Constrictive Bronchiolitis Obliterans: The Fibrotic Airway Disorder

Gary R. Epler

Disclosures

Expert Rev Resp Med. 2007;1(1):139-147. 

In This Article

Abstract and Introduction

Constrictive bronchiolitis obliterans is an important respiratory illness because of its underlying irreversible fibrotic process, and is defined as concentric fibrosis in the bronchiolar submucosal layer with continual external circular scarring. The fibrotic and destructive nature of this lesion is the defining characteristic. Although patchy, the airway may become slit-like or obliterated from this fibrotic process, resulting in bronchiolitis obliterans. Constrictive bronchiolitis is limited to the bronchioles and does not extend into the alveoli. The clinical features of constrictive bronchiolitis consist of a chest radiograph that is often normal, early inspiratory crackles and irreversible airflow obstruction by pulmonary function testing. Chest CT scans show a mosaic pattern, air trapping by the expiratory film, bronchiolectasis and thickened small airway walls. Although idiopathic constrictive bronchiolitis is rare, the lesion is common among lung-transplant recipients. The lesion also occurs from certain types of toxic fumes, some of the connective tissue diseases, specific types of medications and post respiratory infection. Unusual exposures have also been described as a cause of constrictive bronchiolitis, such as consumption of the leafy vegetable Sauropus androgynus in far eastern Asia and from inhaling diacetyl, the ketone butter flavoring used in microwave popcorn production. Empirical treatment consists of corticosteroid and immunosuppressive agents. Antifibrotic agents may be successful in the future. This is generally a nonsteroid-responsive lesion and for disabling disease, lung transplantation can be a successful option.

Constrictive bronchiolitis (CB) obliterans is an important respiratory illness of the small airways because of its fibrotic irreversible nature. For the clinician, the bronchiolar airway obliteration diseases can be divided into two major lesions, one predominantly fibrotic and the other inflammatory. The first lesion is CB, which is an irreversible lesion that develops by concentric fibrosis in the bronchiole submucosa layer with continual external circular scarring. The fibrotic and destructive nature of this lesion is the defining characteristic. Although patchy, the airway may become slit-like or obliterated from the fibrotic process, resulting in bronchiolitis obliterans. The second lesion is proliferative bronchiolitis with intraluminal polyps, which is a steroid-reversible lesion developing from the internal layer that fills the lumen causing bronchiolitis obliterans.

CB is limited to the bronchioles and does not extend into the alveoli. Proliferative bronchiolitis with intraluminal polyps may be limited to the bronchioles, but often extends into respiratory bronchioles and alveoli with intra-alveolar buds of granulation tissue resulting in bronchiolitis obliterans organizing pneumonia (BOOP). The lung architecture is maintained in BOOP without fibrotic destruction. With CB, there may be severe and extensive fibrotic airway remodeling.

CB obliterans and proliferative bronchiolitis with intraluminal polyps are two distinct pathological lesions, probably with different cellular and cytokine pathogenic pathways. Details of these pathways have not yet been fully established. They both appear to begin early with an inflammatory reaction, but the elements of this reaction are probably different as CB proceeds to a fibrotic process and the proliferative bronchiolitis with intraluminal polyps continues as an inflammatory process. Similar to CB, BOOP is also patchy in nature. The BOOP lesion is not a temporal spectrum of disease as first occurring in the bronchioles and later extending into the alveoli, but a simultaneous process occurring in the distal bronchioles, respiratory bronchioles and alveoli.

With regard to causes and coexisting medical conditions, in some situations there is an overlap between CB and proliferative bronchiolitis with intraluminal polyps while in other situations there is no overlap. Both lesions occur in the connective tissue diseases, although one may be more prominent than the other, such as CB occurring in scleroderma and BOOP occurring in lupus and mixed connective tissue disorders. There is no overlap drug-related reactions. Penicillamine may cause CB obliterans and amiodarone causes BOOP. Certain types of toxic fumes, such as sulfur dioxide and ammonia, may cause CB, while nitrogen dioxide causes intraluminal polyps with obliteration. Clinicians need to take a detailed occupational history when evaluating patients with nontransplant bronchiolitis obliterans as the best treatment is prevention from further exposure, and it is important to alert others of the possible risk. For lung transplantation, CB or BOOP may occur in transplant recipients, but for different reasons, CB is from chronic organ rejection, while BOOP is due to a viral infection or nonchronic rejection.

Clinical findings may be indistinguishable between CB and proliferative bronchiolitis occurring in the mid to distal bronchiolar airways. However, the clinical findings are distinctively different between CB and proliferative bronchiolitis, extending into the alveoli as BOOP. For CB obliterans, the chest radiograph is often normal, there are early inspiratory crackles and there is irreversible airflow obstruction by pulmonary function testing. For BOOP, the chest radiograph shows bilateral patchy infiltrates, there are end-inspiratory crackles, there is no airflow obstruction and there is a decreased diffusing capacity by pulmonary function testing.

The response to steroid therapy and prognosis differs widely between the CB and BOOP lesions. CB is not responsive to corticosteroid therapy and has a poor prognosis, while the BOOP lesion is highly responsive to steroid therapy with a cure rate of 65-80%. Therefore, it is important for the pathologist and clinician to distinguish between these two lesions. The treatment challenge for the clinician is to develop a program to successfully manage individuals with CB and to cure individuals with the BOOP lesion. This review will be a discussion of CB regarding the causes and coexisting diseases, as well as the clinical, radiologic and physiological findings.

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