Quality of Life

Bronchiectasis has a significant effect on health related quality of life; mean total scores for the St. Georges Respiratory Questionnaire (a widely used quality of life questionnaire for respiratory disorders) in bronchiectasis range from 36, 41.1, 44.4 to 45.5 in clinically stable patients.[21-24] These values are similar to those observed in other respiratory diseases such as moderate to severe COPD[25] or idiopathic pulmonary fibrosis.[26]

Pulmonary function   

Lung function impairment is highly variable in adults with bronchiectasis. Patients may have airflow obstruction, restriction or even normal spirometry values.[27] Airflow obstruction is often associated with more severe disease. [16, 27–30] A lower FEV₁ is associated with the severity of breathlessness measured by the Medical Research Council dyspnoea scale and is also associated with extent of disease on HRCT.[29] Forced vital capacity may be normal or reduced. Forced expiratory flow_25-75 (FEF_25-75) may be reduced and the RV/TLC ratio may be increased suggestive of small airways disease and air trapping.[27,30,31] The response to bronchodilators is variable; between 1/3 and ¾ of patients with bronchiectasis may have a response to bronchial challenge testing with methacholine or histamine.[27,32] 

Radiology

Although in severe cases the appearances of bronchiectasis may be detected by chest x-ray (figure 1A), radiologically bronchiectasis is defined by a characteristic appearance of bronchial dilatation on HRCT.[12,33] In health, the overall diameter of a bronchus is approximately equal at any given level to its adjacent pulmonary artery. A ratio of bronchus diameter: vascular diameter > 1 denotes abnormal dilatation. Cylindrical/tubular bronchiectasis (figure 1B) is the most common subtype, but varicose (figure 1C) and cystic bronchiectasis are also seen (figure 1D).

Other radiological features associated with bronchiectasis include bronchial wall thickening, mucous plugging, mosaic attenuation, atelectasis, subsegmental, segmental or lobar collapse, and emphysema.[33–36] There is a relationship between the severity of bronchiectasis on CT scanning and the severity of clinical disease, although analysis of this is limited due to different scoring systems.[35,37] Most studies have used scoring systems validated in cystic fibrosis.[38] While airway thickening is often present, this finding is not diagnostic as it is seen in various other airway diseases.

Diagnosis and investigating underlying causes

Bronchiectasis is an under-diagnosed condition.[39] The diagnosis relies on a degree of clinical suspicion as discussed above. One study has shown an average model delay between onset of symptoms and diagnosis of 17 years.[40] Clinical experience suggests that patients are often initially labelled as having COPD or asthma before bronchiectasis is suspected. Bronchiectasis is the final common pathway of a number of disorders, and even if the diagnosis of bronchiectasis is straightforward it is essential to seek underlying causes.

Standardised testing for underlying causes leads to a change in treatment in 7 –57% of cases.[33,40,41] Examples of altered management include immunoglobulin replacement therapy for common variable immunodeficiency, antibiotic treatment for non-tuberculous mycobacteria and corticosteroids and anti-fungals for allergic bronchopulmonary aspergillosis.[12] The involvement of a specialist clinical immunologist can be invaluable in the investigation of patients, particularly where the presentation is unusual or is associated with recurrent infections outside the pulmonary system. No link between aetiology and severity of bronchiectasis has been conclusively proven although it has been suggested Rheumatoid associated bronchiectasis has a worse prognosis and the BTS guidelines recommend closer follow-up of these patients .[12]

Figure 2 shows the prevalence of the most frequent aetiologies identified in adult bronchiectasis patients. All these studies looked at adult populations in a tertiary clinical setting.

The recommended approach to investigations of patients with bronchiectasis is discussed below and summarised in Table 1.[12]

Idiopathic Bronchiectasis

Even after extensive testing, the majority of patients even in specialist centres are classified as idiopathic bronchiectasis.[33] This may change in the future as new research emerges; at least some of the patients currently diagnosed with idiopathic bronchiectasis subtle immune deficiency.[42]

Post infective

Post infective bronchiectasis is diagnosed in patients with a history of significant childhood infection such as whooping cough (pertussis), tuberculosis, complicated measles and pneumonia. A recent study has shown a marked decrease in post-infectious cases, attributed to the UK vaccination programme and the increase in availability of antibiotics.[41] It is essential to exclude immunodeficiency in patients with a “post-infective history” as patients with primary immune disorders often have a history of severe infections at an early age. There has been some discrepancy between the definitions for post infective bronchiectasis: some studies require bronchiectasis symptoms to have started immediately after the initial insult, whereas others allow a 10 year symptom free period for a post infective diagnosis to be made.[40,43] It is also subject to negative recall bias.[40]

Figure 2. Aetiology of bronchiectasis in large cohorts reported to date. Abbreviations CTD= connective tissue disease, ABPA= allergic bronchopulmonary aspergillosis, CF= cystic fibrosis, PCD= primary ciliary dyskinesia, IBD= inflammatory bowel disease, COPD= chronic obstructive pulmonary disease, NTM= non-tuberculous mycobacteria.

Mucociliary Disorders

Failure of the mucociliary escalator leads to recurrent bacterial airway infection and development of bronchiectasis.[43] The most common of these disorders is Primary Ciliary Dyskinesia, a rare genetic disorder.[44] Ciliary function tests should be performed in patients with chronic upper respiratory tract problems, otitis media and male infertility.[12]

Immune deficiency

Bronchiectasis can be associated with almost any immune deficiency.[42] Identification of underlying immune defects is critical as specific treatment for the can be very effective. BTS Guidelines recommend all patients with bronchiectasis should be screened for serum immunoglobulin deficiencies as well as functional responses to vaccination.[12] In severe or complex patients, particularly if there is a history of recurrent non-pulmonary infections liaison with a clinical immunologist can be very valuable. The acronym SPUR (severe, persistent, unusual or recurrent infections) identifies the features of infections that should prompt referral to an immunologist. If in doubt, discuss, and refer.[45]

Allergic Bronchopulmonary Aspergillosis (ABPA)

ABPA is due to an excessive immune response to the fungus Aspergillus fumigatus leading to airway inflammation and damage.[46] It is an important diagnosis to make, as a specific treatment regime is needed, typically consisting of corticosteroids and the anti-fungal itraconzole.[47] It is classically associated with central bronchiectasis and colonisation with Staphylococcus aureus but investigations for ABPA should not be limited to patients with these characteristics.[48]  Early treatment of ABPA is important to prevent irreversible lung damage, and testing for ABPA should be performed in all patients, not only those with asthma and cystic fibrosis.

Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease caused by a mutation in the cystic fibrosis transmembrane conductance regular gene.[49] Although usually diagnosed by neonatal screening or presenting with a severe phenotype in childhood, milder phenotypes are increasingly recognised in adults with bronchiectasis. CF should be suspected in patients <40, particularly in the presence of malabsorption, infertility in males, upper lobe bronchiectasis and sputum cultures with growth of Staphylococcus aureus or Pseudomonas aeruginosa.[12]

Non-tuberculous mycobacteria (NTM)

Non-tuberculous mycobacteria are implicated as both an aetiological factor in bronchiectasis and also a complication of established bronchiectasis. Mycobacterium avium is by far the most common species isolated in the majority of series, with other less frequent isolates being Mycobacterium kansasii, Mycobacterium chelonae and Mycobacterium fortuitum.[50] Cross-sectional studies suggest a prevalence of 2-10% of patients in bronchiectasis centres.(12) As NTM can complicate established bronchiectasis, even if initial Mycobacterial cultures are negative it is recommended that patients have regular sputum cultures sent to monitor for NTM, which should also be repeated if the patient’s condition deteriorates. The management of NTM is outside the scope of this review and new guidelines will shortly be issued by international societies.

Table 1. Recommended investigation approach in newly diagnosed patients with non-CF bronchiectasis. *baseline antibody levels are tested followed by vaccination and remeasurement of antibody responses where they are low.^#induced sputum is a reasonable alternative in this latter situation.