What Is New In Small Airways Research
Ves Dimov, MD
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine
Asthma phenotypes and endotypes: leading the way towards personalized medicine
The paradigm of asthma has shifted from a single-disease concept toward a complex condition with clinical heterogeneity. The study of asthma phenotypes is evolving with investigation into genetic underpinnings and corresponding biomarkers. The old mainstays of asthma treatment, anti-inflammatory and bronchodilator medications, are increasingly being supplemented with a wider array of biologic agents. There is a continuous search for clinically meaningful phenotypes and endotypes using noninvasive biomarkers. This approach could help stratify patients and identify those likely to experience benefit.
Source: Desai M, Oppenheimer J. Elucidating asthma phenotypes and endotypes: progress towards personalized medicine. Annals of Allergy, Asthma and Immunology 2016; 116(5): 394-401. (doi:10.1016/j.anai.2015.12.024)
Image Source: Flow Chart, Open Clipart, free to use
Cells and Culture Systems Used to Model the Small Airway
The pulmonary epithelium is divided into upper, lower, and alveolar (or small) airway epithelia. Of these, the small airway epithelium is the principal area of gas exchange. It also has a high immunological activity, making it a major area of cell biology, immunology, and pharmaceutical research. Unfortunately, animal models do not correctly represent the human pulmonary system and ex vivo human lung samples have limited reliability and availability. Therefore, cell lines and primary cells are widely used as small airway epithelial models. In vitro, these cells are mostly cultured as monolayers (2-dimensional cultures), either media submerged or at air-liquid interface. However, these 2-D cultures lack a three dimensional scaffolding extracellular matrix, which creates the intercellular network in the small airway epithelium. Therefore, 3-dimensional cell culture is currently a major area of development. In 3-D systems, cells are cultured in a matrix or they develop ECM-like scaffolds between them. This review focuses on the commonly used small airway epithelial cells, their 2-D and 3-D culture techniques, and their comparative phenotypes.
Source: Bhowmick R, Gappa-Fahlenkamp H. Cells and Culture Systems Used to Model the Small Airway Epithelium. Lung 2016; 194(3): 419-428. (doi:10.1007/s00408-016-9875-2)
Biomarkers in asthma in clinical practice: are we there yet?
Biomarkers, or biological markers, are traceable substances used to examine organ function or other aspects of health. Asthma is a heterogeneous disease with multiple phenotypes that have variable responses to treatments. The biomarkers most extensively studied at present in asthma are TH2-related. However, the characterization of the T2-low patient is not well-established. T2-low patients have asthma but often do not respond to ICSs, and do not benefit from current biologics. Biomarkers could help define the specific pathophysiology of an asthma phenotypes and identify therapeutic targets. Better understanding of phenotypes, endotypes and biological agents to target specific classes of asthma could provide personalized care to asthmatic patients. The review authors predict that within the next decade, biomarker assessment in asthmatic patients will be like HbA1c assessment in patients with diabetes and become a prerequisite criterion for selection of biological treatments.
Source: Berry A, Busse WW. Biomarkers in asthmatic patients: Has their time come to direct treatment? Journal of Allergy and Clinical Immunology 2016; 137(5): 1317-1324. (doi:10.1016/j.jaci.2016.03.009)