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Thorax. 2025 Jul 2:thorax-2024-222012. doi: 10.1136/thorax-2024-222012. Online ahead of print.
ABSTRACT
Sepsis is a life-threatening syndrome driven by a dysregulated host response to infection. Immune dysregulation arises from responses that initially were activated to protect against pathogens and preserve tissue integrity. Disturbed resistance mechanisms can result in excessive inflammation alongside immunosuppression, each of which is considered important biological drivers of the immunopathology of sepsis. Key inflammatory drivers are excessive proinflammatory cytokine activity, complement and coagulation system activation and endothelial dysfunction. Conversely, sepsis-induced immunosuppression is marked by lymphocyte exhaustion, reduced monocyte human leucocyte antigen-DR expression, and the emergence of myeloid-derived suppressor cells. Within this complex immunological environment, the gut microbiome influences host immunity through the release of short-chain fatty acids and bacterial metabolites. Thus far, immunomodulatory trials in patients with sepsis paid little attention to the identification of dominant biological drivers, which might enrich the population for those who are more likely to respond to a certain intervention. Recently, retrospective analyses of such trials, as well as small prospective trials, have provided proof of concept that subgroups of sepsis patients can be identified with specific immunological profiles, either based on a single biomarker or on high-dimensional data, that respond differently to immunomodulation. This review explores the biological drivers of sepsis immunopathology, highlighting the challenges in translating preclinical insights into effective therapies and the potential of personalised medicine approaches to improve sepsis outcomes.
PMID:40603006 | DOI:10.1136/thorax-2024-222012
Thorax. 2025 Jun 30:thorax-2024-222738. doi: 10.1136/thorax-2024-222738. Online ahead of print.
ABSTRACT
BACKGROUND: While childhood airway outcomes have been associated with prenatal nutrition, few studies examined carotenoids, a group of nutrients with antioxidant properties, as potential modifiers.
OBJECTIVES: In n=677 mother-child dyads enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood cohort, we examined associations between prenatal carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene and zeaxanthin) and child lung function at ages 8-9 years. Maternal-child factors that may modify associations were also assessed.
METHODS: Second-trimester plasma carotenoid concentrations were assayed and corrected for cholesterol. Outcomes included forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC z-scores. We used multivariable linear regression to investigate associations between individual carotenoids and lung function z-scores adjusting for covariates. We also examined effect modification by maternal smoking, body mass index, asthma, and child sex by including cross-product terms.
RESULTS: We did not detect statistically significant associations between individual carotenoid concentrations and child lung function in main effect models. Modifying effects of prenatal smoking were observed between all five carotenoids and FEV1 (all pinteraction<0.05). For example, a twofold increase in α-carotene was associated with an increase in FEV1 z-score of 0.45 (95% CI 0.08 to 0.86) among children whose mothers smoked prenatally versus a 0.01 (-0.08 to 0.10) change in children born to women who did not smoke.
CONCLUSION: A protective association between higher prenatal carotenoid concentrations and FEV1 in middle childhood was observed among children whose mothers smoked during pregnancy.
PMID:40588415 | DOI:10.1136/thorax-2024-222738
Thorax. 2025 Jun 30:thorax-2024-222634. doi: 10.1136/thorax-2024-222634. Online ahead of print.
ABSTRACT
INTRODUCTION: There is a growing trend towards outpatient or home initiation of long-term non-invasive ventilation (NIV) instead of in-hospital initiation. However, evidence supporting the non-inferiority of this strategy is limited in people with neuromuscular diseases (NMDs) or restrictive thoracic disorders (RTDs).
METHODS: Systematic review and network meta-analysis (NMA) to compare the effect of three NIV initiation settings (home, outpatient and in-hospital) on long-term NIV efficacy in people with NMD or RTD. We used MEDLINE, Web of Science and the CENTRAL (Cochrane Central Register of Controlled Trials) to identify randomised controlled trials (RCTs), controlled and uncontrolled prospective studies comparing NIV efficacy between home and outpatient, and in-hospital initiation. Studies published between January 2000 and February 2023 with endpoints ≥1 month were included. The main outcomes were diurnal arterial carbon dioxide pressure (PaCO2) (primary), oxygen partial blood pressure (PaO2), bicarbonate (HCO3-), quality-of-life and NIV adherence.
RESULTS: Eight studies (five RCTs), comprising 350 individuals with PaCO2 measurements (144, 119 and 87 individuals for in-hospital, home and outpatient NIV initiation, respectively) were included. Home and outpatient initiation were not inferior to in-hospital initiation in terms of mean PaCO2 change (Δ) based on the adjusted Bayesian NMA model. No significant difference was found for any secondary outcomes: PaO2, HCO3-, adherence and quality of life.
CONCLUSION: Despite the limited number of studies included in this NMA, we found no evidence suggesting that home or outpatient NIV initiation is less effective than in-hospital initiation for individuals with NMD or RTD who are deemed suitable for home or outpatient care. Home NIV initiation may therefore be a particularly valuable strategy, especially when hospital resources are limited or when patient autonomy is compromised.
PROSPERO REGISTRATION NUMBER: CRD42023403339.
PMID:40588414 | DOI:10.1136/thorax-2024-222634
Thorax. 2025 Jun 27:thorax-2025-223409. doi: 10.1136/thorax-2025-223409. Online ahead of print.
NO ABSTRACT
PMID:40579150 | DOI:10.1136/thorax-2025-223409
Thorax. 2025 Jun 24:thorax-2024-222118. doi: 10.1136/thorax-2024-222118. Online ahead of print.
ABSTRACT
BACKGROUND: It is well established that there are different asthma phenotypes, but whereas determinants of atopic asthma (AA) are well studied, little is known about non-atopic asthma (NAA). We compared risk factors for atopy, AA in atopics and NAA in non-atopics in children in a wide variety of countries.
METHODS: Using four studies, across 23 countries, we assessed asthma status and atopy (skin prick tests) for children aged 6-17, plus risk factors from housing, heating, pets, family, diet and air quality categories. Using mixed-effects logistic regression models, we assessed risk factors over four pathways: pathway 1-non-atopic non-asthma to NAA; pathway 2-non-atopic non-asthma to atopy (no asthma); pathway 3-atopic non-asthma to AA; pathway 4-non-atopic non-asthma to AA. We compared the log odds of risk factors between pathways using the Pearson correlation coefficient (PCC).
RESULTS: Our final sample of 32 741 children comprised 67% with neither atopy nor asthma, 15% with atopy but without asthma, 8% with AA and 10% with NAA. Risk factors were similar between pathway 1 and pathway 3 (PCC=0.81, 95% CI 0.68 to 0.94). In contrast, risk factors differed between pathway 2 and pathway 3 (PCC=-0.06, 95% CI -0.29 to 0.17).
DISCUSSION: These findings indicate that although atopy increases the risk of asthma, the risk factors for subsequently developing asthma are generally the same in those with and without atopy. This raises important questions about the role of atopy in asthma, particularly whether it is an inherent part of the aetiological process or is coincidental.
PMID:40555500 | DOI:10.1136/thorax-2024-222118