Immune Defence Mechanisms: Comparing Upper and Lower Airways in Chronic Airway Diseases

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.