Childhood asthma- pathogenesis and phenotypes

2021 ◽  
pp. 2100731
Author(s):  
Mariëlle W Pijnenburg ◽  
Urs Frey ◽  
Johan C De Jongste ◽  
Sejal Saglani
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Treatment Options ◽  
Critical Factor ◽  
Tobacco Smoke Exposure ◽  
Pathophysiological Mechanism ◽  
Asthma In Children ◽  
Infant Weight Gain ◽  
Inflammatory Phenotypes ◽  
Early Life Exposures

In the pathogenesis of asthma in children there is a pivotal role for a type 2 inflammatory response to early life exposures or events. Interactions between infections, atopy, genetic susceptibility, and environmental exposures (such as farmyard environment, air pollution, tobacco smoke exposure) influence the development of wheezing illness and the risk for progression to asthma. The immune system, lung function and the microbiome in gut and airways develop in parallel and dysbiosis of the microbiome may be a critical factor in asthma development. Increased infant weight gain and preterm birth are other risk factors for development of asthma and reduced lung function. The complex interplay between these factors explains the heterogeneity of asthma in children. Subgroups of patients can be identified as phenotypes based on clinical parameters, or endotypes, based on a specific pathophysiological mechanism. Paediatric asthma phenotypes and endotypes may ultimately help to improve diagnosis of asthma, prediction of asthma development and treatment of individual children, based on clinical, temporal, developmental or inflammatory characteristics. Unbiased, data-driven clustering, using a multidimensional or systems biology approach may be needed to better define phenotypes. The present knowledge on inflammatory phenotypes of childhood asthma has now been successfully applied in the treatment with biologicals of children with severe therapy resistant asthma, and it is to be expected that more personalized treatment options may become available.

Effect of Breastfeeding on Childhood Asthma and Lung Function in a Developing Tropical Country

PEDIATRICS ◽  
2016 ◽  
Vol 137 (Supplement 3) ◽  
pp. 214A-214A
Author(s):  
Harish Kumar ◽  
Dr Amit Devgan
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Tropical Country

A Genomic Approach to Characterize the Vulnerable Patient – a Clinical Update

2019 ◽  
Vol 4 (3) ◽  
pp. 141-144
Author(s):  
Evelin Szabó ◽  
Zsolt Parajkó ◽  
Diana Opincariu ◽  
Monica Chițu ◽  
Nóra Raț ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Ischemia ◽  
Treatment Options ◽  
Ischemic Heart ◽  
Pathophysiological Mechanism ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Vulnerable Patient ◽  
Traditional Risk Factors ◽  
New Treatment

Abstract Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. Systemic risk factors play an important role in the starting and progression of atherosclerosis. The complexity of the disease is caused by its multifactorial origin. Besides the traditional risk factors, genetic predisposition is also a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology may result in new treatment options. Individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic, and metabolomic research may be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

2019 ◽  
Vol 53 (4) ◽  
pp. 1801795 ◽  
Author(s):  
Herman T. den Dekker ◽  
Kimberley Burrows ◽  
Janine F. Felix ◽  
Lucas A. Salas ◽  
Ivana Nedeljkovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Life Course ◽  
Cord Blood ◽  
Childhood Asthma ◽  
Respiratory Health ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Life Course

RationaleWe aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.MethodsWe meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7–13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.ResultsWe identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.InterpretationOur findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

Irreversible Lung Function Deficits in Young Adults With a History of Childhood Asthma

PEDIATRICS ◽  
2007 ◽  
Vol 120 (Supplement 3) ◽  
pp. S128.1-S128
Author(s):  
Timothy Andrews ◽  
James R. Banks
Keyword(s):  
Young Adults ◽  
Lung Function ◽  
Childhood Asthma ◽  
History Of Childhood ◽  
History Of

scholarly journals Bisphenol a Exposure, DNA Methylation, and Asthma in Children

2020 ◽  
Vol 17 (1) ◽  
pp. 298 ◽  
Author(s):  
Chia-Feng Yang ◽  
Wilfried J. J. Karmaus ◽  
Chen-Chang Yang ◽  
Mei-Lien Chen ◽  
I-Jen Wang
Keyword(s):  
Dna Methylation ◽  
Bisphenol A ◽  
Candidate Genes ◽  
Promoter Methylation ◽  
Childhood Asthma ◽  
Methylation Status ◽  
Differential Methylation ◽  
Study Cohort ◽  
Blood Samples ◽  
Asthma In Children

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

Interaction of Glutathione S-Transferase M1, T1, and P1 Genes With Early Life Tobacco Smoke Exposure on Lung Function in Adolescents

CHEST Journal ◽  
2019 ◽  
Vol 155 (1) ◽  
pp. 94-102 ◽  
Author(s):  
Xin Dai ◽  
Shyamali C. Dharmage ◽  
Gayan Bowatte ◽  
Nilakshi T. Waidyatillake ◽  
Jennifer L. Perret ◽  
...  
Keyword(s):  
Lung Function ◽  
Tobacco Smoke ◽  
Early Life ◽  
Smoke Exposure ◽  
Tobacco Smoke Exposure ◽  
Glutathione S Transferase

scholarly journals Current and Future Treatments in the Fight against Non-Alcoholic Fatty Liver Disease

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1714 ◽  
Author(s):  
Benoit Smeuninx ◽  
Ebru Boslem ◽  
Mark A. Febbraio
Keyword(s):  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Critical Factor ◽  
Developed Countries ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Obesity is recognised as a risk factor for many types of cancers, in particular hepatocellular carcinoma (HCC). A critical factor in the development of HCC from non-alcoholic fatty liver disease (NAFLD) is the presence of non-alcoholic steatohepatitis (NASH). Therapies aimed at NASH to reduce the risk of HCC are sparse and largely unsuccessful. Lifestyle modifications such as diet and regular exercise have poor adherence. Moreover, current pharmacological treatments such as pioglitazone and vitamin E have limited effects on fibrosis, a key risk factor in HCC progression. As NAFLD is becoming more prevalent in developed countries due to rising rates of obesity, a need for directed treatment is imperative. Numerous novel therapies including PPAR agonists, anti-fibrotic therapies and agents targeting inflammation, oxidative stress and the gut-liver axis are currently in development, with the aim of targeting key processes in the progression of NASH and HCC. Here, we critically evaluate literature on the aetiology of NAFLD-related HCC, and explore the potential treatment options for NASH and HCC.

Role of Breathing Exercises and Yoga/Pranayama in Childhood Asthma: A Systematic Review

2019 ◽  
Vol 15 (3) ◽  
pp. 175-183 ◽  
Author(s):  
Rashmi Ranjan Das ◽  
Jhuma Sankar ◽  
Sushil Kumar Kabra
Keyword(s):  
Lung Function ◽  
Adverse Events ◽  
Outcome Measures ◽  
Childhood Asthma ◽  
Primary Outcome ◽  
Immunological Parameters ◽  
Breathing Exercise ◽  
Breathing Exercises ◽  
Secondary Outcomes

Background: arious complementary or alternative medicines (including breathing exercises and yoga/pranayama) have been tried as an attractive option to pharmacotherapy in childhood asthma. Objective: To evaluate the role of breathing exercise and yoga/pranayama as add on therapy to the “pharmacologically recommended treatment” of childhood asthma. Methods: We searched the published literature in the major databases: Medline via Ovid, PubMed, CENTRAL, Embase, and Google Scholar till June 2018. Randomized trials comparing breathing exercises and yoga/ pranayama versus control or as part of a composite intervention versus control were included. The primary outcome measures were quality of life and change in asthma symptoms. Secondary outcomes were: decrease in medication use, number of exacerbations, change in lung function and immunological parameters, school absenteeism and adverse events. Results: A total of 10 trials (466 children, 6-14 years age) were included. The severity of asthma varied among the trials. The data for primary outcome measures could not be pooled, there were mixed results for both primary and secondary outcomes. No significant benefit was obtained in acute asthma and the lung function tests [except PEFR % at 4-6 weeks, PEF absolute at 3 months, and FVC absolute at 3 months] in chronic asthma. One trial compared breathing exercise versus yoga and found no difference. Adverse events were not significant. Conclusion: Breathing exercise and yoga/ pranayama may have some additive role in the treatment of childhood asthma. However, at present, it cannot be recommended as a standard of care due to insufficient data.

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