Mechanisms and markers of airway inflammation in cystic fibrosis

Abstract

Airway inflammation is now recognized as a major factor in the pathogenesis of lung disease in cystic fibrosis (CF). Its most characteristic feature is a marked and persistent influx into the airways of neutrophils, which damage the lung by releasing noxious mediators, such as reactive oxygen species and proteolytic enzymes. Recent studies suggest that inflammation occurs very early and may even happen in the absence of infection. Furthermore, links between CF transmembrane conductance regulator dysfunction and both infection and inflammation are postulated; dysregulation of cytokine production and abnormal epithelial host defences have been regarded as causes of sustained inflammation. Bronchoalveolar lavage and the evaluation of neutrophils and inflammatory mediators provide the most accurate picture of airway inflammation. Routine bronchoscopy with bronchoalveolar lavage, however, is unpleasant for the patient and usually is of no immediate benefit to the management of individual cases. Therefore, surrogate markers collected by noninvasive procedures would be of great assistance in the follow-up of cystic fibrosis patients. Several markers have been evaluated in the sputum, serum and urine of cystic fibrosis patients and related to the degree of airway inflammation. Long-term studies are needed to confirm their potential clinical utility and specificity, and to determine which can be used clinically to monitor disease outcome and efficacy of treatment.