| 1. |
- Adjei, Nicholas Kofi, et al.
(författare)
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Impact of Parental Mental Health and Poverty on the Health of the Next Generation : A Multi-Trajectory Analysis Using the UK Millennium Cohort Study
- 2024
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Ingår i: Journal of Adolescent Health. - 1054-139X .- 1879-1972. ; 74:1, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Exposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health.Methods: We used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level.Results: We identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7–6.7), mental health problems (aOR 2.5; CI 1.6–3.9), and cognitive disability (aOR 1.7; CI 1.1–2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty.Discussion: More than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.
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| 2. |
- Adjei, Nicholas Kofi, et al.
(författare)
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Impact of poverty and family adversity on adolescent health : a multi-trajectory analysis using the UK Millennium Cohort Study
- 2022
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Ingår i: The Lancet Regional Health. - : Elsevier BV. - 2666-7762. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes.Methods We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, poor mental health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders.Findings Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent poor parental mental health (11·9%), persistent poverty (22·6%) and persistent poverty and poor parental mental health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent poor parental mental health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 – 8·3), cognitive disability (aOR 2·1; CI 1·5 – 2·8), drug experimentation (aOR 2·8; CI 1·8 – 4·2) and obesity (aOR 1·8; CI 1·3 – 2·5).Interpretation In a contemporary UK cohort, persistent poverty and/or persistent poor parental mental health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health.
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| 3. |
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| 4. |
- Alahmadi, Fahad, et al.
(författare)
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Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Rates of sub-optimal adherence to medications in asthma range up to 70%; the impact in severe asthma is likely to be particularly high. We measured self-reported adherence in participants in the U-BIOPRED cohort prescribed daily prednisolone using the Medication Adherence Response Scale (MARS), and compared to measured urinary prednisolone and metabolites in order to determine: 1. the prevalence of suboptimal adherence by each method; 2. the ability of MARS to predict urinary steroid detection.Methods: Participants completed the MARS, and/or provided urine samples (analysed for prednisolone and metabolites by LCMS). The performance characteristics of the MARS predicting undetected urinary steroid were calculated in the subgroup having both tests.Results: 181 participants currently taking regular oral corticosteroids were included, 59% female, mean (SD) age 54(12)yrs, FEV1 64.7(20.4)% predicted. Sub-optimal adherence (MARS score < 4.5) was reported in 62 participants, and 76 did not have detectable urinary prednisolone or metabolites. Good adherence by both methods was detected in only 52 participants (34%, see table). There was no difference in daily prednisolone dose between detectable and undetectable metabolites groups (p=0.848).Conclusion: Low levels of adherence to treatment in severe asthma is a common problem, when measured either directly or self-reported. There was very poor agreement (48% concordance) between these two methods, and we suggest that, for now both approaches should be used.
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| 5. |
- Andersson, Cecilia K., et al.
(författare)
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Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze
- 2020
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 75:12, s. 3195-3207
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Tidskriftsartikel (refereegranskat)abstract
- Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. Results: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Conclusions: Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.
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| 6. |
- Badi, Yusef Eamon, et al.
(författare)
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Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 149:1, s. 89-101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P <.05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P <.05) and particularly in neutrophilic and mixed granulocytic sputum (P <.05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
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| 7. |
- Brandsma, Joost, et al.
(författare)
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Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers
- 2018
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Ingår i: Metabolomics. - : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.
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| 8. |
- Brandsma, Joost, et al.
(författare)
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Stratification of asthma by lipidomic profiling of induced sputum supernatant
- 2023
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 152:1, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.Methods: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes.Results: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.Conclusion: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.
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| 9. |
- Burg, Dominic, et al.
(författare)
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Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:6, s. 2072-2091
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
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| 10. |
- Emma, Rosalia, et al.
(författare)
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Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort
- 2018
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF(2 alpha) and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF(2 alpha); IS-transcriptomics; BB-transcriptomics; BBrtranscriptomics). Urinary 8-iso-PGF(2 alpha) was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF(2 alpha) was increased in SAs/ex, median (IQR) = 31.7 (24.5 +/- 44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6 +/- 36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4 +/- 47.7), vs. ESA, median (IQR) = 29.4 (22.3 +/- 40.5), and NSA, median (IQR) = 26.5 (19.6 +/- 16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01) indicating an effect of active smoking. Results about FeNO suggest its clinical limitation, as inflammation biomarker, in severe asthma active smokers. These data provide evidence of greater systemic oxidative stress in severe asthma smokers as reflected by a significant changes of NOX2 mRNA expression in the airways, together with elevated urinary 8-iso-PGF(2 alpha) in the smokers/ex-smokers group.
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