Semin Respir Crit Care Med 2018; 39(01): 064-081
DOI: 10.1055/s-0037-1607981
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Advances and Evolving Concepts in Allergic Asthma

Hui-Ying Tung
1  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
,
Evan Li
2  Department of Medicine, Baylor College of Medicine, Houston, Texas
,
Cameron Landers
2  Department of Medicine, Baylor College of Medicine, Houston, Texas
3  Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas
,
An Nguyen
2  Department of Medicine, Baylor College of Medicine, Houston, Texas
,
Farrah Kheradmand
1  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
2  Department of Medicine, Baylor College of Medicine, Houston, Texas
4  Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas
5  Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas
,
J. Morgan Knight
1  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
,
David B. Corry
1  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
2  Department of Medicine, Baylor College of Medicine, Houston, Texas
4  Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas
5  Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas
› Author Affiliations
Further Information

Publication History

Publication Date:
10 February 2018 (online)

Abstract

Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis. Phthalates, another common class of chemical pollutant found in the built environment, are emerging as potentially important mediators or attenuators of asthma. Other biological products such as endotoxin have also been confirmed to be protective in both the indoor and outdoor contexts. Proasthmatic factors are believed to activate, and in some instances initiate, pathologic inflammatory cascades through complex interactions with pattern recognition receptors (PRRs) expressed on many cell types, but especially airway epithelial cells. PRRs initiate the release of proallergic cytokines such as interleukin (IL)-33, IL-25, and others that coordinate activation of innate lymphoid cells type 2 (ILC2), T helper type 2 cells, and immunoglobulin E–secreting B cells that together promote additional inflammation and the major airway remodeling events (airway hyperresponsiveness, mucus hypersecretion) that promote airway obstruction. Proteinases, with airway fungi and viruses being potentially important sources, are emerging as critically important initiators of these inflammatory cascades in part through their effects on clotting factors such as fibrinogen. Recent clinical trials have demonstrated that targeting inflammatory pathways orchestrated through IL-4, IL-5, IL-13, and the prostaglandin receptor CRTH2 is potentially highly effective in adult asthma.