Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis compared with the fibrosing alveolitis of systemic sclerosis.

Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a much worse prognosis after matching for disease severity at presentation. The aims of this study were to gain insights into possible pathogenetic mechanisms contributing to this prognostic difference, by comparing bronchoalveolar lavage (BAL) cellularity in the two diseases, and to evaluate the relationships between BAL findings and the regional and global extent of disease, quantified by thin-section computed tomography (CT) and lung function indices. Patients with CFA were distinguished by more extensive fibrosing alveolitis on CT (p < 0.02) and by higher counts of neutrophils (total per ml, p < 0.02; percentage p < 0.03) and eosinophils (total per ml, p < 0.002; percentages, p < 0.02) in BAL fluid. After adjustment for functional and morphologic measures of disease extent, eosinophil percentages and total counts were increased in CFA (p < 0.05 in all 12 multivariate models), but they were not independently related to regional or global disease severity. Neutrophil percentages and total counts were virtually identical in CFA and FASSc in disease of comparable severity, and they increased with increasingly extensive lobar disease and global disease, as judged by CT, p < 0.0005 in all analyses. Neutrophil levels were more closely linked to the extent of disease on CT than to the severity of functional impairment, on univariate and multivariate analysis. The higher BAL eosinophil levels seen in CFA, compared with those seen in FASSc, after adjustment for disease extent, indicate that an eosinophilic influx may be linked to the pathogenesis of fibrosing alveolitis. By contrast, BAL neutrophil levels increase with increasingly extensive disease on CT, but they do not differ independently between CFA and FASSc, suggesting that neutrophil degradation products are unlikely to account for the excess mortality in CFA, compared with that in FASSc.

[1]  M. Schwarz,et al.  Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis. , 2015, The American review of respiratory disease.

[2]  C D Collins,et al.  Observer variation in pattern type and extent of disease in fibrosing alveolitis on thin section computed tomography and chest radiography. , 1994, Clinical radiology.

[3]  D. Hansell,et al.  Fibrosing alveolitis in systemic sclerosis. Bronchoalveolar lavage findings in relation to computed tomographic appearance. , 1994, American journal of respiratory and critical care medicine.

[4]  A. Masi.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). , 1980, Bulletin on the rheumatic diseases.

[5]  D. Hansell,et al.  High resolution computed tomography as a predictor of lung histology in systemic sclerosis. , 1992, Thorax.

[6]  B. Corrin,et al.  Structural features of interstitial lung disease in systemic sclerosis. , 1991, The American review of respiratory disease.

[7]  G. Weissmann,et al.  Release of inflammatory mediators from stimulated neutrophils. , 1980, The New England journal of medicine.

[8]  T. Tötterman,et al.  Phenotypic and functional activation of alveolar macrophages, T lymphocytes and NK cells in patients with systemic sclerosis and primary Sjögren's syndrome. , 1994, Annals of the rheumatic diseases.

[9]  D. Schwartz,et al.  Determinants of survival in idiopathic pulmonary fibrosis. , 1994, American journal of respiratory and critical care medicine.

[10]  D. Hansell,et al.  Cryptogenic fibrosing alveolitis and the fibrosing alveolitis of systemic sclerosis: morphological differences on computed tomographic scans. , 1997, Thorax.

[11]  P. Lalor,et al.  Bronchoalveolar lavage in the normal volunteer subject. I. Technical aspects and intersubject variability. , 1988, Chest.

[12]  B. Burrows,et al.  Cryptogenic fibrosing alveolitis: clinical features and their influence on survival , 1980, Thorax.

[13]  N. Müller,et al.  Usual interstitial pneumonia: correlation of CT with clinical, functional, and radiologic findings. , 1987, Radiology.

[14]  Jacob Cohen,et al.  Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit. , 1968 .

[15]  T. Honda,et al.  Eosinophil activation in patients with pulmonary fibrosis. , 1995, Chest.

[16]  D. Hansell,et al.  Lymphangiomyomatosis: CT, chest radiographic, and functional correlations. , 1990, Radiology.

[17]  N. Müller,et al.  Fibrosing alveolitis: CT-pathologic correlation. , 1986, Radiology.

[18]  N. Müller,et al.  Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation. , 1987, Radiology.

[19]  K. Fredens,et al.  Eosinophil activation in systemic sclerosis. , 1991, Arthritis and rheumatism.

[20]  J. Fries,et al.  Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. , 1969, The American journal of medicine.

[21]  R. Crystal,et al.  Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis. , 1987, The Journal of clinical investigation.

[22]  A. Salsbury,et al.  Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy. , 1980, Thorax.

[23]  D. Schwartz,et al.  Determinants of progression in idiopathic pulmonary fibrosis. , 1994, American journal of respiratory and critical care medicine.

[24]  N L Müller,et al.  Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings. , 1989, Radiology.

[25]  D. Hansell,et al.  The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis. , 1993, The American review of respiratory disease.

[26]  S. Jimenez,et al.  Elevated levels of eosinophil major basic protein in the sera of patients with systemic sclerosis. , 1995, Arthritis and rheumatism.

[27]  D. Hansell,et al.  Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. , 1994, American journal of respiratory and critical care medicine.

[28]  A. Weaver,et al.  Clinical InvestigationsPulmonary Scleroderma , 1968 .

[29]  P. Venge,et al.  The eosinophil component of the alveolitis in idiopathic pulmonary fibrosis. Signs of eosinophil activation in the lung are related to impaired lung function. , 1989, The American review of respiratory disease.

[30]  K. Murata,et al.  Optimization of computed tomography technique to demonstrate the fine structure of the lung. , 1988, Investigative radiology.

[31]  G. Hunninghake,et al.  Prognostic role of eosinophils in pulmonary fibrosis. , 1987, Chest.

[32]  H. Itoh,et al.  Usual interstitial pneumonia: histologic correlation with high-resolution CT. , 1992, Radiology.

[33]  S. Wagenaar,et al.  Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis. , 1995, Thorax.