Asthma is the most common chronic inflammatory disease of the airways. It affects approximately 34.1 million Americans throughout their lifetime, and the number of people with asthma continues to grow. Standard treatment using an inhaled short-acting beta-2 agonist is only effective against acute symptoms. Though avoiding allergens and irritants while utilizing inhaled corticosteroids may help some patients, these preventatives are still ineffective in completely deterring asthma. Furthermore, cases of asthma will have varying responses to the standard treatments available. Accordingly, finding the specific mechanisms for the defined subgroups of asthma that respond well to various types of treatments is a current critical goal of asthma research. Allergens and environmental irritants play a key role in initiation and maintenance of asthma in children and adults. It is well accepted that airway inflammation plays an important role in the development of airway hyperresponsiveness (AHR) in asthmatic patients. Recent evidence demonstrates airway inflammation during asthma in animals and humans may be at least partially neurogenic in nature. This neurogenic inflammation is induced by neuropeptides released from airway innervating C-fibers of sensory neurons with nodose (ND), jugular, and dorsal root (T1-T6) ganglia (DRG) origin. However, the molecular and physiological mechanisms involving allergens and a combination of allergens and environmental irritants inducing neurogenic inflammation of airways are largely unknown. One of the possibilities is that neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), which trigger neurogenic inflammation, could be released from sensory nerve terminals innervating airways upon stimulation by certain allergens. According to this mechanism, certain allergens would be able to promote neurogenic acute and/or chronic inflammation of the airways. To address this critical question of how exposure to certain allergens results in initiation of neurogenic inflammation of the airways, we hypothesize that certain asthma-inducing mold and house dust mite allergens - DerP1, DerP3&9 and PenC13 - belonging to the protease family initiate inflammation of the airways by activating the sensory neurons innervating these airways and by sensitizing the effects of acrolein and carvacrol (potent tobacco smoke and environmental irritants) on sensory neurons. This conceptually innovative hypothesis which proposes distinct mechanisms of airway inflammation by mold and house dust mite allergens has a strong potential for scientific and medical developments.
The management of asthma represents a major scientific and health care challenge as many of the currently used medications are ineffective in completely deterring asthma or may produce debilitating side effects. Here we propose a novel hypothesis for the initiation of neurogenic inflammation of airways by certain house dust mite and mold asthma-inducing allergens, and by a combination of these allergens and environmental irritants from cigarette smoke, smog and pollution. This conceptually innovative hypothesis has implications for both the scientific and medical fields by expanding our understanding of the role of the peripheral nervous system in initiation of airway inflammation by certain allergens, and by creating a foundation for novel therapeutic strategies aiming to correct the underlying causes of the initiation of asthma by allergens and environmental irritants.
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