Local Mechanisms (1, 2, 3): Over the years, several local and systemic mecha­nisms explaining the interaction between the upper and lower airways have been proposed [1, 2, 4, 6]. These are summarized in Fig.33.1. Mouth Breathing (1): In individuals with rhinitis/rhinosinusitis, the nose may be obstructed, and mouth breathing is favored, thereby eliminating this vital upper airway defense mecha­nism. This abnormal breathing (excluding the passage of air through the sinus system and the loss of function of inamed/infected sinuses) compromises air warming, humidication, and purication from pollutants and irritants, allowing physical and chemical agents to have an impact on the lower airways [2, 6]. In addition, the impairment of air ltering in the presence of sinus disease may increase allergen load reaching the bronchi in allergic patients. Baraldi etal. have proposed a novel and intriguing pathogenetic hypothesis that nitric oxide, which is thought to have a modulating effect on bronchial tone and is an important host­defense molecule, is decreased during sinusitis, and that decreased physiologic autoinhalation may play a role in increasing bronchial reactivity and susceptibil­ity to infection [2, 6]. Aspiration of Nasal Contents (2): The concept that inam­matory secretions from the upper airway of patients with rhinitis or rhinosinusitis are aspirated into the lower airway with negative consequences has traditionally been regarded as one of the primary mechanisms underlying lower airway symp­toms. The few available studies, however, have not conclusively supported this hypothesis [2, 9]. Neural Reexes (3): The presence and signicance of a sinona­sal-bronchial reex, characterized by bronchoconstriction triggered by the activa­tion of a trigeminal afferent-vagal efferent neural pathway, remains a topic of debate in human studies, despite being extensively documented in animal models [6, 9]. Rolla etal. demonstrated that damage to the pharyngeal mucosa in patients with CRS (likely mediated by the drainage of inammatory mediators and cells and/or infected material) increased the sub-mucosal nerve’s exposure to irritants, thereby activating the reex arc [10].