Bronchiectasis

Bronchiectasis is an irreversible and abnormal dilation in the bronchial tree caused by cycles of bronchial inflammation leading to mucous plugging and progressive airway destruction. Bronchiectasis is classified according to etiology as either cystic fibrosis (CF) bronchiectasis or non-CF bronchiectasis (e.g., secondary to severe or protracted pneumonia, immunodeficiency, or COPD). The characteristic clinical feature is a chronic cough with copious mucopurulent sputum. Other symptoms may include dyspnea, rhinosinusitis, and hemoptysis. Physical examination reveals crackles and rhonchi on auscultation, often accompanied by wheezing. High-resolution computed tomography confirms the diagnosis and usually shows thickened bronchial walls, with so-called “signet-ring” and “tram track” signs. Patients can periodically experience an acute worsening of symptoms, referred to as an acute exacerbation of bronchiectasis, which commonly requires antibiotic treatment. The goal of long-term management of bronchiectasis is to control symptoms and prevent exacerbations, and includes pulmonary physiotherapy and pharmacological therapy. Massive hemoptysis is a rare complication of bronchiectasis and requires surgery or pulmonary artery embolization.

• Bronchiectasis: an irreversible and abnormal dilation of the bronchial tree that produces chronic respiratory symptoms (e.g., chronic productive cough)
• Acute exacerbation of bronchiectasis: a deterioration in the symptoms of bronchiectasis that requires a change in the regular treatment (e.g., adding antibiotics, increasing airway clearance techniques) ^[1]

Bronchiectasis requires the combination of two important processes taking place in the bronchi: either local infection or inflammation along with either inadequate clearance of secretions, airway obstruction, or impaired host defenses. These processes result in the permanent dilation of airways.

• Pulmonary infections (i.e., bacterial, viral, fungal), especially severe or chronic infections
• Disorders of secretion clearance or mucous plugging
  • Cystic fibrosis (CF) ^[2]
  • Primary ciliary dyskinesia (PCD)
  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Kartagener syndrome
  • Smoking: associated with poor ciliary motility
• Bronchial narrowing or other forms of obstruction
  • COPD
  • Aspiration
  • Tumors
  • α1-antitrypsin deficiency
  • Other congenital and acquired conditions (e.g., congenital bronchiectasis, tracheomalacia, bronchogenic cyst)
• Immunodeficiency (e.g., common variable immunodeficiency, hypogammaglobulinemia, HIV)
• Chronic inflammatory diseases (e.g., rheumatoid arthritis, Sjogren syndrome, Crohn disease)

Primary prevention of bronchiectasis includes antibiotic control of bronchial and pulmonary infections in predisposed individuals.

References:^[2][3][4]

• Chronic productive cough (lasting months to years) with copious mucopurulent sputum ;
• Auscultation
  • Crackles and rhonchi
  • Wheezing (due to obstruction from secretions, airway collapsibility, or a concomitant condition)
  • Bronchophony
• Rhinosinusitis
• Dyspnea
• Hemoptysis: usually mild or self-limiting, but severe hemorrhage that requires embolization may occur
• Nonspecific symptoms (i.e., fatigue, weight loss, pallor due to anemia)
• Clubbing of nails (uncommon)
• Exacerbations of bronchiectasis
  • Recurrent bouts of pneumonia and acute bacterial infection of sections of dilated bronchi
  • Frequently due to Pseudomonas aeruginosa ^[5]
  • Features
    • Increased production of mucous above baseline
    • Low-grade fever

Bronchiectasis should be suspected in patients with a chronic cough that produces large amounts of sputum.
References: ^[4][6]

Approach ^[7]

• Confirm the diagnosis with imaging studies in patients with features suggestive of bronchiectasis.
  • Poor control or frequent exacerbations in patients with chronic pulmonary disease (e.g., COPD, asthma)
  • Chronic cough or recurrent pulmonary infections in patients with immunosuppression or conditions associated with bronchiectasis
  • Productive cough lasting > 8 weeks in otherwise healthy patients
• Identify the underlying etiology.
  • Routine laboratory studies, sputum culture and smear, and pulmonary function tests
  • Clinical suspicion for a specific etiology: Obtain additional studies based on individual evaluation.

In patients with suspected bronchiectasis, diagnosis is confirmed using imaging studies, preferably a HRCT scan. Additional diagnostic studies are useful to identify the underlying cause and possibly provide specific treatment.

Imaging ^[7][8][9]

• Imaging modalities
  • X-ray chest: best initial test (may not show mild disease)
  • High-resolution computed tomography; (HRCT) chest: confirmatory test
• Findings
  • Bronchial dilation ; ^[7][8]
    • Cylindrical or tubular (most common) : parallel tram track sign and signet ring sign
    • Varicose
    • Saccular or cystic (most severe form)
  • Thickened bronchial walls; , mucus plugging, honeycombing (suggests late-stage bronchiectasis)
  • Specific findings suggestive of the underlying etiology
    • Focal distribution : localized disease (e.g., tumors, foreign bodies, strictures)
    • Diffuse distribution: fibrosing diffuse lung diseases
      • Lower lung predominance (e.g., recurrent aspiration, pulmonary fibrosis, α1-antitrypsin deficiency)
      • Upper or middle lung predominance (e.g., CF, sarcoidosis, ABPA, tuberculosis)
    • Perihilar lymphadenopathies (e.g., sarcoidosis, tuberculosis)
    • Situs inversus (seen in primary ciliary dyskinesia)

Identification of the underlying etiology

Studies to determine the underlying etiology of bronchiectasis are usually requested by a specialist. In many cases, it is not possible to reach a specific diagnosis and the disease may be classified as idiopathic. ^[10]

Initial workup ^[7][11]

Perform at the time of diagnosis to obtain baseline references. Sputum culture and smear, as well as spirometry, are also used for monitoring.

• Laboratory studies ^[7][11]
  • CBC: Findings are variable and depend on the underlying etiology.
    • ↓ Hb
    • Variable leukocyte levels
    • ↑ Thrombocytes
  • Consider ABG (e.g., in patients with ↓ SaO₂ on room air): may show hypercapnia
  • Quantitative measurement of serum immunoglobulins and electrophoresis (IgA, IgG, IgM, and IgG subclasses): to exclude immunodeficiencies ^[11]
  • Aspergillus fumigatus IgG and IgE: to exclude ABPA
• Sputum culture and smear: culture induced sputum or bronchoalveolar lavage for all of the following pathogens to detect infection or colonization ^[7][12]
  • Bacterial cultures: e.g., H. influenzae or P. aeruginosa
  • Fungal cultures: Candida spp. or Aspergillus spp.
  • Mycobacterial culture (with AFB smear microscopy): tuberculosis or nontuberculous mycobacteria
• Spirometry: not needed to establish a diagnosis but useful to monitor disease progression ^[7][13]
  • Mixed obstructive/restrictive pattern
  • Restrictive pattern (i.e., ↓ FEV₁ and FVC with normal or ↑ FEV₁/FVC ratio)
  • Obstructive pattern (i.e., ↓ FEV₁/FVC ratio)

Additional diagnostics ^[7][11]

These studies may be considered depending on clinical suspicion if the initial workup was not diagnostic.

• Laboratory studies
  • Specific antibodies (e.g., rheumatoid factor, ANAs, anti-CCP antibodies, ANCAs): suspected connective tissue or autoimmune diseases
  • Sweat chloride test and/or genetic testing for CFTR mutations: suspected CF
  • HIV testing , serum α1-antitrypsin levels , nasal nitric oxide testing for primary ciliary dyskinesia
• Further studies
  • Bronchoscopy
    • Indicated to visualize tumors, foreign bodies, or other lesions (most useful in patients with localized disease)
    • May also be used in combination with bronchoalveolar lavage (BAL) to obtain specimens for staining and culture
  • Upper GI studies (e.g., upper endoscopy, barium swallow, esophageal manometry): consider for suspected gastroesophageal reflux disease or recurrent pulmonary aspiration
  • Colonoscopy with biopsies: if associated inflammatory bowel disease is suspected (e.g., GI bleeding)

If the initial workup does not identify the underlying cause, perform further studies guided by the patient's clinical features and consider referral to a specialist.

This section focuses on the management of non-CF bronchiectasis. See “Cystic fibrosis” for specific recommendations regarding that condition.

Approach ^[7][11][14]

• Provide supportive treatment and oxygen therapy as needed.
• Optimize mucoactive agents (see “Pharmacotherapy for airway clearance in bronchiectasis”).
• Optimize airway clearance techniques.
• Obtain a new sputum culture and start empiric antibiotic therapy, based on the most recent sputum culture.
• Tailor antibiotics to the most recent sputum culture once available and preferably complete 14 days of therapy.

Monitoring and disposition ^[7][11]

• Outpatient treatment: for hemodynamically stable patients with mild to moderate symptoms
• Consider inpatient treatment in the following cases:
  • Clinical deterioration or no clinical improvement following completion of an oral antibiotic regimen (e.g., lasting 10–14 days)
  • Sepsis or severe pneumonia (see “Pneumonia treatment” and “Acute management checklist for sepsis” for more information)
  • Hemoptysis ≥ 10 mL in 24 hours and clinical deterioration
  • New isolation of P. aeruginosa

Acute exacerbations are defined as acute deterioration or worsening local symptoms and/or additional systemic symptoms such as fever or malaise. Exacerbations are associated with increased inflammation and progressive damage to the lungs. ^[11]

Management goals are to stop or delay disease progression, reduce exacerbation frequency (goal ≤ 2 per year), achieve symptom control, and improve the patient's quality of life.

Approach ^[7][11]

• General measures
  • Educate the patient regarding prognosis and the use of long-term medications.
  • Promote lifestyle changes like regular exercise and smoking cessation.
  • Educate the patient on airway clearance techniques. ^[7][11][15]
    • Bronchopulmonary hygiene and chest physiotherapy: e.g., cupping and clapping, postural drainage, directed cough, hydration
    • Pulmonary rehabilitation: may improve exercise capacity and respiratory symptoms ^[10]
  • Administer vaccinations (i.e., seasonal influenza vaccine, pneumococcal vaccine).
  • Consider treatment with mucoactive agents, bronchodilators, or corticosteroids if airway clearance is difficult.
  • Provide specific treatment for the underlying cause if identified.
• Follow-up: Perform follow-ups every 6–12 months to identify disease progression.
  • Bacterial and fungal sputum culture: every 6–12 months
  • Spirometry: every 12 months
• Disease progression
  • Consider long-term antibiotic therapy for bronchiectasis with ≥ 3 exacerbations per year.
  • Repeat diagnostic studies to assess disease progression.
  • Screen for complications.
    • ECG
    • Consider echocardiogram.
    • Consider CT chest with contrast.
• Advanced disease
  • Ensure respiratory support as needed.
    • Long-term oxygen therapy for chronic respiratory failure (indications are the same as for COPD)
    • Consider oxygen with humidification for patients with respiratory failure with hypercapnia.
  • Invasive procedures: not routinely indicated

Perform a careful reassessment of patients who are progressively deteriorating (i.e., patients with increased frequency and/or severity of exacerbations, frequent hospital admissions, worsening symptoms, rapid decline in lung function). Identify the cause of bronchiectasis if still unknown, and exclude any comorbidities or exacerbating conditions such as new pathogen colonization.

For patients with bronchiectasis and chronic productive cough or difficulty expectorating, consider referral to a trained respiratory physiotherapist for airway clearance techniques. ^[15]

Pharmacotherapy for airway clearance in bronchiectasis

Mucoactive agents

Consider in patients with difficulty expectorating or persistent symptoms despite adequate airway clearance techniques; continue use based on clinical benefits. There is a paucity of evidence for the benefit of mucoactive agents in bronchiectasis. ^[7][16]

• Nebulized mucoactive agents: Trial for at least 3 months. ^[11]
  • Hypertonic saline (3–7% NaCl) ^[7][17][18]
  • Mannitol ^[19]
• Oral mucolytics: Trial for at least 6 months, e.g., N-acetylcysteine .

Bronchodilators

Consider on a case-by-case basis. Evidence to support the use of bronchodilators in bronchiectasis is limited. ^[7][11]

• Short-term bronchodilators (e.g., SABA): in patients with airway reactivity and bronchospasm or prior to inhaled mucoactive treatment ^[15]
• Long-term bronchodilators (e.g., LABA, LAMA): may be used in patients with severe dyspnea
• Regular use of bronchodilators (e.g., for asthma or COPD): Continue as usual.

Corticosteroids

Corticosteroids are not routinely recommended because of the limited benefit and side effects of corticosteroid therapy. ^[7][20]

• Inhaled corticosteroids: Continue if already indicated for asthma or COPD.
• Systemic corticosteroids: indicated in patients with ABPA ^[10]

For patients receiving multiple inhaled treatments and chest physiotherapy, consider the following order of treatment to avoid bronchospasm: bronchodilators, mucoactive agents, respiratory physiotherapy, inhaled antibiotics. ^[11]

Avoid treatment with recombinant human DNase (e.g., dornase alfa), as it can increase the frequency of exacerbations in patients with non-CF bronchiectasis. ^[7][21]

Long-term antibiotic therapy ^[7][11][14]

The goal is to suppress bacterial growth and to reduce symptoms and exacerbations as a measure of secondary prevention in patients with ≥ 3 exacerbations per year. Antibiotic therapy should be administered for at least 3 months and may be extended based on clinical response and tolerability.

Before starting treatment, obtain new sputum cultures with an antibiogram and consult an infectious diseases specialist.

Chronic macrolide use can increase the growth of macrolide-resistant mycobacterial strains. It is recommended to rule out active nontuberculous mycobacterial infection with a negative culture before starting treatment.

Long-term macrolides can lead to QT-prolongation and fatal arrhythmias. Before starting treatment, perform an ECG and review whether any medications the patient is taking are known to alter the QT interval. ^[7][10]

Invasive procedures ^[7]

• Surgical resection of bronchiectatic lung or lobectomy: indicated in pulmonary hemorrhage, inviable bronchus, and poor control of symptoms despite optimal medical therapy in unilateral bronchiectasis with well-localized disease
• Pulmonary artery embolization: indicated in pulmonary hemorrhage
• Lung transplantation: Consider for severe disease or rapid disease progression.

• Recurrent bronchopulmonary infections → chronic obstructive pulmonary disease → respiratory failure and cor pulmonale
• Pulmonary hemorrhage (massive hemoptysis)
• Lung abscess

References: ^[6]

We list the most important complications. The selection is not exhaustive.