Basic, translational and clinical aspects of bronchiectasis in adults

Abstract

Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent respiratory infections. Inflammatory cell infiltration into the lung, in particular neutrophils, is central to the pathophysiology of bronchiectasis. Herein we explore the roles and relationships between infection, inflammation and mucociliary clearance dysfunction in the establishment and progression of bronchiectasis. Microbial and host-mediated damage are important processes underpinning bronchiectasis and the relative contribution of proteases, cytokines and inflammatory mediators to the propagation of inflammation is presented. We also discuss the emerging concept of inflammatory endotypes, defined by the presence of neutrophilic and eosinophilic inflammation, and explore the role of inflammation as a treatable trait. Current treatment for bronchiectasis focuses on treatment of underlying causes, enhancing mucociliary clearance, controlling infection and preventing and treating complications. Data on airway clearance approachesviaexercise and mucoactive drugs, pharmacotherapy with macrolides to decrease exacerbations and the usefulness of inhaled antibiotics and bronchodilators are discussed, finishing with a look to the future where new therapies targeting host-mediated immune dysfunction hold promise.

Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency

“…Prospective data on elastase and 16S rRNA microbiome indicated that some patients are probably using antibiotics inappropriately while others are taking antibiotics late or not at all, even when they are likely to be indicated. Given the role of neutrophil elastase in driving lung damage such as bronchiectasis, 7 , 21 prompt treatment should be directed at bacterial exacerbations associated with a rise in elastase. Prospective monitoring of neutrophil elastase concentration may be a useful guide for antibiotic treatment decisions.…”

Treatable traits models of care

“…Bronchiectasis is a complex and heterogeneous disease, that is under recognized and under diagnosed. 55 Bronchiectasis was highlighted as a treatable trait of asthma and/or COPD, 1 but the approach has since been proposed for the disease itself. 2 This fits well due to the high degree of heterogeneity associated with bronchiectasis.…”

“…The aetiology may be due to infection, inflammation, allergy, auto immune processes, or congenital, genetic (cystic fibrosis and primary ciliary dyskinesia) or structural abnormalities. 55 Boaventura et al, recognize the importance of pulmonary, extra-pulmonary and behavioural and lifestyle traits, but propose a fourth domain of 'aetiological' treatable traits. 2 This allows the traits involved in the development of bronchiectasis (Non-Tuberculosis Mycobacteria infection, allergic bronchopulmonary aspergillosis and immunodeficiency) to be identified.…”

Chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand: TSANZ position statement summary

“…This requires grouping patients by their shared phenoendotypes using clinical, radiographic, spirometric and multiomics-derived criteria and validated biomarkers to allow treatable traits (pulmonary, aetiology, extrapulmonary, behaviour and lifestyle) to be identified and managed, as well as improving clinimetric properties in registry-based studies, 16 and having well balanced arms in high quality, adequately powered randomised controlled trials. 23 Additional strategies addressing heterogeneity require standardising definitions (eg, exacerbations) 24 and adopting patient-focused core outcome sets (an agreed minimum set of critically important outcomes) to improve trial comparisons, meta-analyses and guidelines. 25 Finally, better engagement and investment are also required in allocating resources to culturally and linguistically diverse groups, where disease burden Perspectives is highest and outcomes poorest.…”