Bronchiectasis
Bronchiectasis is a condition in which the airways are permanently dilated, causing mucus to build up and leading to recurrent infections. The burden of the disease on those affected is high, as chronic cough, phlegm and infections significantly impair quality of life.
Non-CF bronchiectasis
Bronchiectasis not caused by cystic fibrosis (non-CF bronchiectasis) …
- represent a heterogeneous group of conditions with many underlying causes and, as such, often pose a diagnostic and therapeutic challenge,
- are characterised by permanent dilation of the bronchi and bronchioles and a vicious circle of chronic infection and inflammation, mucus retention and damage to the airways,
- and, due to the significant clinical symptoms and the chronic, progressive course of the disease, are associated with an extraordinary burden and impairment of daily functioning for the patients affected.
Due to a glaring lack of epidemiological, basic scientific and clinical studies on non-CF bronchiectasis, the evidence base for most of the treatments used is poor. This is particularly evident in the fact that, even in 2018, there is still no approved pharmacological treatment for this indication, and necessary prescriptions must be issued outside the scope of their actual approval (‘off-label’).
What are bronchiectases?
Bronchiectasis in which cystic fibrosis (CF) has been ruled out as the cause are referred to as non-CF bronchiectasis. Treatment approaches aimed at loosening secretions and preventing infections are largely based on the treatment of cystic fibrosis, whilst anti-obstructive treatment regimens are derived from the treatment of COPD.
Bronchiectasis refers to a permanent dilation of the bronchi and bronchioles resulting from the destruction of the smooth muscle and elastic connective tissue. Most commonly, the condition begins with a narrowing of the bronchial tree caused by an infection, which, if it becomes chronic, can lead to the destruction of the epithelium. The disruption of mucociliary clearance results in secretion retention, which predisposes the patient to further infections.
In the past, bronchiectasis usually developed as a post-infectious complication following epidemics of whooping cough, measles and influenza. Today, the post-infectious route remains the most common cause in developing countries. In industrialised nations, the development of antibiotic treatments and vaccinations has led to a steady decline in the incidence of bronchiectasis caused by post-infectious factors. Currently, congenital causes are more common than post-infectious ones.
Causes
A wide variety of mechanisms can lead to the development of bronchiectasis, but the final pathophysiological outcome is the same.
It usually begins with damage to the bronchial epithelium caused by inflammation, with the surrounding tissue becoming infiltrated by inflammatory cells. The destruction of the neighbouring tissue leads to a bulging in the form of cylindrical, varicose and cystic dilations, accompanied by destruction of the surrounding structures. This, in turn, results in defective mucociliary clearance. This leads to secretory retention, which in turn promotes bacterial colonisation with chronic inflammation. Furthermore, there is a thickening of the bronchial mucosa, which histologically shows clear squamous metaplasia, without any increased evidence of malignancy being observed.
Post-infectious
Various respiratory infections can cause bronchiectasis, including:
- Pertussis
- Gram-negative bacteria (Pseudomonas aeruginosa, Haemophilus influenzae)
- Viruses (HIV, paramyxovirus, adenovirus and influenza)
- Tuberculosis
- Atypical mycobacteria.
Congenital causes
The most common congenital cause of non-CF bronchiectasis is primary ciliary dyskinesia (PCD). Inadequate ciliary beating leads to reduced mucus clearance, which in turn results in an increased rate of infection.
Another congenital cause is a mutation in the ENaC gene, which leads to a defective epithelial sodium channel. A hyperactive sodium channel causes a disturbance in salt and water homeostasis in the respiratory mucosa.
Chronic obstructive pulmonary disease
30–50% of patients with advanced chronic obstructive pulmonary disease (COPD) have bronchiectasis. These patients suffer increasingly from shortness of breath and have poor lung function. On CT scans, bronchiectasis in COPD differs morphologically from classic bronchiectasis, as the dilations themselves are not as pronounced, but there is marked peribronchial infiltration. With the rising prevalence of COPD worldwide, bronchiectasis is also becoming increasingly significant.
clinic
Patients with bronchiectasis complain of chronic cough, sputum production and lethargy. Coughing up blood, chest pain, weight loss, bronchospasm, shortness of breath and reduced physical performance may also occur. The frequently mentioned three-layered sputum, consisting of a frothy upper layer, a mucous middle layer and a thick, purulent sediment, is typical of the condition but does not always occur. Some patients are symptom-free in daily life and only show clinical signs during an exacerbation.
Many patients experience regular exacerbations, averaging around 1.5 per year. An exacerbation is defined as the presence of at least four of the following symptoms: increased sputum production with coughing, increased shortness of breath, a fever above 38 °C, increased wheezing, reduced exercise tolerance, fatigue, deteriorating lung function, and radiological signs of infection.
The rate of lung function loss in non-smokers with bronchiectasis is reported to be approximately 50 mL/year. Factors suggesting disease progression include frequent exacerbations, chronic colonisation with Pseudomonas aeruginosa, and evidence of systemic inflammation. In severe bronchiectasis, pulmonary hypertension and systolic and diastolic dysfunction of the left ventricle may also occur.
Diagnosis
A microbiological analysis of sputum is part of the standard diagnostic procedure for bronchiectasis. As the disease progresses, with repeated exacerbations and negative sputum results, a bronchoscopy is indicated to obtain a sample.
The method of choice is high-resolution computed tomography. Often, the nature and location of the radiological changes can already provide clues as to the cause. Bronchiectasis in the proximal airways is typical of allergic bronchopulmonary aspergillosis, whilst multiple nodular bronchiectasis may indicate an infection with Mycobacterium avium complex.
Therapy
There are numerous treatment options for bronchiectasis:
e.g. by replacing missing immunoglobulins in cases of congenital immunodeficiency
e.g. by inhaling a 3–7% saline solution in combination with daily respiratory physiotherapy / autogenic drainage, and rehabilitation measures
e.g. through vaccinations against influenza, pneumococci, whooping cough and Haemophilus influenzae type b, and, where necessary, through antibiotics, including in inhaled form for chronic infections caused by the problematic pathogen Pseudomonas aeruginosa
e.g. by inhaling bronchodilators (beta-agonists or anticholinergics) in accordance with the degree of impaired lung function
e.g. through anti-inflammatory treatment with the macrolide antibiotic azithromycin
(exacerbation), e.g. with antibiotics in tablet form or as an infusion
Summary
Thanks to improved antibiotic treatments and vaccination programmes, congenital causes of bronchiectasis are now more common than post-infectious causes. Various mechanisms lead to bronchiectasis – yet the pathophysiological outcome, involving inflammation and tissue destruction, remains the same.
A sputum sample should be taken for diagnostic purposes; if imaging is used, high-resolution computed tomography is the method of choice.
Treatment of the underlying condition should always be taken into account. The core of the treatment comprises respiratory and physiotherapy measures. Treatment of exacerbations should be carried out in accordance with the results of pathogen diagnosis and antibiotic susceptibility testing. The additional administration of inhaled antibiotics or macrolides must be considered on a case-by-case basis. Surgical options are available for locally confined bronchiectasis.