ABSTRACT
BACKGROUND AND OBJECTIVE: Inhalation of high concentrations of respirable crystalline silica (RCS) can lead to silicosis. RCS contains varying levels of iron, which can cause oxidative stress and stimulate ferritin production. This study evaluated iron-related and inflammatory markers in control and silicosis patients. METHODS: A cohort of stone benchtop industry workers (n = 18) were radiologically classified by disease severity into simple or complicated silicosis. Peripheral blood and bronchoalveolar lavage (BAL) were collected to measure iron, ferritin, C-reactive protein, serum amyloid A and serum silicon levels. Ferritin subunit expression in BAL and transbronchial biopsies was analysed by reverse transcription quantitative PCR. Lipid accumulation in BAL macrophages was assessed by Oil Red O staining. RESULTS: Serum iron levels were significantly elevated in patients with silicosis, with a strong positive association with serum ferritin levels. In contrast, markers of systemic inflammation were not increased in silicosis patients. Serum silicon levels were significantly elevated in complicated disease. BAL macrophages from silicosis patients were morphologically consistent with lipid-laden foamy macrophages. Ferritin light chain (FTL) mRNA expression in BAL macrophages was also significantly elevated in simple silicosis patients and correlated with systemic ferritin. CONCLUSION: Our findings suggest that elevated iron levels during the early phases of silicosis increase FTL expression in BAL macrophages, which drives elevated BAL and serum ferritin levels. Excess iron and ferritin were also associated with the emergence of a foamy BAL macrophage phenotype. Ferritin may represent an early disease marker for silicosis, where increased levels are independent of inflammation and may contribute to fibrotic lung remodelling.
Subject(s)
Ferritins , Silicosis , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Ferritins/analysis , Ferritins/metabolism , Humans , Inflammation/metabolism , Iron/analysis , Iron/metabolism , Lipids , Lung/pathology , Macrophages/metabolism , Silicon DioxideABSTRACT
Of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) have provoked the most debate and discussion. Although the two diseases are distinct entities, diagnosis is not always straightforward and requires a multidisciplinary approach, integrating clinical, radiological and histologic information. Although there is currently no effective treatment for either disease, the importance of differentiating NSIP from IPF lies in the management of the individual patient, with particular focus on outcome and pace of change, and enrollment into novel treatment trials of IPF.