Pathophysiology of asthma
Louis-Philippe Boulet in Applied Respiratory Pathophysiology, 2017
Although there have been suggestions not to use the terms “asthma” or “chronic obstructive pulmonary disease (COPD)” to categorize obstructive airways diseases and to mainly call them according to their characteristics (e.g., chronic eosinophilic bronchitis associated with partly reversible airway obstruction), this type of description is not widely accepted yet [22]. However, in the last decade, as for other diseases such as cancer and arthritis, asthma has been increasingly considered as an “umbrella-like” term that includes various groups with specific phenotypes or endotypes, influenced by genetic and environmental factors among others [23]. A “phenotype” is defined as any observable characteristic of a disease, such as morphology, development, biochemical or physiological properties, or behavior, while an “endotype” refers to the endogenous mechanisms of development/maintenance of a specific condition [24].
Extrapulmonary – Treatable traits
Vibeke Backer, Peter G. Gibson, Ian D. Pavord in The Asthmas, 2023
The underlying pathophysiological mechanism that drives CRSwNP disease is called an endotype, and type-2 inflammation is the most prominent of these. Type-2 inflammation is characterised by the presence of eosinophilic inflammation associated with type-2-related cytokines (IL4, IL5 and IL13) and circulating IgE. Nasal polyps are type-2 active; more Th2 cytokines are found in the nasal polyps than in mucosa biopsies of the inferior turbinate and bronchial tree. Further, a high level of polyp EOS in eCRS is associated with type-2 inflammatory cytokines; as high levels of IL4, IL5 and IL13 have been found in patients with eCRS; patients with mixed CRSwNP/CRSsNP may also have positive levels of type-2 cytokines, but the group with the highest level of these cytokines almost always includes patients with comorbid CRSwNP and asthma. Other cytokines, such as serum periostin, have been found in patients with severe eCRS, as well as in patients with CRSwNP and EOS in the nasal tissue, but not in those with mild or no eCRS. Blood eotaxin3, chemokine (C-C motif) and ligand 26 (CCL26) were significantly higher in patients suffering from eCRSwNP than in those without eCRSwNP, with a positive correlation between a high number of mucosal EOS and high levels of CCL26, but no correlation with other relevant cytokines. In contrast, no relationship was found between blood EOS and CCL26.
Endotypes and Asthma
Jonathan A. Bernstein, Mark L. Levy in Clinical Asthma, 2014
The difference between phenotypes and endotypes is not simply a matter of semantics. The heterogeneity in asthma has two key elements: (i) the existence of multiple pathological entities (different endotypes) and (ii) the variable influences exerted by the environment on the individual’s genotype (variability within a single endotype). Fundamentally, efforts to characterize the heterogeneity of asthma need to focus on the identification of endotypes. By definition, endotypes are stable. Once these are established, the effects of the environment may be understood more clearly.
Monitoring immunomodulation in patients with sepsis
Published in Expert Review of Molecular Diagnostics, 2021
Evdoxia Kyriazopoulou, Evangelos J. Giamarellos-Bourboulis
An endotype is a subclass of a disease or syndrome defined by a function or biology. Existing evidence about sepsis endotypes is summarized in Table 4. Davenport et al. performed one genome-wide transcription profiling of samples of peripheral blood leucocytes coming from 265 sepsis patients admitted in the ICU due to community-acquired pneumonia and ended up with two sepsis response signature (SRS) groups, namely SRS1 and SRS2 [103]. Although over 3,000 genes were differently expressed between the two groups, no differences were found in the expression of pro-inflammatory cytokines. SRS1 was associated with higher mortality compared to SRS2 and it was characterized by downregulation of HLA class II as well as of genes implicated in T-cell activation, hence suggesting immunosuppression. Subsequent studies verified that SRS grouping is independent of the source of infection but fluctuates throughout sepsis course [104]. Post-hoc analysis of the VANISH trial revealed that corticosteroid treatment was disadvantageous in SRS2 endotype, implying for the first time that endotypes may serve for treatment guidance [105].
The concepts of asthma endotypes and phenotypes to guide current and novel treatment strategies
Published in Expert Review of Respiratory Medicine, 2018
Cevdet Ozdemir, Umut Can Kucuksezer, Mubeccel Akdis, Cezmi A. Akdis
In personalized medicine, it is essential to define major keywords and select patients to characterize individual clinical conditions in general conception. Endotype, phenotype, theratype, and biomarker terms account for major keywords in precision/personalized medicine [14–17]. An endotype is a disease condition which is defined by a discrete pathology related to a molecular mechanism. A disease phenotype is an observable characteristic of a disease without being focused on underlying mechanism. A theratype defines clinical responders to a specific therapy. A biomarker is used for examination of any pathogenic or biological process, which may be used for the main biological aspects of diagnosis, patient selection, response to therapy side effects, and so on [17–19]. Asthma can be defined as a syndrome with various phenotypes. As the precision in daily medicine arises as a hot topic nowadays in the management of disease states in many disciplines, asthma also appears as a noteworthy topic in this area. There is still no clear consensus on the specific definition of inflammatory cellular endotypes of asthma. Commonly used classification based on cellular inflammatory type includes eosinophilic and neutrophilic asthma. Patients may exhibit features of both the eosinophilic and neutrophilic endotype, which is termed as mixed-granulocytic asthma. In contrast, paucigranulocytic asthma is known to define the patients in whom both eosinophils and neutrophils were not observed to be increased [20].
Clinical entities, phenotypes, causation, and endotypes based on selected asthma publications
Published in Baylor University Medical Center Proceedings, 2020
Gilbert Berdine, Robert Alexander, Kenneth Nugent
Anderson introduced the term endotype (a contraction of endophenotype) in a review of the pathogenetic mechanisms in asthma in 2008.8 He defined an endotype as a subtype of disease defined functionally or pathologically by a particular molecular mechanism or by a treatment response. This word is a combination of the prefix endo-, from the Greek endon, “within,” and type, from Greek tupos, “impression, figure, type.” The study of endotypes helps focus clinical investigators on the underlying pathogenesis of various asthma subtypes or phenotypes. The identification of endotypes has the potential to create more homogeneous patient groups for clinical studies, such as genetic studies and drug trials. This has the long-term potential to help clinicians prescribe more effective drugs in particular endotypes and limit the use of ineffective drugs in these endotypes.
Related Knowledge Centers
- Asthma
- Nosology
- Phenotype
- Sensitivity & Specificity
- Syndrome
- Pathology
- Signs & Symptoms
- Asymptomatic
- Sensitivity & Specificity
- Heterogeneous Condition