Purpose of review: Asthma is quite common and is better described as a syndrome with a heterogeneous presentation than as a single disease. Although most individuals can be effectively managed using a guideline-directed approach to care, those with the most severe illness may benefit from a more targeted therapy. The review describes our current understanding of how asthma phenotypes (observable characteristics) and endotypes (specific biologic mechanisms) can be employed to gain insight into asthma pathobiology and personalized therapy.

Recent findings: Our understanding of the heterogeneity of asthma is increasing. The concept of asthma phenotype has become more complex, incorporating both clinical and biologic features. Several asthma endotypes (e.g., allergic bronchopulmonary mycosis, aspirin-exacerbated respiratory disease, severe late-onset hypereosinophilic asthma, etc.) have been proposed, but further research is needed to delineate specific mechanisms underlying asthma pathogenesis. Several biologic therapies targeting certain phenotypes are in development and are expected to broaden our armamentarium for treatment of severe asthma.

Summary: Asthma is a heterogeneous condition with diverse characteristics and biologic mechanisms. Severe asthma is associated with significant morbidity and even mortality and represents a major unmet need. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward in terms of more effective and personalized treatment.

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Purpose of review: The Th2 pathway starts with the binding of IL-4 to the IL-4 receptor followed by the phosphorylation of signal transducer and activator of transcription 6 and the activation of GATA3. The most important question relates to the sources of IL-4 and IL-4 related inflammation. Which cells other than Th2 cells are responsible for airway inflammation in asthma?

Recent findings: Accumulating data indicate that basophils contribute to endothelium-related IL-4-dependent inflammation. There is also a dendritic cell-related alternative for the induction of Th2 cells via Notch signalling. GATA3 deoxyribozyme improves asthma that is not clearly related to T-cells. The innate immune response in allergy is linked to mast cells, basophils, and the innate lymphoid cell type 2 (ILC2). ILC2s respond to IL-25, IL-33, thymic stromal lymphopoietin, and leukotrienes by producing IL-4, IL-5, and IL-13. In addition to all this inflammatory-cell-driven asthma, increasing evidence has emerged relating to smooth muscle cell activation, the endothelial and epithelial barrier functions, and improvements in the barrier function. The elevation of intracellular cyclic adenosine monophosphate because of the use of phosphodiesterase inhibitors adds to the prevention of epithelial–endothelial leakage, supports airway smooth muscle relaxation, and is immunosuppressive.

Conclusion and summary: IL-4 is the predominant Th2 cell cytokine. Many more cells, including eosinophils, basophils, mast cells, and ILC2, contribute to the production of IL-4 in the airways. Epithelial cells and endothelial cells lose barrier function in the context of allergic airway inflammation, and this could be at least partially remedied by increasing the intracellular cyclic adenosine monophosphate levels through phosphodiesterase inhibition.

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Purpose of review: Severe asthma is a heterogeneous syndrome. Classification of asthma into phenotypes and endotypes can improve understanding and treatment of the disease. Identification and utilization of biomarkers, particularly those linked to T2 inflammation, can help group patients into phenotypes, predict those who will respond to a specific therapy, and assess the response to treatment.

Recent findings: Biomarkers are present in sputum, exhaled breath, and blood of patients with asthma. These include sputum eosinophils and neutrophils, fractional excretion of nitric oxide, blood eosinophilia, IgE, and periostin. Many of these biomarkers are associated with eosinophilic inflammation propagated mainly by T2 cytokines such as IL-5 and IL-13, which are released from Th2 cells and Type 2 innate lymphoid cells. Biomarkers have been utilized in recent trials of novel biologic agents targeted at T2 inflammation and may contribute to the defining population who would respond to these therapies.

Summary: Despite advances in the identification and utilization of asthma biomarkers, further studies are needed to better clarify the role of biomarkers, individually or in combination, in the diagnosis and treatment of severe asthma. Future therapeutic trials should include the use of biomarkers in their design, which may lead to a more personalized approach to therapy and improved outcomes.

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Related Articles

PURPOSE OF REVIEW: Asthma is quite common and is better described as a syndrome with a heterogeneous presentation than as a single disease. Although most individuals can be effectively managed using a guideline-directed approach to care, those with the most severe illness may benefit from a more targeted therapy. The review describes our current understanding of how asthma phenotypes (observable characteristics) and endotypes (specific biologic mechanisms) can be employed to gain insight into asthma pathobiology and personalized therapy.

RECENT FINDINGS: Our understanding of the heterogeneity of asthma is increasing. The concept of asthma phenotype has become more complex, incorporating both clinical and biologic features. Several asthma endotypes (e.g., allergic bronchopulmonary mycosis, aspirin-exacerbated respiratory disease, severe late-onset hypereosinophilic asthma, etc.) have been proposed, but further research is needed to delineate specific mechanisms underlying asthma pathogenesis. Several biologic therapies targeting certain phenotypes are in development and are expected to broaden our armamentarium for treatment of severe asthma.

SUMMARY: Asthma is a heterogeneous condition with diverse characteristics and biologic mechanisms. Severe asthma is associated with significant morbidity and even mortality and represents a major unmet need. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward in terms of more effective and personalized treatment.

Lire la suite...