BRONCHIECTASIS

Sumera R. Ahmad, MD • Scott E. Kopec, MD

 BASICS

DESCRIPTION

•  Bronchiectasis is an irreversible dilatation of ≥1 airways accompanied by recurrent transmural bronchial infection/inflammation and chronic mucopurulent sputum production.

•  Generally classified into cystic fibrosis (CF) and noncystic fibrosis (non-CF) bronchiectasis

EPIDEMIOLOGY

•  Predominant age: most commonly presents in 6th decade of life

•  Predominant sex: female > male (1)

Incidence

Incidence has decreased in the United States for two reasons:

•  Widespread childhood vaccination against pertussis

•  Effective treatment of childhood respiratory infections with antibiotics

Prevalence

•  In the United States, prevalence estimated to be 52.3/100,000.

•  Prevalence increased substantially with age from 4.2/100,000 persons aged 18 to 34 years to 271.8/100,000 among those aged 75 years and older (1).

ETIOLOGY AND PATHOPHYSIOLOGY

•  CF bronchiectasis: bronchiectasis due to CF

•  Non-CF bronchiectasis

–  Most cases are idiopathic.

–  Most commonly associated with non-CF bronchiectasis is childhood infection.

•  Vicious circle hypothesis: Transmural infection, generally by bacterial organisms, causes inflammation and obstruction of airways. Damaged airways and dysfunctional cilia foster bacterial colonization, which leads to further inflammation and obstruction.

RISK FACTORS

•  Nontuberculous mycobacterial infection is both a cause and a complication of non-CF bronchiectasis.

•  Severe respiratory infection in childhood (measles, adenovirus, influenza, pertussis, or bronchiolitis)

•  Systemic diseases (e.g., rheumatoid arthritis and inflammatory bowel disease)

•  Chronic rhinosinusitis

•  Recurrent pneumonia

•  Aspirated foreign body

•  Immunodeficiency

•  Congenital abnormalities

GENERAL PREVENTION

•  Routine immunizations against pertussis, measles, Haemophilus influenza type B, influenza, and pneumococcal pneumonia

•  Genetic counseling if congenital condition is etiology

•  Smoking cessation

COMMONLY ASSOCIATED CONDITIONS

•  Mucociliary clearance defects

–  Primary ciliary dyskinesia

–  Young syndrome (secondary ciliary dyskinesia)

–  Kartagener syndrome

•  Other congenital conditions

–  α₁-Antitrypsin deficiency

–  Marfan syndrome

–  Cartilage deficiency (Williams-Campbell syndrome)

•  Chronic obstructive pulmonary disease

•  Pulmonary fibrosis, causing traction bronchiectasis

•  Postinfectious conditions

–  Bacteria (Haemophilus influenzae and Pseudomonas aeruginosa)

–  Mycobacterial infections (tuberculosis [TB] and Mycobacterium avium complex [MAC])

–  Whooping cough

–  Aspergillus species

–  Viral (HIV, adenovirus, measles, influenza virus)

•  Immunodeficient conditions

–  Primary: hypogammaglobulinemia

–  Secondary: allergic bronchopulmonary aspergillosis (ABPA), posttransplantation

–  Sequelae of toxic inhalation or aspiration (e.g., chlorine, luminal foreign body)

•  Rheumatic/chronic inflammatory conditions

–  Rheumatoid arthritis

–  Sjögren syndrome

–  Systemic lupus erythematosus

–  Inflammatory bowel disease

•  Miscellaneous

–  Yellow nail syndrome

 DIAGNOSIS

•  Typical symptoms include chronic productive cough, wheezing, and dyspnea.

•  Symptoms are often accompanied by repeated respiratory infections.

•  Once diagnosed, investigate etiology.

HISTORY

•  Any predisposing factors (congenital, infectious, and/or exposure-related)

•  Immunization history

PHYSICAL EXAM

Symptoms are commonly present for many years and include the following:

•  Chronic cough (90%)

•  Sputum: may be copious and purulent (90%)

•  Rhinosinusitis (60–70%)

•  Fatigue: may be a dominant symptom (70%)

•  Dyspnea (75%)

•  Chest pain: may be pleuritic (20–30%)

•  Hemoptysis (20–30%)

•  Wheezing (20%)

•  Bibasilar crackles (60%)

•  Rhonchi (44%)

•  Digital clubbing (3%)

DIFFERENTIAL DIAGNOSIS

•  CF

•  Chronic obstructive pulmonary disease

•  Asthma

•  Chronic bronchitis

•  Pulmonary TB

•  ABPA

DIAGNOSTIC TESTS & INTERPRETATION

•  Spirometry

–  Moderate airflow obstruction and hyperresponsive airways

–  Forced expiratory volume in the 1st second of expiration (FEV₁): <80% predicted and FEV₁/FVC <0.7

–  Special tests

–  Ciliary biopsy by electron microscopy

•  Sputum culture

–  H. influenzae, nontypeable form (42%)

–  P. aeruginosa (18%)

–  Cultures may also be positive for Streptococcus pneumoniae, Moraxella catarrhalis, MAC, and Aspergillus.

–  Screen for TB and non-TB in selected individuals.

–  Of all isolates, 30–40% will show no growth.

•  Special tests

–  Sweat test for CF

–  Purified protein derivative (PPD) test for TB

–  Skin test for Aspergillus

–  HIV

–  Serum immunoglobulins to test for humoral immunodeficiency

–  Protein electrophoresis to test for α₁-antitrypsin deficiency

–  Barium swallow to look for abnormalities of deglutition, achalasia, esophageal hypomotility

–  pH probe to characterize reflux

–  Screening tests for rheumatologic diseases

•  Chest radiograph

–  Nonspecific; increased lung markings or may appear normal

•  Chest computed tomography (CT)

–  Noncontrast high-resolution chest CT is the most important diagnostic tool.

–  Bronchi are dilated and do not taper, resulting in “tram track sign”; parallel opacities seen on scan

–  Varicose constrictions and balloon cysts may be seen.

–  For focal bronchiectasis, rule out endobronchial obstruction.

–  For exclusively upper lobe bronchiectasis, consider CF and ABPA.

Diagnostic Procedures/Other

•  Bronchoscopy may be used to obtain cultures and evacuate sputum.

•  Bronchoscopy for hemoptysis

•  Bronchoscopy may be useful to rule out airway-obstructing lesions with focal bronchiectasis.

Test Interpretation

Bronchoscopy findings include the following:

•  Dilatation of airways and purulent secretions

•  Thickened bronchial walls with necrosis of bronchial mucosa

•  Peribronchial scarring

 TREATMENT

•  Treat underlying conditions.

•  Recognize an acute exacerbation with 4 out of 9 criteria.

–  Change in sputum production

–  Increased dyspnea

–  Increased cough

–  Fever

–  Increased wheezing

–  Malaise, fatigue, lethargy

–  Reduced pulmonary function

–  Radiographic changes

–  Changes in chest sounds

•  Non-CF bronchiectasis: Determine cause of exacerbations; promote good bronchopulmonary hygiene via daily airway clearance.

•  Consider surgical resection of damaged lung for focal disease that is refractory to medical management.

•  Medical management: Reduce morbidity by controlling symptoms and preventing disease progression.

•  Patients with non-CF bronchiectasis may not respond to CF treatment regimens in the same way as patients with CF do.

MEDICATION

•  Insufficient evidence exists to support efficacy of short-course antibiotics in adults and children with bronchiectasis (2).

•  Frequent exacerbations may be treated with prolonged and aerosolized antibiotics (3,4).

•  Role of mucolytics, anti-inflammatory agents, and bronchodilators is still unclear.

First Line

•  Antibiotics

–  Potentially useful in acute exacerbations

–  Chronic therapy decreases sputum production, number of exacerbations, and hospitalizations, but there is a risk of emergence of resistance to antibiotics (5,6).

–  Use of inhaled antibiotics can be considered for selected individuals with gram-negative organisms. Caution needs to be taken with airway and systemic adverse effects noted with inhaled tobramycin and aztreonam (4).

–  Patients may require twice the usual dose and longer treatment for 14 days (10 to 21 days) for an acute exacerbation.

–  Sputum culture and sensitivity should direct therapy; antibiotic selection is complicated by a wide range of pathogens and resistant organisms.

–  Should be administered IV in cases of severe infection (4)

  Augmentin: 500 mg PO q8–12h. Pediatric: base dosing on amoxicillin content

  Trimethoprim (TMP)/sulfamethoxazole (SMX): 160 mg TMP/800 mg SMX PO q12h. Pediatric: ≥2 months, 8 mg/kg TMP and 40 mg/kg SMX PO/24 hours, administered in two divided doses q12h

  Doxycycline and cefaclor given PO are also effective.

  Nebulized aminoglycosides (tobramycin): 300 mg by aerosol BID

  Ciprofloxacin: 750 mg PO q12h for adults for susceptible strain of Pseudomonas

  Macrolides: appear to have immunomodulatory benefits

•  Chronic use of azithromycin as an oral macrolide for 6 to 12 months in non-CF bronchiectasis has been shown to reduce exacerbations. Needs caution with respect to cardiovascular deaths, where it is a QTc-prolonging medication.

•  All patients considered for chronic therapy with azithromycin should be screened for non-TB mycobacterium infection prior (4).

•  Bronchodilators

–  Chronic use of β2-agonists (e.g., albuterol) reverses airflow obstruction (2).

•  Inhaled corticosteroids

–  Inhaled corticosteroids may improve lung function, but the effect is small (6).

  Fluticasone propionate: 110 to 220 μg inhaled BID

–  Use of combination of long-acting bronchodilator with inhaled corticosteroid may reduce dyspnea, wheeze, and cough (6).

  Budesonide 160 μg/formoterol 4.5 μg 2 puffs inhaled BID

Second Line

Other broad-spectrum antimicrobials, including those with antipseudomonal coverage

ADDITIONAL THERAPIES

Sputum clearance techniques, including chest physiotherapy (percussion and postural drainage) and pulmonary rehabilitation (improves exercise tolerance)

SURGERY/OTHER PROCEDURES

•  Surgery if area of bronchiectasis is localized and symptoms remain intolerable despite medical therapy or if disease is life-threatening (3)

•  Surgery effectively improves symptoms in 80% of these cases.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Bronchiectasis can present as life-threatening massive hemoptysis. In this situation, in addition to airway protection and resuscitation, bronchial artery embolization or surgical intervention is necessary to control bleeding (2).

 ONGOING CARE

Long-term outpatient treatment recommendations for bronchiectasis in children and adults (3):

•  Children and adults with CF and non–CF-related bronchiectasis should be treated by comprehensive interdisciplinary chronic disease management programs.

•  In children, aim to achieve normal growth and development.

•  Patients with primary and secondary immune deficiencies should be under joint care with a clinical immunologist.

•  Patient with CF should be referred to a CF center.

•  Patient should be informed of the various techniques for airway clearance.

•  Nebulized saline or hypertonic saline (7% saline) use prior to airway clearance techniques can help augment sputum production (3)[B].

•  Whereas nebulized dornase and high dose anti- inflammatory agents such as ibuprofen have some benefit in CF-related bronchiectasis, there is no role of such agents in non–CF-related bronchiectasis. In fact, nebulized dornase in adults can be harmful with more frequent exacerbations and decline in lung function.

•  Pulmonary rehabilitation should be offered to patients with symptoms of breathlessness affecting activities of daily living (3)[B].

•  In situation of an acute exacerbation, use and modify antibiotics as per sputum microbiology

•  Consider suitability of long-term antibiotics for patients with recurrent exacerbations.

•  Noninvasive ventilation can improve quality of life in patients with chronic respiratory failure and can reduce hospitalizations.

•  Consider lung transplant evaluation in patients with declining respiratory status and FEV1<30%. However, since non-CF bronchiectasis has significantly lower mortality hazard compared to CF-related bronchiectasis, separate referral and listing criteria should be considered (7).

FOLLOW-UP RECOMMENDATIONS

Regular exercise is recommended.

Patient Monitoring

•  Serial spirometry at least annually (3)

•  Chest CTs to monitor progression of disease may be indicated with some conditions such as bronchiectasis with MAC infections.

•  Routine microbiologic sputum analysis

PATIENT EDUCATION

http://www.lungusa.org/

PROGNOSIS

•  Mortality rate (death due directly to bronchiectasis) is 10.6–29.7% (7).

•  Pseudomonas infection, low body mass index, and advanced age are associated with poorer prognosis (5).

COMPLICATIONS

•  Hemoptysis

•  Recurrent pulmonary infections

•  Pulmonary hypertension

•  Cor pulmonale

•  Lung abscess

REFERENCES

1.  Weycker D, Edelsberg J, Oster G, et al. Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005;12(4):205–209.

2.  Wurzel D, Marchant JM, Yerkovich ST, et al. Short courses of antibiotics for children and adults with bronchiectasis. Cochrane Database Syst Rev. 2011;(6):CD008695.

3.  Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010;65(Suppl 1):i1–i58.

4.  O’Donnell AE. Bronchiectasis: which antibiotics to use and when. Curr Opin Pulm Med. 2015;21(3):272–277.

5.  Hnin K, Nguyen C, Carson KV, et al. Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults. Cochrane Database Syst Rev. 2015;(8):CD001392.

6.  Welsh EJ, Evans DJ, Fowler SJ, et al. Interventions for bronchiectasis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2015;(7):CD010337.

7.  Hayes D Jr, Kopp BT, Tobias JD, et al. Survival in patients with advanced non-cystic fibrosis bronchiectasis versus cystic fibrosis on the waitlist for lung transplantation. Lung. 2015;193(6):933–938.

 CODES

ICD10

•  J47.9 Bronchiectasis, uncomplicated

•  J47.1 Bronchiectasis with (acute) exacerbation

•  J47.0 Bronchiectasis with acute lower respiratory infection

CLINICAL PEARLS

•  Symptoms of bronchiectasis include chronic productive cough, wheezing, and dyspnea often accompanied by repeated respiratory infections.

•  A chest x-ray has poor sensitivity and specificity for the diagnosis; a noncontrast high-resolution chest CT is the most important diagnostic tool.

•  Current practice guidelines recommend treating acute exacerbations with a 14-day course of antibiotics. Frequent exacerbations may be treated with prolonged and aerosolized antibiotics.