The way in which bronchiectasis develops in the airways is poorly understood. The primary cause is not known in conditions other than CF, primary ciliary dyskinesia (PCD) syndromes and primary immunodeficiency syndromes. In CF, impairment of mucociliary clearance is the result of abnormal airway hydration due to CF transmembrane regulator (CFTR) mutations. In PCD it is due to abnormal structure and function of cilia. In other groups of patients with bronchiectasis, it is assumed that infection and/or perturbed innate or acquired immunity are important factors, with secondary impairment of mucociliary clearance.
In established disease, there is a vicious cycle of inflammation driven by neutrophils, recurrent or persistent infection, primarily with Haemophilus influenzae and injury to epithelium and bronchial and bronchiolar structures (figure 2). The anatomical damage further impairs mucociliary clearance; inflammation through proteases impairs some important aspects of innate immunity in the airways, causing further persistence of this vicious cycle. While this process is widely accepted as a paradigm for the condition, there are a number of key parts of the pathway which are poorly understood.
In people with bronchiectasis, a diagnosis of an underlying associated condition can be made in about 50% of cases. Many studies of diagnosis begin by excluding people with CF, and in some diagnostic and treatment guidelines the condition is labelled as non-CF bronchiectasis, to capture all of the other conditions. However, there is no intrinsic pathological difference between bronchiectasis associated with CF and bronchiectasis due to other conditions. In general, in CF, lung disease is more aggressive and associated with a higher prevalence of Gram-negative infection, particularly with P. aeruginosa . Bronchiectasis is almost universal in people with CF (see chapter 14). It is also a common complication of PCD and primary immune deficiency disorders, particularly common variable and X-linked immunodeficiency associated with reduced blood concentrations of immunoglobulin (Ig)G. Bronchiectasis also occurs, uncommonly but with increased frequency, in a number of systemic immune conditions, particularly rheumatoid arthritis and inflammatory bowel disease. Bronchiectasis is associated with infection due to HIV, non-tuberculous mycobacteria and Mycobacterium tuberculosis. The pathophysiological connection between these conditions and bronchiectasis is poorly understood. However, in many patients with a diagnosis of bronchiectasis, there is no clear association with another underlying disease. Childhood infections, such as whooping cough (pertussis) and measles, have been considered as strongly associated or causative. However, problems with recall bias make it very difficult to know the importance of this association.
Bronchiectasis may also complicate a range of other lung diseases: it can be identified in some patients with chronic obstructive pulmonary disease (COPD), severe asthma and interstitial lung disease. In these conditions, bronchiectasis is usually found in the context of severe disease and is then not considered the primary disease. However, when it occurs alongside these conditions, it is associated with a higher incidence of infective pulmonary exacerbations and some of the management strategies used for primary bronchiectasis may be effective.