ANSWER: Respiratory Bronchiolitis Interstitial Lung Disease (RB-ILD)
The low-power view of the biopsy specimen shows a terminal and a respiratory bronchiole surrounded by scar tissue and alveolar septal thickening. The presence of brown pigmented macrophages abundant in the airspace adjacent to the affected bronchioles led to a diagnosis of respiratory bronchiolitis interstitial lung disease (RB-ILD).
RB-ILD was first described by Myers and colleagues1 in 1987 in their report on 6 heavy smokers who had clinical, radiological, and physical evidence of interstitial lung disease. Open lung biopsy specimens showed respiratory bronchioles with inflammatory cellular infiltration, thickened alveolar septa, and a clustering of light brown–pigmented macrophages in the airspaces.
A rare interstitial lung disease, RB-ILD is almost always associated with a history of smoking, with rare exceptions related to inhalation of noxious substances.2 RB-ILD may represent a progression of smoking-related respiratory bronchiolitis (smokers’ bronchiolitis), a very common asymptomatic histopathological finding, first described in 1974 by Niewoehner and associates.3
The distinction between smokers’ bronchiolitis and RB-ILD lies in the onset of symptoms and biopsy findings of interstitial inflammation and/or fibrosis. Both conditions share the characteristic findings of bronchiolar inflammation and a clustering of light brown–pigmented macrophages. Until 1989, the largest series of RB-ILD were from 2 studies involving a total of 24 patients.1,4 Since then, a handful of published case series have described 200 cases. Based on this collective experience, patients present in the fourth or fifth decade with dyspnea and cough that is sometimes productive, accompanied by mild restriction and reduction in carbon monoxide–diffusing capacity.
The chest radiographic findings are abnormal in 70% to 80% of cases.5 CT scans and chest radiographs most frequently demonstrate ground-glass opacities that are known to correlate with macrophage accumulation in the alveolar spaces and alveolar ducts.6
RB-ILD is similar in many respects to another interstitial lung disease, desquamative interstitial pneumonia (DIP). Many authors believe both diseases should be addressed as one under the term “smoking-related interstitial lung disease.” Both share a common presentation and radiological and pathological findings. Smoking is highly associated with both conditions, occurring in more than 90% of cases.6
The pathological distinction between RB-ILD and DIP pertains to the distribution and extent of involvement: the disease process in RB-ILD centers on the small airways with some extension into the airspace, in contrast to a more uniform and widespread pattern with DIP.7 This apparently simple differentiation is often difficult to make because of overlap.
Treatment of both RB-ILD and DIP includes smoking cessation, supportive care, and a consideration of corticosteroids. Case reports suggest remission of the disease process with complete smoking cessation,6,8 including avoidance of secondary tobacco smoke exposure. Many report remission with administration of corticosteroids over several months, but concluding efficacy is difficult because of the concurrent abstinence of smoking. The course of RB-ILD appears stable and benign, although radiological findings can persist for many years. Deaths have been reported in patients with DIP but not in those with RB-ILD.
Outcome in this case
The patient’s symptoms, exercise tolerance, and pulmonary function gradually improved following a regimen of oral prednisone(Drug information on prednisone) for 14 months that was tapered down to 7.5 mg/d. Unfortunately, complete abstinence from tobacco has been difficult to achieve despite strong encouragement and education. We are optimistic that she will return to her former job in the near future. This case emphasizes the need to consider alternative diagnoses in a patient unresponsive to conventional asthma medications.9