Materiały źródłowe

• #1 Pediatric Asthma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551631/

  Pediatric asthma is characterized by variable expiratory airway limitation and persistent respiratory symptoms, including wheezing, coughing, shortness of breath, and chest tightness. […] Asthma often starts in childhood, with nearly half of all infants wheezing in their first year, and most developing persistent asthma by age 6. A complex interplay between genetic predisposition and environmental factors underscores its prevalence and severity. Additionally, patients commonly experience airway hyperresponsiveness and inflammation. […] The key to the development of clinical asthma lies in the activation of mast cells by cytokines and other mediators. Following initial allergen inhalation, affected patients exhibit an overexpression of the T-helper 2 subset (Th2) of lymphocytes relative to the Th1 type, leading to the production of specific IgE antibodies. The cytokines, including IL-4, IL-5, and IL-13, produced by Th2 lymphocytes promote IgE and eosinophilic responses in atopy.

• #2 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Asthma is a common chronic disease worldwide and affects approximately 25 million persons in the United States. It is the most common chronic disease in childhood, affecting an estimated 6 million US children. The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present.

• #3 Childhood asthma: pathogenesis and phenotypes – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34711541/

  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 and tobacco smoke exposure) influence the development of wheezing illness and the risk of 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 personalised treatment options may become available.

• #4 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Asthma is a heterogeneous lung disease with variable phenotypes (clinical presentations) and distinctive endotypes (mechanisms). Over the last decade, considerable efforts have been made to dissect the cellular and molecular mechanisms of asthma. Aberrant T helper type 2 (Th2) inflammation is the most important pathological process for asthma, which is mediated by Th2 cytokines, such as interleukin (IL)-5, IL-4, and IL-13. Approximately 50% of mild-to-moderate asthma and a large portion of severe asthma is induced by Th2-dependent inflammation. Th2-low asthma can be mediated by non-Th2 cytokines, including IL-17 and tumor necrosis factor-α. There is emerging evidence to demonstrate that inflammation-independent processes also contribute to asthma pathogenesis. Protein kinases, adapter protein, microRNAs, ORMDL3, and gasdermin B are newly identified molecules that drive asthma progression, independent of inflammation.

• #5 Pediatric Asthma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1000997-overview

  Chronic inflammation of the airways is associated with increased BHR, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease. […] New insights in the pathogenesis of asthma suggest that lymphocytes play a role. Airway inflammation in asthma may represent a loss of normal balance between two „opposing” populations of T helper (Th) lymphocytes. Two types of Th lymphocytes have been characterized: Th1 and Th2. Th1 cells produce interleukin (IL)-2 and interferon- (IFN-), which are critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines (interleukin-4 [IL-4], IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation.

• #6 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  The pathological mechanisms of asthma are complex, varying in different phenotypes caused by different environmental triggers, ages, obesity, genetic factors, etc. In addition to airway inflammation, there is emerging evidence to suggest that inflammation-independent processes also contribute to asthma pathogenesis. […] Th2 inflammation has two major phases: 1. Sensitization: When allergens enter the low airways, antigen-presenting cells process and present the allergens to Th2 cells, which secret Th2 cytokines, including IL-5, IL-4, and IL-13. 2. Challenge: When the same allergens enter the airways, they bind to IgE, which induces mast cells to release mediators, such as leukotrienes (LTs), histamine, and ILs. In addition, IL-5 facilitates eosinophil production, maturation, and recruitment to the lungs. Eosinophils also release mediators, including major basic protein (MBP), which stimulates mast cells to release histamines and LTs.

• #7 Physiology & Pathophysiology | Childhood Asthma

  https://u.osu.edu/childhoodasthma/physiology-pathophysiology/

  Bronchial hyperresponsiveness […] Fibroblast proliferation […] Epithelial injury […] Airway scarring. […] IL-8 […] Activates neutrophils […] Exaggerates the inflammatory response. […] IL-13 […] Lessens mucociliary clearance […] Boosts fibroblast secretion […] Contributes to bronchoconstriction. […] IL-17 […] Increases neutrophilic inflammation. […] IL-22 […] Triggers airway epithelial cells […] Further innate and adaptive immune responses […] Cytokine release […] Chemotaxis of inflammatory mediators. […] Late Asthmatic Response […] Occurs within 4-8 hours of early response and includes: […] Air trapping/continued bronchoconstriction […] Hyperinflation distal to obstructions […] Increases work of breathing and hypoxemia […] Leads to dyspnea from inability of air to release due to lingering obstruction.

• #8 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  The pathological mechanisms of asthma are complex, varying in different phenotypes caused by different environmental triggers, ages, obesity, genetic factors, etc. In addition to airway inflammation, there is emerging evidence to suggest that inflammation-independent processes also contribute to asthma pathogenesis. […] Th2 inflammation has two major phases: 1. Sensitization: When allergens enter the low airways, antigen-presenting cells process and present the allergens to Th2 cells, which secret Th2 cytokines, including IL-5, IL-4, and IL-13. 2. Challenge: When the same allergens enter the airways, they bind to IgE, which induces mast cells to release mediators, such as leukotrienes (LTs), histamine, and ILs. In addition, IL-5 facilitates eosinophil production, maturation, and recruitment to the lungs. Eosinophils also release mediators, including major basic protein (MBP), which stimulates mast cells to release histamines and LTs.

• #9 Pediatric Asthma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551631/

  Additional allergen inhalation results in the cross-linking of allergen-specific IgE antibodies on the mast cell surface, causing rapid degranulation and release of histamine, prostaglandin D2 (PGD2), and cysteinyl leukotrienes such as LTC4, LTCD4, and LTCE4. […] This process triggers contraction of the airway smooth muscle within minutes and may also stimulate reflex neural pathways. Subsequently, an influx of inflammatory cells, such as monocytes, dendritic cells, neutrophils, T lymphocytes, eosinophils, and basophils, may cause delayed bronchoconstriction 7 hours later. […] Variable narrowing of the airway lumen throughout the tracheobronchial tree results in differing levels of airflow obstruction. Several factors contribute to this narrowing, including the contraction of airway smooth muscle, thickening of the airway wall due to edema, mucus plugging in the airways, and airway remodeling.

• #10 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Recent studies demonstrated that the airway epithelium produces cytokines in response to injury, infection, and pollutants. These epithelial-derived cytokines include thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP, IL-25, and IL-33 activate type 2 innate lymphoid cells (ILC2), which generate Th2 cytokines, such as IL-5 and IL-13 and induce Th2 lung inflammation. […] IL-17 has been proposed to play an important role in Th2-low asthma. Variants in the IL-17 pathway genes may be related to asthma pathology. Higher levels of IL-17 are found in serum, sputum, and bronchoalveolar lavage fluid (BALF) of patients with asthma, which is associated with asthma severity. […] The role of IL-17 cytokines in asthma is still under investigation. IL-17 cytokines may stimulate epithelial cells and fibroblasts to release neutrophil chemoattractants CXCL1/5/8 and granulocyte–macrophage colony-stimulating factor, which recruit neutrophils to the lungs. Furthermore, IL-17A, but not IL-17F, enhances airway smooth muscle contraction, migration, and proliferation, which facilitates airway hyperresponsiveness (AHR) and airway remodeling, key characteristics of asthma. […] However, there is accumulating evidence to suggest that inflammation-independent processes are also associated with asthma progression. For instance, recent studies demonstrate that protein kinases, adapter proteins, and other molecules contribute to asthma pathogenesis.

• #11 Asthma: Pathogenesis and Phenotypes | Thoracic Key

  https://thoracickey.com/asthma-pathogenesis-and-phenotypes/

  The release of epithelial cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), appears to be the key upstream event that initiates type 2 immune responses and the allergic inflammatory environment in asthma. […] The mechanisms of persistent type 2 immune responses in asthma are not well understood. One possibility is that aberrant immune programs become fixed because they are established during critical time windows in early life when the immune system is plastic. […] Current concepts hold that upstream events in the airway epithelium involving master regulators such as IL-33 result in increased activity of type 2 cytokines in the airway, secreted mainly by CD4 + T cells, and driving a cascade of downstream events, including IgE-mediated hypersensitivity, activation of airway epithelial cells, chemoattraction of effector cells (mast cells, eosinophils, and basophils), and remodeling of the epithelium and subepithelial matrix.

• #12 Airway epithelial dysfunction contributes to the pathogenesis of asthma – MedCrave online

  https://medcraveonline.com/JLPRR/airway-epithelial-dysfunction-contributes-to-the-pathogenesis-of-asthma.html

  The structural changes in the airways can be detected by bronchial biopsy histopathology, and non-invasively by computed tomography (CT) as thickening of the airway wall, increase in wall area (WA), and WA%, and is accompanied by greater centrilobular air trapping compared with health controls. The lung structural changes contribute to the severity of asthma, and correlates with lung function abnormalities. Airways remodeling is due to immune responses orchestrated by pro-fibrotic cytokines, such as interleukin-13 (IL-13), IL-25, IL-33, and TSLP secreted by Th2 cells, ILC2, eosinophils, basophils, mast cells, and also by epithelial cells. Epithelial injury in asthmatic patients promotes increased release of growth factors secreted by immune and structural cells, such as TGF-1, which plays an important role in airway remodeling.

• #13 Airway epithelial dysfunction contributes to the pathogenesis of asthma – MedCrave online

  https://medcraveonline.com/JLPRR/airway-epithelial-dysfunction-contributes-to-the-pathogenesis-of-asthma.html

  Airway epithelial dysfunction contributes to the pathogenesis of asthma. Asthma is a significant public health problem, affecting more than 358 million individuals globally, and it is the most common chronic inflammatory respiratory disease in children. There are several distinct immunopathological pathways, and many immune and structural cells in the airways involved in the pathophysiology of asthma. The roles of type 2 T helper cells (Th2), innate lymphoid cells group 2 (ILC2), dendritic cells, mast cells, and eosinophils are well established in the pathogenesis of asthma. However, the part played by structural cell such as the epithelial sentinel cells is not fully understood. […] Airway dysfunction plays a central role in sensitization to allergens and pathogenesis of asthma. Epithelial damage occur in all phenotypes of asthma, and in childhood asthma, suggesting that epithelial dysfunction occurs early in the pathogenesis of the disease. Impaired epithelial barrier function renders the airway vulnerable to early life virus infections, which prime immature dendritic cells (DCs) toward directing Th2 responses, and local allergen sensitization. Dysfunctional airway epithelium is susceptible to environmental insults, such as increased permeability to allergen proteases, viral infections, chemical irritants, and pollutants. It exhibits impaired repair responses which contribute to persistent asthma. Continued airway injury and repair lead to increase in deposition of extracellular matrix (ECM) proteins, such as collagens, laminin, lumican, fibronectin, and tenascin in the epithelial lamina reticularis. This promotes subepithelial fibrosis, thickening and non-compliant airway wall, and fixed airflow obstruction.

• #14 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma. […] The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present.

• #15 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma. […] The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present.

• #16 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease.

• #17 Bronchial Asthma: Etiology, Pathophysiology, Diagnosis and Management

  https://austinpublishinggroup.com/pulmonary-respiratory-medicine/fulltext/ajprm-v9-id1085.php

  Bronchial asthma is a chronic inflammatory disease of the respiratory passages, occurring with the participation of mast cells, eosinophils and T-lymphocytes, the release of a large number of inflammatory mediators. […] The main pathophysiological characteristics of asthma are inflammation and airway remodeling, which include goblet cell hyperplasia, subepithelial fibrosis, collagen deposition, mucosal gland, hyperplasia, smooth muscle hypertrophy, and changes in the extracellular matrix. These changes can result in immune system imbalance, eventually leading to airway hyperresponsiveness. […] Long-standing inflammation will damage airways, and induces airway remodelling, entailing subepithelial fibrosis under the basement membrane, smooth muscle hypertrophy, and submucosal gland hyperplasia. This results in intractable asthma, presenting irreversible airflow limitation and persistent airway hyperresponsiveness.

• #18 Asthma: pathophysiology, causes and diagnosis – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/asthma-pathophysiology-causes-and-diagnosis

  If an attack is left untreated, eosinophils, T-helper cells and mast cells migrate into the airways. Excess mucus production caused by goblet cells plug the airway and, together with increased airway tone and airway hyperresponsiveness, this causes the airway to narrow and further exacerbates symptoms. […] There is some evidence to suggest that airway remodelling can occur if asthma is poorly controlled over a period of years. Chronic inflammation causes bronchial smooth muscle hypertrophy, the formation of new vessels and interstitial collagen deposition, which results in persistent airflow obstruction similar to that seen in patients with chronic obstructive pulmonary disease (COPD).

• #19 Airway epithelial dysfunction contributes to the pathogenesis of asthma – MedCrave online

  https://medcraveonline.com/JLPRR/airway-epithelial-dysfunction-contributes-to-the-pathogenesis-of-asthma.html

  Furthermore, defective epithelial repair is characterized by overexpression of epidermal growth factor (EGF) with receptor activation, which correlates with disease severity. The extent of epithelial expression of EGF receptors correlates with immunoreactive CXCL8 (IL-8), a very potent chemoattractant for neutrophils, which is critical in the pathogenesis of neutrophilic asthma. There is clear evidence suggesting that epithelial cells play an active role in inducing structural changes in the airways, also termed as airway remodeling. Airway remodeling is due to complex interaction between the airway epithelium and the underlying mesenchyme, resulting from reactivation of the developmental epithelial-mesenchymal transition unit (EMTU), which is responsible for lung morphogenesis during fetal life.

• #20 The Immunopathogenesis of Asthma | Thoracic Key

  https://thoracickey.com/the-immunopathogenesis-of-asthma/

  It had been proposed that repeated cycles of inflammation resulting from allergen exposure resulted in the development of structural airway changes, however, experiments using a neonatal mouse model and findings from cross-sectional studies that have investigated asthma pathology in children have shown that the key pathophysiological changes of allergic asthma (airway hyperresponsiveness, eosinophilic inflammation, and airway remodeling) develop in parallel. […] The airway structural cells are not just altered in quantity in asthma, but they are immunologically active and have a fundamentally altered functional phenotype which contributes to asthma pathogenesis as well.

• #21 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Recent studies demonstrated that the airway epithelium produces cytokines in response to injury, infection, and pollutants. These epithelial-derived cytokines include thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP, IL-25, and IL-33 activate type 2 innate lymphoid cells (ILC2), which generate Th2 cytokines, such as IL-5 and IL-13 and induce Th2 lung inflammation. […] IL-17 has been proposed to play an important role in Th2-low asthma. Variants in the IL-17 pathway genes may be related to asthma pathology. Higher levels of IL-17 are found in serum, sputum, and bronchoalveolar lavage fluid (BALF) of patients with asthma, which is associated with asthma severity. […] The role of IL-17 cytokines in asthma is still under investigation. IL-17 cytokines may stimulate epithelial cells and fibroblasts to release neutrophil chemoattractants CXCL1/5/8 and granulocyte–macrophage colony-stimulating factor, which recruit neutrophils to the lungs. Furthermore, IL-17A, but not IL-17F, enhances airway smooth muscle contraction, migration, and proliferation, which facilitates airway hyperresponsiveness (AHR) and airway remodeling, key characteristics of asthma. […] However, there is accumulating evidence to suggest that inflammation-independent processes are also associated with asthma progression. For instance, recent studies demonstrate that protein kinases, adapter proteins, and other molecules contribute to asthma pathogenesis.

• #22 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Asthma is a heterogeneous lung disease with variable phenotypes (clinical presentations) and distinctive endotypes (mechanisms). Over the last decade, considerable efforts have been made to dissect the cellular and molecular mechanisms of asthma. Aberrant T helper type 2 (Th2) inflammation is the most important pathological process for asthma, which is mediated by Th2 cytokines, such as interleukin (IL)-5, IL-4, and IL-13. Approximately 50% of mild-to-moderate asthma and a large portion of severe asthma is induced by Th2-dependent inflammation. Th2-low asthma can be mediated by non-Th2 cytokines, including IL-17 and tumor necrosis factor-α. There is emerging evidence to demonstrate that inflammation-independent processes also contribute to asthma pathogenesis. Protein kinases, adapter protein, microRNAs, ORMDL3, and gasdermin B are newly identified molecules that drive asthma progression, independent of inflammation.

• #23 Common Childhood Asthma Not Rooted in Allergens, Inflammation | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/common-childhood-asthma-not-rooted-allergens-inflammation

  Little is known about why asthma develops, how it constricts the airway, or why response to treatments varies among patients. […] Their report, in Science Translational Medicine, reveals that an overactive gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body. […] Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma. […] What makes this pathway unique, investigators say, is that it is not related to allergens and has nothing to do with inflammation. […] Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis, says the studys senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

• #24 Common Childhood Asthma Not Rooted in Allergens, Inflammation | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/common-childhood-asthma-not-rooted-allergens-inflammation

  Little is known about why asthma develops, how it constricts the airway, or why response to treatments varies among patients. […] Their report, in Science Translational Medicine, reveals that an overactive gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body. […] Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma. […] What makes this pathway unique, investigators say, is that it is not related to allergens and has nothing to do with inflammation. […] Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis, says the studys senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

• #25 Airway Remodeling Creates Susceptibility to Frequent Asthma Exacerbations in Children – Research Horizons

  https://scienceblog.cincinnatichildrens.org/airway-remodeling-creates-susceptibility-to-frequent-asthma-exacerbations-in-children/

  Asthma is a common allergic respiratory disease found in both children and adults. Yet the mechanisms underlying asthma pathogenesis and exacerbation frequency have been understudied, despite the high healthcare costs and morbidity rates associated with frequent asthma exacerbators in both populations. […] In a study led by first author Kieran Phelan and senior author Gurjit “Neeru” Khurana Hershey, MD, PhD, researchers for the first time implicated the nervous system as having a role in recurrent exacerbation pathology in children with asthma. […] Among their findings, researchers discovered that FEs displayed a unique increase in gene signatures associated with nervous system processes, while the airways of non-FEs were characterized by the expression of allergic inflammation previously known to be involved in asthma.

• #26 Airway Remodeling Creates Susceptibility to Frequent Asthma Exacerbations in Children – Research Horizons

  https://scienceblog.cincinnatichildrens.org/airway-remodeling-creates-susceptibility-to-frequent-asthma-exacerbations-in-children/

  The study’s results suggest that more frequent asthma exacerbations don’t lead to more severe exacerbations. Instead, repeated exacerbations result in neuronal airway remodeling that prime it to react the same way it has in the past. […] “Our findings highlight fundamental differences in these exacerbations and suggest that therapy targeting neuronal pathways may be necessary to adequately prevent and/or treat frequent exacerbations,” Khurana Hershey says.

• #27 Childhood asthma phenotypes and endotypes: a glance into the mosaic | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00159-1

  Asthma is an inflammatory lung disease that constitutes the most common noncommunicable chronic disease in childhood. Childhood asthma shows large heterogeneity regarding onset of disease, symptoms, severity, prognosis, and response to therapy. […] Evidence suggests that this variability is due to distinct pathophysiological mechanisms, which has led to an exhaustive research effort to understand and characterize these distinct entities currently designated as endotypes. […] This has resulted in many studies aiming at disentangling this heterogeneity using different and novel strategies. […] The heterogeneity in childhood asthma is due to different pathological mechanisms originating from the complex interplay between genetic, epigenetic, and environmental factors. […] Genetics also plays an important role in childhood asthma, where family history of asthma remains one of the most important risk factors.

• #28 Physiology & Pathophysiology | Childhood Asthma

  https://u.osu.edu/childhoodasthma/physiology-pathophysiology/

  Chronic obstructive pulmonary disorder of the bronchial mucosa […] Episodes of bronchospasm and inflammation in the bronchial airways. […] Familial disease […] 100 genes identified as playing a role in the development. […] Early Asthmatic Responses […] IgE is activated, leading to: […] Degranulation of mast cells; […] Release of inflammatory mediators. […] IgE release causes: […] Vasodilation; […] Bronchospasm; […] Mucosal edema; […] Increased capillary permeability; […] Tenacious mucous secretions. […] Early Asthmatic Response: Immune Response Stimulation […] Dendritic cells […] Activated by antigen exposure to the bronchial mucosa […] Present antigen to CD4+ T cells. […] IL-4 […] B-cell activation […] Production of IgE. […] IL-5 […] Activation of eosinophils

• #29 Childhood asthma phenotypes and endotypes: a glance into the mosaic | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00159-1

  Noteworthy is the 17q12-21 locus, which has been replicated several times and is associated with early-onset asthma in childhood. […] The most common and best-described endotype is the T2-high (eosinophilic), which is also present in the adult population. This endotype has been described in children with mild, moderate, and severe asthma and is characterized by a high degree of atopy, increased eosinophils (in sputum and serum), high levels of T2 cytokines (IL-4, IL-5, and IL-13), and early signs of airway remodeling. […] The neutrophilic inflammatory endotype has been identified in children with STRA and is characterized by neutrophilic infiltration of the airways, where a Th1 or/and Th17 skewed immune profile has been implicated. […] In summary, different inflammatory endotypes have been described, and their detailed characterization may direct research towards new therapeutics and contribute to an adequate evidence-based selection of the best treatment for specific groups of asthmatic children.

• #30 🇬🇧 Breakthrough in molecular mechanisms of childhood asthma » Luxembourg Institute of Health

  https://www.lih.lu/en/event/breakthrough-in-molecular-mechanisms-of-childhood-asthma/

  Airway diseases are still among the top 5 common causes of death and represent a major healthcare problem. Asthma is chronic obstructive disease that develops in some children in the very early life. Massive genotyping was conducted to identify risk alleles, but only revealed hits with n-numbers beyond thousands. One locus that stands out is the 17q21 locus carrying 9 genes. These genes are not specifically related to the immune system and their implication in asthma pathogenesis has been subject to many speculations. […] In the clinic it was observed that 17q21 children are initially suffering from viral infections. […] Surprisingly, the gene expression analysis revealed a clear picture, identifying GSDMB as the key gene, that is related to a downstream inflammatory cascade. In the presentation a pathogenesis pathway will be illustrated representing a first causative asthma model on a genetic risk allele.

• #31 Airway epithelial dysfunction contributes to the pathogenesis of asthma – MedCrave online

  https://medcraveonline.com/JLPRR/airway-epithelial-dysfunction-contributes-to-the-pathogenesis-of-asthma.html

  Genetic and environmental factors play an important role in the pathogenesis of asthma. Environmental factors, such as allergens, microbacteria and viruses, irritant chemicals, pollutants, and environmental tobacco smoke interact with genes through epigenetic mechanisms that influence gene expression. The interaction between the airway epithelium and the underlying mesenchyme plays a central role in the pathophysiology of airway remodeling and pathogenesis of different phenotypes of asthma. There are several genes associated with asthma susceptibility expressed in the airway epithelium and the underlying mesenchyme. This indicates that responses at airway epithelial surface, and lung may play an important role in the pathogenesis of the disease. […] Notably, a few epithelial genes are shared among asthmatics, such as IL-33, and TSLP, indicating that alarmin cytokines play a central role in the pathogenesis of asthma. Furthermore, the expression of IL33 and TSLP are both elevated in the airways of patients with severe refractory asthma. The airway epithelium is the first cell layer of contact with environmental insults, such as allergens, microbes, viruses, chemical irritants, and pollutants. Dysfunctional airway epithelium orchestrate the inflammatory responses, and remodeling in patient with asthma. The epithelium is a suitable therapeutic target for discovery and development of new biologics, and therapeutic interventions for the treatment of severe uncontrolled asthma.

• #32 Childhood asthma: causes, risks, and protective factors; a role of innate immunity

  https://smw.ch/index.php/smw/article/download/1952/2784?inline=1

  Childhood asthma is an umbrella of multifactorial diseases with similar clinical features such as mast cell and eosinophil infiltration causing airway hyper responsiveness, inflammation, and airway obstruction. There are various factors that are implicated in childhood asthma pathogenesis. A combined contribution of genetic predisposition, environmental insults, and epigenetic changes account for polarisation of the immune system towards T helper (Th) type 2 cell responses that include production of pro-inflammatory cytokines, IgE, and eosinophil infiltrates, shown to associate with asthma. […] The pathogenetic sources of asthma remain unknown and although genetic, environmental, and epigenetic factors have been identified, an effective therapeutic intervention is yet to be established. […] A number of diverse factors have been implicated in asthma pathogenesis in children. These include genetic predisposition (asthmatic parents), environmental stimuli during prenatal and early childhood that include allergens (mite, cat, dog, grass, pollen, and mould), maternal infection and smoking during pregnancy, environmental tobacco smoke, mode of birth delivery (i.e., Casearean section), viral respiratory illnesses, obesity, diet, hygiene, and toxic exposures.

• #33

  https://journals.lww.com/pidj/fulltext/2003/02001/respiratory_syncytial_virus_bronchiolitis_and_the.11.aspx

  There is now convincing evidence that children who develop lower respiratory symptoms during infection with respiratory syncytial virus (RSV) in early life are at increased risk of developing asthma-like symptoms during the school years. […] Current evidence suggests that both genetic and environmental factors determine the type of immune response to the acute RSV infection and that this response, in turn, may affect the development of the control mechanisms involved in the regulation of airway tone. […] Despite these consistent characteristics, the mechanisms by which the pathogenesis of pediatric asthma evolves, in particular in association with certain predisposing factors to its development, such as RSV disease, require further elucidation. […] It has been proposed that in a genetically susceptible individual, the cytokine response to virus infection with high gene expression of interleukin (IL)-4 and IL-5, accompanied by low gene expression of IL-2 and interferon-gamma (IFN-gamma), may contribute to increased airway inflammation, pulmonary function deficits and influence long term outcomes, including postbronchiolitic wheezing and asthma.

• #34 The Role and Potential Pathogenic Mechanism of Particulate Matter in Childhood Asthma: A Review and Perspective. – Document – Gale Academic OneFile

  https://go.gale.com/ps/i.do?id=GALE%7CA619215437&sid=googleScholar&v=2.1&it=r&linkaccess=fulltext&issn=23148861&p=AONE&sw=w

  Asthma, the most common chronic respiratory disease in children, affects numerous people worldwide. Accumulating evidence suggests that exposure to high levels of particulate matter (PM), either acutely or chronically, is associated with the exacerbation and incidence of pediatric asthma. However, the detailed pathogenic mechanisms by which PM contributes to the incidence of asthma remain largely unknown. […] In this short review, we summarize studies of relationships between PM and pediatric asthma and recent advances on the fundamental mechanisms of PM-related asthma, with emphases on cell death regulation and immune system responses. […] We further discuss the inadequacy of current studies and give a perspective on the prevention strategies for pediatric asthma.

• #35 Asthma: Pathogenesis and Phenotypes | Thoracic Key

  https://thoracickey.com/asthma-pathogenesis-and-phenotypes/

  One compelling hypothesis for the cause of the increase in asthma and allergies in Westernized countries is the hygiene hypothesis. This holds that the rise in allergies in children is an unintended consequence of the success of domestic hygiene in reducing the rate of infections or exposure to bacterial products in early childhood. […] One potential link between changes in hygiene and allergic disease is the effect that improved hygiene may have on our indigenous microbiota and the role this microbiota may play in shaping our immune system. […] In parallel with, and distinct from, the emergence of the Hygiene Hypothesis, there has been significant progress in documenting and understanding the role that viral respiratory tract infections play in the development of asthma. […] An accepted view now is that environmental stimuli in early childhood activate airway epithelial cells to initiate allergic airway responses and asthma in children who are susceptible because they have preexisting atopy, specific genetic risk factors, and other less well-understood vulnerabilities.

• #36 Asthma: Pathogenesis and Phenotypes | Thoracic Key

  https://thoracickey.com/asthma-pathogenesis-and-phenotypes/

  One compelling hypothesis for the cause of the increase in asthma and allergies in Westernized countries is the hygiene hypothesis. This holds that the rise in allergies in children is an unintended consequence of the success of domestic hygiene in reducing the rate of infections or exposure to bacterial products in early childhood. […] One potential link between changes in hygiene and allergic disease is the effect that improved hygiene may have on our indigenous microbiota and the role this microbiota may play in shaping our immune system. […] In parallel with, and distinct from, the emergence of the Hygiene Hypothesis, there has been significant progress in documenting and understanding the role that viral respiratory tract infections play in the development of asthma. […] An accepted view now is that environmental stimuli in early childhood activate airway epithelial cells to initiate allergic airway responses and asthma in children who are susceptible because they have preexisting atopy, specific genetic risk factors, and other less well-understood vulnerabilities.

• #37 The Microbiome and the Pathophysiology of Asthma | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-016-0479-4

  The so-called hygiene hypothesis contends that exposure to soil, dust, microbes, antibiotics, vaccinations, farm animals and family size in addition to factors such as caesarean section birth versus vaginal birth and exclusive formula feeding versus breastfeeding can all in some part determine asthma risk. […] It is believed that microaspiration, which occurs in healthy individuals but has a higher prevalence in asthmatics, could in part explain the presence of oral microbiota in the lower lung. […] The disappearing microbiota hypothesis contends that as we become less colonised by ancient commensal microorganisms, which aid in a multitude of processes such as vitamin uptake and immunity, we become more susceptible to attack by potential pathogenic microorganisms. […] There is an emerging consensus that the microbiome potentially plays a critical role in disease development, including in the pathogenesis of airway conditions such as asthma.

• #38 The Microbiome and the Pathophysiology of Asthma | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-016-0479-4

  The so-called hygiene hypothesis contends that exposure to soil, dust, microbes, antibiotics, vaccinations, farm animals and family size in addition to factors such as caesarean section birth versus vaginal birth and exclusive formula feeding versus breastfeeding can all in some part determine asthma risk. […] It is believed that microaspiration, which occurs in healthy individuals but has a higher prevalence in asthmatics, could in part explain the presence of oral microbiota in the lower lung. […] The disappearing microbiota hypothesis contends that as we become less colonised by ancient commensal microorganisms, which aid in a multitude of processes such as vitamin uptake and immunity, we become more susceptible to attack by potential pathogenic microorganisms. […] There is an emerging consensus that the microbiome potentially plays a critical role in disease development, including in the pathogenesis of airway conditions such as asthma.

• #39 Childhood asthma: pathogenesis and phenotypes – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34711541/

  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 and tobacco smoke exposure) influence the development of wheezing illness and the risk of 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 personalised treatment options may become available.

• #40 Dynamics of the upper airway microbiome in the pathogenesis of asthma-associated persistent wheeze in preschool children | bioRxiv

  https://www.biorxiv.org/content/10.1101/222190v1.full

  Repeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. […] This suggests underlying pathogenic interactions between allergic sensitization and antibacterial mechanisms. […] Understanding patterns of airway microbial colonization and its association with ARIs and subsequent wheeze phenotypes is an important first step towards the potential manipulation of the microbiome in treating or preventing acute or chronic respiratory disease. […] Our longitudinal data show the NPM can be highly dynamic within individuals. […] Throughout the first five years of life, NPM samples collected during ARIs showed a greater abundance of, and were more commonly dominated by, specific Streptococcus, Moraxella and Haemophilus OTUs, consistent with expectations regarding common respiratory pathogens S. pneumoniae, M. catarrhalis and H. influenzae to which these OTU sequences were most closely related.

• #41 Childhood asthma phenotypes and endotypes: a glance into the mosaic | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00159-1

  Asthma is an inflammatory lung disease that constitutes the most common noncommunicable chronic disease in childhood. Childhood asthma shows large heterogeneity regarding onset of disease, symptoms, severity, prognosis, and response to therapy. […] Evidence suggests that this variability is due to distinct pathophysiological mechanisms, which has led to an exhaustive research effort to understand and characterize these distinct entities currently designated as endotypes. […] This has resulted in many studies aiming at disentangling this heterogeneity using different and novel strategies. […] The heterogeneity in childhood asthma is due to different pathological mechanisms originating from the complex interplay between genetic, epigenetic, and environmental factors. […] Genetics also plays an important role in childhood asthma, where family history of asthma remains one of the most important risk factors.

• #42 Childhood asthma phenotypes and endotypes: a glance into the mosaic | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00159-1

  Noteworthy is the 17q12-21 locus, which has been replicated several times and is associated with early-onset asthma in childhood. […] The most common and best-described endotype is the T2-high (eosinophilic), which is also present in the adult population. This endotype has been described in children with mild, moderate, and severe asthma and is characterized by a high degree of atopy, increased eosinophils (in sputum and serum), high levels of T2 cytokines (IL-4, IL-5, and IL-13), and early signs of airway remodeling. […] The neutrophilic inflammatory endotype has been identified in children with STRA and is characterized by neutrophilic infiltration of the airways, where a Th1 or/and Th17 skewed immune profile has been implicated. […] In summary, different inflammatory endotypes have been described, and their detailed characterization may direct research towards new therapeutics and contribute to an adequate evidence-based selection of the best treatment for specific groups of asthmatic children.

• #43 The Immunopathogenesis of Asthma | Thoracic Key

  https://thoracickey.com/the-immunopathogenesis-of-asthma/

  Development of allergic sensitization is a key component of asthma pathogenesis in children. Sensitization may develop to food or aero-allergens and is initiated at mucosal or barrier surfaces where there is an epithelial layer. […] The cytokines and chemokines released following eosinophil degranulation promote longevity of eosinophils in tissues, which leads to the cyclical nature of signaling, activation, and survival. […] IL-5 is released by Th2 cells in asthma and results in the induction and recruitment of eosinophils from the peripheral circulation to the airways. IL-5 also promotes eosinophil differentiation, growth, and survival. […] The predominant airway inflammatory phenotype of pediatric asthma is eosinophilic, and this is independent of disease severity or duration. […] The inflammation is accompanied by the presence of structural airway wall changes, or airway remodeling.

• #44 Childhood asthma phenotypes and endotypes: a glance into the mosaic | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00159-1

  Noteworthy is the 17q12-21 locus, which has been replicated several times and is associated with early-onset asthma in childhood. […] The most common and best-described endotype is the T2-high (eosinophilic), which is also present in the adult population. This endotype has been described in children with mild, moderate, and severe asthma and is characterized by a high degree of atopy, increased eosinophils (in sputum and serum), high levels of T2 cytokines (IL-4, IL-5, and IL-13), and early signs of airway remodeling. […] The neutrophilic inflammatory endotype has been identified in children with STRA and is characterized by neutrophilic infiltration of the airways, where a Th1 or/and Th17 skewed immune profile has been implicated. […] In summary, different inflammatory endotypes have been described, and their detailed characterization may direct research towards new therapeutics and contribute to an adequate evidence-based selection of the best treatment for specific groups of asthmatic children.

• #45 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Recent studies demonstrated that the airway epithelium produces cytokines in response to injury, infection, and pollutants. These epithelial-derived cytokines include thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP, IL-25, and IL-33 activate type 2 innate lymphoid cells (ILC2), which generate Th2 cytokines, such as IL-5 and IL-13 and induce Th2 lung inflammation. […] IL-17 has been proposed to play an important role in Th2-low asthma. Variants in the IL-17 pathway genes may be related to asthma pathology. Higher levels of IL-17 are found in serum, sputum, and bronchoalveolar lavage fluid (BALF) of patients with asthma, which is associated with asthma severity. […] The role of IL-17 cytokines in asthma is still under investigation. IL-17 cytokines may stimulate epithelial cells and fibroblasts to release neutrophil chemoattractants CXCL1/5/8 and granulocyte–macrophage colony-stimulating factor, which recruit neutrophils to the lungs. Furthermore, IL-17A, but not IL-17F, enhances airway smooth muscle contraction, migration, and proliferation, which facilitates airway hyperresponsiveness (AHR) and airway remodeling, key characteristics of asthma. […] However, there is accumulating evidence to suggest that inflammation-independent processes are also associated with asthma progression. For instance, recent studies demonstrate that protein kinases, adapter proteins, and other molecules contribute to asthma pathogenesis.

• #46 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Recent studies demonstrated that the airway epithelium produces cytokines in response to injury, infection, and pollutants. These epithelial-derived cytokines include thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP, IL-25, and IL-33 activate type 2 innate lymphoid cells (ILC2), which generate Th2 cytokines, such as IL-5 and IL-13 and induce Th2 lung inflammation. […] IL-17 has been proposed to play an important role in Th2-low asthma. Variants in the IL-17 pathway genes may be related to asthma pathology. Higher levels of IL-17 are found in serum, sputum, and bronchoalveolar lavage fluid (BALF) of patients with asthma, which is associated with asthma severity. […] The role of IL-17 cytokines in asthma is still under investigation. IL-17 cytokines may stimulate epithelial cells and fibroblasts to release neutrophil chemoattractants CXCL1/5/8 and granulocyte–macrophage colony-stimulating factor, which recruit neutrophils to the lungs. Furthermore, IL-17A, but not IL-17F, enhances airway smooth muscle contraction, migration, and proliferation, which facilitates airway hyperresponsiveness (AHR) and airway remodeling, key characteristics of asthma. […] However, there is accumulating evidence to suggest that inflammation-independent processes are also associated with asthma progression. For instance, recent studies demonstrate that protein kinases, adapter proteins, and other molecules contribute to asthma pathogenesis.

• #47 Editor’s Pick: Sex Differences in Paediatric and Adult Asthma – European Medical Journal

  https://www.emjreviews.com/respiratory/article/editors-pick-sex-differences-in-paediatric-and-adult-asthma/

  Asthma is the most common chronic condition in Western countries. Affecting 1 in 7 children and 1 in 12 adults, asthma is responsible for 350,000 avoidable deaths every year. […] While boys are more likely to develop asthma than girls, this pattern is reversed after puberty. This indicates that sex-specific factors, such as fluctuations in hormone levels, play a role in the diseases pathogenesis. […] The review will show that both experimental and epidemiological evidence suggest that circulating sex hormone levels are important contributors to asthma symptoms in post-pubertal females, while their role in males and children has not been yet established. In addition, the mechanisms associated with these hormonal influences on airway inflammation and hyper-reactivity have not been yet elucidated.

• #48 Editor’s Pick: Sex Differences in Paediatric and Adult Asthma – European Medical Journal

  https://www.emjreviews.com/respiratory/article/editors-pick-sex-differences-in-paediatric-and-adult-asthma/

  The pathogenesis of the disease involves a number of mechanisms in different cell types, most of which remain understudied. Inflammation is a key component of asthma and involves early and late phase responses, which are characterised by the recruitment of specific immune cells. […] The observed sex differences of asthma incidence in children 18 years of age in the USA (9.2% in boys versus 7.2% in girls) and in adults (6.2% in men versus 10.4% in women) suggest that hormonal changes occurring during puberty may contribute to the increased incidence in adult women. […] Studies in animal models have suggested the involvement of sex hormones in mechanisms of lung inflammation and asthma. […] Together, these studies indicate that changes in oestrogen and androgen circulating levels might be the reason why asthma is more prevalent in females after reaching puberty. […] Overall, ovarian hormones have been found to increase, and testosterone to decrease, airway inflammation in asthma, but the mechanisms remain unclear. […] Despite this evidence, the specific mechanisms of action for sex hormones to promote or prevent asthma remain unclear.

• #49 Editor’s Pick: Sex Differences in Paediatric and Adult Asthma – European Medical Journal

  https://www.emjreviews.com/respiratory/article/editors-pick-sex-differences-in-paediatric-and-adult-asthma/

  The pathogenesis of the disease involves a number of mechanisms in different cell types, most of which remain understudied. Inflammation is a key component of asthma and involves early and late phase responses, which are characterised by the recruitment of specific immune cells. […] The observed sex differences of asthma incidence in children 18 years of age in the USA (9.2% in boys versus 7.2% in girls) and in adults (6.2% in men versus 10.4% in women) suggest that hormonal changes occurring during puberty may contribute to the increased incidence in adult women. […] Studies in animal models have suggested the involvement of sex hormones in mechanisms of lung inflammation and asthma. […] Together, these studies indicate that changes in oestrogen and androgen circulating levels might be the reason why asthma is more prevalent in females after reaching puberty. […] Overall, ovarian hormones have been found to increase, and testosterone to decrease, airway inflammation in asthma, but the mechanisms remain unclear. […] Despite this evidence, the specific mechanisms of action for sex hormones to promote or prevent asthma remain unclear.

• #50 The Immunopathogenesis of Asthma | Thoracic Key

  https://thoracickey.com/the-immunopathogenesis-of-asthma/

  Development of allergic sensitization is a key component of asthma pathogenesis in children. Sensitization may develop to food or aero-allergens and is initiated at mucosal or barrier surfaces where there is an epithelial layer. […] The cytokines and chemokines released following eosinophil degranulation promote longevity of eosinophils in tissues, which leads to the cyclical nature of signaling, activation, and survival. […] IL-5 is released by Th2 cells in asthma and results in the induction and recruitment of eosinophils from the peripheral circulation to the airways. IL-5 also promotes eosinophil differentiation, growth, and survival. […] The predominant airway inflammatory phenotype of pediatric asthma is eosinophilic, and this is independent of disease severity or duration. […] The inflammation is accompanied by the presence of structural airway wall changes, or airway remodeling.

• #51 Asthma: Pathogenesis and Phenotypes | Thoracic Key

  https://thoracickey.com/asthma-pathogenesis-and-phenotypes/

  Asthma is a common disease whose prevalence has increased throughout the world for several decades. More recently, studies of the epidemiology, natural history, and pathogenesis have clearly demonstrated that asthma is a heterogeneous disease, with multiple etiologies and contributing cofactors, complex pathobiologic mechanisms, and different molecular phenotypes. Understanding these differences is critical for developing therapeutic strategies that will be effective for the various phenotypes of asthma. […] The strongest risk factor for asthma is a family history of atopy. This increases the risk of developing allergic rhinitis by fivefold and the risk of asthma by threefold to fourfold. In children 3 to 14 years old, both positive skin tests and increases in total serum IgE are strongly associated with asthma. Serum IgE also correlates strongly with bronchial hyperresponsiveness.

• #52 Asthma – Diagnosis – Management – Attacks – TeachMePaediatrics

  https://teachmepaediatrics.com/respiratory/lower-respiratory-tract/asthma/

  Asthma is a multi-factorial disease in which susceptible individuals have an exaggerated response to various stimuli. The disease process is driven by as vast array of mediators that lead to airway obstruction, and in more severe disease, airway remodelling. […] Classical allergic asthma is driven by Th2 type T-cells. Allergens are presented to these cells by dendritic cells, which in these individuals leads to a disproportionate immune response. […] The Th2 cells are activated by dendritic cells, and cytokines released from them result in the activation of the humoral immune system, with an increased proliferation of mast cells, eosinophils and dendritic cells as a result. […] In turn, cytokines released by these cell contribute to the underlying inflammatory process and bronchoconstriction. One particular example of this is leukotriene C4, which is directly toxic to epithelial cells. Other mediators further exacerbate the situation by favouring the production of an exudate, such as the histamine released from mast cells.

• #53 The role of regulatory B cells in immune regulation and childhood allergic asthma | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00174-2

  As the most common chronic disease in childhood, asthma displays a major public health problem worldwide with the incidence of those affected rising. As there is currently no cure for allergic asthma, it is mandatory to get a better understanding of the underlying molecular mechanism. […] By producing IgE antibodies upon allergen contact, B cells play a pivotal role in allergic asthma. Besides that, IL-10-secreting B cell subsets, namely regulatory B cells (Bregs), are reported in mice and humans to play a role in allergic asthma. […] Knowledge about the exact function of human Bregs in allergic asthma is still very limited. This review aims to summarize the current knowledge on Bregs. We discuss different human Breg subsets, several ways of Breg induction as well as the mechanisms through which they exert immunoregulatory functions, and their role in (childhood) allergic asthma.

• #54 The role of regulatory B cells in immune regulation and childhood allergic asthma | Molecular and Cellular Pediatrics | Full Text

  https://molcellped.springeropen.com/articles/10.1186/s40348-023-00174-2

  Knowledge about the impact of B cells and Bregs on asthma is still rather limited. IgE production upon allergen contact is the main described role of B cells in allergic asthma, which is mandatory for the initiation of the allergic cascade. […] Allergic asthma is the predominant form of asthma in childhood, which has been characterized by sensitization to specific allergens, high IgE levels, eosinophilia, a type 2 shifted immune response, and decreased innate immunity gene expression. […] Recent research has concentrated on the role of Bregs in allergic asthma. As mentioned above, Bregs express the anti-inflammatory cytokine IL-10, which is thought to have a positive effect on asthma pathophysiology by suppressing the IgE-mediated allergic cascade and decreasing airway inflammation. […] It seems that Bregs are important for both children and adults with allergic asthma and that the appropriate number and function of Bregs may be mandatory to control asthma by releasing suppressive signals to decrease TH2 inflammation.

• #55 Advances in the pathogenesis and personalised treatment of paediatric asthma | BMJ Medicine

  https://bmjmedicine.bmj.com/content/2/1/e000367

  The diversity of pathology of severe paediatric asthma demonstrates that the one-size-fits-all approach characterising many guidelines is inappropriate. […] Advances in the understanding of the underlying pathogenesis and the identification of clinical phenotypes and molecular endotypes has prompted a shift towards personalised treatment for children and young people with asthma. […] Healthcare professionals caring for children and young people with asthma should be aware of how to use objective measurements to make the diagnosis, and the advances in understanding of the pathogenesis of paediatric asthma that are substantially changing the management of asthma. […] The in-depth examination of the airway and identification of traits enables a better understanding of airway inflammation in asthma and identification of coexisting and alternative airway pathologies.

• #56 KLINIK RESPIRASI. Klinik Dokter THT di Malang, Klinik Dokter Paru di Malang, Klinik Jantung di Malang, Klinik Dokter Paru di Surabaya, Klinik Dokter Penyakit Dalam di Malang, Klinik Dokter Gigi di Malang, Klinik Dokter Gigi di Serpong

  https://klinikrespirasimalang.com/news/3538-childhood-asthma–pathogenesis-and-phenotypes

  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. […] 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.

• #57 Advances in the pathogenesis and personalised treatment of paediatric asthma | BMJ Medicine

  https://bmjmedicine.bmj.com/content/2/1/e000367

  However, we now appreciate that „asthma” is an umbrella term comprising many different phenotypes and endotypes, and so The Lancet Commission defined asthma in purely clinical terms with no assumptions about the underlying pathology. […] The absence of these cytokines with persistent eosinophilia in severe, treatment resistant asthma has led to the hypothesis that innate mediators such as IL33, which appear to be relatively steroid resistant, could dominate the immune response in severe, treatment resistant asthma. […] In summary, not all paediatric severe asthma is driven by type 2 inflammation or will respond to anti-IL5 strategies. Critically determining what is driving the airway pathology is key to personalising treatment.

• #58 DUPIXENT® (dupilumab) Mechanism of Action For Asthma

  https://www.dupixenthcp.com/asthma/about/mechanism-of-action

  DUPIXENT is the only dual inhibitor of IL-4 and IL-13 signaling, two of the key drivers of local and systemic type 2 inflammation in asthma. […] The mechanism of dupilumab action has not been definitively established. […] IL-13 is a key source of local type 2 inflammation. When activated, it contributes to epithelial barrier dysfunction, eosinophilic inflammation, mucus overproduction and smooth muscle contraction. […] IL-4 is a key source of systemic type 2 inflammation that causes eosinophil trafficking to the site of inflammation. Eosinophils release eosinophilic cationic protein or ECP, eosinophil peroxidase or EPO, and other chemical mediators that contribute to asthma pathology. […] DUPIXENT binds to the IL-4 receptor blocking IL-4 and IL-13 intracellular signaling. […] DUPIXENT also binds to the IL-13 receptor preventing IL-13 receptor binding with IL-13 as well as complexing of IL-13 receptor with the IL-4 receptor complex. […] IL-4 and IL-13 contribute to multiple systemic inflammatory effects in asthma. […] IL-4 and IL-13 contribute to multiple local inflammatory effects in the bronchial tubes.

• #59 Airway Remodeling Creates Susceptibility to Frequent Asthma Exacerbations in Children – Research Horizons

  https://scienceblog.cincinnatichildrens.org/airway-remodeling-creates-susceptibility-to-frequent-asthma-exacerbations-in-children/

  The study’s results suggest that more frequent asthma exacerbations don’t lead to more severe exacerbations. Instead, repeated exacerbations result in neuronal airway remodeling that prime it to react the same way it has in the past. […] “Our findings highlight fundamental differences in these exacerbations and suggest that therapy targeting neuronal pathways may be necessary to adequately prevent and/or treat frequent exacerbations,” Khurana Hershey says.

• #60 Current Understanding of Asthma Pathogenesis and Biomarkers

  https://www.mdpi.com/2073-4409/11/17/2764

  Recent studies demonstrated that the airway epithelium produces cytokines in response to injury, infection, and pollutants. These epithelial-derived cytokines include thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP, IL-25, and IL-33 activate type 2 innate lymphoid cells (ILC2), which generate Th2 cytokines, such as IL-5 and IL-13 and induce Th2 lung inflammation. […] IL-17 has been proposed to play an important role in Th2-low asthma. Variants in the IL-17 pathway genes may be related to asthma pathology. Higher levels of IL-17 are found in serum, sputum, and bronchoalveolar lavage fluid (BALF) of patients with asthma, which is associated with asthma severity. […] The role of IL-17 cytokines in asthma is still under investigation. IL-17 cytokines may stimulate epithelial cells and fibroblasts to release neutrophil chemoattractants CXCL1/5/8 and granulocyte–macrophage colony-stimulating factor, which recruit neutrophils to the lungs. Furthermore, IL-17A, but not IL-17F, enhances airway smooth muscle contraction, migration, and proliferation, which facilitates airway hyperresponsiveness (AHR) and airway remodeling, key characteristics of asthma. […] However, there is accumulating evidence to suggest that inflammation-independent processes are also associated with asthma progression. For instance, recent studies demonstrate that protein kinases, adapter proteins, and other molecules contribute to asthma pathogenesis.

• #61 Common Childhood Asthma Not Rooted in Allergens, Inflammation | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/common-childhood-asthma-not-rooted-allergens-inflammation

  Little is known about why asthma develops, how it constricts the airway, or why response to treatments varies among patients. […] Their report, in Science Translational Medicine, reveals that an overactive gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body. […] Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma. […] What makes this pathway unique, investigators say, is that it is not related to allergens and has nothing to do with inflammation. […] Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis, says the studys senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

• #62 Asthma | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201525

  Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by a combination of inflammation and structural remodelling that might begin in utero. Disease progression occurs in the context of a developmental background in which the postnatal acquisition of asthma is strongly linked with allergic sensitization. Most asthma cases follow a variable course, involving viral-induced wheezing and allergen sensitization, that is associated with various underlying mechanisms (or endotypes) that can differ between individuals. Each set of endotypes, in turn, produces specific asthma characteristics that evolve across the lifecourse of the patient. Strong genetic and environmental drivers of asthma interconnect through novel epigenetic mechanisms that operate prenatally and throughout childhood. Asthma can spontaneously remit or begin de novo in adulthood, and the factors that lead to the emergence and regression of asthma, irrespective of age, are poorly understood. Nonetheless, there is mounting evidence that supports a primary role for structural changes in the airways with asthma acquisition, on which altered innate immune mechanisms and microbiota interactions are superimposed. On the basis of the identification of new causative pathways, the subphenotyping of asthma across the lifecourse of patients is paving the way for more-personalized and precise pathway-specific approaches for the prevention and treatment of asthma, creating the real possibility of total prevention and cure for this chronic inflammatory disease.

• #63 Possible molecular mechanisms linking air pollution and asthma in children | BMC Pulmonary Medicine | Full Text

  https://bmcpulmmed.biomedcentral.com/articles/10.1186/1471-2466-14-31

  Air pollution has many negative effects on pediatric health and it is recognised as a serious health hazard. There seems to be an association of air pollution with an increased risk of asthma exacerbations and acute respiratory infections. […] However, further studies are needed in order to clarify the specific mechanism of action of different air pollutants, identify genetic polymorphisms that modify airway responses to pollution, and investigate the effectiveness of new preventive and/or therapeutic approaches for subjects with low antioxidant enzyme levels. […] Moreover, as that epigenetic changes are inheritable during cell division and may be transmitted to subsequent generations, it is very important to clarify the role of epigenetics in the relationship between air pollution and lung disease in asthmatic and healthy children.

Zobacz więcej