Articles: pulmonary-fibrosis-etiology.
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Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. ⋯ Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.
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Arch. Pathol. Lab. Med. · Mar 2016
Review Comparative StudyUpdate on Pulmonary Fibrosis: Not All Fibrosis Is Created Equally.
Three distinct patterns of pulmonary fibrosis, including usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis, can be identified on surgical lung biopsies. ⋯ Although there may be overlap, identification of the dominant form of fibrosis in a particular case can provide a general category of disease and assist in identifying an etiology.
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Fibroblasts are key cells in the fibrotic process. Their profibrotic phenotype is influenced by the environment in which they operate, both extracellular matrix and mediators which they are exposed. The pharmacologic modulation of the fibroblast phenotype allows to identify potential therapeutic targets which might interrupt the vicious cycle of pulmonary fibrogenesis.
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One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. ⋯ The authors focus the discussion on the thesis that mechanical ventilation-or more specifically, that ventilator-induced lung injury-may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress-induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.