Front. Biosci. (Landmark Ed) 2023; 28(5): 96 https://doi.org/10.31083/j.fbl2805096 Copyright: © 2023 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license. Publisher’s Note: IMR Press stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Review Silicosis: New Challenges from an Old Inflammatory and Fibrotic Disease Claudia-Mariana Handra 1,† , Irina-Luciana Gurzu 2,† , Marinela Chirila 3, *, Isabel Ghita 4 1 Occupational Medicine Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania 2 Occupational Medicine Department, “Gr. T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 3 Faculty of Pharmacy, Titu Maiorescu University, 040441 Bucharest, Romania 4 Pharmacology and Pharmacotherapy Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania *Correspondence: marinela.chirila@prof.utm.ro (Marinela Chirila) † These authors contributed equally. Academic Editors: Soriful Islam and Most Mauluda Akhtar Submitted: 28 February 2023 Revised: 23 April 2023 Accepted: 9 May 2023 Published: 22 May 2023 Abstract Silicosis, an occupational lung disease that can be prevented, is still a significant public health concern in many countries, despite its considerably decreased incidence over the years. The latency period for silicosis ranges from a few years to several decades, depending on the duration and intensity of exposure to silica dust. The complex pathogenic mechanisms of the disease are not fully understood, but it is known to be characterized by inflammation, the formation of silicotic nodules, and progressive and irreversible fibrosis. The aim of this paper was to present the current sources of exposure to silica dust and summarize the updates on risk factors (e.g., socioeconomic status, genetic susceptibility) and sex differences, silico-tuberculosis, prognostic markers including 16-kDa Clara cell secretory protein, antifibrotic treatment, and other therapeutic possibilities with promising results. There are no effective treatment options for silicosis, and prevention remains the primary tool to significantly reduce the risk of disease. There are promising new treatments under investigation including antifibrotic, cellular, and immunomodulatory therapies, but further research is needed to demonstrate the efficacy and safety of these therapies in adequately powered clinical trials. Keywords: silicosis; inflammation; fibrosis; current treatment; antifibrotic treatment 1. Introduction Silicosis, one of the oldest occupational diseases, is a pneumoconiosis caused by the long-term inhalation of in- organic dust with high concentrations (>10%) of free crys- talline silica (SiO 2 ). This interstitial lung disease is charac- terized by inflammation, formation of silicotic nodules, and fibrosis, which are progressive and irreversible [1]. The latency period for silicosis ranges from a few years to several decades, depending on the duration and intensity of exposure to silica dust. In some occupational pulmonary diseases, such as silicosis, mesothelioma, and asbestosis, the diagnosis can be delayed due to the long la- tency period, leading to unfavorable disease outcomes [2]. Thus, it is important to increase awareness of the disease, impose strict safety guidelines and regulations, and follow them in order to minimize workers’ exposure to silica dust. Apart from prevention measures, the long-term health mon- itoring of individuals who have been exposed to silica dust is also important for the early identification of any potential health problems. Awareness of the health problems related to silica dust exposure and a rigorous occupational history are essential tools for an early diagnosis. This is especially important, as an accurate diagnosis might be associated with a better prognosis. The migration of workers globally may result in a lack of adequate health monitoring or failure to account for prior exposure to silica dust. The International Labour Organization (ILO) and the World Health Organization set a goal in 1995 to eliminate silicosis from workplaces by 2030 through the Global Pro- gram to Eliminate Silicosis [3]. This goal cannot be eas- ily reached since new sources of silica dust are identified in new technological processes, and the effectiveness and feasibility of dust control methods and technologies vary in different countries. Silicon dioxide, also known as silica, is a widespread mineral that makes up part of the structure of the Earth’s crust. It is formed from silicon and oxygen under increased pressure and temperature conditions. There are two forms of silica: crystalline and amorphous. The crystalline form is very aggressive in lung tissue [4]. Occupational exposure to silica can occur in many workplaces or industries such as mining, metallurgical and car manufacturing industries, abrasive materials, glass, porcelain, or the tile industry [5]. In addition, occupational exposure to silica particles has also been identified in the case of new technological pro- cesses such as jewelry manufacturing, denim sandblasting or manufacturing, and processing of artificial stones [6–8], which are associated with accelerated forms of silicosis and the rapid degradation of lung function in young people [9]. The results of a study by Hua et al.[9] identified a possi- ble significant emerging population of young stoneworkers