Hospital Medicine

Bronchiolitis obliterans

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Bronchiolitis obliterans

I. What every physician needs to know.

Bronchiolitis obliterans (BO) refers to non-specific inflammation of the small airways, which causes a clinical syndrome characterized by persistent cough and dyspnea. The nomenclature is confusing as there are multiple clinical and pathologic entities that share the terms 'bronchiolitis' and 'obliterans'.

BO is related to bronchiolitis obliterans organizing pneumonia (BOOP), which is now referred to as Organizing Pneumonia (OP), but OP refers specifically to a process that additionally involves the alveoli and is not restricted to the bronchioles alone. There also exists an entity called bronchiolitis obliterans syndrome (BOS), which is a distinct entity characterized by specific pulmonary function test abnormalities in lung transplant patients. BOS can also develop in hematopoietic cell transplant recipients, and even more so in those who develop Graft versus Host Disease (GVHD).

Patients with BOS are suspected to have pathologic evidence of bronchiolitis obliterans, but obtaining tissue in post-lung transplant patients is not recommended, so the entity is defined based on clinical grounds with spirometry. The remainder of this article will discuss only pure BO.

BO can be seen in a wide variety of clinical situations. Etiologies include toxic fume inhalation, pulmonary infections (usually viral or atypical bacterial infections), medications (gold, busulfan, penicillamine), and cocaine inhalation. It can be also be associated with connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s and scleroderma) and inflammatory bowel disease. Finally, in many cases, it is idiopathic.

As a clinical syndrome, BO is often misdiagnosed as chronic obstructive pulmonary disease (COPD) or asthma, especially when there is no classic history of drug or toxic fume inhalation.

There are multiple pathologic forms of BO, but the two most common categories are constrictive bronchiolitis and proliferative bronchiolitis. These can occur simultaneously. In general, the proliferative form is much more common and much more likely to respond to therapy, whereas the constrictive form is more likely to be progressive and has a poor prognosis.

II. Diagnostic Confirmation: Are you sure your patient has bronchiolitis obliterans?

BO should be considered in a patient who has persistent cough and dyspnea, especially with a history of fume inhalation or offending drug use.

In particular, exposure to mustard gas, ammonia gas, paraquat-containing herbicide, diacetyl, (found in microwave popcorn butter flavoring factories), and nitrogen dioxide (to which many industrial workers such as silo fillers, welders, and metal picklers can be exposed to) can be the culprit.

A. History Part I: Pattern Recognition:

Typically, patients describe a gradual (weeks to months) onset of non-productive cough and progressive dyspnea. Consider in patients who don't have classic features of asthma or COPD (i.e., non-smokers, too late in life to develop asthma).

Generally, those who have been exposed to toxic fumes develop BO 2-8 weeks after the initial exposure.

B. History Part 2: Prevalence:

The lack of uniformly utilized nomenclature for BO in the medical literature makes the epidemiology unclear.

Predisposing factors include toxic fume inhalation, crack cocaine use, gold or penicillamine therapy, recent viral respiratory infection, organ transplantation, and connective tissue disease.

C. History Part 3: Competing diagnoses that can mimic bronchiolitis obliterans.

Diagnoses to include in the differential include asthma, COPD, sarcoidosis, and hypersensitivity pneumonitis.

D. Physical Examination Findings.

There are no significant physical findings that would differentiate BO from other causes of cough and dyspnea; however, early inspiratory crackles with occasional squeaks are usually present.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Although there are no laboratory tests that are diagnostic for BO it would be reasonable to evaluate for infectious (eg. viral PCR or antibodies) and/or autoimmune etiologies (e.g., anti-CCP, rheumatoid factor, etc.) in the right clinical setting.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A high-resolution chest computed tomography (CT) with inspiration and expiration films should be ordered. It will usually show expiratory air trapping – delineated by patchwork of regions of different attenuation (mosaic attenuation), bronchial wall thickening, and bronchiolectasis (dilation of bronchioles).

Pulmonary function tests (PFTs) with diffusion capacity measurement may be normal early on in the disease process. However, as BO progresses, these measurements will decline. In constrictive BO, an obstructive pattern is seen without significant reversibility. Residual volume can also be increased. Forced expiratory flow (FEF25-75) is almost never normal, so it is sensitive, but not specific. Ambulatory oximetry may also be abnormal.

In many cases, the history, chest CT, and PFTs would be sufficient to make the diagnosis of BO. Only if there is uncertainty is a lung biopsy is needed. A biopsy also helps make the distinction between constrictive and proliferative bronchiolitis, which is important for prognosis. Given the patchy involvement of BO, a transbronchial biopsy often does not provide enough tissue; therefore, open lung biopsy is usually required to make the diagnosis.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

The diagnosis of BO is often the result of a work-up which excludes alternate diagnoses. As a result, there are few "wasted" tests by the point lung biopsy and high resolution CT are obtained.

III. Default Management.

A. Immediate management.

Unfortunately there is weak evidence to support any particular treatment regimen for BO.

Immediate management can include the use of inhaled albuterol, cough suppressants, and supplemental oxygen. There has been some anecdotal success with macrolide antibiotics and steroids in BOS patients, which has been extrapolated to BO. Although this is not felt to be an infectious process, macrolides are thought to help throughimmunomodulation.

B. Physical Examination Tips to Guide Management.

Monitor oxygen (O2) saturation and O2 requirement.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Repeat PFTs and chest CT will be needed to identify complete resolution of the disease process.

D. Long-term management.

Steroids (prednisone 60 mg daily) and macrolide antibiotics (azithromycin 250 mg three times a week) are often empirically prescribedt. If symptoms improve, the steroid and antibiotic should be continued for 2-3 months and then gradually tapered down.

E. Common Pitfalls and Side-Effects of Management

For patients on steroids, glucose, blood pressure and weight should be monitored; obtain bone density testing and manage accordingly for those on long-term steroids. Patients should be monitored for the development of infections.

IV. Management with Co-Morbidities

A. Renal Insufficiency.

No change in standard management.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard management.

E. Diabetes or other Endocrine issues

Glucose monitoring will be more important given the steroid use.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

Steroids used to treat BO will cause immunosuppression. In addition, BO is often associated with syndromes such as connective tissue disease and organ transplantation, making it more common in patients who are relatively immunosuppressed.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

No change in standard management.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

N/A

B. Anticipated Length of Stay.

This syndrome is mostly managed in the outpatient setting. If the patient is hospitalized, the length of stay should be short (24-48 hours) if there are no other comorbidities.

C. When is the Patient Ready for Discharge?

The patient is ready for discharge when O2 saturation with reasonable exercise is adequate or when appropriate home O2 is arranged.

D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom?

Patients should be followed-up in general medicine clinic for routine management of steroids and O2 supplementation if needed. Pulmonary clinic follow-up should also be arranged for confirmation of diagnosis and management of the disease.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

  • O2 saturation

  • Full Pulmonary Function Testing with bronchodilator administration

E. Placement Considerations.

N/A

F. Prognosis and Patient Counseling.

Prognosis depends on the pathologic disease process. Most patients with proliferative bronchiolitis improve completely. Patients with constrictive bronchiolitis often have a more progressive course, but the epidemiology is not studied well enough to provide statistics.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Deep vein thrombosis (DVT) prophylaxis is indicated. Pneumococcal vaccine and seasonal influenza vaccination should be provided.

VII. What's the evidence?

Aguilar, PR, Michelson, AP, Isakow, W. "Obliterative Bronchiolitis". Transplantation. vol. 100. 2016 Feb. pp. 272-83.

Lynch, J, Weigt, S, DerHovanessian, A, Fishbein, M, Gutierrez, A, Belperio, J. "Obliterative (Constrictive) Bronchiolitis". Semin Respir Crit Care Med. vol. 33. 2012. pp. 509-532.

Epler, GR. "Constrictive Bronchiolitis Obliterans: the fibrotic airways disorder". Expert Rev Respir Med. vol. 1. 2007 Aug. pp. 139-47.

Ryu, JH, Myers, JL, Swensen, SJ. "Bronchiolar disorders". Am J Respir Crit Care Med. vol. 168. 2003. pp. 1277-92.

Devakonda, A, Raoof, S, Sung, A, Travis, WD, Naidich, D. "Bronchiolar disorders: a clinical-radiological diagnostic algorithm". Chest. vol. 137. 2010. pp. 938-51.

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