**2.3. Pathology of the CF lung**

As might be expected, the buildup of thick mucus in the CF lungs often has severe clinical implications The significant reduction or loss of mucus clearance often results in infection and leads to inflammation due to the dramatic ~1,500-fold increase in airway neutrophils [14]. Coupling the inflammation and buildup of mucus, it is not surprising that the overall lung capacity of CF patients decreases dramatically throughout life. This can be tested using a series of pulmonary function tests (PFTs) [15]. These often involve a spirometry test, which is a measure of the forced efflux volume in one second (FEV1), or how much air the patient can forcefully exhale in one second. This is a hallmark test for overall lung volume and strength. Clinically it has been shown that the FEV1 of a CF patient will be approximately 10% below the expected for a healthy individual of the same age [16].

In older patients, the prolonged effects of the disease often lead to chronic infections. These invading organisms can then be cultured and analyzed to determine the best treatment strategy. While we will be covering the type of infections further in this chapter, it is important to note that clinically, this also affects the patient in other ways, primarily leading to inflam‐ mation of the respiratory system and decreased airway capacity [17]. This inflammation is often brought on by increased neutrophil accumulation in the lungs, which not only serve to act as a preliminary means of immune defense, but also to recruit macrophages. These neutrophils and macrophages will phagocytose bacteria and dead immune cells, but also produce pro-inflammatory cytokines that exacerbate the inflammatory process. These cytokines not only attract other immune cells, but also serve as a trigger for the release of proteases and elastases by the immune cells. Normally, these help eradicate the bacteria that triggered this response, but theior over-production in the CF lung can actually damage epithelial cells, leading to the fibrotic nature of cells associated with this disease [18].
