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

BACKGROUND: The therapeutic effects of exercise has 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 randomised controlled trial in 46 adults with asthma randomised to either 1) 45min moderate-intensity exercise training three times/week, 2) 30min vigorous-intensity exercise training three times/week, or 3) control group. Asthma-related quality of life (AQLQ), asthma control (ACQ), cardiorespiratory fitness, body composition, and airway and systemic inflammation were assessed pre- and post-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 to 0.93) p<0.001) and ACQ [-0.51 (-0.83 to -0.19), p=0.003] relative to control. The vigorous-intensity group had a statistically, but not clinically, significant improvement in AQLQ [0.46 (0.14 to 0.80, p=0.007] and ACQ [-0.36 (-0.69 to -0.02, p=0.040] relative to control. Following moderate-intensity training, there was a reduction in sputum macrophage [-1341 (-2491 to -191)x104/mL, p=0.024] and lymphocyte [-114 (-220 to -8)x104/mL, p=0.036] 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=0.030) and reduced sputum IL-6 (rs=0.422, p=0.013). CONCLUSION: 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.

Effects of Plant-Based Protein Interventions, with and without an Exercise Component, on Body Composition, Strength and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Maintaining muscle mass, strength, and function is crucial for our aging population. Exercise and dietary protein intake are recommended strategies; however, animal proteins have been the most studied. Plant-based protein sources have lower digestibility and incomplete amino acid profiles. However new innovative plant-based proteins and products may have overcome these issues. Therefore, this systematic review aimed to synthesize the current research and evaluate the effects of plant-based protein interventions compared to placebo on body composition, strength, and physical function in older adults (≥60 years old). The secondary aim was whether exercise improved the effectiveness of plant-based protein on these outcomes. Randomized controlled trials up to January 2023 were identified through Medline, EMBASE, CINAHL, and Cochrane Library databases. Studies contained a plant-protein intervention, and assessed body composition, strength, and/or physical function. Thirteen articles were included, all using soy protein (0.6-60 g daily), from 12 weeks to 1 year. Narrative summary reported positive effects on muscle mass over time, with no significant differences compared to controls (no intervention, exercise only, animal protein, or exercise + animal protein interventions). There was limited impact on strength and function. Meta-analysis showed that plant-protein interventions were comparable to controls, in all outcomes. In conclusion, plant-protein interventions improved muscle mass over time, and were comparable to other interventions, warranting further investigation as an anabolic stimulus in this vulnerable population.

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.

Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

BACKGROUND: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated. OBJECTIVE: We sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection. METHODS: We studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells. RESULTS: Intranasal acetate administration induced basal upregulation of IFN-ß, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-ß and IFN-λ gene expression during RV infection. CONCLUSIONS: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection.

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.

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 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.

Evidence for lifestyle interventions in asthma.

Asthma is a chronic inflammatory airways disease, estimated to affect 300 million people worldwide. Asthma management plans focus on optimisation of asthma pharmacotherapy. Lifestyle interventions also hold great promise for asthma sufferers as they are accessible, low cost and have minimal side-effects, thus making adherence more likely. This review explores lifestyle interventions that have been tested in asthma, including improving nutrition, increasing physical activity and introduction of relaxation therapies such as yoga and massage therapy. Available evidence suggests a protective effect of increasing fruit, vegetable and wholegrain intake and increasing physical activity levels in asthma. Weight loss is recommended for obese asthmatic patients, as just 5-10% weight loss has been found to improve quality of life and asthma control in most obese asthmatic patients. Other lifestyle interventions such as meditation, yoga and massage therapy show promise, with positive effects on asthma seen in some studies. However, the study protocols are highly variable and the results are inconsistent. Additional research is needed to further develop and refine recommendations regarding lifestyle modifications that can be implemented to improve asthma. KEY POINTS: Improving diet quality, by increasing fruit, vegetable and wholegrain intake and reducing saturated fat intake, should be recommended in asthma, as there is evidence suggesting that this leads to improvements in airway inflammation, asthma control and exacerbation risk.Regular physical activity should be promoted for people with asthma, as it can improve quality of life and lung function, as well as general health.In obese asthmatic patients, weight loss should be recommended, as it leads to numerous health benefits, including improvements in asthma. Even small amounts of weight loss in adults (5-10% body weight) have been shown to improve asthma quality of life and asthma control in the majority of people with asthma.There is some evidence of benefit of meditation, yoga and breathing exercises for adults with asthma, while massage therapy shows promise in children with asthma. However, the evidence is inconsistent and more research is needed to make definitive recommendations. EDUCATIONAL AIMS: To summarise current knowledge on lifestyle interventions in asthma.To improve awareness of how lifestyle modification can be used in asthma management.To identify areas for future research on lifestyle interventions in asthma.

The neurotrophic tyrosine kinase receptor TrkA and its ligand NGF are increased in squamous cell carcinomas of the lung.

The neurotrophic tyrosine kinase receptor TrkA (NTRK1) and its ligand nerve growth factor (NGF) are emerging promoters of tumor progression. In lung cancer, drugs targeting TrkA are in clinical trials, but the clinicopathological significance of TrkA and NGF, as well as that of the precursor proNGF, the neurotrophin co-receptor p75NTR and the proneurotrophin co-receptor sortilin, remains unclear. In the present study, analysis of these proteins was conducted by immunohistochemistry and digital quantification in a series of 204 lung cancers of different histological subtypes versus 121 normal lung tissues. TrkA immunoreactivity was increased in squamous cell carcinoma compared with benign and other malignant lung cancer histological subtypes (p < 0.0001). NGF and proNGF were also increased in squamous cell carcinoma, as well as in adenocarcinoma (p < 0.0001). In contrast, p75NTR was increased across all lung cancer histological subtypes compared to normal lung (p < 0.0001). Sortilin was higher in adenocarcinoma and small cell carcinoma (p < 0.0001). Nerves in the tumor microenvironment were negative for TrkA, NGF, proNGF, p75NTR and sortilin. In conclusion, these data suggest a preferential therapeutic value of targeting the NGF-TrkA axis in squamous cell carcinomas of the lung.