Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla, Merin; Lee, F. Eun-Hyung; Lee, Gwo‐Bin

doi:10.1007/s12016-018-8712-1

Cited by 726 publications

(702 citation statements)

References 95 publications

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“…An asthma endotype is characterized by the presence of a specific pathobiological marker or mechanism (for example, sIgE levels, the number of eosinophils in induced sputum, and fractional expired nitric oxide (FeNO)), which may be a target for pathogenetic therapy of the disease [15]. The term "asthma" is recognized as a diagnosis that combines several endotypes and various phenotypes, each of which being manifested by wheezing, coughing, shortness of breath, chest tightness, decreased expiratory airflow, hyperreactivity, airway remodeling, and mucus hyperproduction [16]. It is known that even within the same endotype, patients may have both different degrees of disease severity and a response to the treatment [17].…”

Section: Asthmamentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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Section: Asthmamentioning

confidence: 99%

“…Stratification of patients by the inflammatory endotype is recognized as the basis for developing asthma treatment strategies [16]. Both innate and adaptive immunity play an important role in the immunological mechanisms of asthma.…”

Section: Asthmamentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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“…An important molecular mechanism of asthma is the chronic inflammation of conducting airways, even during asymptomatic periods. This inflammation is different in various asthma endotypes and may broadly be divided into Th2 high (atopic, eosinophilic) and Th2 low (non-atopic, non-eosinophilic) endotypes [55].…”

Section: Pathogenesis Of Asthmamentioning

confidence: 99%

Role of viruses in asthma

et al. 2020

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Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), the common cold virus, is clearly the most prevalent pathogen constantly circulating in the community. This virus also stands out from other viral factors due to its large diversity (about 170 genotypes), very effective replication, a tendency to create Th2-biased inflammatory environment and association with specific risk genes in people predisposed to asthma development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased airway microbiome), and nutritional deficiencies (low in vitamin D and fish oil) increase risk to RV and other virus infections. It is intensively debated whether viral illnesses actually cause asthma. Respiratory syncytial virus (RSV) is the leading causative agent of bronchiolitis, whereas RV starts to dominate after 1 year of age. Breathing difficulty induced by either of these viruses is associated with later asthma, but the risk is higher for those who suffer from severe RV-induced wheezing. The asthma development associated with these viruses has unique mechanisms, but in general, RV is a risk factor for later atopic asthma, whereas RSV is more likely associated with later non-atopic asthma. Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease RV-induced wheezing and asthma exacerbations. The anti-RSV monoclonal antibody, palivizumab, decreases the risk of severe RSV illness and subsequent recurrent wheeze. A better understanding of personal and environmental risk factors and inflammatory mechanisms leading to asthma is crucial in developing new strategies for the prevention and treatment of asthma.

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“…Quite distinctly, non-allergic asthma showed increased pro-inflammatory interleukin (IL)-1β/IL-17shifted neutrophilic inflammation and insufficient suppression of IL-5, IL-13, and interferon (IFN)-γ by Tregs [4]. In adulthood, endotyping further includes a Th2-low and Th2-high endotype, which is subdivided into early-onset allergic asthma, late-onset eosinophilic asthma, and aspirin-exacerbated respiratory disease [7]. Th2-low asthma shows no eosinophilia and a lack of response to corticosteroid therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Th2-low asthma shows no eosinophilia and a lack of response to corticosteroid therapy. It has also been linked to Th1high and Th17-high inflammation [7].…”

Section: Introductionmentioning

confidence: 99%

Role of early life immune regulation in asthma development

2019

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Development of childhood asthma is complex with a strong interaction of genetic, epigenetic, and environmental factors. Ultimately, it is critical how the immune system of a child responds to these influences and whether effective strategies for a balanced and healthy immune maturation can be assured. Pregnancy and early childhood are particularly susceptible for exogenous influences due to the developing nature of a child's immune system. While endogenous influences such as family history and the genetic background are immutable, epigenetic regulations can be modulated by both heredity and environmental exposures. Prenatal influences such as a mother's nutrition, smoking, or infections influence the complex interplay of innate and adaptive immune regulation as well as peri-and postnatal influences including mode of delivery. Early in life, induction and continuous training of healthy maturation include balanced innate immunity (e.g., via innate lymphoid cells) and an equilibrium of T-cell subpopulations (e.g., via regulatory T cells) to counterregulate potential pro-inflammatory or exuberant immune reactions. Later in childhood, rather compensatory immune mechanisms are required to modulate deviant regulation of a child's already primed immune trajectory. The specific effects of exogenous and endogenous influences on a child's maturing immune system are summarized in this review, and its importance and potential intervention for early prevention and treatment strategies are delineated.

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Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Cited by 726 publications

References 95 publications

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Role of viruses in asthma

Role of early life immune regulation in asthma development

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