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Management of bronchiectasis

Dr. Susanna So-Shan Ng
Division of Respiratory Medicine
Department of Medicine and Therapeutics
Chinese University of Hong Kong
10 Dec 2019

Introduction

Bronchiectasis is a major chronic disease associated with progressive and irreversible dilatation of the bronchi and is characterized by frequent respiratory tract infections as well as chronic symptoms of cough and sputum production, with a significant impact on patients’ quality of life.1, 2 The prevalence is age-related, with some geographical variation reported in incidence, prevalence and clinical features. In a recent large multicentre dataset collated from across Europe, the majority of non-cystic fibrosis (CF) bronchiectasis cases were found to be idiopathic, with postinfectious cause being the most commonly identified. Chronic obstructive pulmonary disease (COPD)-related bronchiectasis was associated with a higher Bronchiectasis Severity Index (BSI) score.3 Although idiopathic bronchiectasis is still common among Asian countries, postinfectious aetiologies are predominant across Asia, especially secondary to tuberculosis.4

Bronchiectasis is associated with repeated exacerbations, which occur at rates of 1.5–6.5 episodes per patient per year,5, 6 as well as an increased risk of hospital admission and readmission and high healthcare costs. In Hong Kong, idiopathic disease predominates (82 percent), and patients with bronchiectasis are mainly female with high hospitalization and mortality rates (21.9 cases per 100,000 and 2.7 cases per 100,000, respectively).7, 8 Moreover, exacerbation characterized by increased symptoms requiring antibiotic treatment is associated with disease progression and significant mortality.9, 10 In this article, we report a case of recurrent bronchiectasis exacerbation and discuss the use of macrolide in updated treatment guidelines.

Presentation and management

A 40-year-old security guard presented to our respiratory clinic with recurrent chest infection for 1 year. He was diagnosed with bronchiectasis at the age of 20 years, with recurrent sputum culture showing Haemophilus influenzae, Klebsisella species and Pseudomonas aeruginosa. He had no family history of ciliary dyskinesia or lung disease, and had no definite childhood measles or chest infection. He had been a nonsmoker.

The patient presenting complaint was recurrent and increased production of greenish sputum with cough, which usually resolved after a course of antibiotics. His exercise tolerance was reduced to one flight of stairs only. Physical examination revealed bilateral finger clubbing and coarse crepitations during auscultation at bilateral lung. Spirometry showed an obstructive pattern, with forced expiratory volume in 1 second (FEV1) at 46 percent predicted while FEV1/forced vital capacity (FVC) ratio was 56 percent without reversibility. Chest X-ray showed peribronchial thickening at bilateral lower zones. (Figure 1) CT scan showed bilateral diffuse moderate-degree bronchiectatic lung changes involving all lung lobes. The left lingular segment and right middle lobe were most affected, with cystic appearance. (Figure 2)

CUHK1

CUHK2 

After the introduction of inhaler therapy for concomitant COPD and education on airways clearance techniques, he still experienced more than four exacerbations per year with sputum growing organisms not restricted to P. aeruginosa. Low-dose clarithromycin (250 mg daily) was started and well tolerated. At 12-month follow-up after the initiation of long-term low-dose clarithromycin therapy, the patient reported decreased sputum production and no further exacerbation.

Discussion

Investigation for bronchiectasis is recommended in patients with persistent production of mucopurulent or purulent sputum, especially in those with COPD, which is a common comorbidity. In patients with bronchiectasis, spirometry is recommended and the use of inhaler therapy should be maximized. Updated guidelines also recommend considering bronchiectasis in patients with COPD with frequent exacerbations (≥2 episodes annually) and/or positive sputum cultures for potentially pathogenic micro-organisms while stable.6 Investigation for bronchiectasis should include a baseline chest X-ray, which is a useful first-line test to exclude other pathologies, and a thin-section CT of the chest, as chest X-ray lacks both sensitivity and specificity in the diagnosis of bronchiectasis.

 

Monitoring in patients with bronchiectasis involves the use of a severity score such as the BSI, thin-section chest CT scan, sputum culture for bacteria and mycobacteria, assessment of aetiology and comorbidities, as well as baseline spirometry and oxygen saturation. Annual follow-up involves measurement of Body Mass Index, assessment of exacerbations, sputum culture for bacteria, measurement of Medical Research Council (MRC) dyspnoea score, as well as spirometry and oxygen saturation evaluation.

The BSI score is a strong predictor of 1-year and 4-year morbidity and mortality for patients with non-CF bronchiecastis.11 This severity assessment tool was also found to provide excellent predictions of hospital admissions, exacerbations and quality of life. (Table)

CUHK4

Macrolide antibiotics are widely used in the treatment of infection, providing broad-spectrum coverage against Gram-positive bacteria such as Streptococcus pneumoniae, and intracellular bacteria such as Mycoplasma pneumoniae, Chlamydia and Legionella species. In addition to their antimicrobial activity, 14- and 15-member-ring macrolides (roxithromycin, clarithromycin, erythromycin and azithromycin) have been used as anti-inflammatory and immunomodulatory drugs in several respiratory diseases, such as diffuse panbronchiolitis and persistent uncontrolled asthma,12,13 because of their inhibition of proinflammatory cytokine synthesis and secretion, as well as their effects on neutrophil activity via inhibition of neutrophil migration to sites of inflammation.
14, 15 The latest bronchiectasis treatment guidelines published by the British Thoracic Society recommend  long-term macrolide treatment for patients with ≥3 exacerbations per year without P. aeruginosa infection.6 (Figure 3)

CUHK3

A recent meta-analysis, conducted using individual participant data from three randomized controlled trials carried out in the Netherlands, Australia and New Zealand,16-18 found that long-term macrolide treatment significantly reduced the frequency of exacerbations.19 However, the conclusion of equal benefit in all subgroups was likely premature as the sample size of each subgroup was small and a mixture of effect of erythromycin and azithromycin was seen in different studies. Nevertheless, there was a trend for greater benefit of treatment in patients ≥50 years of age. Another limitation of the meta-analysis was that the severity of bronchiectasis (eg, radiological extent of disease) was not collected in the original trial databases.

It is also worth noting that clarithromycin, another macrolide with proven anti-inflammatory effect, was not investigated in bronchiectasis except in a paediatric study of limited sample size.20

The use of macrolide antibiotics requires careful monitoring of adverse effects and subsequent evaluation of response, aiming at detection of cardiotoxicity, ototoxicity and hepatotoxicity. Moreover, colonization of non-tuberculous mycobacteria needs to be excluded.

More treatment options supported by updated guidelines and recent literature have become available for bronchiectasis. Multidisciplinary collaboration among physicians, physiotherapists and pharmacists, as well as patient empowerment, are the keys to success in management of bronchiectasis.

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