undertaken by using the fixed-effects model or the random effects model to calculate the pooled risk of significant heterogeneity. Two writers were designated to perform the study selection and data extraction. The primary outcome was clinically diagnosed asthma; the secondary outcomes included wheeze, allergic rhinitis, and a positive aeroallergen skin-prick test result. Results: Seventeen randomized controlled trials, which composed a total of 5264 children, were analyzed. The pooled data for risk of developing asthma after probiotic supplementation showed no significant reduction compared with controls (risk ratio [RR] 0.86 [95% confidence interval {CI}, 0.73-1.01]; I² = 0%; p = 0.06). A subgroup of strains indicated that Lactobacillus rhamnosus GG supplementation only had a reduction to the occurrence of asthma (RR 0.75 [95% CI, 0.57-0.99]; I² = 11%; p = 0.04). The supplement in the postnatal group had a similar result, but the incorporated data were limited. Meanwhile, it is failed to identify that probiotic supplementary therapy have a clear benefit to the secondary outcomes: wheeze, allergic rhinitis, positive aeroallergen skin-prick test result. Conclusion: This study showed a significant benefit that supplementation with probiotics in pre- and postnatal periods was likely to play an essential strategic role in the prevention of asthma. However, these effects were based on the type of probiotics used, which also need more large-sample and high-quality RCTs to confirm the reliability of this study.

Efficacy of a Mediterranean diet supplemented with fatty fish in ameliorating inflammation in paediatric asthma: a randomised controlled trial.

BACKGROUND: Childhood asthma is the most common respiratory disorder worldwide, being associated with increased morbidity and a decreased quality of life. Omega-3 fatty acids have anti-inflammatory and immunomodulating properties; however, their efficacy in asthma is controversial. The present study aimed to examine the efficacy of a Mediterranean diet supplemented with a high omega-3 'fatty' fish intake in Greek asthmatic children. METHODS: A single-centred, 6-month, parallel randomised controlled trial compared the consumption of a Mediterranean diet supplemented with two meals of 150 g of cooked fatty fish weekly (intervention) with the usual diet (control) with respect to pulmonary function in children (aged 5-12 years) with mild asthma. Pulmonary function was assessed using spirometry and bronchial inflammation by fractional exhaled nitric oxide analysis. RESULTS: Sixty-four children (52% male, 48% female) successfully completed the trial. Fatty fish intake increased in the intervention group from 17 g day-1 at baseline to 46 g day-1 at 6 months (P < 0.001). In the unadjusted analysis, the effect of the intervention was of borderline significance (P = 0.06, ß = -11.93; 95% confidence interval = -24.32 to 0.46). However, after adjusting for age, sex, body mass index and regular physical activity, a significant effect was observed (P = 0.04, ß = -14.15 ppb; 95% confidence interval = -27.39 to -0.91). No difference was observed for spirometry, asthma control and quality of life scores. CONCLUSIONS: A Mediterranean diet supplemented with two fatty fish meals per week might be a potential strategy for reducing airway inflammation in childhood asthma. Future robust clinical trials are warranted to replicate and corroborate these findings.

Adherence to the Mediterranean diet and inflammatory markers in children with asthma.

INTRODUCTION: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. METHODS: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. RESULTS: KIDMED score did not differ between the two groups (P=0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P=0.007; Beta: 0.57, P=0.010; Beta: -0.62, P=0.017, respectively). CONCLUSION: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children.

Effect of omega-3 fatty acid supplementation on resolvin (RvE1)-mediated suppression of inflammation in a mouse model of asthma.

Objective: ResolvinE1 (RvE1), an endogenous lipid mediator derived from omega 3 fatty acids contributes to resolution of allergic inflammatory responses. We investigated effects of RvE1 (R) and omega 3 fatty acids (O) on airway reactivity and inflammation using allergic mice. Methods: Mice were divided into control (nonasthmatic; CON) and allergen sensitized-challenged (asthmatic; SEN) groups, and were sensitized i.p. on days 1, 6 with 0.2 µg ovalbumin (OVA) followed by 5% OVA aerosol challenges on days 11-13. RvE1 was administered i.p. postallergen challenge, while omega 3 fatty acids (fish oil) were administered via oral gavage once daily (days 1-13). Whole body plethysmography and bronchoalveolar lavage (BAL) studies were performed on day 14. Results: RvE1 attenuated airway responsiveness to methacholine (48 mg/ml) in treated asthmatic mice vs. nontreated (150 ± 27.88% in SEN vs. 54 ± 7.52% in SEN + R, p < .05). No difference was observed with omega-3 supplementation (115 ± 19.28% in SEN + O) or treatment with both RvE1 and omega 3 fatty acids (39 ± 12.37% in SEN + R + O vs. 54 ± 7.52% in SEN + R). Differential BAL cell analysis showed that RvE1 decreased eosinophils and neutrophils in SEN mice (p < .005) while no difference was observed with omega-3 fatty acids. SEN + R + O group had similar results as RvE1 treated mice, suggesting that only RvE1 attenuated inflammation. Conclusions: RvE1 attenuated airway responsiveness and inflammation in asthmatic mice. Omega-3 fatty acids, although a precursor for RvE1 formation, had no additive effects on RvE1 decreases in airway inflammation and airway reactivity. Our data suggests that omega-3 supplementation has little effect on airway inflammation and reactivity in our model of asthma.

Diet effects in the asthma treatment: A systematic review.

INTRODUCTION: Obesity in asthmatic patients has important relationships with asthma control, pulmonary function, and quality of life. The objective of this study was to conduct a systematic review of the literature on the effect of diet on asthma management in adults. METHODS: We searched PubMed, Embase, and Scopus (January 1948-October 2014) for randomized clinical trials that evaluated the effects of diet in adults with asthma. RESULTS: Of 12,215 studies identified, 21 were included. A reduction in weight of at least 7.5% from baseline as a result of caloric restriction can be beneficial for improving disease control, quality of life, and pulmonary function in obese patients with asthma. A dietary pattern rich in foods with potential antioxidant effect had an impact in improving asthma control, but with little clinical significance. Studies involving antioxidant supplementation showed improvements in asthma control with magnesium supplementation and less decline in lung function with vitamin C supplementation. Studies of fatty acid supplementation demonstrated effects on weight loss and improvement of asthma control and lung function. Studies of supplementation with propolis and caffeine reported significant increases in FEV1. Conversely, studies of high dietary salt intake reported greater declines in lung function. CONCLUSIONS: The evidence shows that, for obese adults with asthma, the best dietary intervention seems to be caloric restriction, regardless of specific dietary components.

The role of fish intake on asthma in children: A meta-analysis of observational studies.

BACKGROUND: The evidence is mixed on the use of long chain Omega-3 fatty acids in the prevention and management of childhood asthma. METHODS: We conducted a systematic search and meta-analysis investigating the role of fish intake, the main dietary source of long chain omega-3 fatty acids, on asthma in children. RESULTS: A total of 1119 publications were identified. Twenty-three studies on fish intake in association with childhood asthma were included in the final review. In 15 of 23 studies, early introduction of fish (6-9 months) and regular consumption (at least once a week) improved asthma symptoms and reduced risk in children 0-14 years as compared to no fish consumption; 6 of 23 showed no effect and 2 of 23 studies suggest adverse effects. Meta-analysis revealed an overall "beneficial effect" for "all fish" intake on "current asthma" [OR: 0.75; 95%CI: 0.60-0.95] and "current wheeze" [OR: 0.62; 95%CI: 0.48-0.80] in children up to 4.5 years old. An overall protective effect of "fatty fish" intake as compared to "no fish" intake in children 8-14 years old was also observed [OR: 0.35; 95%CI: 0.18-0.67]. CONCLUSION: This meta-analysis suggests that introduction of fish early in life (6-9 months) and regular consumption of all fish (at least once a week) reduces asthma and wheeze in children up to 4.5 years old, while fatty fish intake may be beneficial in older children. Future well-designed clinical trials are recommended to confirm the promising findings documented in this literature analysis.

Longitudinal study of diet quality and change in asthma symptoms in adults, according to smoking status.

It has been hypothesised that increased asthma prevalence in westernised countries is associated with changes in lifestyle factors, including a poorer diet. However, little is known regarding the association between diet quality and asthma. In the diet-asthma association, the role of BMI as a potential mediator needs clarification; moreover, potential effect modification by non-diet sources of oxidants, such as smoking, merits investigation. We investigated the association between diet quality and change in asthma symptoms, as well as assessed effect modification by smoking, while accounting for BMI as a potential mediator. Using data from the French prospective Epidemiological study on the Genetics and Environment of Asthma study, we assessed diet quality using the Alternate Healthy Eating Index 2010 (AHEI-2010) at baseline and change in asthma symptoms (stable (reference), worsening, improved; mean follow-up time: 7 years). Mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by BMI. The analyses included 969 adults (mean age 43 years; 49 % men; 42 % ever asthma). We observed a significant interaction between smoking and AHEI-2010 on change in asthma symptoms (P for interaction=0·04). Among never smokers (n 499), we observed a positive total effect (multivariable OR 1·39; 95 % CI 1·07, 1·80) and a positive direct effect (OR 1·41; 95 % CI 1·09, 1·80) of the AHEI-2010 (per ten-point increment) on improved symptoms. No indirect effect mediated through BMI was observed (OR 0·99; 95 % CI 0·91, 1·07). Among former and current smokers, all effects were statistically non-significant. Better diet quality was associated with improved asthma symptoms over time in never smokers, independently of BMI.

Boysenberry ingestion supports fibrolytic macrophages with the capacity to ameliorate chronic lung remodeling.

Lung fibrosis negatively impacts on lung function in chronic asthma and is linked to the development of profibrotic macrophage phenotypes. Epidemiological studies have found that lung function benefits from increased consumption of fruit high in polyphenols. We investigated the effect of boysenberry consumption, in both therapeutic and prophylactic treatment strategies in a mouse model of chronic antigen-induced airway inflammation. Boysenberry consumption reduced collagen deposition and ameliorated tissue remodeling alongside an increase in the presence of CD68+CD206+arginase+ alternatively activated macrophages in the lung tissue. The decrease in tissue remodeling was associated with increased expression of profibrolytic matrix metalloproteinase-9 protein in total lung tissue. We identified alternatively activated macrophages in the mice that consumed boysenberry as a source of the matrix metalloproteinase-9. Oral boysenberry treatment may moderate chronic tissue remodeling by supporting the development of profibrolytic alternatively activated macrophages expressing matrix metalloproteinase-9. Regular boysenberry consumption therefore has the potential to moderate chronic lung remodeling and fibrosis in asthma and other chronic pulmonary diseases.