Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction

Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long actingβ2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control.

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Extracellular Vesicles and Asthma—More Than Just a Co-Existence

International Journal of Molecular Sciences ◽

10.3390/ijms22094984 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4984

Author(s):

Bilal Alashkar Alhamwe ◽

Daniel P. Potaczek ◽

Sarah Miethe ◽

Fahd Alhamdan ◽

Lukas Hintz ◽

...

Keyword(s):

Extracellular Vesicles ◽

Association Studies ◽

Airway Remodeling ◽

Airflow Obstruction ◽

Cell Communication ◽

Therapeutic Interventions ◽

Inflammatory Disorder ◽

Diagnostic Potential ◽

Functional Relevance ◽

Reversible Airflow Obstruction

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

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Faculty Opinions recommendation of Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12401.469892 ◽

2006 ◽

Author(s):

Michael Kabesch

Keyword(s):

Airway Remodeling ◽

Airflow Obstruction ◽

Reversible Airflow Obstruction

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Mechanisms of Remodeling in Asthmatic Airways

Journal of Allergy ◽

10.1155/2012/316049 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 44

Author(s):

Adrian Shifren ◽

Chad Witt ◽

Chandrika Christie ◽

Mario Castro

Keyword(s):

Airway Hyperresponsiveness ◽

Structural Changes ◽

Airway Remodeling ◽

Airflow Obstruction ◽

Asthma Treatment ◽

Airway Wall ◽

Lung Function Decline ◽

Airway Wall Thickness ◽

Asthma Patients ◽

Reversible Airflow Obstruction

Asthma is a chronic inflammatory airway disorder characterized by airway hyperresponsiveness and reversible airflow obstruction. Subgroups of asthma patients develop airflow obstruction that is irreversible or only partially reversible and experience an accelerated rate of lung function decline. The structural changes in the airways of these patients are referred to as airway remodeling. All elements of the airway wall are involved, and remodeled airway wall thickness is substantially increased compared to normal control airways. Airway remodeling is thought to contribute to the subphenotypes of irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity. Reversal of remodeling is therefore of paramount therapeutic importance, and mechanisms responsible for airway remodeling are feasible therapeutic targets for asthma treatment. This paper will focus on our current understanding of the mechanisms of airway remodeling in asthma and potential targets for future intervention.

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IGF1R as a Potential Pharmacological Target in Allergic Asthma

Biomedicines ◽

10.3390/biomedicines9080912 ◽

2021 ◽

Vol 9 (8) ◽

pp. 912

Author(s):

Elvira Alfaro-Arnedo ◽

Icíar P. López ◽

Sergio Piñeiro-Hermida ◽

Álvaro C. Ucero ◽

Francisco J. González-Barcala ◽

...

Keyword(s):

Allergic Asthma ◽

Kinase Inhibitor ◽

Airway Remodeling ◽

Airflow Obstruction ◽

Allergic Inflammation ◽

Allergic Airway Inflammation ◽

Dust Mite ◽

Pharmacological Target ◽

Igf1r Signaling ◽

Reversible Airflow Obstruction

Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. Methods: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. Results: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. Conclusions: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

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Regulation of Eosinophilia in Asthma—New Therapeutic Approaches for Asthma Treatment

Cells ◽

10.3390/cells10040817 ◽

2021 ◽

Vol 10 (4) ◽

pp. 817

Author(s):

Ruth P. Cusack ◽

Christiane E. Whetstone ◽

Yanqing Xie ◽

Maral Ranjbar ◽

Gail M. Gauvreau

Keyword(s):

Drug Targets ◽

Airflow Obstruction ◽

Chronic Inflammatory Disease ◽

Therapeutic Approaches ◽

Eosinophilic Asthma ◽

Airway Eosinophilia ◽

Gm Csf ◽

New Therapeutic Approaches ◽

Cellular Apoptosis ◽

Reversible Airflow Obstruction

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

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Persistent airflow obstruction in inner-city children with asthma

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210043 ◽

2021 ◽

Vol 42 (4) ◽

pp. 310-316

Author(s):

Kenny Y. Kwong ◽

Yang Z. Lu ◽

Emilio Jauregui ◽

Lyne Scott

Keyword(s):

Lung Function ◽

Inner City ◽

Airway Remodeling ◽

Airflow Obstruction ◽

Later Life ◽

Forced Expiratory Volume ◽

Initial Visit ◽

Asthma Care ◽

Increased Risk ◽

Children With Asthma

Background: Airway remodeling has been shown to be persistent in patients with asthma despite treatment with controller medications. Patients with early airflow obstruction may continue to experience poor lung function despite treatment. Objectives: To determine whether early airflow obstruction in inner-city children with asthma persists despite guideline-based asthma care. Methods: In a retrospective study that used a cohort of inner-city children with asthma treated by using an asthma-specific disease management system, the patients were stratified into “low” or “high” lung function groups at the time of the initial visit (high, forced expiratory volume in the first second of expiration [FEV1] % predicted and FEV1/forced vital capacity [FVC] ≥ 80%; and low, FEV1% predicted and FEV1/FVC < 80%). These patients then received National Heart, Lung, and Blood Institute guideline‐based asthma treatment at regular follow-up intervals with spirometry performed at these visits as part of regular care. FEV1% predicted and FEV1/FVC were followed up for up to 10 years for both the high and low cohorts. Results: Over 10 years, the patients initially in the “high” group maintained FEV1% predicted and FEV1/FVC at values similar to the initial visit (94 to 96% and 87 to 89%, respectively), whereas those in the low group had only slight increases of FEV1% predicted and FEV1/FVC over the same time (77 to 82% and 78 to 82%, respectively). Low FEV1% predicted and FEV1/FVC at the time of the first visit was significantly associated with an increased risk of low values of these lung functions over the next 3‐5 years despite treatment. African American ethnicity and male gender were also associated with lower lung function over time. Conclusion: Early airflow obstruction in inner city children asthma is associated with poor lung function in later life despite guideline-based asthma care. Current asthma therapy may not affect pathways and leads to airway remodeling in children with asthma.

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