In 50 of 94 patients with bronchiolitis obliterans we found no apparent cause or associated disease, and the bronchiolitis obliterans occurred with patchy organizing pneumonia. Histologic characteristics included polypoid masses of granulation tissue in lumens of small airways, alveolar ducts, and some alveoli. The fibrosis was uniform in age, suggesting that all repair had begun at the same time. The distribution was patchy, with preservation of background architecture. Clinically, there was cough or flu-like illness for 4 to 10 weeks, and crackles were heard in the lungs of 68 per cent of the patients. Radiographs showed an unusual pattern of patchy densities with a "ground glass" appearance in 81 per cent. Physiologically, there was restriction in 72 per cent of the patients, and 86 per cent had impaired diffusing capacity. Obstruction was limited to smokers. The mean follow-up period was four years. With corticosteroids, there was complete clinical and physiologic recovery in 65 per cent of the subjects; two died from progressive disease. This disorder differs from bronchiolitis obliterans with irreversible obstruction. It was confused most often with idiopathic pulmonary fibrosis. In view of the benign course and therapeutic response, a histologic distinction is important.

Bronchiolitis obliterans organizing pneumonia.

Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures.

The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8) Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are involved Under these circumstances, intraluminal organization can mediate the fusion of adjacent alveolar structures by intraluminal connective tissue

Intraluminal fibrosis in interstitial lung disorders.

Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.

Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients.

This report is based on 43 cases where a diagnosis of either bronchiolitis obliterans with organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), or small airways disease (SAD) was established by lung biopsy. The severity of histologic abnormalities in the peripheral airways and interstitial spaces were measured on these biopies using semiquantitative techniques and compared with the clinical data available in 42 of 43 cases, preoperative chest radiographs in 31 of 43, and preoperative pulmonary function tests in 29 of 43. The data show that when a diagnosis of BOOP was made, there was a higher total pathologic score for membranous bronchiolitis (MB) and respiratory bronchiolitis (RB) than for UIP and SAD (p < 0.005). This was due to peribronchiolar inflammation and the presence of loose connective tissue in the RB lumen. The pathologic changes in the interstitial space were less severe in SAD than in BOOP or UIP (p < 0.005). Clubbing was more frequent in UIP (p < 0.01), and symptoms were of sho...

Scott Worthen

Papers

Bronchiolitis Obliterans: Report of Three Cases with Detailed Physiologic Studies

Report of Three Cases with Detailed Physiologic Studies