Understanding the Pathophysiology of Cystic Fibrosis

Cystic fibrosis (CF) is a prevalent genetic condition globally, affecting a substantial number of individuals, with approximately 70,000 cases reported worldwide. 

CF is attributed to mutations in the human cystic fibrosis transmembrane regulator (CFTR) gene, with more than 2000 mutations identified in individuals with CF. These CFTR mutations lead to physiological alterations that give rise to persistent lung infections, primarily caused by an atypical form of Pseudomonas aeruginosa  known as "mucoid."

The airway lining plays a crucial role as a protective barrier between the body and the external environment. It safeguards against the entry of inhaled particles, chemicals, allergens, and pathogens. When inhaled substances enter the airways, they are trapped in mucus and eliminated through a process called mucociliary clearance (MCC). This process involves the coordinated movement of motile cilia, which propel the particles upwards and out of the respiratory tract. Maintaining proper hydration of the airway lining and the mucus layer is essential for effective MCC.

The CFTR gene is responsible for producing an ion channel found in the epithelial cells. This channel facilitates the movement of chloride (Cl-) and bicarbonate (HCO3) ions out of the cells and into the airway lumen. Water follows these ions, which helps keep the airway surface layer (ASL) and the mucus layer covering the airway lining adequately hydrated. 

In individuals with cystic fibrosis (CF), the CFTR channel is either absent or defective, resulting in a dehydrated ASL and the accumulation of thick, sticky mucus that cannot be cleared by MCC. As a consequence, pathogens become trapped in abnormal lung secretions, leading to persistent inflammation and chronic infections.

One of the primary culprits responsible for long-term lung infections in CF patients is a type of bacteria called mucoid Pseudomonas aeruginosa (PA). In the CF airway, these bacteria form "microcolonies," consisting of gram-negative bacilli surrounded by a polysaccharide called alginate. These microcolonies clump together in biofilms and exhibit a mucoid appearance due to the presence of alginate.