Asthma, a complex disease characterized by persistent airway inflammation, remains an urgent global health concern. We explored the critical role of allergic biomarkers and dysregulated immune system in asthma through an extensive literature review in databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. This review summarizes the growing data on the pivotal role of allergic biomarkers and dysregulated immune system in the development and evolution of asthma. Recent studies have uncovered several biomarkers that elucidate intrinsic allergic mechanisms in individuals with asthma. This article highlights these biomarkers’ potential in predicting asthma onset, assessing its intensity, guiding therapeutic interventions, and tracking disease progression. We also explore the innovative therapeutic prospects arising from the convergence of allergy and dysregulated immune system in asthma and emphasize the potential for precision medicine approaches. Understanding allergic biomarkers intertwined with a dysregulated immune system heralds a new era in asthma treatment and points to improved and individualized treatment modalities.

https://www.mdpi.com/2077-0383/13/19/5775

Background: Three anti–IL-5 pathway–directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available.

Objective: We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts.

Methods: This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEV1. An ITC was performed in patients with Asthma Control

https://www.jacionline.org/article/S0091-6749(18)31278-8/fulltext

Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.

https://pubmed.ncbi.nlm.nih.gov/34918742/

The development of monoclonal antibody therapies targeting specific components of the pathways relevant to asthma pathophysiology has revolutionized treatment of severe asthma both in adults and children and helped to further unravel the heterogeneity of this disease. However, the availability of multiple agents, often with overlapping eligibility criteria, creates a need for pragmatic guidance for specialists undertaking care of patients with severe asthma. In this review, we provide an overview of the data supporting the clinical efficacy of biologics in distinct asthma phenotypes/endotypes. We also focus on the role of biomarkers and treatable traits, including comorbidities, in the choice of asthma biologics, highlight which treatments have been demonstrated to be steroid sparing in corticosteroid dependent asthma, and provide practical guidance that can drive shared decision making on treatment choice with patients. In addition, we summarize what is known to date regarding long-term safety of these drugs, and lastly, discuss future directions in biologics research.

https://www.resmedjournal.com/article/S0954-6111(23)00302-5/fulltext

What is already known about this topic? Poor adherence to asthma and chronic obstructive pulmonary disease medications is commonplace despite the known risks for adverse health outcomes and associated consumption of costly health care resources.

What does this article add to our knowledge? Implementing programs to improve adherence to inhaled medicines can be cost-effective, reducing medical costs and consumption of health care resources and improving disease control and patient-reported outcomes.

How does this study impact current management guidelines? Implementation of proven adherence promotion programs (eg, using digitally enhanced care and one-to-one counseling) is cost-effective and could help improve asthma and chronic obstructive pulmonary disease control and aid management of health care budgets.

https://www.jaci-inpractice.org/article/S2213-2198(24)00006-0/fulltext

A type-2 immune response usually sustains wheezing and asthma in children. In addition, dysbiosis of digestive and respiratory tracts is detectable in patients with wheezing and asthma.  Probiotics may rebalance immune response, repair dysbiosis, and mitigate airway inflammation. As a result, probiotics may prevent asthma and wheezing relapse. There is evidence that some probiotic strains may improve asthma outcomes in children. In this context, the PROPAM study provided evidence that two specific strains significantly prevented asthma exacerbations and wheezing episodes. Therefore, oral probiotics could be used as add-on asthma therapy in managing children with asthma, but the choice should be based on documented evidence.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9316460/

Asthma is chronic inflammation of the airways characterized by airway hyper-responsiveness, wheezing, cough, and dyspnea. Asthma affects >350 million people worldwide. The Th2 immune response is a major contributor to the pathophysiology of asthma. Targeted therapy modulating cell signaling pathways can be a powerful strategy to design new drugs to treat asthma. The potential molecular pathways that can be targeted include IL-4-IL-13-JAK-STAT-MAP kinases, adiponectin-iNOS-NF-κB, PGD2-CRTH2, IFNs-RIG, Wnt/β-catenin-FAM13A, FOXC1-miR-PI3K/AKT, JNK-Gal-7, Nrf2-ROS, Foxp3-RORγt, CysLTR, AMP, Fas-FasL, PTHrP/PPARγ, PAI-1, FcɛRI-LAT-SLP-76, Tim-3-Gal-9, TLRs-MyD88, PAR2, and Keap1/Nrf2/ARE. Therapeutic drugs can be designed to target one or more of these pathways to treat asthma

https://www.nature.com/articles/s41392-019-0079-0

In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the disease such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbations. However, only half the asthmatics have this ‘‘type 2-high’’ signature, and ‘‘type 2-low’’ asthma is more associated with obesity, presence of neutrophils, and unresponsiveness to corticosteroids, the mainstay asthma therapy. Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated in clinical studies targeting specific immune pathways.

https://www.cell.com/cell/pdf/S0092-8674(21)00166-5.pdf

To address pediatric asthma disparities on the South Side of Chicago, a community health worker (CHW) home visiting intervention was implemented collaboratively by academic institutions and community based health centers. This evaluation assessed the effectiveness of this longitudinal quality improvement CHW intervention in reducing asthma morbidity and healthcare utilization. All patients aged 2–18 who met the high-risk clinical criteria in outpatient settings or those who visited the ED due to asthma were offered the program. A within-subject study design analyzed asthma morbidity and healthcare utilization at baseline and follow-up. Multivariable mixed-effects regression models, adjusted for baseline demographic and asthma characteristics, were used to assess changes over time. Among 123 patients, the average age was 8.8 (4.4) years, and 89.3% were non-Hispanic black. Significant reductions were observed in the average daytime symptoms days (baseline 4.1 days and follow-up 1.6 days), night-time symptoms days (3.0 days and 1.2 days), and days requiring rescue medication (4.1 days and 1.6 days) in the past two weeks (all p<0.001). The average number of emergency department visits decreased from 0.92 one year before to 0.44 one year after program participation, a 52% reduction (p<0.001). No significant difference was found in hospital admissions. These results support the use of a collaborative approach to implement the CHW home visiting program as part of standard care for pediatric asthma patients in urban settings. This approach has the potential to reduce asthma disparities and underscores the valuable role of CHWs within the clinical care team.

SSPAC paper Comm Health 2024.pdf