Bronchiectasis (out of print)

Bronchiectasis remains a significant cause of morbidity and mortality in the developed world. The true prevalence of the condition remains elusive, in part, because of the innate difficulty in determining causation, when more than one respiratory condition exists in the same patient, but also due to the increasing rate of diagnosis by radiological means where no clinical symptoms are present. The wide ranging aetiology of bronchiectasis will be discussed in this chapter; however, some aspects will be discussed in greater detail throughout this Monograph.

The diagnosis of bronchiectasis should be the beginning of a targeted search for causation, which may lead to directed treatment, thereby limiting the disease progression. Over the next 5 years a reduction in the number of cases labelled as idiopathic bronchiectasis should be expected, as the continual expanding knowledge of immunology and immunogenetics, with respect to large studies of patients with bronchiectasis, can be applied.

The clinical presentation of bronchiectasis occurs after initial irreversible damage to the airway has occurred. The clinician then has to control symptoms and limit the progression of the disease. A clearer understanding of the pathogenesis of this disease will enable the development of better treatment strategies.

Bronchiectasis is a multi-factorial disease process in which there are a number of key steps, although they are not always clinically identifiable. There is often an initiator or damaging event such as a viral infection which, in an individual with a predisposing risk such as a degree of immune dysfunction or an impaired mucociliary clearance system, leads to persistent and damaging bacterial infections. These infections go on to provoke an inappropriate and self-damaging inflammatory response in which neutrophil activity leads to progressive tissue damage and a relentless cycle of infection, inflammation and bronchial wall injury. Persistent infection and chronic inflammatory cell infiltration further amplify the local inflammatory milieu and may lead to systemic complications.

Imaging plays a crucial role in the diagnosis and monitoring of bronchiectasis and the management of complications. Chest radiography is useful as an initial screening tool and during acute exacerbations, but has limited sensitivity and specificity. High-resolution computed tomography (HRCT) is the reference standard for diagnosis and quantification of bronchiectasis, providing detailed morphological information. Computed tomography (CT) is also valuable in diagnosing and managing complications. Routine surveillance using HRCT has been mooted, particularly in cystic fibrosis (CF), where advances in treatment have increased life expectancy considerably, but cumulative radiation dose remains a concern.

Pulmonary magnetic resonance imaging is an evolving technique that provides both structural and functional information. Its advantage is the lack of ionising radiation. Limitations include cost, availability and its inferior spatial resolution compared to CT. The technique requires further evaluation, but has potential benefits where serial follow-up imaging is being considered, such as in CF. Evaluation of mucociliary clearance using radionuclide scintigraphy may be of value, particularly in drug development.

Fungal spores are ubiquitously present in the air. Inhalation of these spores by humans causes disease in susceptible patients; most prevalent are invasive aspergillosis and allergic bronchopulmonary aspergillosis (ABPA). This chapter provides an overview of the pathogenecity, clinical appearance, diagnosis and treatment of ABPA.

ABPA is a hypersensitivity lung disease limited to patients with asthma or cystic fibrosis (CF) with a prevalence of 1–2% and 2–15%, respectively within these groups. It is triggered by the exposure to Aspergillus fumigatus. Although it is not clear what initiates this hypersensitivity response, polymorphisms in genes that drive innate and adaptive immune mechanisms as well as loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) are associated with ABPA development. The chronic inflammatory conditions in ABPA eventually result in airway remodelling and functional impairment.

The diagnosis of ABPA is based both on clinical symptoms, laboratory testing and diagnostic imaging. Treatment consists of a two tiered approach, glucocorticoids to control immunological activity and antifungal agents to suppress fungal load.

Primary ciliary dyskinesia (PCD) is a genetic disorder of cilia structure and function, chronic infections of the respiratory tract, fertility problems and disorders of organ laterality. Establishing a definitive diagnosis can be challenging, requiring a compatible phenotype and detection of ciliary functional and ultra-structural defects, along with newer screening tools such as nasal nitric oxide and genetics testing. 10 known PCD-causing mutations within two genes are now available in a clinical panel, and in the future, comprehensive genetic testing may serve to identify young infants with PCD to improve the long-term outlook for patients with the disease. Therapy includes regular pulmonary function testing and monitoring of sputum flora to allow a targeted approach to treatment. Referral to an academic centre with expertise in bronchiectasis and/or PCD is prudent to ensure access to the most recent diagnostic testing and therapies. With increased understanding of the disease it is likely that we will expand the definitions of classic and non-classic PCD, as well as its relationship to less common ciliopathies.

The two major inflammatory bowel diseases (IBD), ulcerative colitis and Crohn’s disease (CD), can involve the respiratory system in several ways. The most typical pattern of involvement is in the form of airway inflammation and narrowing, which may involve specific areas of the tracheobronchial tree from the trachea to the bronchioles or which can be diffuse. Marked inflammation, which can be granulomatous in CD, causes, at times, marked airway obstruction. This pattern of involvement is amenable to different forms of inhaled and oral corticosteroid therapy. Drugs used to treat IBD are though to have no responsibility in causing the syndrome. This is in contrast to parenchymal lung disease in IBD. Colectomy may trigger the onset of airway involvement and will not improve or cure established airway inflammation in IBD.

The association between bronchiectasis and autoimmune disease is well recognised, and best described with rheumatoid arthritis. The prevalence of bronchiectasis in rheumatoid arthritis varies considerably in studies, with obliterative bronchiolitis a common feature. The prognosis of rheumatoid arthritis with bronchiectasis seems to be worse than either condition alone. The advent of high-resolution computed tomography has increased the sensitivity of detecting bronchiectasis, but this should be assessed for clinical significance. Traction bronchiectasis results from interstitial fibrosis pulling the airway wider, rather than damage weakening the bronchial wall, and is less likely to lead to bronchial suppuration. Bronchial wall damage in bronchiectasis is caused by inflammation, but it is difficult to differentiate damage caused by severe or recurrent infections, predisposed to by immunosuppression related to the autoimmune disease itself or its treatment, from damage caused by the autoimmune process. Increased use of new immunomodulatory or immunosuppressive agents has proved successful in modifying autoimmune disease processes, but has also led to emergence of infective complications that can cause bronchiectasis or exacerbate pre-existing disease.

Although the use of anti-inflammatory therapies in bronchiectasis remains an attractive proposition, there is currently insufficient evidence to support the use of inhaled and oral corticosteroids, non-steroidal anti-inflammatory drugs and macrolides. Individual patient trials may be warranted for inhaled corticosteroids and macrolides. It is hoped that recently completed and ongoing randomised control trials of macrolides will better define the use and safety in bronchiectasis. There remains an urgent need to perform adequately powered multicentre trials of other potentially useful therapies.

It is anticipated that specialised bronchiectasis clinics will provide greater opportunities to study disease epidemiology and pathogenesis and allow better definition of study population for inclusion within future trials. There is a need for a more defined study population and a widely accepted definition of a pulmonary exacerbation in bronchiectasis which may be applied uniformly across studies to allow direct comparison of study outcomes. Finally, care should be taken to ensure adequate follow-up to detect potential adverse effects of new therapies, particularly on microbial resistance patterns.

Surgical resection for bronchiectasis should be reserved for patients with localised disease who have failed medical management and have persistent symptoms that negatively affect their quality of life. Patients with unilateral segmental disease have the best outcomes. The key to successful surgical intervention includes: 1) complete resection of all affected areas; 2) relatively early intervention to prevent development of resistant organisms and spread to adjacent lung segments; 3) pre-operative targeted antimicrobial therapy based on in vitro sensitivities; 4) continuation of antimicrobial therapy post-operatively; 5) pre-operative nutritional supplementation when indicated; and 6) anticipation of potential complications that may alter the surgical approach. Surgical resection can be accomplished with minimal morbidity and mortality and it can usually be completed with a video-assisted thoracoscopic approach. The only surgical option for diffuse bronchiectasis is bilateral lung transplantation and is mainly employed when treating patients with cystic fibrosis.