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The aim of this study was to evaluate an epidemiologic association of asthma and chronic rhinosinusitis (CRS) using a national sample cohort of the Korean population. We collected data from the Korean Health Insurance Review and Assessment Service-National Sample Cohort between 2002 and 2013, and two different case-control cohorts were designed (1st: asthmatic patients matched in a 1:1 ratio with 204,119 non-asthmatics as control I, 2nd: CRS patients matched in a 1:4 ratio with 124,020 non-CRS patients as control II). Bidirectional association was examined using Cox proportional hazard models stratified by age, sex, income, and region of residence. Patients with asthma had an increased risk of developing CRS [adjusted hazard ratio (95% confidence interval) = 1.74 (1.67-1.80)], both with nasal polyps [1.55 (1.36-1.78)], without nasal polyps [1.74 (1.67-1.81)]. In the second cohort, patients with CRS had increased risk of developing asthma [1.85 (1.80-1.91)] with similar results for those with and without nasal polyps. The strongest association for risk of CRS was in 20-39 years old men with asthma [2.41 (1.97-2.96)], while the strongest association for increased risk of asthma in those with CRS group was also seen in this same subgroup [2.40 (2.18-2.63)]. CRS and asthma had a bidirectional influence on each other. CRS increased the risk of asthma, and asthma increased the risk of CRS, especially in young men.

Studies demonstrated that pneumonia can decrease vitamin A productions and vitamin A reduction/deficiency may promote asthma development. Our previous study showed that neonatal Streptococcus pneumoniae (S. pneumoniae) infection promoted asthma development. Whether neonatal S. pneumoniae pneumonia induced asthma was associated with vitamin A levels remains unclear. The aim of this study was to investigate the effects of neonatal S. pneumoniae pneumonia on vitamin A expressions, to explore the effects of vitamin A supplement after neonatal S. pneumoniae pneumonia on adulthood asthma development. Non-lethal S. pneumoniae pneumonia was established by intranasal inoculation of neonatal (1-week-old) female BALB/c mice with D39. S. pneumoniae pneumonia mice were supplemented with or without all-trans retinoic acid 24 hours after infection. Vitamin A concentrations in lung, serum and liver were measured post pneumonia until early adulthood. Four weeks after pneumonia, mice were sensitized and challenged with OVA to induce allergic airway disease (AAD). Twenty-four hours after the final challenge, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. We stated that serum vitamin A levels in neonatal S. pneumoniae pneumonia mice were lower than 0.7µmol/L from day 2-7 post infection, while pulmonary vitamin A productions were significantly lower than those in the control mice from day 7-28 post infection. Vitamin A supplement after neonatal S. pneumoniae pneumonia significantly promoted Foxp3 + Treg and Th1 productions, decreased Th2 and Th17 cells expressions, alleviated airway hyperresponsiveness (AHR) and inflammatory cells infiltration during AAD. Our data suggest that neonatal S. pneumoniae pneumonia induce serum vitamin A deficiency and long-time lung vitamin A reduction, vitamin A supplement after neonatal S. pneumoniae pneumonia inhibit the progression of asthma by altering CD4 + T cell subsets.

Our previous study showed Tai-Chi-Chuan (TCC) training, a moderate exercise, at school improved pulmonary function and inflammation profiles in children with mild asthma. However, habitual practice is hard to maintain with the lack of continuous family and peer support. We investigated whether parental intervention with social media could enhance children's adherence to exercise at home and improve asthmatic outcome measures. Parents were opted to attend a 12-week TCC classroom training, supervise home practice, and report to a four-step web-based social media platform to stay updated and motivated through logging activity and tracking competition. Fractional exhaled nitric oxide (FeNO), FEV1/FVC and peak expiratory flow (PEF) were measured before and after 12 weeks of training. Fifty-three asthmatic children were allocated into non-TCC (control, n = 12), TCC groups with moderate-to-severe (TCC-S, n = 26) and mild-to-moderate (TCC-M, n = 15) asthma. We found both TCC groups exhibited better pulmonary function than the non-TCC control. TCC increased FVC in mild-to-moderate asthma children while more pronounced improvement in FEV1, FEV1/FVC, PEF and FeNO was noticed in moderate-to-severe asthmatic children. All TCC subjects retained greater participation and better interaction online except for low-ranking families who dramatically dropped their practice 9 weeks later. For asthmatic children, moderate exercise improves pulmonary functions in a severity-dependent fashion. Parent-based Learn-Practice-Persuade-Award wheel is a useful platform to motivate children engagement in physical activity. Classical social persuasive skills could enhance general parent-child relationship but tend to decrease in persuasiveness over time in low-ranking families., (© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: This study analyzes the research output of India in asthma during the period from 1999 till 2008. It analyzes the growth, rank and global publications share, citation impact, share of international collaborative papers, contribution of major collaborative partner countries and contribution of various subject fields. It also analyzes the characteristics of most productive institutions, authors and high-cited papers. Materials and Methods: SCOPUS database has been used to retrieve the data on publication output in asthma research. Results: India ranks 15th position among the top 23 countries in asthma research, with its global publication share of 1.27% (862 papers), registering an average citation per paper of 3.43 and achieved an h-index of 33 during 1999-2008. Conclusion: Indian research output on asthma is quite low in the global context as reflected from its publication output per thousand population (0.001) and its world publication share (1.27%) during 1999-2008. Also, the impact and quality of Indian research is low compared to select developed and developing countries. [ABSTRACT FROM AUTHOR]

aims to perform a systematic assessment of the influence of physical exercise on asthma patients and discuss the intervention effects of different exercises on the lung function FEV1 (%pred) and quality of life among asthma patients so as to lay a scientific foundation for improving asthma symptoms. Methods: Both Chinese and English databases were retrieved, including PubMed, Web of Science, Embase, The Cochrane Library, CBM, CNKI, Wan Fang Data, and VIP, whose retrieval period started from the founding date of each database to 1st, November 2021. Randomized controlled trials (RCT) studying the symptom indicators of asthma patients were collected. Those collected papers were screened according to the Inclusion Criteria and Exclusion Criteria. Then, methodological quality assessments were conducted on the included papers, and combined effect sizes were analyzed by using software ReMan 5.3.5. Results: The meta analysis showed that physical exercise could significantly improve lung function FEV1 (%pred) and quality of life score. Trails containing breathing exercise are the main source of heterogeneity, and the subgroup of breathing exercise may have better performance than the subgroup of aerobic exercise in improving FEV1 (%pred). Conclusion: Physical exercise can significantly improve the symptoms and quality of life of asthma patients. Except the breathing exercise that showed heterogeneity, the subgroup of aerobic exercise could improve the capacity of FEV1 (%pred) more effectively, which led to a significant difference in the influence of quality of life. However, with regard to the gymnastic exercise including breathing exercise, there are limited same intervention methods and insufficient same outcome indicators. Therefore, more precise and high-quality researches are needed to make deeper verification in the future. [ABSTRACT FROM AUTHOR]

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item. [ABSTRACT FROM AUTHOR]

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today 1 . The asthma-protective effect of farms appears to be associated with rich home dust microbiota 2,3 , which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts 4 that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children 2 and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.

Aim: To identify the latent profiles and predictors of family management styles for children with asthma. Design: This is a secondary data analysis. The demographic data of 506 primary caregivers of children with asthma and their scores of the Family Management Scale in a cross‐sectional study were used. Latent profile analysis and multiple logistic regression analyses were employed. Results: Three family management styles were identified: Thriving (Profile 1), Accommodating (Profile 2), and Enduring (Profile 3) Family Management Style. The child's age, gender, mother's education level, family structure, influence of illness on parents' work and family life, whether they had follow‐up plans and whether their parents had read disease and health knowledge pamphlets were found to be the predictors of different styles. Conclusion: Three distinct family management styles exist for children with asthma. Future interventions designed to enhance family management for children with asthma should be based on their demographic characteristics and family management styles. Implications for the Profession and Patient Care: The precise classification of family management styles in this study can serve as a guide to form multi‐disciplinary teams of physicians and nurses to provide individualized care and conduct in‐depth research to explore the mechanisms of biomedicine and the social psychology of asthma in the future. Impact: This paper aims to identify the latent profiles and predictors of family management styles of children with asthma.Thriving, accommodating, and enduring family management styles were identified in this paper. Child's characteristics, family and organizational factors were the predictors of different family management styles.Findings of this paper provide guidance for physicians and nurses to offer individualized care and conduct in‐depth research to explore the mechanisms of biomedicine and the social psychology of asthma in the future. Reporting Method: The article was reported according to the STROBE Checklist. Patient or Public Contribution: No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Introduction and aim. Eosinophilic myocarditis is a rare subtype of myocarditis with serious morbidity and mortality. We present and analyse the case of 19-year-old male with 1 year history of eosinophilic pneumonia who later developed acute eosinophilic myocarditis. Description of the case. The patient presented to the hospital with increasing shortness of breath. Patient's medical history include bronchial asthma, allergic rhinitis, recent Bartonella henselae and Bartonella hominis infections, and electronic cigarette smoking prior to the disease. Previously, extensive laboratory testing (including tests for ANCA autoantibodies and parasitic infections) was performed hoping to determine the cause of eosinophilic pneumonia, but no clear cause was found. Two days after the start of hospitalisation the patient developed sharp squeezing chest pain. Laboratory tests, ECG and ultrasound imaging was performed, revealing the development of myocarditis. Several chest X-rays were performed during the hospitalisation showing increasing inflammatory changes. The patient did not improve despite the treatment. Pulmonary ventilation and later extracorporeal membrane oxygenation were used to compensate for increasing respiratory and cardiac insufficiency. 8 days after the patient died due to cardiac arrest, ultrasound revealed immobile heart muscle and left ventricle thrombosis. Post-mortem histopathological analysis of the heart muscle revealed eosinophilic infiltrates, confirming the diagnosis of eosinophilic myocarditis. Conclusion. This case report highlights the diagnostic and therapeutic challenges encountered in managing a patient with eosinophilic pneumonia complicated by acute myocarditis, as well as the importance of monitoring patients with eosinophilic pneumonia for potential cardiac involvement. [ABSTRACT FROM AUTHOR]

Introduction: Aerosol pollutants are known to raise the risk of development of non-communicable respiratory diseases (NCRDs) such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, and allergic rhinitis. Sub-Saharan Africa's rapid pace of urbanization, economic expansion, and population growth raise concerns of increasing incidence of NCRDs. This research characterizes the state of research on pollution and NCRDs in the 46 countries of Sub-Saharan Africa (SSA). This research systematically reviewed the literature on studies of asthma; chronic bronchitis; allergic rhinitis; and air pollutants such as particulate matter, ozone, NOx, and sulfuric oxide.Methods: We searched three major databases (PubMed, Web of Science, and Scopus) using the key words "asthma", "chronic bronchitis", "allergic rhinitis", and "COPD" with "carbon monoxide (CO)", "sulfuric oxide (SO)", "ozone (O3)", "nitrogen dioxide (NO2)", and "particulate matter (PM)", restricting the search to the 46 countries that comprise SSA. Only papers published in scholarly journals with a defined health outcome in individuals and which tested associations with explicitly measured or modelled air exposures were considered for inclusion. All candidate papers were entered into a database for review.Results: We found a total of 362 unique research papers in the initial search of the three databases. Among these, 14 met the inclusion criteria. These papers comprised studies from just five countries. Nine papers were from South Africa; two from Malawi; and one each from Ghana, Namibia, and Nigeria. Most studies were cross-sectional. Exposures to ambient air pollutants were measured using spectrometry and chromatography. Some studies created composite measures of air pollution using a range of data layers. NCRD outcomes were measured by self-reported health status and measures of lung function (spirometry). Populations of interest were primarily schoolchildren, though a few studies focused on secondary school students and adults.Conclusions: The paucity of research on NCRDs and ambient air pollutant exposures is pronounced within the African continent. While capacity to measure air quality in SSA is high, studies targeting NCRDs should work to draw attention to questions of outdoor air pollution and health. As the climate changes and SSA economies expand and countries urbanize, these questions will become increasingly important. [ABSTRACT FROM AUTHOR]

Given the ongoing rise in the occurrence of allergic disorders, alterations in dietary patterns have been proposed as a possible factor contributing to the emergence and progression of these conditions. Currently, there is a significant focus on the development of dietary therapies that utilize natural compounds possessing anti-allergy properties. Dietary polyphenols and plant metabolites have been intensively researched due to their well-documented anti-inflammatory, antioxidant, and immunomodulatory characteristics, making them one of the most prominent natural bioactive chemicals. This study seeks to discuss the in-depth mechanisms by which these molecules may exert anti-allergic effects, namely through their capacity to diminish the allergenicity of proteins, modulate immune responses, and modify the composition of the gut microbiota. However, further investigation is required to fully understand these effects. This paper examines the existing evidence from experimental and clinical studies that supports the idea that different polyphenols, such as catechins, resveratrol, curcumin, quercetin, and others, can reduce allergic inflammation, relieve symptoms of food allergy, asthma, atopic dermatitis, and allergic rhinitis, and prevent the progression of the allergic immune response. In summary, dietary polyphenols and plant metabolites possess significant anti-allergic properties and can be utilized for developing both preventative and therapeutic strategies for targeting allergic conditions. The paper also discusses the constraints in investigating and broad usage of polyphenols, as well as potential avenues for future research. [ABSTRACT FROM AUTHOR]

New digital interventions have shown potential in managing asthma and improving patients' quality of life compared with conventional interventions. Our objective was to conduct an exhaustive survey of the application of digital health technologies in evaluating, treating, and self-managing psychological and psychopathological elements linked to asthma. We analyzed a compendium of research papers pertaining to asthma, encompassing themes such as outdoor air pollution, early life wheezing disorders, atopic dermatitis, digital strategies for asthma self-management, psychiatric conditions and asthma, familial impacts on pediatric asthma, and the utilization of mobile health apps for managing asthma. We scrutinized six chosen studies to evaluate the capacity of digital health technologies to enhance the management and treatment outcomes of psychological factors related to asthma. The studies under review indicate that eHealth interventions, mixed reality instruments, mHealth technology-augmented nurse-led interventions, and smartphone apps incorporating Bluetooth-enabled sensors for asthma inhalers can markedly enhance self-management of symptoms, quality of life, and mental health outcomes, particularly in children and adolescents with asthma. Nonetheless, additional research is required to ascertain their efficacy and practicability across diverse populations and environments. Customized interventions that cater to the unique needs and preferences of asthma patients and associated psychological elements are vital to ensure the persistent and equitable adoption of these technologies. We underscore the significance of addressing psychological elements in the management and treatment of asthma and advocate for ongoing research and development in this domain. [ABSTRACT FROM AUTHOR]

"Epidemiology of comorbidities and their association with asthma control" (Tomisa, G., Horváth, A., Sánta, B. et al. Epidemiology of comorbidities and their association with asthma control. Allergy Asthma Clin Immunol 17, 95 (2021). https://doi.org/10.1186/s13223-021-00598-3) is an interesting paper reflecting data collection from more than 12,000 asthmatic patients in Hungary regarding their condition and associated comorbidities. We found it valuable that the paper provides an overview of asthma comorbidities not usually considered in similar reports. Nevertheless, we believe that chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP or CRSsNP) should have been listed due to its high incidence and prevalence, its association with asthma which is also endorsed in both GINA and EPOS, as well as in several peer-reviewed scientific papers, and to reflect the role of this comorbidity in poor control and a most severe presentation of asthma for the patient. Consequently, several targeted therapies (especially monoclonal antibodies) used for several years in severe forms of asthma are now indicated also for the effective treatment of nasal polyps. [ABSTRACT FROM AUTHOR]

Benzo [a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Asthma exacerbations are an important cause of emergency department visits but much remains unknown about the role of environmental triggers including viruses and allergenic pollen. A better understanding of spatio-temporal variation in exposure and risk posed by viruses and pollen types could help prioritize public health interventions., Objective: Here we quantify the effects of regionally important Cupressaceae pollen, tree pollen, other pollen types, rhinovirus, seasonal coronavirus, respiratory syncytial virus, and influenza on asthma-related emergency department visits for people living near eight pollen monitoring stations in Texas., Methods: We used age stratified Poisson regression analyses to quantify the effects of allergenic pollen and viruses on asthma-related emergency department visits., Results: Young children (<5 years of age) had high asthma-related emergency department rates (24.1 visits/1,000,000 person-days), which were mainly attributed to viruses (51.2%). School-aged children also had high rates (20.7 visits/1,000,000 person-days), which were attributed to viruses (57.0%), Cupressaceae pollen (0.7%), and tree pollen (2.8%). Adults had lower rates (8.1 visits/1,000,000 person-days) which were attributed to viruses (25.4%), Cupressaceae pollen (0.8%), and tree pollen (2.3%). This risk was spread unevenly across space and time; for example, during peak Cuppressaceae season, this pollen accounted for 8.2% of adult emergency department visits near Austin where these plants are abundant, but 0.4% in cities like Houston where they are not; results for other age groups were similar., Conclusions: Although viruses are a major contributor to asthma-related emergency department visits, airborne pollen can explain a meaningful portion of visits during peak pollen season and this risk varies over both time and space because of differences in plant composition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Particulate matter with aerodynamic diameters ≤2.5 µm (PM 2.5 ) is a major environmental risk factor for acute asthma exacerbation, and the underlying mechanism is not completely understood. Studies have indicated that DNA methylation is a potential mechanism linking PM 2.5 to its health effects. We conducted a panel study involving 24 adult patients with asthma in Beijing,China between 2017 and 2019. PM 2.5 and other atmospheric pollutant exposure data were repeatedly measured. Blood samples were collected for genome-wide DNA methylation analysis. A linear mixed-effects (LME) model was conducted to identify differentially methylated probes (DMPs) associated with PM 2.5 exposure. After filtering out probes that did not meet the criteria through quality control, 811,001 CpG sites were included in the LME model, and 36 DMPs were strongly associated with personal PM 2.5 exposure at false discovery rate (FDR) < 0.05, of which 22 and 14 DMPs negatively and positively correlated with personal PM 2.5 exposure, respectively. Functional analysis revealed that DMPs affected smooth muscle cell contraction and development, extracellular matrix synthesis and secretion, T cell activation and differentiation, and inflammatory factor production. This study provides evidence linking personal PM 2.5 exposure to genome-wide DNA methylation in adult patients with asthma. Identifying enrichment pathways can provide biological insights into the acute health effects of PM 2.5 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to assess the specific PM 2.5 -bound metallic elements that contribute to asthma emergency department visits by using a case-crossover study design., Methods: This study analyzed data from 11,410 asthma emergency department visits as case group and 22,820 non-asthma onset dates occurring one week and two weeks preceding the case day as controls from 2017 to 2020. PM 2.5 monitoring data and 35 PM. 2.5 -bound metallic elements from six different regions in Taiwan were collected. Conditional logistic regression models were used to assess the relationship between asthma and PM 2.5 -bound metallic elements., Results: Our investigation revealed a statistically significant risk of asthma emergency department visits associated with PM 2.5 exposure at lag 0, 1, 2, and 3 during autumn. Additionally, PM 2.5 -bound hafnium (Hf), thallium (Tl), rubidium (Rb), and aluminum (Al) exhibited a consistently significant positive correlation with asthma emergency department visits at lags 1, 2, and 3. In stratified analyses by area, age, and sex, PM 2.5 -bound Hf showed a significant and consistent correlation., Conclusions: This study provides evidence of PM 2.5 -bound metallic elements effects in asthma exacerbations, particularly for Hf. It emphasizes the importance of understanding the origins of these metallic elements and pursuing emission reductions to mitigate regional health risks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wei-Te Wu reports administrative support was provided by Department of Atmospheric Environment, Ministry of Environment, Executive Yuan, Taiwan. Wei-Te Wu reports administrative support was provided by Health and Welfare Data Science Center, Ministry of Health and Welfare, Executive Yuan, Taiwan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent studies have shown that cellular senescence is involved in the pathogenesis of severe asthma (SA). The objective of this study was to investigate the role of cellular senescence-related genes (CSGs) in the pathogenesis of SA. Here, 54 differentially expressed CSGs were identified in SA patients compared to healthy control individuals. Among the 54 differentially expressed CSGs, 3 CSGs (ETS2, ETS1 and AURKA) were screened using the LASSO regression analysis and logistic regression analysis to establish the CSG-based prediction model to predict severe asthma. Moreover, we found that the protein expression levels of ETS2, ETS1 and AURKA were increased in the severe asthma mouse model. Then, two distinct senescence subtypes of SA with distinct immune microenvironments and molecular biological characteristics were identified. Cluster 1 was characterized by increased infiltration of immature dendritic cells, regulatory T cells, and other cells. Cluster 2 was characterized by increased infiltration levels of eosinophils, neutrophils, and other cells. The molecular biological characteristics of Cluster 1 included aerobic respiration and oxidative phosphorylation, whereas the molecular biological characteristics of Cluster 2 included activation of the immune response and immune receptor activity. Then, we established an Random Forest model to predict the senescence subtypes of SA to guide treatment. Finally, potential drugs were searched for each senescence subgroup of SA patients via the Connectivity Map database. A peroxisome proliferator-activated receptor agonist may be a potential therapeutic drug for patients in Cluster 1, whereas a tachykinin antagonist may be a potential therapeutic drug for patients in Cluster 2. In summary, CSGs are likely involved in the pathogenesis of SA, which may lead to new therapeutic options for SA patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV 1 (β = 0.06; 95 %CI: 0.03, 0.09 I 2  = 4.03 %, p < 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I 2  = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = -0.04; 95 %CI: -0.07, -0.02, I 2  = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02-1.05; p<0.001), 1.02 (95 % CI: 1.01-1.03; p<0.001), and 1.03 (95 % CI: 1.01-1.04; p<0.001), respectively. Moreover, particulate matter with an aerodynamic diameter ≤ 2.5 µm was assigned the highest weight across all three exposure periods. Relatively high weights were assigned to suspended particulate matter and photochemical oxidants during pregnancy, carbon monoxide during infancy, and photochemical oxidants during childhood. Our study showed that a mixture of low-level air pollutants has a detrimental association with childhood persistent asthma., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akihiro Shiroshita reports financial support was provided by the Japanese Respiratory Society Research Grants Program and Japanese Respiratory Foundation Grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA + MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Asthma is a complex disease with mechanisms involving multiple factors, and there is still a lack of highly effective and low-side-effect drugs. Traditional Chinese medicine Fagopyrum Dibotrys Rhizoma (FDR) has been applied for the treatment of acute and chronic bronchitis as well as bronchial asthma due to its favorable pharmacological activity. However, the exact mechanism of FDR remains unclear., Objective: A mouse model of asthma was created using OVA and HDM. To investigate the mechanism of FDR in asthma treatment, a combination of network pharmacology, lipidomics, and molecular biology approaches was employed., Methods: To evaluate the therapeutic effects of FDR on asthma, we established two distinct models of asthma in C57BL/6 J mice using OVA and HDM, respectively. We then employed LC-MS to analyze the major chemical constituents in FDR. Next, the network pharmacology approach was used to predict the potential targets and mechanisms of FDR in asthma treatment. Additionally, lipidomics analysis of mouse serum was conducted using LC-MS. Finally, the impact of FDR on the ERK -cPLA 2 signaling pathway was investigated through Western Blotting assay., Results: FDR treatment has been shown to improve histomorphological changes, lung function and inflammation in models of OVA and HDM-induced asthma. Using UPLC/LTQ-Orbitrap-MS, we were able to identify 12 potential active components. Network pharmacology analysis revealed that FDR shares 75 targets with asthma. Further analysis using GO and KEGG pathways demonstrated the involvement of key pathways such as PI3K-Akt, TNF, and MAPK. Additionally, lipidomics analysis of the serum from OVA and HDM induced asthma mice showed disturbances in lipid metabolism, which were effectively ameliorated by FDR treatment. Mechanistically, FDR inhibits ERK1/2-cPLA 2 , leading to a reduction in lysophospholipids and restoration of lipid balance, thereby aiding in the treatment of asthma., Conclusion: FDR has been shown to improve lipid metabolism disorder in the serum of asthmatic mice, thereby potentially serving as a treatment for asthma. This can be achieved by regulating the activation levels of ERK1/2 and p38MAPK. Consequently, the production of lysophosphatide is reduced, thereby alleviating the disorder of lipid metabolism and achieving the desired therapeutic effect in asthma treatment., Competing Interests: Declaration of competing interest The authors affirm that they have no known financial conflicts of interest or personal relationships that might have influenced the work presented in this paper. During the preparation of this work the authors used ChatGPT3.5 in order to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. In accordance with the guidelines and policies of Phytomedicine, we hereby declare our potential competing interests that may have influenced our work presented in this submission. We understand the importance of transparency in research and scholarly publishing and have taken the necessary steps to disclose any potential conflicts of interest. We affirm that the information provided in this declaration is accurate and complete to the best of our knowledge. Additionally, we have complied with the requirement to provide detailed disclosures of our interests as part of the separate Declaration of Interest form, which is on record with Phytomedicine for official documentation., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Rationale and Objectives: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease., Materials and Methods: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing 1 H MRI, 129 Xe MRI, spirometry, and oscillometry. A subset of participants (n = 23) performed chest CT and another subset of participants with asthma (n = 19) repeated 1 H MRI following the administration of a bronchodilator. VDP was calculated for both PREFUL and 129 Xe MRI. Additionally, the percent of functional small airways disease was determined from CT parametric response maps (PRM fSAD )., Results: PREFUL VDP measured pre-bronchodilator (19.1% [7.4-43.3], p = 0.0002) and post-bronchodilator (16.9% [6.1-38.4], p = 0.0007) were significantly greater than that of healthy controls (7.5% [3.7-15.5]) and was significantly decreased post-bronchodilator (from 21.9% [10.1-36.9] to 16.9% [6.1-38.4], p = 0.0053). PREFUL VDP was correlated with spirometry (FEV 1 % pred : r = -0.46, p = 0.0023; FVC% pred : r = -0.35, p = 0.024, FEV 1 /FVC: r = -0.46, p = 0.0028), 129 Xe MRI VDP (r = 0.39, p = 0.013), and metrics of small airway disease (CT PRM fSAD : r = 0.55, p = 0.021; Xrs 5 Hz : r = -0.44, p = 0.0046, and AX: r = 0.32, p = 0.044)., Conclusion: PREFUL-derived VDP is responsive to bronchodilator therapy in asthma and is associated with measures of airflow obstruction and small airway dysfunction. These findings validate PREFUL VDP as a physiologically relevant and accessible ventilation imaging outcome measure in asthma., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Svenningsen reports financial support was provided by Canada Research Chairs program. Parameswaran Nair reports financial support was provided by Frederick E. Hargreave Teva Innovation Chair in Airways Disease. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease., Objectives: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms. Furthermore, it explores the involvement of IL-2 family cytokines in the pathogenesis of chronic respiratory diseases, with a specific focus on chronic obstructive pulmonary disease (COPD) and asthma., Methods: A thorough literature review was conducted to gather insights into the molecular biology, receptor interactions, and signalling pathways of IL-2 family cytokines. Additionally, studies investigating the roles of these cytokines in chronic respiratory diseases, particularly COPD and asthma, were analysed to discern their implications in wider pathophysiology of disease., Results: IL-2 family cytokines exert pleiotropic effects on immune cells, modulating cellular proliferation, differentiation, and survival. Dysregulation of IL-2 family cytokines has been implicated in the pathogenesis of chronic respiratory illnesses, including COPD and asthma. Elevated levels of IL-2 and IL-9 have been associated with disease severity in COPD, while IL-4 and IL-9 play crucial roles in asthma pathogenesis by promoting airway inflammation and remodelling., Conclusion: Understanding the intricate roles of IL-2 family cytokines in chronic respiratory diseases provides valuable insights into potential therapeutic targets for these conditions. Targeting specific cytokines or their receptors may offer novel treatment modalities to attenuate disease progression and improve clinical outcomes in patients with COPD and asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Asthma is a heterogeneous disease, and its development is the result of a combination of factors, including genetic factors, environmental factors, immune dysfunction and other factors. Its specific mechanism has not yet been fully investigated. With the improvement of disease models, research on the pathogenesis of asthma has made great progress. Immunological disorders play an important role in asthma. Previously, we thought that asthma was mainly caused by an imbalance between Th1 and Th2 immune responses, but this theory cannot fully explain the pathogenesis of asthma. Recent studies have shown that T-cell subsets such as Th1 cells, Th2 cells, Th17 cells, Tregs and their cytokines contribute to asthma through different mechanisms. For the purpose of the present study, asthma was classified into distinct phenotypes based on airway inflammatory cells, such as eosinophilic asthma, characterized by predominant eosinophil aggregates, and neutrophilic asthma, characterized by predominant neutrophil aggregates. This paper will examine the immune mechanisms underlying different types of asthma, and will utilize data from animal models and clinical studies targeting specific immune pathways to inform more precise treatments for this condition., (© 2024. The Author(s).)

Allergic asthma is a chronic inflammatory airway disease with a high mortality rate and a rapidly increasing prevalence in recent decades that is closely linked to environmental change. Previous research found that high humidity (HH) and the traffic-related air pollutant NO 2 both aggregated allergic asthma. Their combined effect and mechanisms on asthma exacerbation, however, are unknown. Our study aims to toxicologically clarify the role of HH (90%) and NO 2 (5 ppm) on allergic asthma. Ninety male Balb/c mice were randomly assigned to one of six groups (n = 15 in each): saline control, ovalbumin (OVA)-sensitized, OVA + HH, OVA + NO 2 , OVA + HH + NO 2 , and OVA + HH + NO 2 +Capsazepine (CZP). After 38 days of treatment, the airway function, pathological changes in lung tissue, blood inflammatory cells, and oxidative stress and inflammatory biomarkers were comprehensively assessed. Co-exposure to HH and NO 2 exacerbated histopathological changes and airway hyperresponsiveness, increased IgE, oxidative stress markers malonaldehyde (MDA) and allergic asthma-related inflammation markers (IL-1β, TNF-α and IL-17), and upregulated the expressions of the transient receptor potential (TRP) ion channels (TRPA1, TRPV1 and TRPV4). Our findings show that co-exposure to HH and NO 2 disrupted the Th1/Th2 immune balance, promoting allergic airway inflammation and asthma susceptibility, and increasing TRPV1 expression, whereas CZP reduced TRPV1 expression and alleviated allergic asthma symptoms. Thus, therapeutic treatments that target the TRPV1 ion channel have the potential to effectively manage allergic asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m 3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 μM FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) - sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4 + T cells and Th2 + T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4 + T cells and Th2 + T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4 + T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4 + T cells and Th2 + T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4 + T cells and Th2 + T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4 + T cells. T cell exhaustion plays an important role in AIT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Previous studies have suggested that living close to green spaces has protective health effects, but potential effects on asthma are contradictory. We investigated the association between the amount of greenness in the residential area during pregnancy and early life and development of asthma in the first 27 years of life. The study population included all 2568 members of the Espoo Cohort Study, Finland. We calculated individual-level exposure to green space measured as cumulative Normalized Difference Vegetation Index (cumNDVI in unit-months) within 300 m of the participant's residence during pregnancy and the first two years of life in both spring and summer seasons. The onset of asthma was assessed using information from the baseline and follow-up surveys. Exposure to residential greenness in the spring season during pregnancy was associated with an increased risk of asthma up to 6 years of age, with an adjusted hazard ratio (aHR) of 3.72 (95% confidence interval (CI): 1.11, 12.47) per 1 unit increase in cumNDVI. Increased greenness in the summer during pregnancy associated with asthma up to 6 years, with an aHR of 1.41 (95% CI: 0.85, 2.32). The effect was found to be related to increased greenness particularly during the third trimester of pregnancy, with an aHR of 2.37 (95% CI: 1.36, 4.14) per 1 unit increase of cumNDVI. These associations were weaker at the ages of 12 and 27 years. No association was found between NDVI in the first two years of life and the development of asthma. Our findings provide novel evidence that exposure to greenness during pregnancy increases the risk of developing asthma. The adverse effects were strongest for the prenatal greenness in the spring season and in the third trimester of pregnancy. Both the season and trimester of exposure to greenness are critical in the development of asthma., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jouni J.K. Jaakkola reports financial support was provided by Research Council of Finland. Jouni J.K. Jaakkola reports a relationship with Horizon Europe that includes: funding grants. Jouni J.K. Jaakkola reports being member of Sustainability Panel and stocks of pharmaceutical industry. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between long-term exposure to ozone (O 3 ) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking., Objectives: To examine the causal association between long-term O 3 exposure and AOA., Methods: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O 3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O 3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding., Results: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O 3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O 3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O 3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O 3 exposure and AOA risk, but not for low-level O 3 exposure. No significant associations between O 3 exposure and accidental injury were observed., Conclusion: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O 3 and increased risks of AOA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIP Cre ) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIP Cre mice, despite being TXNIP deficient, TXNIP Cre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)