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EBioMedicine Aug 2023Asthma is a heterogeneous chronic respiratory disease that impacts nearly 10% of the population worldwide. While cellular senescence is a normal physiological process,... (Review)
Review
Asthma is a heterogeneous chronic respiratory disease that impacts nearly 10% of the population worldwide. While cellular senescence is a normal physiological process, the accumulation of senescent cells is considered a trigger that transforms physiology into the pathophysiology of a tissue/organ. Recent advances have suggested the significance of cellular senescence in asthma. With this review, we focus on the literature regarding the physiology and pathophysiology of cellular senescence and cellular stress responses that link the triggers of asthma to cellular senescence, including telomere shortening, DNA damage, oncogene activation, oxidative-related senescence, and senescence-associated secretory phenotype (SASP). The association of cellular senescence to asthma phenotypes, airway inflammation and remodeling, was also reviewed. Importantly, several approaches targeting cellular senescence, such as senolytics and senomorphics, have emerged as promising strategies for asthma treatment. Therefore, cellular senescence might represent a mechanism in asthma, and the senescence-related molecules and pathways could be targeted for therapeutic benefit.
Topics: Humans; Cellular Senescence; Asthma; Phenotype; Inflammation
PubMed: 37442061
DOI: 10.1016/j.ebiom.2023.104717 -
The European Respiratory Journal Nov 2023Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To... (Observational Study)
Observational Study
BACKGROUND
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.
METHODS
First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
RESULTS
In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex.
CONCLUSIONS
Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Topics: Female; Humans; Male; Analysis of Variance; Asthma; Coronary Artery Disease; Genome-Wide Association Study; Myocardial Infarction; Polymorphism, Single Nucleotide; Risk Factors; Mendelian Randomization Analysis
PubMed: 37945032
DOI: 10.1183/13993003.01788-2023 -
The Journal of Allergy and Clinical... Feb 2024
Topics: Humans; Asthma; Occupational Diseases; Occupational Exposure
PubMed: 38336395
DOI: 10.1016/j.jaip.2023.11.042 -
Critical Care Nursing QuarterlyAsthma is a common chronic respiratory condition that affects approximately 10% of adult women in the United States. Pregnancy can present unique challenges for women... (Review)
Review
Asthma is a common chronic respiratory condition that affects approximately 10% of adult women in the United States. Pregnancy can present unique challenges for women with asthma, as changes in the body can alter the severity and management of asthma-related respiratory symptoms. In this article, we review the current understanding of asthma during pregnancy, including the direct effects of the disease state on the pregnant woman and fetus, risk factors for poor control of disease, as well as current treatment recommendations.
Topics: Pregnancy; Adult; Humans; Female; Pregnancy Complications; Asthma; Risk Factors
PubMed: 37684738
DOI: 10.1097/CNQ.0000000000000478 -
Frontiers in Immunology 2023Asthma is a heterogeneous disease, and the involvement of neurogenic inflammation is crucial in its development. The standardized treatments focus on alleviating...
BACKGROUND
Asthma is a heterogeneous disease, and the involvement of neurogenic inflammation is crucial in its development. The standardized treatments focus on alleviating symptoms. Despite the availability of medications for asthma, they have proven to be inadequate in controlling relapses and halting the progression of the disease. Therefore, there is a need for novel drug targets to prevent asthma.
METHODS
We utilized Mendelian randomization to investigate potential drug targets for asthma. We analyzed summary statistics from the UK Biobank and then replicated our findings in GWAS data by Demenais et al. and the FinnGen cohort. We obtained genetic instruments for 734 plasma and 73 brain proteins from recently reported GWAS. Next, we utilized reverse causal relationship analysis, Bayesian co-localization, and phenotype scanning as part of our sensitivity analysis. Furthermore, we performed a comparison and protein-protein interaction analysis to identify causal proteins. We also analyzed the possible consequences of our discoveries by the given existing asthma drugs and their targets.
RESULTS
Using Mendelian randomization analysis, we identified five protein-asthma pairs that were significant at the Bonferroni level ( < 6.35 × 10). Specifically, in plasma, we found that an increase of one standard deviation in IL1R1 and ECM1 was associated with an increased risk of asthma, while an increase in ADAM19 was found to be protective. The corresponding odds ratios were 1.03 (95% CI, 1.02-1.04), 1.00 (95% CI, 1.00-1.01), and 0.99 (95% CI, 0.98-0.99), respectively. In the brain, per 10-fold increase in ECM1 (OR, 1.05; 95% CI, 1.03-1.08) and PDLIM4 (OR, 1.05; 95% CI, 1.04-1.07) increased the risk of asthma. Bayesian co-localization found that ECM1 in the plasma (coloc.abf-PPH4 = 0.965) and in the brain (coloc.abf-PPH4 = 0.931) shared the same mutation with asthma. The target proteins of current asthma medications were found to interact with IL1R1. IL1R1 and PDLIM4 were validated in two replication cohorts.
CONCLUSION
Our integrative analysis revealed that asthma risk is causally affected by the levels of IL1R1, ECM1, and PDLIM4. The results suggest that these three proteins have the potential to be used as drug targets for asthma, and further investigation through clinical trials is needed.
Topics: Humans; Mendelian Randomization Analysis; Bayes Theorem; Brain; Asthma; Mutation; Extracellular Matrix Proteins
PubMed: 37809092
DOI: 10.3389/fimmu.2023.1240517 -
The Journal of Asthma : Official... Dec 2023Asthma imposes a significant health and socioeconomic burden with an average prevalence impacting 5-10% of the global population. The aim of this narrative review is to... (Review)
Review
OBJECTIVE
Asthma imposes a significant health and socioeconomic burden with an average prevalence impacting 5-10% of the global population. The aim of this narrative review is to update the current literature on topics related to asthma diagnosis.
DATA SOURCES
Original research articles were identified from PubMed using the search terms "asthma diagnosis" and "asthma misdiagnosis".
STUDY SELECTIONS
Recently published articles ( = 51) detailing the diagnosis, misdiagnosis of asthma, and the updated recommendations of the European and international asthma guidelines.
RESULTS
Emerging evidence revealed that asthma might represent a rather heterogenous clinical entity with varying underlying molecular mechanisms. Attempts have been made to unravel these traits to better provide accurate diagnosis and a more efficient patient-based management approach. The lack of a gold standard test for asthma diagnosis has contributed to its over- and underdiagnosis. This is problematic, given that overdiagnosis might lead to delay of both diagnosis and prompt treatment of other diseases, while underdiagnosis might substantially impact quality of life due to progression of asthma by increased rate of exacerbations and airway remodeling. In addition to poor asthma control and potential patient harm, asthma misdiagnosis is also associated with excessive costs. As a result, current international guidelines emphasize the need for a standardized approach to diagnosis, including objective measurements prior to treatment.
CONCLUSION
Future research is warranted to define the optimal diagnostic and treatable traits approach especially for patients with severe asthma, as they may benefit from the advent of newly targeted asthma management.
Topics: Humans; Asthma; Quality of Life; Prevalence; Phenotype
PubMed: 37358228
DOI: 10.1080/02770903.2023.2228911 -
The Journal of Allergy and Clinical... Sep 2023Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in...
BACKGROUND
Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma.
OBJECTIVE
To analyze the response and remission in the German Asthma Net severe asthma registry cohort.
METHODS
We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy.
RESULTS
Group A included 233 and group B 210 patients, the latter receiving omalizumab (n = 33), mepolizumab (n = 40), benralizumab (n = 81), reslizumab (n = 1), or dupilumab (n = 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A.
CONCLUSIONS
Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Omalizumab; Adrenal Cortex Hormones; Biological Products
PubMed: 37301433
DOI: 10.1016/j.jaip.2023.05.047 -
Ugeskrift For Laeger Apr 2024Managing asthma during pregnancy is crucial for both the mother and the developing child. Adequate control lowers risks as do continuation of prescribed medication and... (Review)
Review
Managing asthma during pregnancy is crucial for both the mother and the developing child. Adequate control lowers risks as do continuation of prescribed medication and maintaining of regular check-ups. Signs of deterioration should not be ignored and treating asthma during pregnancy should follow guidelines for non-pregnant women with asthma as described in this review. Effective medication and counseling are essential for a safe pregnancy, emphasizing that well-controlled asthma is key.
Topics: Female; Humans; Pregnancy; Anti-Asthmatic Agents; Asthma; Mothers; Pregnancy Complications
PubMed: 38606708
DOI: 10.61409/V12230754 -
International Journal of Molecular... Sep 2023Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population,...
Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population, despite recent advancements in their treatment and prevention [...].
Topics: Humans; Prevalence; Rhinitis, Allergic; Asthma; Food Hypersensitivity
PubMed: 37762615
DOI: 10.3390/ijms241814312 -
Journal of Hazardous Materials Oct 2023No previous study has examined the impact of air pollution on the cardiovascular disease (CVD) trajectory, especially among asthmatic subjects. Based on the UK Biobank...
No previous study has examined the impact of air pollution on the cardiovascular disease (CVD) trajectory, especially among asthmatic subjects. Based on the UK Biobank cohort, we retrieved 292,227 adults free of asthma and CVD aged 37-73 years at recruitment (2006-2010). Annual mean concentrations of particulate matter (PM and PM) and nitrogen oxides (NO and NO) were assessed at each individual's addresses. We used multi-state models to estimate the associations of air pollution with the trajectory from healthy to incident asthma, subsequent CVD, and death. During a median follow-up of 11.7 years, a total of 6338 (2.2%) participants developed asthma, among which, 638 (10.1%) subsequently proceeded to CVD. We observed significant impacts of various air pollutants on the CVD dynamic transitions, with a more substantial effect of particulate matter pollutants than gaseous air pollutants. For example, the hazard ratios (95% confidence intervals) for per interquartile range increase in PM and PM were 1.28 (1.13, 1.44) and 1.27 (1.13, 1.43) for transitions from incident asthma to subsequent CVD. In conclusion, long-term air pollution exposure could affect the CVD trajectory. Distinguishing the effect of air pollutants on CVD transition stages has great significance for CVD health management and clinical prevention, especially among asthma patients.
Topics: Adult; Humans; Cardiovascular Diseases; Air Pollution; Asthma; Air Pollutants; Particulate Matter
PubMed: 37633014
DOI: 10.1016/j.jhazmat.2023.132372