Pathogenesis, clinical features of asthma COPD overlap, and therapeutic modalities

AJP Lung Cellular and Molecular Physiology, Journal Year: 2021, Volume and Issue: 322(1), P. L64 - L83

Published: Oct. 25, 2021

Both asthma and COPD are heterogeneous diseases identified by characteristic symptoms functional abnormalities, with airway obstruction common in both diseases. Asthma overlap (ACO) does not define a single disease but is descriptive term for clinical use that includes several overlapping phenotypes of chronic airways different underlying mechanisms. This literature review was initiated to describe published studies, identify gaps knowledge, propose future research goals regarding the pathology ACO, especially remodeling changes inflammation aspects. Airway occurs COPD, there differences structures affected prime anatomic site at which they occur. Reticular basement membrane thickening cellular infiltration eosinophils T-helper (CD4+) lymphocytes prominent features asthma. Epithelial squamous metaplasia, wall fibrosis, emphysema, bronchoalveolar lavage (BAL) neutrophilia, (CD8+) T-cytotoxic lymphocyte infiltrations COPD. There no universally accepted definition nor clearly defined pathological characteristics differentiate from Understanding etiological concepts within purview ACO would allow better management these patients.

Language: Английский

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Mouse models of atopic dermatitis: a critical reappraisal

Experimental Dermatology, Journal Year: 2020, Volume and Issue: 30(3), P. 319 - 336

Published: Dec. 24, 2020

Abstract Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool testing new candidate AD therapeutics and interrogating pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so‐called “AD” mouse satisfactorily reflect clinical complexity human AD, but imitate more “allergic” or “irriant” contact conditions. This limits predictive value outcomes tested instructiveness pathophysiology research. Here, propose to initiate a rational debate on minimal criteria that model should meet order be considered relevant AD. We suggest valid at least following criteria: (a) AD‐like epidermal barrier defect with reduced filaggrin expression along hyperproliferation, hyperplasia; (b) increased thymic stromal lymphopoietin (TSLP), periostin and/or chemokines such as TARC (CCL17); (c) characteristic dermal immune cell infiltrate overexpression some key cytokines IL‐4, IL‐13, IL‐31 IL‐33; (d) distinctive “neurodermatitis” features (sensory skin hyperinnervation, defective beta‐adrenergic signalling, neurogenic inflammation triggering aggravation lesions by perceived stress); (e) response experimentally induced standard therapy. Finally, why humanized (human xenotransplants SCID mice) offer particularly promising alternative models.

Language: Английский

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Eosinophilic esophagitis: Immune mechanisms and therapeutic targets

Clinical & Experimental Allergy, Journal Year: 2022, Volume and Issue: 52(10), P. 1142 - 1156

Published: July 2, 2022

Abstract Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation alterations squamous epithelium, such as basal zone hyperplasia (BZH) dilated intercellular spaces (DIS), are thought to contribute dysfunction symptoms. Corroborative clinical discovery science‐based studies have established that EoE underlying allergic response, in part, related IL‐13/CCL26/eosinophil axis driving dysregulation several key epithelial barrier proliferative regulatory genes kallikrein (KLK) serine proteases, calpain 14 (CAPN14) anoctamin 1 (ANO1). The contribution these processes histological manifestations not fully elucidated. Herein, we discuss immune molecules cells underlie pathologic therapeutics targeting for treatment EoE.

Language: Английский

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The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1702 - 1702

Published: Jan. 30, 2024

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, responsiveness to therapy. From the perspective an effective approach patient, different inflammatory mechanisms involved in pathogenesis EoE biologics, particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, most relevant dupilumab, which interferes with both interleukin (IL)-4 IL-13 binding IL-4 receptor α, only mAb approved European Medicine Agency US Food Drug Administration for treatment EoE. Other mAbs investigated include mepolizumab, reslizumab, benralizumab (interfering IL-5 axis), cendakimab dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), many others. Despite undeniable economic impact biologic therapies, near future, there will be room further reflection about opportunity prescribe agents, not as last-line therapy selected cases such patients comorbidities involving common pathways. Although recent findings very encouraging, road permanent success still long, studies needed determine long-term effects discover new potential targets.

Language: Английский

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Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 14, 2020

Endometriosis is a hormonal disease, as well chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there wanton lack of bigger picture on how these coordinated work concertedly. Since endometriotic lesions experience cyclical bleeding, they fundamentally wounds that undergo repeated tissue injury and repair (ReTIAR). In this study, we attempted characterize the role platelets regulatory T (Tregs) modulating lesional microenvironment its subsequent effects progression fibrogenesis. Through two mouse experiments, show that, by disrupting predominantly type 2 response microenvironment, both Tregs depletion decelerated fibrogenesis, likely through suppression TGF-β1/Smad3 PDGFR-β/PI3K/Akt signaling pathways. particular, platelet resulted significantly reduced expression thymic stromal lymphopoietin (TSLP), leading aggregation macrophages alternatively activated (M2) macrophages, Tregs, helper (Th2) Th17 but increased Th1 cells, lesions, which, turn, yields retarded Similarly, aggregation, M2 Th2 lesions. Thus, fibrogenesis immunity microenvironment. Taken together, suggests may induce conducive

Language: Английский

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TSLP as druggable target – a silver-lining for atopic diseases?

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 217, P. 107648 - 107648

Published: Aug. 3, 2020

Language: Английский

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Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma

Biomedicines, Journal Year: 2021, Volume and Issue: 9(9), P. 1108 - 1108

Published: Aug. 29, 2021

Alarmins are innate cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), which mainly produced by airway epithelium exert a prominent role in asthma pathobiology. In particular, several environmental factors such as allergens, cigarette smoking, airborne pollutants, infectious agents trigger the release of alarmins, turn act upstream activators pro-inflammatory pathways underlying type 2 (T2-high) asthma. Indeed, alarmins directly activate group lymphoid cells (ILC2), eosinophils, basophils, mast also stimulate dendritic to drive commitment naïve T helper (Th) towards Th2 immunophenotype. Therefore, TSLP, IL-33, IL-25 represent suitable targets for add-on therapies severe Within this context, fully human anti-TSLP monoclonal antibody tezepelumab has been evaluated very promising randomized clinical trials. Tezepelumab other anti-alarmins thus likely become, near future, valuable therapeutic options biological treatment uncontrolled

Language: Английский

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Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma

Allergology International, Journal Year: 2022, Volume and Issue: 72(1), P. 24 - 30

Published: Dec. 2, 2022

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a vital role in the induction of type 2 inflammation via both innate and acquired immune cascades. Tezepelumab, human IgG2 monoclonal antibody inhibits binding TSLP to receptor, latest biologic for asthma. To evaluate efficacy mechanism tezepelumab asthma, PATHWAY, NAVIGATOR, NOZOMI, UPSTREAM, CASCADE, SOURCE, DESTINATION studies have been conducted. These results suggested broad-target biologic, which expected be effective patients with poorly controlled moderate severe asthma regardless phenotype, although its oral corticosteroids-dependent biological non-type long-term safety remain unknown. In this review, we summarize clinical trials discuss differences between other biologics.

Language: Английский

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Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5972 - 5972

Published: May 29, 2024

Thymic stromal lymphopoietin (TSLP), is a protein belonging to class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP key player in the immune response environmental insults, initiating number downstream inflammatory pathways. performs its role by binding high-affinity heteromeric complex composed thymic receptor (TSLPR) chain IL-7Rα. In recent years, important proinflammatory etiopathogenesis various chronic diseases such as asthma, rhinosinusitis with nasal polyposis (CRSwNP), obstructive pulmonary (COPDs), spontaneous urticaria has been studied. Although alarmins have found be mainly implicated mechanisms type 2 inflammation, studies on monoclonal antibodies against demonstrate partial efficacy even patients whose inflammation not definable T2 so-called low T2. Tezepelumab human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating safety disorders. this review, we will highlight major advances understanding functional TSLP, involvement Th2-related diseases, suitability target for biological therapies.

Language: Английский

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IL-22 in Atopic Dermatitis

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1398 - 1398

Published: Aug. 22, 2024

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due the suboptimal efficacy existing treatment options. Nonetheless, recent progress in elucidating underlying mechanisms disease has facilitated identification new potential therapeutic targets promising drug candidates. In this review, we summarize newest data, considering multiple connections between IL-22 AD. presence circulating been found correlate with severity identified as critical factor driving response associated condition. Elevated levels patients are correlated increased proliferation keratinocytes, alterations microbiota, impaired epidermal barrier function. Collectively, these factors contribute manifestation characteristic symptoms observed

Language: Английский

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