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Wise et al.

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depends on the size of the inhaled particles. Small molecules, such as molds and cat dander, are more associated with an increased risk for asthma, whereas larger molecules, such as tree and grass pollen, are primarily associated with upper airway symptoms. The role of preferential mouth breathing in the development of asthma is unclear. 346 Although there is a relationship between postnasal drip and coughing, no direct association has been proven between overproduction of nasal secretions and bronchial hyperreactivity. Moreover, after nasal application, deposits of radioactive-labeled allergen can be found in the digestive tract but not in the respiratory tract. 347 Stimulation of pharyngolaryngeal receptors is more likely to be responsible for a postnasal drip-related cough. 348 Interestingly, cough is not induced in patients with rhinitis or healthy controls in simulated models of postnasal drip. 349 There is not much evidence supporting the nasobronchial reflex as an important contributor to the unified airway. Nasal allergen challenge can be blocked with a vasoconstrictor but not with lidocaine. Moreover, lower airway responses after allergen challenge are in general more delayed than would be expected following a nasal-bronchial reflex. 350 Allergen provocation studies represent a good model to study nasal-bronchial crosstalk in allergic airway disease. In patients with AR, segmental bronchial or nasal provocation can induce allergic inflammation in both the nasal and bronchial mucosa. 347-349 Presumably, absorption of inflammatory mediators (eg, IL-5 and eotaxin) from sites of inflammation into the systemic circulation results in the release of eosinophils, basophils, and their progenitor cells from the bone marrow. 351 The systemic allergic response is further characterized by increased expression of adhesion molecules, such as vascular cell adhesion molecule 1 and E-selectin on nasal and bronchial endothelium, which facilitates the migration of inflammatory cells into the tissue. 352 Increases in CD34+ cells capable of eosinophil differentiation, as well as other circulatory mediators (IL-5, eotaxin, and cysteinyl leukotrienes), are associated with impaired lung function parameters and enhanced mucosal inflammation in asthmatic patients, 353 and react to local corticosteroids in AR. 354 Treatment with anti-IL-5 and other interleukins relevant in the eosinophilic pathway has been shown to be effective in asthma, with some beneficial results in eosinophilic upper airway disease. 342 In conclusion, these studies demonstrate that the same mechanisms behind AR may be important in airway inflammation throughout the respiratory tract, even in the absence of clinical asthma. Systemic factors, such as the number of circulatory eosinophils and atopic severity are indicative of more extensive airway disease. A variety of cells are involved in the pathophysiology of AR. Due to the nature of the disease, with different mechanisms and endotypes, it is practically impossible to comprehensively describe each of these inflammatory cells in detail. This suggests a need for an extensive endotyping and characterization of the cellular infiltrate for each endotype. 355 In addition, many studies focusing on cell types in allergic diseases, including recently

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IV.D. Cellular inflammatory infiltrates

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.