Definition, Etiology, Clinical FeaturesTop
Bronchiolitis obliterans refers to fibrosis of the bronchioles that leads to their narrowing and obliteration.
Causes: Connective tissue diseases (particularly rheumatoid arthritis [RA]); infections (viruses, mycoplasmas); inhalation of toxic substances (including nitrogen oxide, ammonia, welding fumes); drugs (gold salts, penicillamine); inflammatory bowel disease; complications of lung, heart, or bone marrow transplantation as a form of graft-versus-host disease (bronchiolitis obliterans syndrome [BOS]).
Symptoms: Exertional breathlessness and cough. Lung auscultation may demonstrate inspiratory crackles, wheeze, or occasional inspiratory squawk. The disease is often progressive and may lead to chronic respiratory failure.
The diagnostic gold standard traditionally has involved histopathologic evaluation of samples obtained from surgical lung biopsy. A working diagnosis is often established via a combination of clinical, physiologic, and radiographic features. The term BOS is generally reserved for patients after lung or hematopoietic stem cell transplantation who develop chronic lung allograft dysfunction characterized by spirometric evidence of airflow obstruction with no other identified causes. A diagnosis of BOS does not require surgical lung biopsy.
Spirometry reveals irreversible airway obstruction, but restriction or a mixed ventilatory defect can also be observed. Diffusing capacity of the lungs for carbon monoxide (DLCO) is usually reduced. Chest radiographs are normal in one-third of patients; in some individuals signs of hyperinflation may be observed. Bronchiectases on radiographs are rare. High-resolution computed tomography (HRCT) may show mosaic perfusion, bronchiectases, and characteristic air trapping during expiration. Centrilobular nodules may also be observed. Bronchoscopy and bronchoalveolar lavage are nonspecific but may identify features of an alternative diagnosis, such as infection, malignancy, sarcoidosis, or hypersensitivity pneumonitis (the last two are usually associated with lymphocytic alveolitis).
Treatment of bronchiolitis obliterans is often ineffective. Symptomatic treatment with an inhaled beta-adrenergic agonist and systemic or inhaled glucocorticoid may be tried. In patients with BOS the intensity of immunosuppressive treatment may be increased (although the efficacy of this is questionable). Observational data suggest benefits of inhaled fluticasone, azithromycin, and montelukast (FAM) in slowing disease progression in hematopoietic stem cell transplant patients with early-onset BOS.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data and indirectness to other clinical situations. Williams KM, Cheng GS, Pusic I, et al. Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016 Apr;22(4):710-716. doi: 10.1016/j.bbmt.2015.10.009. Epub 2015 Oct 22. PubMed PMID: 26475726; PubMed Central PMCID: PMC4801753. In patients with RA, discontinue gold salts and penicillamine when used; a trial course of immunosuppression escalation, a high-dose oral glucocorticosteroid, or azithromycin may be attempted, although data to support such interventions are minimal.