PULMONARY PERSPECTIVES®: Bronchiectasis

Bronchiectasis, once characterized as an orphan disease, is experiencing resurgence in North America and around the world. Pulmonary physicians are encountering increasing numbers of patients who need evaluation and treatment for their bronchiectasis and the resultant infectious and noninfectious complications of the permanently damaged airways. Bronchiectasis is defined as permanent dilatation of bronchi and bronchioles with associated airway wall damage; it is thought to be a consequence of the vicious cycle of infection and inflammation. Bronchiectasis is found in patients across the span of age (pediatric to geriatric) and in both genders and all ethnic groups. Women are more frequently affected than men in North America, and older adults have a higher prevalence than children and the young and middle-aged. Patients with bronchiectasis present to their physicians with chronic cough, usually productive of significant mucus. CT scan of the chest with high resolution cuts (HRCT) is the gold standard for diagnosing bronchiectasis; some patients will be referred to pulmonologists because a CT scan, done for a different clinical indication, demonstrates bronchiectatic findings (Fig 1).

Recognizing Bronchiectasis

Patients with bronchiectasis usually have a chronic productive cough; other symptoms are wheezing, exertional dyspnea, and hemoptysis. Some patients with bronchiectasis have a nagging dry cough. Patients are often initially diagnosed as having recurrent bronchitis or pneumonia; imaging studies are needed to confirm the presence of bronchiectasis. Although bronchiectasis may be suspected based on plain chest radiographic imaging, HRCT scan is the diagnostic imaging study that confirms the presence of bronchiectasis. High resolution thin cut slices through the chest are needed to detect more subtle findings in bronchiectasis and to help characterize the severity and extent of the disease. Traditionally, bronchiectasis is characterized as cylindrical, varicose, or cystic based on the CT findings of airway involvement and associated destruction of surrounding lung tissue.

Bacterial infection of bronchiectatic airways is common, and bacterial cultures of expectorated sputum should be obtained in all patients who are diagnosed with bronchiectasis. If expectorated sputum is not available, induced sputum collection or bronchoscopy with bronchoalveolar lavage may be necessary to obtain adequate material for culture. About one-third of patients with bronchiectasis is infected with Pseudomonas aeruginosa; Haemophilus influenzae and other gram-negative bacteria are also exceedingly common. Some patients with bronchiectasis are infected with gram-positive organisms including Streptococcus pneumoniae and Staphylococcus aureus. In North America, nontuberculous mycobacterial (NTM) organisms are frequently cultured from the respiratory secretions of patients with bronchiectasis. Mycobacterium avium complex (MAC) is the most commonly encountered NTM organism; rapid growing organisms like Mycobacterium abscessus are also seen but in fewer patients.

The pathophysiology of infection in bronchiectasis is not entirely clear. Whether the infection precipitates bronchiectasis, particularly in the case of NTM infection, or whether NTM infection is a consequence of bronchiectasis has not yet been conclusively determined (Griffith and Aksamit. Clin Chest Med. 2012;33[2]:283). There are some radiographic correlations between infecting organisms and severity of bronchiectasis; P aeruginosa is associated with more severe disease and cystic bronchiectasis. MAC infection is often associated with nodular bronchiectasis, particularly in the right middle lobe and lingula, significant mucus plugging of the airways, and "tree in bud" small airway mucus impaction.

Causes

Many congenital and acquired systemic and pulmonary diseases can cause bronchiectasis, but over 50% of cases are thought to be idiopathic. Another 25% to 30% of patients with bronchiectasis had a prior chest infection (recent or remote) that resulted in the damaged airways. Genetic causes of bronchiectasis include cystic fibrosis, primary ciliary dyskinesia, congenital disorders of humoral immunity, inherited connective tissue disorders, and alpha₁- antitrypsin (AAT) deficiency. Acquired immunodeficiency syndromes, swallowing dysfunction/aspiration or gastroesophageal reflux, rheumatologic disorders, and inflammatory bowel disease also cause bronchiectasis. Allergic bronchopulmonary aspergillosis is associated with central "finger in glove" bronchiectasis. Determining an etiology for the bronchiectasis can be important for prognosis and treatment decisions. Of note, an association between bronchiectasis and moderate to severe COPD is being increasingly recognized; bronchiectasis has been associated with an increased risk of all-cause mortality in this patient group (Martinez-Garcia et al. [Published online ahead of print Feb 7, 2013.] Am J Respir Crit Care Med.

Treatment

There are no current US Food and Drug Administration (FDA)-approved treatments for bronchiectasis or for bronchiectasis-associated infections. However, there is a number of phase 2 and 3 clinical trials underway that will hopefully address this gap in therapy. In the meantime, there are several therapeutic modalities that can be individualized to the patient in order to potentially mitigate symptoms, improve quality of life, and reduce infectious exacerbations. These treatments include airway clearance, exercise/pulmonary rehabilitation, chronic antiinflammatory therapy and chronic antibiotic therapies, and surgical resection. Many patients can be treated conservatively; if daily symptoms are minimal to mild, then airway clearance and exercise may be effective. If patients are having frequent troublesome symptoms of cough and mucus production, then therapy can be scaled up to include mechanical and pharmacologic airway clearance measures, chronic antiinflammatory therapy with inhaled steroids, and oral macrolides. Chronic maintenance antibiotic therapy (inhaled or oral) may be indicated for patients who experience exacerbation (and require systemic antibiotic therapy) more than two or three times per year. All antibiotic therapy, whether maintenance or for exacerbations, should be targeted at the organisms known to be present on culture. Care must be taken to evaluate the patient for nontuberculous mycobacterial infection. Not all patients infected with NTM organisms require treatment, but if antibiotic treatment is indicated, it must be done with careful attention to efficacy and side effects. Surgery is a consideration for localized bronchiectasis to control otherwise untreatable bleeding or to debulk the worst areas of infection. Other supportive treatments for patients with bronchiectasis include appropriate immunizations and nutritional support, if needed. If there is an identified primary treatable cause of bronchiectasis, such as immunoglobulin deficiency, AAT deficiency, or allergic bronchopulmonary aspergillosis, then treatment aimed at those disorders may help to control the bronchiectasis.