First recognized as an occupational disorder, obliterative bronchiolitis is now the primary noninfectious pulmonary complication of allogeneic hematopoietic stem-cell transplantation and lung transplantation. A new review includes an update on recognition, treatment, and prevention.
The histopathological features of obliterative bronchiolitis suggest that injury and inflammation of small-airway epithelial cells and subepithelial structures lead to excessive fibroproliferation, which is due to ineffective epithelial regeneration and aberrant tissue repair in response to tissue injury. The diverse medical conditions and exposures that result in obliterative bronchiolitis suggest that it is a final common pathway, in which various insults can lead to similar microscopic, physiological, and clinical results.
• What sources of airway injury have been associated with the development of obliterative bronchiolitis?
Several sources of injury to the airway have been associated with the development of obliterative bronchiolitis, including viral respiratory infection, chronic gastroesophageal reflux, and long-standing exposure to high levels of air pollutants. The condition is also attributed to an alloimmune reaction that is believed to represent chronic allograft rejection in patients who have undergone lung transplantation and chronic graft-versus-host disease (GVHD) in patients who have undergone allogeneic HSCT [hematopoietic stem-cell transplantation]. In addition, autoimmune responses to airway proteins, including those directed against collagen and K-alpha 1 tubulin, have been identified as having potential importance in the pathogenesis of obliterative bronchiolitis.
• What are the typical features of obliterative bronchiolitis on pulmonary function testing?
In its most common presentation, obliterative bronchiolitis is characterized by the physiological features of respiratory obstruction. The major findings on spirometry are a normal, or slightly decreased, forced vital capacity (FVC), a reduced forced expiratory volume in 1 second (FEV1), and a reduced ratio of FEV1 to FVC, with a poor response to inhaled bronchodilators. Lung volumes indicate air trapping, with a normal total lung capacity and high residual volume. However, obstructive impairment is not universal. A subset of patients has normal results on spirometry, a restrictive pattern characterized by a low FVC and a normal FEV1:FVC ratio, or a mixed pattern of obstruction and restriction. The diffusing capacity for carbon monoxide is initially normal but may decrease with disease progression.
Morning Report Questions
Q: What are the characteristic imaging findings in patients with obliterative bronchiolitis on high-resolution CT (HRCT)?
A: HRCT, performed near total lung capacity and near residual volume without the administration of contrast material, has become a definitive noninvasive test for obliterative bronchiolitis. Patchy areas of decreased lung density associated with reduced vascular caliber are identified on HRCT. This pattern has been referred to as mosaic perfusion or mosaic attenuation, in which areas of decreased attenuation that represent bronchial or bronchiolar air trapping are enhanced on expiratory HRCT scans. In advanced cases, there may be dilatation and thickening of large airways, which are characteristic of bronchiectasis. Expiratory CT scans may facilitate the early detection of obliterative bronchiolitis, since they may show air trapping before impairment can be detected on pulmonary-function tests. A characteristic feature of the disease is the paucity of ground-glass opacities, which would be seen in pneumonia or organizing pneumonia.
Q: What is the optimal treatment of obliterative bronchiolitis due to toxic inhalation?
A: Although the symptoms of exposure to toxic fumes may be nonspecific, management involves applying the principles of medical surveillance to workers and the workplace, including screening workers for pulmonary function; removing workers from a potential or suspected source of exposure; conducting an epidemiologic investigation; monitoring the workplace and its surroundings, equipment, and any chemical additives used; and educating workers, health authorities, and industry. There is no curative treatment for obliterative bronchiolitis due to toxic inhalation, and various responses to therapy have been reported. Bronchodilating medication and inhaled glucocorticoids, oral N-acetylcysteine, and interferon gamma have been shown to improve both clinical symptoms and the results of pulmonary-function tests in patients exposed to mustard gas. However, in nine workers at a popcorn-production plant who had obliterative bronchiolitis, treatment with oral glucocorticoids (in seven of the workers) or with glucocorticoids and cyclophosphamide (in two) did not improve pulmonary function.