Mini-Symposium: Non-CF Bronchiectasis
Pathogenesis of bronchiectasis

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Summary

Non-cystic fibrosis bronchiectasis is a heterogeneous condition and its pathogenesis is still not well defined. A combination of a defect in host defense and bacterial infection allows microbial colonization of the airways resulting in chronic inflammation and lung damage. An ongoing cycle of infection and inflammation may be established. Typically, the walls of the small airway are infiltrated by inflammatory cells causing obstruction whilst mediators, such as proteases released predominantly by neutrophils, damage the large airways resulting in bronchial dilatation. Adjacent parenchyma is also involved in the inflammation. Lung function testing generally demonstrates mild to moderate airflow obstruction that progresses over time. There are a large number of different aetiologic factors associated with bronchiectasis. A variety of different microbial pathogens is involved and they change as disease progresses.

Introduction

Bronchiectasis remains a common and important cause of respiratory disease and is defined by the presence of permanent and abnormally dilated bronchi. It is usually diagnosed by high resolution computed tomography scanning (HRCT). In very young children it may not be possible to use HRCT and patients may be classified as having clinical bronchiectasis. This article will focus on non-cystic fibrosis (CF) bronchiectasis.

Bronchiectasis arises from chronic airway inflammation that is driven by persistent infection. The main clinical manifestation is a productive cough. The pathogenesis of this condition is complex and still not well defined with a range of different factors that result in chronic airway damage. This review will discuss a variety of areas which give insights into the pathogenesis of this condition.

Section snippets

Cystic fibrosis/non-cf bronchiectasis

A primary manifestation of cystic fibrosis is bronchiectasis. There is still some controversy about the differentiation between cystic fibrosis and non-CF bronchiectasis.

Cystic fibrosis arises from a defect in the cystic fibrosis transmembrane regulator (CFTR) which functions as a chloride channel in epithelium (present in the lung, gastro-intestinal tract (GIT) and skin). Deficiency of the CFTR is thought to be associated with abnormal chloride transport that probably predisposes to dehydrated

Prevalence and epidemiology

The prevalence of bronchiectasis has not been well defined and probably varies significantly between different populations. It was thought that the introduction of antibiotics would effectively cure bronchiectasis and this has led to a low index of suspicion with consequent underdiagnosis. The advent of HRCT has made the diagnosis much easier and it has become apparent that bronchiectasis remains a major cause of respiratory disease.

Weyeker et al have estimated that there are at least 110 000

Localized/generalized disease

Bronchiectasis may be arbitrarily classified into localized (one lobe) or generalized disease (multilobar). It may also only involve the lower respiratory tract or it may be accompanied by upper respiratory tract disease.

Localized disease usually appears to arise in the context of bronchial obstruction. This obstruction may be from a slow-growing tumour or inhaled foreign body. On a world-wide basis probably the most common form is in the context of a mycobacterial infection. This has been

Pathophysiology of bronchiectasis

Bronchiectasis is characterized by intense airway inflammation which arises from infection with microorganisms predominantly bacteria. There are no animal models of bronchiectasis nor are there studies of the early pathologic changes in this condition. As such the pathophysiology of this condition is still not well defined.

The most well recognized model of the development of bronchiectasis is the “Vicious cycle hypothesis” described by Cole14. He proposed that there was an initial event (e.g. a

Pathology

Pathology studies in bronchiectasis have demonstrated that the key features are dilatation of the subsegmental airways which are inflamed, tortuous and obstructed by secretions. Bronchioles are involved in the inflammatory process and there may be fibrosis. There is also usually parenchymal lung damage. Pulmonary arteries may thrombose and recanalize but the vascular supply arises predominantly from hypertrophied bronchial arteries. Reid described 3 main subtypes of bronchiectasis; 1) tubular

Lung function

Patients with bronchiectasis usually have mild to moderate airflow obstruction and over-time develop progressively worsening airflow obstruction23, 24, 25. This may be surprising as the cardinal feature of bronchiectasis is airway dilatation. This paradox can be explained by the pathology findings from Whitwell's study which demonstrated that whilst the large airways were dilated the small airways were obstructed; as most of the pulmonary tree is composed of small airways the net effect is

Specific causes of bronchiectasis

There are a large number of aetiologic factors that have been described to cause bronchiectasis. As there is generally a very long history before a definitive radiological diagnosis of bronchiectasis it may be difficult to be certain of the exact role of such factors in the pathogenesis of bronchiectasis. There also may be multiple factors in the same patient. It may be more appropriate to consider them as risk factors (e.g. as in risk factors for hypertension or ischaemic heart disease) rather

Microbiology

A large number of different pathogens have been described to be present in the sputum of subjects with bronchiectasis. The pattern of isolates does vary significantly between different institutions/locations. The main two pathogens reported in previous studies have been H. influenzae and P. aeruginosa. Other prominent isolates include S. pneumoniae, Moxarella catarrhalis and non tuberculous mycobacteria (NTM). Staphylococcus aureus is uncommon and its isolation suggests the possible presence of

Outcome

Cole's vicious cycle proposes that bronchiectasis becomes a self-sustaining inflammatory airways disease that leads to progressive lung damage. The pathology studies of Whitwell and the decline in lung function are consistent with this theory. Adults have also been described to develop progressively worse symptoms over time as well decline in lung function. Factors associated with decline include volume of sputum23, systemic inflammation, colonization by P. aeruginosa and severe exacerbations25

Chronic suppurative lung disease/chronic bronchitis

Many adults appear to have chronic infective bronchitis with significant sputum production and improvement with antibiotics but do not have evidence of bronchiectasis on HRCT.

There are often significant logistical problems in obtaining HRCT scans in children. Chang et al have described the clinical phenotype of children with a chronic wet cough as having chronic suppurative lung disease (CSLD)51, 52.

It has not been proven if CSLD in children and chronic infective bronchitis in adults evolves

Conclusion

Bronchiectasis is a heterogeneous condition with a large number of potential contributory factors and poorly understood pathogenesis. The vicious cycle hypothesis proposes that bronchiectasis is characterized by a self-sustaining cycle of infection and inflammation that results in progressive lung disease.

Pathology studies have demonstrated infiltration of the walls of the small airways by a cellular infiltrate causing obstruction. The inflammatory process damages the large airways causing

Acknowledgements

The author would like to thank Associate Professor Peter Holmes for his help with this work.

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