Abstract
Several epidemiological, pathophysiologic and clinical data demonstrate the interrelationship between upper and lower airways, and common features between inflammatory pathways and disorders of the nasal and bronchial mucosa have been emphasized both in the clinic (ARIA guidelines [1]) and in basic science, and reflected by numerous reviews on this topic. In contrast, detailed comparative analysis of basic defence mechanisms in upper versus lower airways and its clinical relevance is lacking. It is becoming increasingly clear that airway epithelium plays a key role in driving key initiating steps of immune defence (either protective or deleterious) against inhaled antigens and particles. Epithelial cells respond to changes in the external environment by secreting a large array of antimicrobial host defence molecules, cytokines and chemokines following exposure to and activation by pathogen molecular patterns, and link in concert with dendritic cells innate to antigen-specific adaptive immunity. However, the type of epithelial response to ‘pathogens’ and danger signals may differ between upper and lower airways, as well as according to genetic background. This review provides an updated, extensive and comparative review of immune defence mechanisms of the respiratory tract, in upper versus lower airways, including most relevant changes observed during chronic airway diseases and how these may translate into different clinical features.
Keywords: Mucosal immunity, chronic respiratory disease, upper airway, lower airway, airway inflammation, alveolar macrophages, pattern recognition receptors, COPD, Allergic Rhinitis, Chronic Rhinosinusitis, endoscopy, Asthma, CELLULAR INFILTRATION, effector leukocytes, regulatory leukocytes, CRSwNP, pathogen related receptors, Toll-like receptors, pathogen associated molecular patterns, PAMPs, Remodelling, Mucociliary Clearance, airway surface liquid, chronic sinusitis, secretory leukocyte proteinase inhibitor, SLPI, Mucins, Lysozyme, Lactoferrin, pIgR, IgA, nasal associated lymphoid tissue, NALT, bronchial associated lymphoid tissue, BALT, Surfactant Proteins, Clara Cell Protein, sPLA2, Phospholipase A2, Neutral Endopeptidase, Annexins, lipocortin-1, calpactin II, Defensins, Cathelicidins, Anti-Proteinases, Lipid Mediators, Eicosanoids, Cysteinyl leukotrienes, Prostaglandins, Lipoxins, Cytokines, T-cell-derived cytokines, Regulatory T cells, TSLP, Thymic stromal lymphopoietin, BAFF, B cell activating factor
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