Basic science for the chest physician:Pseudomonas aeruginosaand the cystic fibrosis airway: Figure 1

Pseudomonas aeruginosa is the most frequently encountered lung pathogen in patients with cystic fibrosis (CF). Following initial, often intermittent, episodes of infection, it becomes a permanently established component of the chronically infected lung in more than 80% of patients and confers an adverse prognosis. The predisposition of the CF airway to P aeruginosa is incompletely understood but our current concept of the sequence of events leading from initial acquisition of infection through to the chronic state with severe but often ineffective inflammation is becoming clearer. The defect in ion transport resulting from abnormal CF transmembrane conductance regulator protein leads to a dehydrated airway surface. Mucociliary clearance suffers and either shed bacterial components, such as flagella, or, more controversially, the bacteria themselves, trigger inflammatory responses via direct contact with cell surface glycoproteins. Increased expression of pro-inflammatory cytokines leads to neutrophil influx from the systemic circulation. Although at early stages of infection P aeruginosa can be successfully eradicated from the airway, the CF inflammatory response has been shown to be both exaggerated (out of proportion with the bacterial load) and prolonged (failing to be successfully regulated by the usual ‘switch-off’ signals such as lipoxins); both likely contribute to the destructive changes in the airway wall characteristic of the disease. If the initial infecting bacteria survive, they lose their flagella, becoming thereby less detectable to the host immune system. They enter a sessile state and reproduce making use of the high concentrations of amino acids in the sputum to extremely high bacterial densities (often ≥109 colony-forming units ml−1). They appear to be attracted to the hypoxic environment in CF mucus plugs and this hypoxia, and other environmental conditions, may encourage a number of genetic and phenotypic switches as the bacteria adapt to the chronically infecting state. Phagocytosis, long considered the major …