KEYSTONE, COLO. — Anybody who needs two or more courses of antibiotics within a year for respiratory tract infections deserves to be evaluated for bronchiectasis, Dr. Gwen A. Huitt asserted at a meeting sponsored by the National Jewish Medical and Research Center.
“It's not normal for anyone to need any antibiotics during the year. By the time you get to somebody who needs two, three, or four courses of antibiotics for, say, a bronchitis or sinusitis—and remember, it's called the sinopulmonary tree—we need to think about underlying predisposing conditions,” according to Dr. Huitt, director of the adult infectious disease care unit at the Denver center.
She believes that bronchiectasis is far more common in primary care settings than most physicians realize. This conviction is based in part on the large number of telephone and e-mail consults she handles through National Jewish's “Lung Line” (800-222-5864 or lungline@njc.org
High-resolution chest CT is the diagnostic cornerstone. It will readily show the permanently dilated, grossly distorted bronchi and bronchioles that define bronchiectasis anatomically. The pathogenesis involves some sort of initial inflammatory process leading to a cytokine cascade, including tumor necrosis factor, interleukins, and elastases, along with accumulation of white blood cells. This inflammatory gunk predisposes to bacterial infection, which in turn damages mucociliary function. This process leads to a vicious cycle in which stagnant mucus attracts bacterial pathogens—Pseudomonas aeruginosa is the No. 1 infectious agent—further impairing the lungs' ability to clear mucus, resulting in more infections.
Although bronchiectasis is often thought of as a “wet” condition in which patients constantly hack up purulent phlegm, patients can in fact be “dry” and yet still have severe bronchiectasis, Dr. Huitt stressed.
Once it's determined that a patient has bronchiectasis, it's important to try to identify the etiology. Although bronchiectasis is the disease that defines cystic fibrosis, it has numerous other potential causes. These include α1-antitrypsin (A1A) deficiency, Young's syndrome, allergic bronchopulmonary aspergillosis, autoimmune diseases, a severe pneumonia, and even gastroesophageal reflux disease (GERD).
Dr. Huitt routinely orders sputum cultures, a genetic screen for cystic fibrosis, an α1-antitrypsin level and phenotype, an antinuclear antibody test, quantitative immunoglobulins, an esophagram, and pulmonary function tests to sift through the following potential causes of bronchiectasis:
▸ Cystic fibrosis. At last count, roughly 1,300 genetic mutations have been identified that can contribute to the widely varied presentations of this disease. In patients with bronchiectasis, National Jewish physicians routinely order the Genzyme test that covers 97 of the most common ones. The traditional sweat chloride test is not worth ordering in adults where cystic fibrosis is a possibility; the results are generally normal even in affected patients. “Go straight to genotyping, and I believe you'll get a lot better data,” Dr. Huitt said.
▸ Infection. Worldwide, the No. 1 cause of bronchiectasis is undoubtedly tuberculosis. But other severe pulmonary infections—for example, pertussis or measles pneumonia—can also damage the mucociliary clearance mechanism and trigger the bronchiectatic process.
▸ A1A deficiency. Although it's classically an emphysematous condition, some affected patients instead present chiefly with recurrent pulmonary infections and bronchiectasis. Dr. Huitt orders both the A1A level and phenotype for screening because of recent data indicating not just homozygotes but phenotypic MZ heterozygotes may benefit from augmentation therapy.
▸ Autoimmune diseases. Rheumatoid arthritis, scleroderma, Sjögren's syndrome, vasculitis, and mixed connective tissue diseases are very common in patients with bronchiectasis, and it's not at all unusual for the pulmonary manifestations to precede diagnosis of the autoimmune disease. Indeed, it's for this reason Dr. Huitt advocates screening all bronchiectatic patients with an antinuclear antibody test. In addition, she routinely orders separate serologies for anti-SSA and anti-SSB because she finds a large number of bronchiectatic patients have previously undiagnosed Sjögren's syndrome.
▸ HIV. Although highly active antiretroviral therapy (HAART) effectively controls viral replication, there remains an ongoing inflammatory state affecting the pulmonary system. Expect to encounter a lot more cases of bronchiectasis due to underlying HIV in coming years as HAART-treated patients survive far longer than in the epidemic's early years.
▸ GERD. Although it is considered controversial as a cause of bronchiectasis, Dr. Huitt believes that GERD is actually an important cause, and that the controversy exists only because of limitations in current methods of evaluating reflux. GERD can be clinically silent. Radiologists have taught Dr. Huitt two CT pearls that are indicators of esophageal hypertrophy secondary to reflux: an esophageal wall thickness in excess of 3 mm, or more than 15 mm of retained air in the esophageal lumen.
Sputum cultures should be obtained at baseline and every 6 months. Knowledge of the predominant chronic lung pathogen guides maintenance antimicrobial therapy aimed at preventing acute exacerbations of bronchiectasis that will require hospitalization and several weeks of intravenous antibiotics.