Bronchiectasis is a lung disorder in which one or more bronchi (air passages leading from the trachea) are abnormally widened and distorted, with damaged linings. Bronchiectasis commonly develops during childhood and was once associated with infections such as measles and pertussis (whooping cough). The condition may also be a complication of  cystic fibrosis. Bronchiectasis results in pockets of long-term infection within the airways and the continuous production of large volumes of green or yellow sputum (phlegm). Extensive bronchiectasis may cause shortness of breath. Symptoms are usually controlled with antibiotic drugs and postural drainage,a technique that clears secretions from the lungs. If the condition is confined to one area of lung, surgical removal of the damaged area may be recommended.

Bronchiectasis in more detail

Bronchiectatic lung contains permanently dilated subsegmental airways that are inflamed, tortuous, and often partially or totally obstructed with secretions. It arises as a result of the combination of an infectious insult with associated impaired clearance mechanisms: local obstruction and infection distal to the obstruction are both required. Causes include developmental defects, immune deficiency, mucociliary clearance defects and mechanical obstruction, but in many cases (40–60%) the cause is unknown.

Clinical features

Investigation

Immune deficiency

Immune deficiency is an important cause of bronchiectasis because treatment with immunoglobulins, where appropriate, will correct the defect and should prevent progression of the condition.

Childhood bronchiectasis should trigger an extensive assessment of phagocytic and cellular immune defences. X-linked hypogammaglobulinaemia, a rare disorder, presents early in life, with bronchiectasis a frequent complication if untreated. Adult-onset acquired panhypogammaglobulinaemia frequently presents with recurrent respiratory infection and is complicated by bronchiectasis if untreated. Selective immunoglobulin deficiencies of IgG and IgM, and IgG subclass deficiencies are also treatable causes of bronchiectasis.

The importance of functional antibody deficiencies in the presence of normal immunoglobulin levels has been recognized as a risk factor for recurrent respiratory tract infections and development of bronchiectasis. In subjects with low levels of specific antibodies it is advisable to evaluate the antibody response to both the Haemophilus influenzae type b conjugate vaccine as well as pneumococcal vaccine. Failure to mount and maintain adequate responses to antigen challenge may be associated with bronchiectasis and represent a risk for more severe disease. Patients with functional antibody deficiency and normal immunoglobulin levels can be managed with antibiotic therapy but may require immunoglobulin therapy if there is evidence of disease progression despite best antibiotic therapy.

Immune defects may be secondary to malignancy or be related to treatment with immunosuppressive agents. In addition, bronchiectasis is now a recognized complication of HIV disease.

Excessive immune response

Damage may occur as a result of the host response to chronic airway infection. ABPA is a condition in which the excessive reaction to a ‘noninfecting’ organism seems to be the main factor in producing the associated characteristic proximal upper-lobe bronchiectasis. The appearance of obliterative bronchiolitis and subsequent bronchiectasis in lung transplant rejection further highlights the role of a damaging immune response in the development of the condition.

Disorders of mucociliary clearance

Cystic fibrosis provides the archetypal model of a genetic predisposition for the development of bronchiectasis. In this disorder (described in Chapter 18.10) there is dysfunction of the cystic fibrosis transmembrane regulator (CFTR), a transmembrane chloride channel and ion transport regulatory protein. The resulting abnormal salt and water transport across respiratory epithelia predisposes to respiratory infection and the effects of the vicious cycle are clearly demonstrated as a structurally normal lung suffers progressive airway damage and the development of bronchiectasis.

In primary ciliary dyskinesia (PCD) ineffective ciliary function impairs mucociliary clearance, leading to mucus retention and recurrent infections in the paranasal sinuses, middle ear, and lungs, with progression to bronchiectasis. It is an inherited disorder, mostly in an autosomal recessive pattern, with an estimated incidence of 1 in 15 000 to 1 in 30 000 births. The diagnosis is made on electron microscopic appearance, which indicates the component of the cilia affected. Nasal nitric oxide concentrations are extremely low in PCD and provide a useful screening test to identify patients for further investigation with nasal brush biopsy to examine of ciliary beat frequency and ultrastructural analysis with transmission electron microscopy. In the largest subgroup of this syndrome, in which electron microscopic appearances were originally described, the cilia were found to lack dynein arms, the structure responsible for movement of cilia or spermatozoa. Subsequently it has been appreciated that a range of components of the cilia are affected, but the link between the ultrastructural changes and the genetic defects have been difficult to unravel because defects in any of the 250 proteins that constitute a cilium could potentially result in disease. However, we are now a step nearer genetic testing as the gene that encodes the human intermediate dynein, DNAI1, has been shown to exhibit recessively inherited mutations in some PCD families. Furthermore, mutations in DNAH5, the gene encoding a heavy chain of the outer dynein arm, have been shown in almost one-half of PCD subjects that have defects of this dynein arm.

The intriguing observation that about 50% of all subjects with immotile cilia syndrome have situs invervus is true for most subgroups, apart from those who have absent cilia or those whose main characteristic is lack of the two central microtubules. When ciliary dyskinesia is associated with abnormal situs the condition is called Kartagener’s syndrome after the paediatrician who described four patients with the association of dextrocardia, sinusitis, and bronchiectasis in 1933.

Young’s syndrome seems to represent an acquired defect of mucociliary clearance in which obstructive azospermia is associated with sinusitis and broncheictasis. The condition may occur after successful parentage and may be associated with mercury poisoning from ‘tooth powders’ used in infancy (Pink’s disease). Secondary ciliary dyskinesia refers to the situation in which cilia are intrinsically normal but ciliary beating is reduced because of toxic damage from neutrophil or bacterial products. Tobacco smoke and other environmental pollutants have also been implicated in reducing ciliary beat frequency.

Toxic insult

In some patients, e.g. fire victims, there is a clear history of an inhalation accident or exposure to hot gases. Aspiration of gastric contents is another important cause of bronchiectasis, in that treatment to prevent aspiration will prevent further airway damage.

Mechanical obstruction

Bronchiectasis confined to a single lobe may be the result of a local mechanical obstruction either in the lumen (intrinsic), e.g. tumour or foreign body, or originating outside the lumen (extrinsic), e.g. from lymph node enlargement from tuberculosis or tumour.

Postinfective

The true incidence of postinfective bronchiectasis is difficult to confirm, as studies are retrospective, relying on histories obtained ‘second hand’ from parents. The microorganisms known to cause infection likely to progress to bronchiectasis are Bordetella pertussis, measles virus, adenoviruses, Trypanosoma cruzi, and Mycobacterium tuberculosis.

As mentioned above, the pattern of bronchiectasis has changed since the introduction of vaccinations and widespread availability of antibiotics in the developed world. The gross saccular bronchiectasis associated with severe repeated childhood respiratory infections in the preantibiotic era has been superseded by a population with cylindrical bronchiectasis, which may be associated with a childhood history of a chesty cough, a long period of remission of symptoms through teens and twenties, followed by the onset of symptoms of cough productive of purulent sputum and/or sinusitis in the third or fourth decade of life. Some of these patients may report a childhood episode of whooping cough or measles, but it is more useful not to label them as postinfective unless symptoms have been persistent, without remission since childhood.

Associated conditions

The association of rheumatoid arthritis with bronchiectasis is well recognized. Treatment needs to achieve the right balance of immunosuppression, which helps the underlying inflammatory disease process, but may impair antimicrobial defences. The association between inflammatory bowel disease and bronchiectasis highlights the usefulness of immunosuppression, as some patients with both conditions report an improvement in chest symptoms when they take systemic corticosteroids for flares of inflammatory bowel symptoms. Indeed, corticosteroid therapy is beneficial in bronchiectasis associated with ulcerative colitis.

Idiopathic

Even in specialist bronchiectasis clinics, the underlying cause of bronchiectasis remains unknown in 40 to 60% of patients, who are currently labelled as having ‘idiopathic’disease.

Clinical Features

History

Bronchiectasis should be suspected when there is a history of persistent cough productive of mucopurulent or purulent sputum throughout the year. Patients have often been treated for recurrent chest infections and labelled as ‘bronchitic’, often despite the absence of a smoking history. Patients presenting in adulthood often recall a ‘chesty cough’ or ‘wheezy bronchitis’ associated with upper respiratory tract infections in childhood. They then report a complete resolution of symptoms in teens and early adult life but return of symptoms after a viral trigger.

Early in the disease patients may produce mucoid sputum until they suffer an exacerbation associated with viral upper respiratory tract infection, when the sputum becomes purulent. Exacerbations may be associated with pleuritic chest pain, haemoptysis, and fever, and patients may also become wheezy.

About 80% of patients with bronchiectasis have upper respiratory tract symptoms, with postnasal drip being the most common. About 30% have chronic sinus sepsis, with fewer having recurrent ear infections, although the latter are almost invariably present in ciliary dyskinesia. Patients with bronchiectasis also suffer from undue tiredness, which many find more troublesome than the productive cough.

Examination

‘Classical’ severe cases of bronchiectasis seen in the preantibiotic era or in less developed countries are associated with obvious clinical signs including finger clubbing and widespread coarse crackles. Nowadays it is much more likely for clinical examination to be normal: the absence of clubbing or lung crackles does not exclude bronchiectasis.

Pulmonary function tests often show airflow obstruction, but mild restriction is also recognized, particularly in patients with loss of volume in a single lobe.

Radiological imaging

The gold standard for the diagnosis of bronchiectasis is thin-section high-resolution CT of the chest, which has replaced the more invasive investigation of bronchography. The diagnostic criteria for bronchiectasis on high-resolution CT depend on the findings of both dilatation and thickening of the affected bronchi. Dilatation is present if the internal diameter of the bronchus is greater than the diameter of its accompanying pulmonary artery. The classic appearance of a cross-section of a thick-walled dilated bronchus next to the accompanying pulmonary artery is the ‘signet ring’. Bronchial dilatation is also recognized when airways are seen in longitudinal section on CT and there is a failure of tapering as the bronchus courses towards the periphery.

There is a morphological spectrum of bronchiectasis, with cylindrical broncheictasis forming one group, cystic or saccular broncheictasis at the other end of the spectrum, and an intermediate group termed varicose broncheictasis also recognized. The CT appearances are well described: in cylindrical bronchiectasis there is uniform dilatation of the bronchi as they extend towards the periphery; cystic bronchiectasis is recognized by rings representing the markedly dilated bronchi, which may be clustered together and may contain air fluid levels; varicose bronchiectasis produces a beaded appearance, best shown when bronchi are imaged in the plane of the scan.

In addition to defining the extent of bronchiectasis, CT scanning may suggest the need for bronchoscopy, e.g. if there is a bronchial obstruction, possibly due to foreign body or tumour.

The chest radiograph is normal in at least 50% of patients with CT or bronchographic evidence of bronchiectasis. If the chest radiograph is abnormal, the findings relate to abnormal thickened and dilated bronchi which produce tramline opacities and ring shadows. Retained mucus may be manifest as tubular opacities, and there may be associated volume loss of the affected lobe.

Determining the state of disease

Once high-resolution CT has proven the presence of bronchiectasis, investigations are directed at defining the current status of the disease and then at attempting to define an underlying cause. 

Examination of a sputum specimen is crucial, it being important to document the character of the sputum, i.e. mucoid or purulent, and to determine the colonizing organism. The typical colonizing organisms are nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. H. influenzae is the most common (40–60%). P. aeruginosa is usually associated with worsening symptoms and more severe lung disease. As patient’s sputum microbiology may alter over time it is helpful to obtain repeated samples to ensure that an appropriate antibiotic management plan is in place.

Measurement of inflammatory markers allows an assessment of the patient’s current ‘inflammatory burden’. Patients may come to accept persistent purulent sputum over a period of time and not complain of being particularly unwell, in which case a raised erythrocyte sedimentation rate and/or C-reactive protein would weight the argument in favour of early antibiotic intervention.

Determining the cause of disease

It is important to recognize that ABPA is a treatable cause of bronchiectasis, with corticosteroid treatment producing major improvements in symptoms and well being, restoring lung function, and preventing the development of further bronchiectasis. Similarly, the appreciation that chronic aspiration is the precipitant of lung damage leads to appropriate therapeutic manoeuvres aimed at prevention of further damage.

Opportunistic mycobacteria in bronchiectasis

Primary infection with the Mycobacterium avium complex is a recognized cause of bronchiectasis, particularly in white women over 60 years of age. In contrast to reported families suffering from disseminated opportunistic mycobacterial infection, this has not been shown to be associated with mutations in the interferon-γ receptor pathway, but the possibility remains that these patients have a defect in processing of intracellular pathogens that has yet to be identified.

Infection with the opportunistic (sometimes called nontuberculous) mycobacteria can also complicate pre-existing bronchiectasis. It is therefore important to obtain cultures for acid-fast bacilli at first assessment and when there is deterioration in clinical status.

Cystic fibrosis/bronchiectasis overlap

The diagnosis of cystic fibrosis should be considered in any patient with unexplained bronchiectasis, but particularly in the presence of upper lobe bronchiectasis or colonization with Staphylococcus aureus and P. aeruginosa, and also in the presence of aspergillus and nontuberculous mycobacteria. Male infertility and a family history are useful pointers when present, but a normal sweat test does not exclude the diagnosis, in particular in mutations which produce mild disease. The diagnostic label of atypical cystic fibrosis has been coined to describe patients with mild nonclassic cystic fibrosis: where there is diagnostic doubt the patient should be referred to a specialist cystic fibrosis centre for further investigations.

Management 

The principles of management of bronchiectasis are outlined below:

Principles of management of bronchiectasis:

• ◆ Medical treatment specific to the determined cause of bronchiectasis (if available)
• ◆ Medical treatment for bronchiectasis:
  • • Sputum clearance
  • • Physiotherapy
  • • Mucolytic therapy
  • • Antimicrobial therapy
  • • Chronic prophylactic therapy
  • • Acute exacerbation
  • • Anti-inflammatory therapy
  • • Bronchodilator therapy
• ◆ Surgical treatment:
  • • Resection of ‘single’ lobe bronchiectasis
  • • Lung transplantation for endstage disease 

The medical approach is two-pronged, with close attention given to treating any underlying cause while also treating the established bronchiectasis.

Sputum clearance

As mucociliary clearance is reduced in bronchiectasis, it seems sensible to aid sputum clearance by employing physiotherapy. This does not simply prevent mucus retention but also allows a patient to expectorate sputum at a chosen convenient time, rather than coughing throughout the day or night. There are no controlled trials to prove or disprove its usefulness in terms of disease modification or survival.

The use of mucolytics in bronchiectasis is controversial: the success of recombinant human DNase in cystic fibrosis was not repeated in patients with bronchiectasis not due to cystic fibrosis, with those treated showing an accelerated decline in lung function and an increase in exacerbations.

New approaches currently under investigation to enhance mucociliary clearance in bronchiectasis include the use of nebulized hypertonic saline and inhalation of dry powdered mannitol.

Antimicrobial therapy

There are two approaches to the use of antimicrobial therapy in bronchiectasis: one involves the treatment of acute exacerbations; the other is based on the ‘vicious cycle’ hypothesis, suggesting that chronic targeted antimicrobial therapy should reduce bacterial numbers, thereby reducing the host response and hence reducing the potential for further lung damage. Whilst the latter approach has theoretical merits it has not been proved in randomized controlled trials. The modern approach to antimicrobial treatment in bronchiectasis has been derived from regimens used in cystic fibrosis which have yielded impressive improvements in survival. 

Developing an antibiotic regime for treatment of bronchiectasis depends on knowledge of a patient’s colonizing organism, but several principles apply regardless of the bacterial species. First, high doses are often required to penetrate scarred, thickened bronchial walls, and the tenacious secretions act as a physical barrier to reduce antibiotic penetration to the microbes while harbouring drug-inactivating enzymes such as β-lactamases. Secondly, to avoid a high oral dose of an antibiotic, which may result in unacceptable side effects, the nebulized or parenteral route is often employed to achieve high levels of drug in the bronchial wall and secretions. Thirdly, to determine the best treatment regimen for a patient it is worth assessing their initial response to an agent appropriate for the colonizing organism, in particular the rapidity of return of purulent sputum. If purulent sputum becomes mucoid after a 14-day course of oral antibiotics and remains mucoid until the next viral trigger, then one is likely to recommend ‘exacerbation only’ treatment. By contrast, if sputum returns to purulent within a few days of treatment finishing, it is likely that chronic suppressive therapy will be required.

Bronchodilator therapy

Patients with bronchiectasis may have a restrictive or an obstructive picture. Some patients will have significant reversibility, hence it is worth assessing each individual for their response to β₂-agonists and anticholinergic agents.

Anti-inflammatory therapy

The ‘vicious cycle’ hypothesis suggests that the addition of anti-inflammatory therapy to antibiotics should be of benefit. Trials of oral corticosteroids have shown significant benefit in terms of lung function in cystic fibrosis. Short-term trials of inhaled corticosteroids have been carried out in bronchiectasis, but the evidence for long-term use is limited and further trials are required. There is a suggestion that patients chronically infected with P. aeruginosa may be more likely to benefit from inhaled corticosteroids in terms of reduction in sputum volume and exacerbation frequency, and it is worth noting that where there is reversible airflow obstruction a trial of steroids is warranted. If there is a documented improvement in lung function after a 2-week course of oral steroids, then one is justified in introducing inhaled steroids.

Monitoring response to treatment

As each patient requires a tailored management plan, it is critical that both the patient and physician agree defined criteria for assessing response. Clearly lung function produces an objective measure of response to corticosteroids, but the introduction of antibiotics may not alter lung function to a great degree, although it does improve sputum colour, volume, and consistency, and there may be improvement in general well-being. Diary cards documenting these parameters have proved helpful, and studies have confirmed the validity of grading sputum colour as a marker of the microbial and inflammatory load in these patients. This approach also facilitates patient education and self-management plans.

Surgery

Surgery is the only ‘curative’ treatment for a select group of patients and should be carefully considered. In particular, for single-lobe, focal bronchiectasis secondary to bronchial obstruction, surgery removes the need for lifelong medical therapy. However, it is important that patients undergo careful assessment regarding the distribution of bronchiectasis and the possibility of underlying causes which would predispose to disease progression. Surgery is unlikely to produce a cure if bronchiectasis is present in several lobes, and lobar resection is then indicated only if there is uncontrolled bleeding unresponsive to bronchial artery embolization, or if it is felt—after a failure of aggressive antimicrobial therapy—that a particular lobe is acting as a ‘sump’ of infection which prevents good control of symptoms with medical therapy.

Lung transplantation

Lung transplantation provides an effective treatment for endstage bronchiectasis, providing that an underlying cause has been carefully assessed and treated and is unlikely to jeopardize the transplanted organs; e.g. patients with immunoglobulin deficiencies are not discounted from transplant assessment provided they are receiving adequate immunoglobulin replacement therapy.

The most common complication to precipitate hospital admission in patients with bronchiectasis is infective exacerbation, which may be associated with pleuritic chest pain and minor haemoptysis. Massive haemoptysis is rare nowadays, but is managed by bronchial artery embolization. Metastatic spread of infection rarely occurs in the developed world with good control of pulmonary infection with antibiotics, and for similar reasons empyema is now very rare. Amyloidosis is described as a ‘classic’ complication of bronchiectasis, but is now extremely rare in the United Kingdom. Arthropathy is a complication of bronchiectasis which seems to flare in association with the chest disease, and antimicrobial treatment will often result in remission of joint pain. Some patients may suffer vasculitic skin lesions in association with flares of bronchiectasis.

Prognosis

It was reported in 1940 that 70% of 400 patients with bronchiectasis were dead before the age of 40. The situation is clearly different now, as in the developed world we do not see the florid postinfective saccular type of bronchiectasis, but more commonly see patients presenting in their fourth and fifth decade of life with symptoms developing after a trigger illness and CT findings of cylindrical bronchiectasis. In 1981a study following 116 patients for 14 years revealed that only 20% of patients treated medically and 17% of surgically treated patients died at a mean age of 53 years. A Finnish study published in 1997 used the national hospital discharge register to identify patients with newly diagnosed bronchiectasis from 1982 to 1986, comparing them with 842 age- and sex-matched patients with chronic obstructive pulmonary disease (COPD) and asthma discharged at the same time. Over a 10-year follow-up the prognosis for those with bronchiectasis was better that that for patients with COPD but poorer than that those with asthma. Bronchiectasis was the main cause of death in 13% of patients with the condition.

Further studies are required to identify the main factors which affect prognosis. For example, chronic colonization with P. aeruginosa may be a bad prognostic factor, but this may be negated by aggressive antimicrobial therapy, hence study of homogenous groups of patients (with respect to aetiology and colonizing organisms) should help assess various management regimens with regard to their effect on decline in lung function and survival.

It is likely that a careful search for genetic factors which affect lung defences will yield new causes of bronchiectasis and allow the current so called ‘idiopathic’ group to be assigned a cause.

The role of the macrolide antibiotics as immunomodulators in chronic airway inflammation and infection, with well-defined benefits in cystic fibrosis, has led to preliminary studies in bronchiectasis which suggest that large trials are warranted.