BRONCHIECTASIS
Bronchiectasis is structural damage to conducting airways leading to
chronic cough, sputum production, recurrent infective exacerbations, and loss
of lung function. Bronchiectasis was first described in 1819 by Laennec as an
abnormal dilatation of bronchi and bronchioles caused by a vicious cycle of
airway infection and inflammation; this definition still holds true today.
Bronchiectasis is being diagnosed with increasing frequency both in the
developed and underdeveloped world because of improved diagnostic techniques
(high-resolution computed tomography [HRCT] scans) and awareness.
CAUSE
Causes of bronchiectasis may be categorized as an
underlying systemic disease or anatomic abnormality, postinfectious or
idiopathic. The most common causes differ by age (children vs. adults) and by
country.
Systemic Disease
The most important inherited cause of bronchiectasis
is cystic fibrosis (CF). CF is reviewed in Plates 4-45 to 4-47; the remainder of
this review focuses on non-CF bronchiectasis. Primary ciliary dyskinesia (PCD)
is another well-recognized cause of bronchiectasis. PCD is an autosomal
recessive, genetically heterogeneous disorder characterized by
oto-sino-pulmonary disease caused by abnormal structure and function of cilia.
Patients with PCD present with chronic rhinitis, recurrent otitis media and
sinusitis, neonatal respiratory distress, chronic cough, and situs inversus (in
50%). Nasal nitric oxide measurements are a valuable screening tool, with low
concentrations seen almost uniformly in patients with PCD. Evaluation of
ciliary ultrastructure from a nasal scrape remains the best method of
diagnosis. Most PCD patients (90%) have ultrastructural defects of cilia involving
the outer dynein arm (ODA), inner dynein arm (IDA), or both. Genetic diagnosis
is becoming increasingly possible. Mutations in DHAI1 and DNAH5 (encoding ODA
proteins) are found in about 40% of PCD patients with ODA defects.
α1-antitrypsin disease is
increasingly recognized as a cause of bronchiectasis. Although emphysema
remains the most common pulmonary feature, 27% of patients in one series had
clinically important bronchiectasis.
Immune deficiencies may contribute to bronchiectasis,
including IgG subclass deficiencies; hypogammaglobulinemia; or, more rarely,
chronic granulomatous disease or other causes of abnormal neutrophil adhesion,
respiratory burst, and chemotaxis. HIV/AIDS is also a risk factor for
bronchiectasis.
Autoimmune or immune-related diseases such as allergic
bronchopulmonary aspergillosis (ABPA), collagen vascular diseases (particularly
Sjögren syndrome and rheumatoid arthritis) and inflammatory bowel diseases may
be associated with bronchiectasis.
Anatomic Abnormality
Patients with chronic obstructive pulmonary disease
may have associated bronchiectasis, affecting up to 50% of those with severe
but stable disease in one series. Other anatomic lung diseases associated with
diffuse bronchiectasis include tracheobronchomegaly
(Mounier-Kuhn disease), congenital cartilage deficiency
(Williams-Campbell syndrome), and yellow nail syndrome. Obstructive airway
lesions, such as endobronchial tumors, granulomatous disease, or foreign
bodies, may lead to focal bronchiectasis distal to the obstruction. Other
processes, such as unilateral hyper-lucent lung (Swyer-James syndrome) and
pulmonary sequestration, may also lead to focal bronchiectasis.
Postinfectious Bronchiectasis
The prevalence of postinfectious bronchiectasis plum-
meted in the developed world with the introduction of antibiotic therapy for
lower respiratory infections and routine childhood immunizations. However, it
remains the most common cause in the developing world. Although any lower
respiratory tract infection can potentially lead to bronchiectasis, infections
that place individuals at greatest risk include adenovirus, pertussis, measles,
and tuberculosis, as well as Klebsiella pneumoniae, Staphylococcus
aureus, and Haemophilus influenzae.
Nontuberculous mycobacteria (NTM), particularly Mycobacterium
avium complex (MAC), are associated with and may cause nodular bronchiectasis. MAC may present with
bronchiectasis, particularly of the lingula and right middle lobe, in
immunocompetent individuals without preexisting lung disease. The typical
patient is an elderly, thin, white woman. A joint statement on NTM disease by
the American Thoracic Society and the Infectious Disease Society of America
emphasized the role of NTM in bronchiectasis.
DIAGNOSIS
The diagnosis of bronchiectasis should be considered
in individuals presenting with chronic cough and sputum production. Other
symptoms may include dyspnea, hemoptysis, and systemic symptoms such as fatigue
or malaise. Among adults, bronchiectasis is more common in women than men.
Idiopathic bronchiectasis occurs most frequently in middle-aged women who are
lifelong nonsmokers. HRCT is the gold standard for diagnosis of bronchiectasis. Plain
radiography is insufficiently sensitive, and contrast bronchography no longer
plays a role. The extent of disease on HRCT has been correlated with functional
change and clinical outcomes.
An underlying cause of bronchiectasis is more
frequently identified in children than in adults. In two series from the United
Kingdom, among 136 children, the cause of bronchiectasis was identified as an
immunodeficiency in 34%, aspiration in 18%, PCD in 16%, and idiopathic in 25%.
In two adult series from the United Kingdom, idiopathic bronchiectasis was
diagnosed in 25% to 47% of individuals.
Examinations to consider in patients with HRCT-
diagnosed bronchiectasis may include a sweat chloride test and CF genetic
analysis to evaluate for CF, nasal nitric oxide and nasal scrape for PCD,
immuno-deficiency evaluation (quantitative immunoglobulins with IgG subclasses,
antibody response to vaccines with tetanus, H. influenzae), barium
esophagram for gastroesophageal reflux, α1-antitrypsin levels, sputum culture,
and acid-fast baeilli (AFB). In focal bronchiectasis, evaluation for an airway
lesion should be considered.
CLINICAL COURSE
The clinical course of non-CF bronchiectasis is highly
variable, depending on the underlying cause and management. Some individuals
have daily symptoms, frequent exacerbations, and progressive loss of lung
function, but others have minimal daily symptoms and relative preservation of
lung function. Factors associated with more rapid decline in lung function
include colonization with Pseudomonas aeruginosa, more frequent
exacerbations, and evidence of systemic inflammation.
MANAGEMENT
There have been few randomized, controlled trials of
therapies in individuals with bronchiectasis, partly because of the
heterogeneity of the disease. Although the rationale for therapy may be similar
in CF and non-CF bronchiectasis, therapies must be tested specifically in this
population. For example, because in general, lung function and mortality are
less impacted in non-CF bronchiectasis, therapies may be best directed to
decreasing exacerbation rates rather than slowing lung function decline.
Whereas rhDNase is a mainstay of therapy in CF, it has been demonstrated to have
an adverse safety profile in adults with bronchiectasis.
Airway Clearance
Although airway clearance techniques are a mainstay of
treatment in non-CF bronchiectasis patients, there are no long-term trials in
this population. There is also interest in inhaled hyperosmolar agents such as
7% saline and mannitol to rehydrate airway surface liquid. Mechanical clearance
techniques, such as chest physiotherapy and flutter valves, are useful but less
proven in non-CF
bronchiectasis as important methods of airway clearance.
Antibiotic Therapy
Treatment of exacerbations should be undertaken with
antibiotics tailored to the most recent sputum culture. The most common
organisms isolated from patients with bronchiectasis include nonenteric
gram-negative rods, S. aureus, and nontuberculous mycobacteria. About
one-third of adults with bronchiectasis are chronically colonized with P.
aeruginosa. For patients with chronic P. aeruginosa colonization,
agents include intravenous antibiotics and oral ciprofloxacin. A recent study showed
modest microbial benefit but no clinical benefit to the addition of inhaled
tobramycin to oral ciprofloxacin for the treatment of acute exacerbations caused
by infection with P. aeruginosa.
The role of maintenance or prophylactic antibiotics is unclear. Several small pilot studies with agents,
including inhaled tobramycin, inhaled colistin, and rotating oral antibiotics, have suggested potential
for microbiologic and clinical stability, but longer term studies with more attention to acquisition of resistant
organisms are needed.
Antiinflammatory Therapy
Inhaled corticosteroids may reduce airway inflammation
and improve clinical outcomes in adults with bronchiectasis, but the long-term
safety profile is unclear. In small pilot studies, oral macrolides (erythromycin
and azithromycin) may improve lung function and reduce exacerbations, but
larger scale trials are needed. Caution must be taken to avoid improper
treatment of unrecognized NTM infection, thus causing the emergence of
resistant organisms.
Surgery
Surgery may be indicated for resection of areas of
focal bronchiectasis hat have led to uncontrolled infection or hemoptysis.
