Epidemiology

It is generally believed that the incidence of bronchiectasis has declined since the 1950s, when prevalence in the United Kingdom (UK) was estimated at 100 per 100,000 population, based on mass chest x-ray findings. There are no recent studies in the UK to confirm this belief, and the overall incidence remains unknown. Evidence from other European countries, however, shows a reduction in hospital admissions and new diagnoses of bronchiectasis since the 1970s, attributed to reduced incidence of tuberculosis and more effective treatment of pulmonary infections.

Bronchiectasis remains a significant cause of childhood morbidity in developing countries. Prevalence of non–cystic fibrosis (CF) bronchiectasis in indigenous communities in New Zealand and Australia is reported to be among the highest worldwide, along with Inuit populations of the Northern Hemisphere. Poverty, barriers to medical care (e.g., antibiotic therapy, vaccination), and poor education are contributing factors. Mortality from respiratory disease, including bronchiectasis, is also higher in rural versus urban areas in China; epidemiologic studies are lacking, however, and these populations likely face similar barriers to medical care and therefore antibiotic availability. There are no studies to illustrate the effect of antibiotic therapy or immunization programs on the incidence in countries where it has only recently become available.

Pathology

The most comprehensive description of bronchiectasis pathology remains that of Whitwell, who examined 200 consecutive resected surgical specimens in 1952. The findings revealed dilated, thickened bronchi, often containing pus with distortion of the bronchial lumen. The inflammatory reaction, visible macroscopically, was shown often to cause complete occlusion of the smaller bronchioles. These findings may be widespread or localized depending on the cause. Microscopically, examination of the bronchial epithelium showed ulceration with granulation tissue in areas where healing had begun. Other specimens had evidence of infiltration of inflammatory cells in the subepithelial tissues and hyperplasia of mucous glands. Supporting connective “elastic” tissues may also be damaged to varying degrees. These features may all be present in varying degrees, in keeping with the varying clinical symptomatology and severity of the disease.

Whitwell classified bronchiectasis into three groups based on pathologic findings—saccular, atelectatic, and follicular—and although these terms may have changed, the descriptions remain the same. Cylindrical bronchiectasis is characterized by bronchi showing a regular outline, with dilated airways only and usually ending abruptly. Varicose bronchiectasis has similarities to the appearance of varicose veins, with dilation that is deformed by areas of relative constriction. These bronchi also have a distorted and bulbous end. Cystic (saccular) bronchiectasis is considered the most severe form of bronchiectasis; its most prominent feature is progressively increasing dilation as the bronchi progress toward the lung periphery and airways, ending in cystlike clusters. These three basic forms of bronchiectasis are demonstrated in Figure 45-1 by high-resolution computed tomography (HRCT) scanning.

Figure 45-1 A, Bilateral cystic bronchiectasis. B, Moderate cylindrical bronchiectasis in right middle lobe, as demonstrated by classic signet ring sign (arrow). C, Bilateral severe varicose bronchiectasis, more marked on the left side, with associated bronchial wall thickening.

Pathogenesis

The cause of non-CF bronchiectasis may only be identifiable in up to 50% of patients. However, a number of recognized conditions and factors are associated with bronchiectasis, and an underlying cause should be assessed in all patients (Box 45-1).

The genetic influence on the development of non-CF bronchiectasis is the subject of ongoing research, often on the role of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation of this gene, ΔF508 (F508del), is associated with severe CF (see Chapter 44). Numerous other mutations have been identified and associated with a milder clinical phenotype. As a consequence, late first presentation of CF has been described in patients who would otherwise have been considered to have idiopathic non-CF bronchiectasis. It is now recognized that mutations of the CFTR gene are more frequently observed in patients with bronchiectasis and a normal sweat chloride test than in the general population. Studies show that the spectrum of CFTR genotypes is associated with a continuum of CFTR dysfunction in the airways. Phenotypes range from patients with bronchiectasis, normal sweat test, and no other features suggestive of CF to those with classic CF. Also, some evidence suggests the CFTR mutations are associated with non-CF bronchiectasis and rheumatoid arthritis. Therefore, CFTR dysfunction can be identified as a cause of bronchiectasis in patients previously diagnosed with idiopathic non-CF bronchiectasis, but without fulfilling the diagnostic criteria for CF. How this affects patient management is currently unknown.

Establishing a cause for bronchiectasis depends on an accurate recollection of events by patients, making it difficult to establish a direct cause and effect in most patients. Nonetheless, an infective insult undoubtedly plays a role in establishing and maintaining the pathologic changes seen in bronchiectasis. This is demonstrated by the falling incidence since the widespread use of antibiotic therapy and immunizations in childhood. The role of infection is further emphasized by the association between the immune defects, and therefore increased susceptibility to infection, and the development of bronchiectasis.

The “vicious cycle” hypothesis of bronchiectasis suggests an initial failure or overwhelmed host defenses, leading to a host-mediated chronic inflammatory response, which in turn causes new or further impairment of mucociliary clearance and defenses, amplifying the problem. This interaction between chronic infection and excessive inflammation, which is predominantly neutrophilic, ensures ongoing damage to the airways and the development and maintenance of the features seen in bronchiectasis. Inflammatory mediators such as the neutrophil chemoattractant interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) are found in bronchial mucosal biopsies and secretions from bronchiectatic airways, in addition to tissue neutrophilia. This initiation of the inflammatory reaction results in the recruitment of phagocytes, dendritic cells, and lymphocytes, which contribute to the adaptive response (Figure 45-2).

Figure 45-2 Infectious inflammatory cycle of bronchiectasis. Damage to airway results in impaired mucociliary clearance, leading to bacterial colonization, which stimulates neutrophilic inflammation. This not only damages the tissues further, but also disturbs the local immune status, resulting in establishment and maintenance of colonization. Neutrophilic proteinases damage immunoglobulins, reduce antibacterial properties, reduce ciliary beat frequency, and damage airway epithelium, all leading to increased bacterial adherence and retention.

Clinical Features

The severity of clinicopathologic events varies widely in patients with bronchiectasis. At the milder end of the spectrum, patients may have occasional exacerbations, with little or no intervening sputum production. Others have frequent exacerbations with chronic production of purulent sputum, even in the stable state. Symptoms can include hemoptysis, especially during exacerbations, and breathlessness, characterized by mild to moderate airflow obstruction, lethargy, and reduced health status. Hemoptysis may be only a minor problem, although erosion of mucosal neovascular arterioles during an acute exacerbation can result in massive hemoptysis. Quantitative analysis of HRCT scanning in bronchiectasis shows that the airflow obstruction is primarily linked to disease of small and medium-sized airways and not to bronchiectatic abnormalities in large airways, emphysema, or retained endobronchial secretions. Nonspecific chest pain varying in severity is also reported with increased frequency in bronchiectatic patients.

Diagnosis and patient assessment

Blood Tests

Inflammatory markers include white blood cell (WBC) count, neutrophil count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and can be used as nonspecific tests of disease activity and exacerbation severity. These tests can also be used to guide the need for and response to antibiotics in the absence of changes in clinical state or symptomatology of bronchiectatic patients (Box 45-2).

Box 45-2

Diagnostic Testing in Patients with Bronchiectasis

Investigation

Nonspecific inflammatory markers (WBC count, ESR, neutrophils, CRP)

Serum immunoglobulins

Serum electrophoresis

Functional antibodies

Total IgE, specific IgG to Aspergillus

In Some Patients

IgG subclasses

Rheumatoid factor

Alpha₁-antitrypsin levels

Cystic fibrosis screening

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IgE, immunoglobulin E; IgG, immunoglobulin G; WBC, white blood cell.

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