Detecting early lung disease in cystic fibrosis: are current techniques sufficient?

The philosophy underlying treatment at most cystic fibrosis (CF) clinics is essentially preventative—that is, early detection, treatment and hopefully resolutions of problems before they become major clinical issues. The introduction of newborn screening programmes around the world is also based on the idea that early detection and treatment will result in an improved outcome for patients. Progressive lung disease represents the greatest threat to the health and well being of patients with CF. The goal of treatment is to prevent or delay progressive lung disease, so early detection and monitoring of effective treatments would be expected to improve the health and life expectancy of children with CF.

Lung disease in CF is characterised by a progression from bacterial colonisation to mucosal infection and finally invasive infection. This is accompanied by a host inflammatory response characterised by cytokine secretion and influx of neutrophils. The neutrophils appear to be drawn to the lungs largely by a chemotactic protein, interleukin 8 (IL-8), that is found in increased levels in the sputum and lavage of patients with CF.^1,2 Increased numbers of neutrophils result in increased levels of the products of activated neutrophils such as neutrophil elastase (NE). Unbound NE is thought to be responsible for much of the lung damage seen in CF.³ Breakdown products of elastin found in the urine of patients with CF are thought to originate in the lung,³ indicating that lung destruction is occurring.

Recent studies provide strong evidence that lung disease begins during early life in most children with CF. Bronchoalveolar lavage (BAL) performed in infants and young children with CF shows evidence of inflammation and …