Lung Disease Associated with Progressive Systemic Sclerosis: Assessment of Interlobar Variation by Bronchoalveolar Lavage and Comparison with Noninvasive Evaluation of Disease Activity

Abstract

Progressive systemic sclerosis (PSS), or scleroderma, is a disease of unknown etiology that involves many organ systems, including the lungs. The interstitial lung disease of systemic sclerosis is becoming an increasing cause of morbidity and mortality. This process has been previously evaluated with single-site bronchoalveolar lavage (BAL), gallium scanning, pulmonary function testing, and, occasionally, by open lung biopsy. As BAL has been shown to correlate well with open lung biopsy in systemic sclerosis, we sought to determine if single-site BAL accurately reflects alveolitis in a second site in the lung, and if BAL results correlate with other noninvasive tests of lung inflammation: gallium uptake, chest radiography, or arterial blood gas analysis. We performed 17 studies in 13 patients with scleroderma and found no significant lobar differences in lavage results or gallium scanning. By our criteria for normal versus active alveolitis, only two of 17 patient lavages would have been classified as normal by one side and abnormal by the other side. Although percent gallium uptake was equal bilaterally and supported the concept of alveolitis uniformity, gallium uptake intensity did not correlate with activity as measured by BAL. Furthermore, chest radiograph and arterial blood gas analysis did not correlate with BAL results or gallium scanning. We believe these data support the suitability of single-site lavage in the investigation of systemic-sclerosis-associated alveolitis and diminish the importance of gallium scanning in the investigation of systemic sclerosis pulmonary disease.

Correlation of Cough With Disease Activity and Treatment With Cyclophosphamide in Scleroderma Interstitial Lung Disease

“…[8][9][10][11][12] The need for BAL has diminished as experience with HRCT scanning has increased, because the presence of GGOs appears to correlate with an infl ammatory BAL, providing a noninvasive mechanism for identifying active disease and patients at risk of progressive fi brosis. 13,[29][30][31] However, whereas early studies showed a correlation between GGO resolution and CYC treatment, supporting the concept that alveolitis was improving, more recent investigations have not shown a correlation between improvement in GGO and CYC treatment, suggesting that GGOs may represent heterogeneous conditions including infl ammatory alveolitis, subresolution fi brosis, and/or…”

Pulmonary Complications of Collagen Vascular Disease

“…Bronchoalveolar lavage, a technique whereby inflammatory and immune effector cells are retrieved from the lower respiratory tract at the time of bronchoscopy, has demonstrated increases in inflammatory cells [activated alveolar macrophages (AMs), polymorphonuclear leukocytes (PMNs), lymphocytes], neutrophil and AM-products, immune complexes, and immunoglobulins in patients with idiopathic pulmonary fi brosis (3-5) and in subsets of patients with collagen vascular disease (6, 7, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Although the role of BAL as a prognostic guide in CILD associated with CVD had not been established, increases in BAL neutrophils and/or lymphocytes, consistent with alveolitis, may occur even in asymptomatic patients with CYO, and may identify patients at risk for clinical deterioration (6, 7).…”

“…The presence of these foci supports the concept that active alveolitis may antedate and be respon sible for the development of late fibrosis (21,24,40). Several recent inves tigations have demonstrated exaggerated amounts of infl ammatory cells and phlogistic mediators on BAL and increased intrapulmonary uptake of gallium in 50-75% of PSS patients (2 0, [22][23][24][25][26].…”

“…Increased burdens of PMNs, eosinophils, lymphocytes, activated AMs, AM products (fibronectin, growth factors), neutrophil chemotactic activity, immune complexes, collagenase, IgG, and antibodies to types I and 4 collagen have each been demonstrated in BAL fl uid in patients with PSS (20)(21)(22)(23)(24)(25)(26). Although disparate results have been reported, both BAL neutrophilia (22,25,26) and BAL lymphocytosis (20,22) have been associ ated with more severe impairment in pulmonary function or abnormalities on chest radiographs.…”

“…Increased intrapulmonary uptake of gallium (consistent with alveolitis) has been noted in approximately three quarters of patients with PSS and CILD (20,23,24). Gallium scans have correlated with a higher percentage of lymphocytes on BAL in some studies (20), while others have failed to find any relationship between gallium scan and BAL cell profi les, chest radiographic scores, or clinical symptoms (23,24).…”