Pathophysiology of Bronchiectasis

Abstract

Bronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes. Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis. Despite the dominant of neutrophilic disease, eosinophilic subtypes are recognized and may require specific treatments. Neutrophilic inflammation is associated with elevated bacterial loads and chronic infection with organisms such as Pseudomonas aeruginosa. Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes. Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia. Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells. The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. The heterogeneity of the disease is the most challenging aspect of management. An understanding of the pathophysiology of disease and their biomarkers can help to guide personalized medicine approaches utilizing the concept of “treatable traits.”

Complexity and Heterogeneity in Bronchiectasis: Towards a Personalized Medicine

“…The endotype linked to the type of inflammation is probably the best characterized. Although the majority of bronchiectasis cases present predominantly neutrophilic inflammation [45][46][47] , there is increasing evidence that eosinophilic inflammation can be substantial, and even predominant, in some patients, even in the absence of asthma and underlying diseases associated with a greater degree of eosinophilia. It is also important not to overlook the role played by T cells in the inflammatory picture of bronchiectasis [48][49] .…”

“…Neutrophils play a crucial role in the pathophysiology of most bronchiectasis patients, particularly those with bronchial infection by pathogenic microorganisms. Neutrophils are capable of inducing and producing a large amount of pro-inflammatory molecules with proteolytic and elastolytic characteristics that, along with bacterial products, cause damage in the bronchial wall and the local defence mechanisms [45][46][47] . Of all these molecules, neutrophil elastase is one of the most significant and, moreover, it has proved to be a promising biomarker of inflammatory activity at a bronchial level, as confirmed by several studies that have observed its relationship with the severity of bronchiectasis.…”

Respiratory prehabilitation in pediatric anesthesia in children with muscular and neurologic disease

“…Healthy lungs clear particulate matter and infections via 3 principal mechanisms: the mucociliary elevator, normal breathing cycles, and cough 5 . In disease, increased mucous volume, impaired ciliary function, and poor cough combine to disrupt the normal mobilization of secretions, leading to increased risk of infection and engendering a vicious cycle of recurrent infections, inflammation, and damage to the airways 6 …”

In vitroandin vivomodulation of NADPH oxidase activity and reactive oxygen species production in human neutrophils by α1-antitrypsin

“…With a prominent presence in a number of airways diseases including cystic fibrosis [ 16 ], COPD [ 17 ], bronchiectasis and asthma [ 18 , 19 ], neutrophils are now recognised as central players in the development of persistent chronic inflammation. Studies exploring neutrophil function have reported dysregulated neutrophil chemotaxis in cystic fibrosis [ 16 ], COPD [ 20 ] and in AATD [ 4 ], with increased neutrophil extracellular traps in sputum samples from individuals with bronchiectasis correlating with worse clinical outcomes [ 21 ].…”