Mechanisms of increased epithelial lung clearance of DTPA in diffuse fibrosing alveolitis

Abstract

The aim of this study was to elucidate possible mechanisms of increased epithelial lung clearance in diffuse fibrosing alveolitis (DFA). We investigated the relationships between epithelial lung clearance as assessed by the clearance of aerosolized 99mTc-diethylene-triamine-penta-acetic acid (RC-DTPA), luminal alveolitis as assessed by bronchoalveolar lavage, and pulmonary function, in 30 nonsmokers with DFA. In 14 of these patients, RC-DTPA and lung function were determined before and during therapy with prednisolone (0.5 mg.kg-1 daily). RC-DTPA was higher in patients with DFA (4.45 +/- 2.50%.min-1) than in normal subjects (1.18 +/- 0.31%.min-1). RC-DTPA did not correlate with the number of alveolar neutrophils, but correlated positively with the number of alveolar lymphocytes, and negatively with vital capacity (VC). RC-DTPA decreased from 6.1 +/- 2.8 to 3.8 +/- 1.9%.min-1 with prednisolone. RC-DTPA before prednisolone correlated positively with the prednisolone-associated improvement in VC. We conclude that in patient with DFA, RC-DTPA is increased, and decreases but does not return to normal with corticosteroid therapy. Our data suggest that in DFA the increase in RC-DTPA could be related to the recoil-induced stretch of the respiratory epithelium and to alveolar lymphocytic inflammation.

Clearance of inhaled technetium-99m-DTPA as a clinical index of pulmonary vascular disease in systemic sclerosis

“…The specific mechanism of increased clearance times in FA is still unclear but has been thought to be secondary to the stretching of epithelial junctions in the alveolar wall as a result of fibrotic traction or lymphocytic infiltration [12,21]. The present findings support the hypothesis that the alveolar±capillary barrier is intact in cases of SSc with vascular disease and that the alveolar epithelial integrity is significantly impaired in matching patients with parenchymal fibrosis.…”

Randomized Trials Describing Lung Inflammation after Pleurodesis with Talc of Varying Particle Size

“…Therefore, we chose to use the half time of the epithelial lung clearance of aerosolized DTPA as the primary outcome for this trial. DTPA clearance predominantly assesses the permeability of the epithelium of the terminal respiratory units to solutes and is a sensitive index of lung inflammation in diffuse inflammatory lung disease (16)(17)(18), including acute minor pneumonitis after radiotherapy to the other lung (17). Measurements of DTPA clearance are influenced by smoking and position.…”

“…We hypothesized that inflammation in the lung contralateral to a pleurodesis might be detectable by 99m technetium-labeled DTPA lung scanning because this test is capable of identifying subtle lung inflammation in other settings (16)(17)(18)(19). This hypothesis led to the two randomized trials reported here.…”

Prediction of disease progression in idiopathic pulmonary fibrosis

“…Confidence to change these management strategies is required. The studies by AGUSTI et al [13] and LABRUNE et al [18] in this month's issue of the Journal, taken together with other recently published articles on prognostic indicators, have shown that it is now possible to design appropriate studies to answer these important issues in early and advanced disease, and in treated and untreated patients. The important question, notably the difficult problem of prevention of deterioration, will require studies involving reasonably large numbers of patients, seen in specialist centres with an interest in diffuse lung disorders and a multinational, co-ordinated strategy.…”

“…In a recent retrospective study, abnormally rapid clearance of 99m Tc-DTPA at initial measurement was found to identify fibrosing alveolitis patients at higher risk of a decline in functional indices over the subsequent 3 yrs [17]. LABRUNE et al [18] set out to evaluate possible mechanisms of increased 99m Tc-DTPA clearance in fibrosing alveolitis and, by studying the effects of corticosteroid therapy, were able to demonstrate a reversible and irreversible component of rapid clearance. The observation of decrease in clearance in response to treatment is important and further emphasizes the value of clearance measurements in determining the need for treatment, particularly as the greatest rates of clearance were associated with the largest improvement in vital capacity in response to treatment.…”