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.

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 pointsImproving 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 aimsTo 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.

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Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with anti-microbial 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 which 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 in adults) were included, of which 8/13 studies (61%) in adults reported a decrease in at least one systemic inflammatory biomarker. Immune function improved in 6/8 studies (75%) in adults, with changes in immune cell populations in 2/6 studies (33%), and changes in immune cell activity in 2/5 studies (40%). RTI outcomes reduced in 6/10 studies (60%) (n=5 in adults, n=5 in children), with decreased incidence in 3/9 (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 (SMD): -0.09; 95% CI: -0.82, 0.65], or natural killer (NK) cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children [odds ratio (OR): 0.78; 95% CI: 0.61, 0.98] but not adults [OR: 1.00; 95% CI: 0.76, 1.32]. Clinical studies on Lf supplementation are limited, though findings show 200mg/day Lf reduces systemic inflammation, while formulas containing 35-833mg/day Lf 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. PROSPERO registration number: CRD42021232186

Prebiotics, synbiotics and short-chain fatty acids (SCFA) have been shown to decrease systemic inflammation and play a protective role in chronic respiratory conditions. However, the effect on infection and immune function are unclear. The objective of this systematic review was to summarise the current evidence for prebiotic, synbiotic and SCFA supplementation on respiratory tract infections (RTIs) and immune function. 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 (RCTs) reporting on RTIs in infants and children. Meta-analysis indicated that the number 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 (SMD 0.74, 95% CI [0.42, 1.06], P &lt; 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 pre- and synbiotic treatment may alter immune function by increasing NK cell activity, though effects on immunophenotype were less clear.

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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.