Bronchiectasis

Definition, Etiology, PathogenesisTop

Bronchiectasis is a permanent abnormal dilation and destruction of bronchial walls, which involve both the major bronchi and bronchioles.

The pathophysiology of bronchiectasis is often described as a vicious cycle: an underlying infection or inflammation leads to airway remodeling, and with abnormal dilation and destruceuction of bronchial walls, patients are unable to adequately mobilize secretions. This leads to neutrophilic inflammation and bacterial overgrowth, and the ongoing recurrent infections and inflammation starts the cycle over again. The process is progressive, as patients have worsening obstructive lung disease and develop chronic bacterial colonization and antimicrobial resistance.

Classification:

1) Congenital bronchiectasis is associated with impaired mucociliary clearance (cystic fibrosis [CF], Young syndrome [bronchiectasis with normal ciliary structure, sinusitis, bronchitis, oligospermia, azoospermia], primary ciliary dyskinesia [bronchiectasis, nonseasonal rhinosinusitis, neonatal respiratory distress syndrome, laterality defects including situs inversus]), primary immunodeficiencies, alpha1-antitrypsin deficiency, and other rare congenital diseases.

2) Acquired bronchiectasis:

a) Infectious causes include childhood respiratory infections (especially pertussis, measles) or prior severe or necrotizing pneumonias. Mycobacterial infections (nontuberculous mycobacterium [NTM] disease, tuberculosis [TB]), secondary immunodeficiencies (leading to chronic or recurrent infections), and HIV may also lead to bronchiectasis.

b) Allergic causes include allergic bronchopulmonary aspergillosis (ABPA).

c) Inhalational and obstructive airway etiologies include aspiration/reflux, toxic inhalation or thermal injury, foreign bodies, and endobronchial lesions. This typically leads to focal bronchiectasis.

d) Inflammatory/autoimmune causes include rheumatoid arthritis and inflammatory bowel disease, among others.

e) Pulmonary fibrosis with associated traction bronchiectasis.

Clinical Features and Natural HistoryTop

1. Symptoms: The most common symptom is chronic cough (≥90%) with production of large amounts of sputum, usually purulent. In some cases exertional dyspnea, wheezing, hemoptysis, recurrent lower respiratory tract infections, and low-grade fever may be present.

2. Signs: Fine and coarse crackles, sometimes bronchial breath sounds, prolonged expiration, wheezes. Patients with advanced disease may develop cyanosis, clubbing of digits, and cachexia.

3. Acute exacerbations are defined by deterioration of ≥2 of the following symptoms lasting ≥48 hours and accompanied by a change in the management, with exclusion of other potential causes: cough, sputum volume, sputum purulence, dyspnea, fatigue/malaise, and hemoptysis. If available, spirometry can be helpful, as a drop in the forced expiratory volume in 1 second (FEV1) from the patient’s baseline is further evidence of a likely pulmonary exacerbation.

4. Natural history: The onset is insidious, with a progressive development of chronic productive cough, which can be followed by gradually developing respiratory failure. Notably, Pseudomonas aeruginosa colonization is associated with higher rates of exacerbations and a worse prognosis.

5. Microbiology: Sputum microbiology is important to monitor in bronchiectasis, as it helps guide antimicrobial choice during exacerbations. The presence of these organisms may also serve as a signal for clinicians to investigate for bronchiectasis. Typical microbiology in non-CF bronchiectasis includes Haemophilus influenzae, Streptococcus pneumonia, Moraxella catarrhalis, and P aeruginosa. Less common organisms include Staphylococcus aureus, Stenotrophomonas maltophilia, and Achromobacter. Mycobacterial cultures should also be assessed, as nontuberculous mycobacteria can lead to bronchiectasis or colonize patients with bronchiectasis.

DiagnosisTop

Diagnostic Tests

1. Imaging studies:

1) Chest radiography: Chest radiographs can be normal at the early stage of the disease. In patients with advanced bronchiectasis, possible findings include linear atelectasis; peripheral opacifications from mucous plugging; cystic air spaces (some with fluid levels); volume loss; and thickened, dilated bronchial walls demonstrating a “tram tracks” appearance.

2) High-resolution computed tomography (HRCT): HRCT is the gold standard test to confirm the diagnosis of bronchiectasis. Furthermore, the distribution of bronchiectasis on HRCT is often useful in narrowing the differential diagnosis. Diagnostic features include a bronchoarterial ratio >1 to 1.5 (“signet ring” sign), lack of bronchial tapering, and presence of bronchial structures within <1 cm from the chest wall. Other indirect signs include bronchial wall thickening, mucous impaction, and mosaic attenuation/air trapping on expiratory scans.

2. Bronchoscopy should be considered in patients with localized bronchiectasis, a short history of symptoms, hemoptysis, and/or an inability to expectorate. Bronchoscopy may be helpful in these patients to exclude an endobronchial lesion or foreign body or to provide microbiologic samples. Typically it is not required in those with diffuse disease who are able to expectorate.

3. Other studies may be used to diagnose underlying conditions, including sputum cultures, tests for primary or secondary immunodeficiencies (IgG, IgA, IgM, and/or serum protein electrophoresis), and investigations for allergic bronchopulmonary aspergillosis (complete blood count [CBC] with differential to assess peripheral eosinophilia, total IgE, and Aspergillus sensitization testing via Aspergillus-specific IgE or Aspergillus skin prick testing). Investigations for congenital causes such as CF (with sweat chloride testing and genetic screen) and primary ciliary dyskinesia (via nasal nitric oxide testing, genetic screen, or both) should be tailored to the patient’s risk factors. Consider testing for rheumatoid factor (RF), anti–cyclic citrullinated peptide (anti-CCP) antibodies, antinuclear antibodies (ANAs), and antineutrophil cytoplasmic antibodies (ANCAs) in patients with coexisting rheumatologic features of arthritis, connective tissue disease, and/or systemic vasculitis. Further investigations may be warranted in cases of panacinar emphysema (testing for alpha1-antitrypsin deficiency), HIV risk factors (HIV serology), symptoms of aspiration/reflux (videofluoroscopic swallow study), and inflammatory bowel disease (colonoscopy).

4. Sputum microbiology testing (culture and acid-fast bacilli [AFB] testing) is recommended for all patients with bronchiectasis when possible. Sputum cultures should be followed serially if patients are persistently expectorating.

5. Spirometry is recommended in all patients. The most common abnormality found is an obstructive ventilatory defect characterized by a low FEV1 and FEV1 to forced vital capacity (FEV1/FVC) ratio, the severity of which often correlates with the stage of the disease.

6. Diagnostic workup of patients hospitalized with an acute exacerbation: Sputum microbiology (optimally the sputum sample should be collected before the start of antimicrobial treatment), viral testing (eg, nasopharyngeal swab), chest radiographs, pulse oximetry (or blood gases when indicated), blood cultures (in the case of fever), monitoring of the daily amounts of produced sputum. As hemoptysis is often an indication of infection, patients presenting with hemoptysis and known bronchiectasis should be treated with antibiotics.

Diagnostic Criteria

The diagnosis of bronchiectasis may be suggested by the clinical history, physical examination, and chest radiography, but confirmation requires evidence of bronchial dilation on HRCT (gold standard):

1) Broncho-arterial ratio >1 to 1.5 (ie, “signet ring” sign).

2) Lack of bronchial tapering.

3) Airway visibility within 1 cm of a costal pleural surface.

Differential Diagnosis

Other diseases associated with cough and sputum production (see Cough).

TreatmentTop

1. Airway clearance techniques and other approaches to facilitate the removal of bronchial secretions, ideally with assistance from a chest physiotherapist, have been reported to improve quality of life. These include chest percussion, oscillatory positive expiratory pressure devices, and active cycle of breathing/huffing techniques.

2. Mucoactive therapies, which include inhaled hypertonic saline (3% or 7%), can be considered to help with persistent symptoms and improve airway clearance. The usual dose is 4 mL of 7% hypertonic saline, which can be nebulized with a compressor. It is recommended that patients take a short-acting bronchodilator before their treatment to help with tolerability. Evidence shows that it can improve quality of life but has demonstrated no effect on exacerbations, hospitalizations, or lung function. Routine use of inhaled recombinant human DNAse is not recommended in non-CF bronchiectasis, as it increases the risk of exacerbations in these patients.

3. Inhalers can be helpful in patients with significant dyspnea and should be continued in patients who have concurrent asthma or chronic obstructive pulmonary disease (COPD). The overall evidence is weak, but inhalers can improve symptoms in some patients. If the patient has concurrent asthma, suggest a long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) + LAMA as the initial inhaler choice.

4. Antimicrobial treatment:

1) Chronic macrolide therapy may be considered to reduce pulmonary exacerbations and improve quality of life. Supporting evidence is derived mainly from azithromycin. Macrolides can be associated with adverse effects; therefore, prior to starting long-term use of macrolides, ensure that sputum cultures are negative for NTM infection and screen for QT prolongation as well as baseline hearing loss.

2) Inhaled antibiotics can be considered in bronchiectasis associated with chronic P aeruginosa infection to reduce pulmonary exacerbations. The typical therapy is tobramycin 80 mg inhaled bid (compared with higher doses used in CF). Prior to initiating inhaled aminoglycosides, patients should be screened for baseline hearing loss, chronic kidney disease, and concomitant use of nephrotoxic medications. Colistin 75 mg inhaled bid is an alternative option but requires special approval in Canada.

3) Pseudomonas eradication should be considered in patients with their first isolation of P aeruginosa. A typical regimen consists of 2 weeks of ciprofloxacin followed by 3 months of inhaled antibiotic therapy (tobramycin or colistin). Then sputum cultures should be repeated to assess for eradication. Up to 3 attempts at eradication can be made, and if P aeruginosa persists, then long-term inhaled antibiotics can be considered.

5. Pulmonary rehabilitation program may be helpful in patients with bronchiectasis; however, evidence on its effects is lacking.

6. Surgical treatment is used in selected cases; typically partial lung resection (usually including a lobe or several segments) in patients with a severe clinical course and localized bronchiectasis. Lung transplant may be considered in those with poor lung function and major complications of bronchiectasis including massive hemoptysis, severe pulmonary hypertension, and recurrent admissions for respiratory failure requiring noninvasive ventilation, intensive care unit–level care, or both.

7. Vaccination against pneumococcal disease, coronavirus disease 2019 (COVID-19), and influenza is recommended.

Acute Exacerbations

1. Empiric antimicrobial therapy should be tailored to previous culture data, with antibiotics used for ≥10 to 14 days. In the absence of prior culture data, oral amoxicillin 500 mg tid for 14 days may be reasonable for mild exacerbations; if previous culture yielded P aeruginosa, treat the patient with oral ciprofloxacin 750 mg bid for 14 days (if renal function is normal). There is a low threshold to initiate IV antibiotics in these patients. A single-antibiotic coverage of P aeruginosa will typically suffice.

2. Hemoptysis is a relatively common feature of bronchiectasis exacerbations. In addition to IV antibiotics, consider additional treatments such as tranexamic acid, vitamin K, and, in refractory cases, bronchial artery embolization if life-threatening hemoptysis is present.