Advances and Evolving Concepts in Allergic Asthma

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.

Silent hypoxaemia in COVID‐19 patients

“…Secondary factors, such as cytokines, may independently either trigger or suppress dyspnoea, depending on how the specific cytokine interacts with immune cells (Tung et al . 2018; Galeas‐Pena et al . 2019), such as the ‘cytokine storm’ typically associated with ARDS (Malhotra, 2007).…”

“…Therefore, the corollary discharge hypothesis describes a disconnect that can occur between the control of breathing and respiratory sensation, when anticipated responses to stimuli do not occur because of impaired lung or chest wall mechanics (Banzett et al 1989;Chen et al 1992). Secondary factors, such as cytokines, may independently either trigger or suppress dyspnoea, depending on how the specific cytokine interacts with immune cells (Tung et al 2018;Galeas-Pena et al 2019), such as the 'cytokine storm' typically associated with ARDS (Malhotra, 2007).…”

Anti-asthmatic effect of laurotetanine extracted from Litsea cubeba (Lour.) Pers. root on ovalbumin-induced allergic asthma rats, and elucidation of its mechanism of action

“…Allergic asthma is a common, intractable, allergyrelated airway disease that is seriously affecting the quality of life of millions people of all ages around the world [1,2]. Allergic asthma is characterized by severe airway inflammatory reactions, airflow obstruction, airway hyperreactivity, and excessive sputum in airways [3,4].…”

Neurokinin 1 receptor promotes rat airway smooth muscle cell migration in asthmatic airway remodelling by enhancing tubulin expression

“…Airway remodelling refers to changes in the airway wall structure of asthma patients resulting from airway inflammation, tissue damage, and subsequent abnormal repair. As airway remodelling is the main cause of airway hyper-responsiveness and asthma chronicity, substantial research efforts have focused on elucidating the mechanism of airway remodelling in asthma to identify potential targets for treatment (5). Many imaging techniques, including chest computed tomography, bronchial ultrasound, and transbronchial needle aspiration (6)(7)(8)(9), have been used to evaluate bronchial wall layers to study airway remodelling.…”