Regulation of immunity in bronchiectasis

Abstract

Bronchiectasis is a chronic, progressive lung disease where there is irreversible, abnormal dilatation of one or more bronchi, with chronic airway inflammation, associated chronic cough and sputum production, recurrent chest infections, and airflow obstruction. As such it is essentially a pathological endpoint with several underlying causes. Allergic bronchopulmonary aspergillosis (ABPA) is an important cause of bronchiectasis and aspergillus related lung disease sometimes complicates established bronchiectasis. A diagnosis of bronchiectasis is made clinically and confirmed with high-resolution computed tomography (HRCT) of the thorax. Progressive lung damage results from a 'vicious cycle' of recurrent bacterial infection and a poorly regulated inflammatory response. There appear to be two stages to the disease process: the initial insult that sets off the disease and then the ongoing, inflammatory process encompassing recurrent infection and progressive lung damage. Abnormalities in innate and adaptive immunity may predispose to bronchiectasis at both stages. Recent immunogenetic evidence suggests that there may be a link between the level of natural killer (NK) cell activation and disease susceptibility, implicating a predisposing role for innate immune mechanisms. A role for adaptive immune mechanisms is suggested by the genetic association of HLA-DR1, DQ5 with increased susceptibility to idiopathic bronchiectasis.