A. Characteristics [1]

1. BO and BO with Organizing Pneumonia (BOOP) are distinct but related entities
2. The distinction is important because BOOP responds well to glucocorticoids; BO does not
3. Pathological Diagnosis of BO
   1. Obliteration of bronchioles by inflammatory cells
   2. Fibrotic process primarily affecting the small bronchioles
   3. Alveoli adjacent to the affected brochi are usually involved
   4. Intersitium usually spared
4. BO occurs in variety of clinical situations
   1. Toxic Fume Exposure including microwave popcorn workers (2,3-butanedione) [2]
   2. Post-infectious - mainly viral, mycoplasma, legionella; usually young persons
   3. Connective Tissue Diseases: Rheumatoid arthritis, SLE, Inflammatory Myositis
   4. Lung Transplantation - over 65% of recipients develop BO [3]
   5. Organ and Bone Marrow Transplantation
   6. Paraneoplastic Pemphigus
   7. Idiopathic forms of disease
   8. Penicillamine reaction
5. Pure Bronchiolitis
   1. Infection of lower respiratory tract which occurs in persons <1 year old
   2. Most commonly associated with respiratory syncitial virus
   3. Exposure to tobacco smoke may increase risk
   4. Wheezing is a common component (along with shortness of breath)
   5. Dexamethasone (1mg/kg) had no benefit over placebo in 120 infant trial [8]

B. Diagnosis

1. Transient inspiratory squeak present in most cases
2. Radiographic appearance similar to COPD
3. Obstructive, Restrictive or Mixed Ventilatory defects on PFTs
4. Must distinguish from idiopathic pulmonary fibrosis (IPF)
   1. IPF usually (~75%) has decreased lung volumes (FVC)
   2. BO usually (~75%) has normal lung volumes

C. Classification of Bronchiolitis Obliterans (Epler and Colby) [1]

1. Definition
   1. Relatively rare, pneumonia-like disorder
   2. Clinicopathological syndrome including clinical, radiographic and pathologic features
   3. Usually occurs ages 40s through 50s, men slightly more than women
   4. May be caused by infections, neoplasms, inflammatory diseases, or drug reaction
   5. Also occurs with recurrent gastroesophageal reflux and occult aspiration [9]
   6. Sjogren Syndrome should be considered with concommitant dry eyes, mouth [7]
   7. Reported reaction to sirolimus in renal transplant recipients [6]
   8. However, true BOOP (versus BO) is probably most commonly a reaction to infection
2. Symptoms
   1. Acute, dramatic onset of flu-like illness
   2. Persistent, usually non-productive cough (~84%)
   3. Dyspnea on exertion (~65%)
   4. Rales (~65%)
   5. Wheezing (~30%)
3. Signs
   1. Arterial hypoxemia
   2. Normal pulmonary function ~20%
   3. Restrictive and/or obstructive ventilatory defects may be present
   4. DLCO nearly always reduced
4. Distinct subclasses on chest radiography (CXR) [9]
   1. Patchy, migratory (waxing and waning) pneumonic foci
   2. Bilateral, diffuse interstitial disease
   3. Solitary focus of pneumonia - excellent prognosis (no long term residua)
   4. Ground-glass or alveolar opacities may be seen in any of these
   5. May progress to acute respiratory distress syndrome (ARDS) [4]
5. Pathology
   1. Specific pathological findings define BOOP
   2. Patchy interstitial inflammation and airspace granulation tissue
   3. This "organized pneumonia" is localized to small airways, alveolar duct, alveolar spaces
   4. Foamy macrophages common
   5. Fibroblastic infiltration is moderate only
   6. Minor interstital fibrosis occurs
   7. Frank honeycomb appearance (as in idiopathic pulmonary fibrosis) is unusual
6. Treatment
   1. Glucocorticoids (1.5-2mg/kg per day prednisone or other initially) are very effective
   2. Underlying disease should be treated aggressively
   3. Death from progressive disease is uncommon

E. Toxic Fume Exposures

1. Clinical Patterns
   1. Mild: cough, dyspnea, fatigue, cyanosis, vomiting, hemoptysis, hypoxemia, vertigo
   2. Moderate: progression, loss of consciousness, bronchiolitis (hours-days)
   3. Serious Acute: Adult Respiratory Distress Syndrome
   4. Serious Chronic: initial recovery with later (4-8 week) development of Bronchiolitis
2. Treatment
   1. Initial hospitalization with observation
   2. Intubation / CPAP for ARDS
   3. Glucocorticoids for chronic problems including Bronchiolitis obliterans

Resources

Aa Gradient

References

1. Epler GR and Colby TV. 1983. Chest. 83:161
2. Kreiss K, Gomaa A, Kullman G, et al. 2002. NEJM. 347(5):330
3. Scott JP, Peters SG, McDougall JC, et al. 1997. Mayo Clin Proc. 72(2):170
4. Waxman AB, Shepard JO, Mark EJ. 2003. NEJM. 348(19):1902 (Case Record)
5. Lohr RH, Boland BJ, Doublas WW, et al. 1997. Arch Intern Med. 157(12):1323
6. Champion L, Stern M, Israel-Biet D, et al. 2006. Ann Intern Med. 144(7):505
7. Harris RS and Mark EJ. 2001. NEJM. 344(22):1701 (Case Record)
8. Roosevelt G, Sheehan K, Grupp-Phelan J, et al. 1996. Lancet. 348:292
9. Fleming CM, Shepard JO, Mark EJ. 2003. NEJM. 348(20):2019 (Case Record)