Articles: pulmonary-fibrosis-etiology.
-
Fibrotic respiratory diseases severely disrupt lung function and currently have an extremely poor prognosis. This is attributable to the limited amount of treatment options available, in part due to our lack of understanding of the mechanisms driving disease pathogenesis. Although the majority of cases appear to be idiopathic, a number of factors are known to cause pulmonary fibrosis, such as the inhalation of silica crystals (silicosis), asbestos fibers (asbestosis) and certain drugs such as bleomycin. ⋯ Moreover, data suggests that inhibition of the inflammasome activation pathway and/or inflammasome-mediated cytokines can attenuate the fibrotic response in in vitro and in vivo models of disease. In this review, we discuss the evidence suggesting that the NLRP3 inflammasome plays an important role in the pathogenesis of fibrotic respiratory diseases, and the potential mechanisms by which activation of the NLRP3 inflammasome may occur. It is possible that fibrotic respiratory diseases with a known cause may share a common mechanism with idiopathic pulmonary fibrosis, providing possible strategies for future drug therapies.
-
Despite public health campaigns discouraging smoking, 1,000 American children every day become smokers, ensuring that tobacco-related health complications will be with us for decades to come. Smoking is the greatest risk factor for both chronic obstructive lung disease and interstitial lung disease. ⋯ In this review, we explore common and divergent biological forces tilting the lung homeostatic balance away from health and toward emphysema or pulmonary fibrosis. We emphasize recent insights that highlight the greatest contrasts or similarities in the pathogenesis of these two chronic lung disease phenotypes.
-
Semin Respir Crit Care Med · Oct 2012
ReviewImmunopathology, diagnosis, and management of hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by a wide variety of organic particles and certain small-molecular weight chemical compounds that provoke an exaggerated immune response in susceptible individuals. The clinical manifestations are heterogeneous and have been classically described as acute, subacute and chronic. The chronic form has an insidious onset over a period of months or years, with progressive dyspnea and often evolves to fibrosis. ⋯ The cornerstone of therapy is antigen avoidance. Although clinical trials are scanty, corticosteroids are usually indicated based upon expert opinion. In this review we summarize the current evidence regarding the diagnostic criteria and therapeutic strategies as well as the immunopathological mechanisms putatively implicated in the development of the disease.
-
Pulmonary fibrosis occurs in a variety of clinical settings, constitutes a major cause of morbidity and mortality, and represents an enormous unmet medical need. However, the disease is heterogeneous, and the failure to accurately discern between forms of fibrosing lung diseases leads to inaccurate treatments. ⋯ Although animal models of fibrosis imperfectly recapitulate IPF, they have yielded numerous targets for therapeutic intervention. Understanding the heterogeneity of these diseases and elucidating the final common pathways of fibrogenesis are critical for the development of efficacious therapies for severe fibrosing lung diseases.
-
Although substantial progress has been made in understanding the clinical, radiological, and pathological manifestations of fibrosing interstitial lung diseases (ILD), it remains difficult for the clinician to predict the clinical course or the response to therapy for the subtypes of ILD, even from individual to individual with the same diagnosis. This article reviews the genetic and environmental causes of pulmonary fibrosis, specifically focusing on genetic and epigenetic variants of MUC5B and several types of ILD, to discuss why only some individuals with the MUC5B promoter polymorphism develop pulmonary fibrosis. Once we discover how these genetic and epigenetic risks lead to the development of ILD, we and others can apply these discoveries to: (1) identify individuals at risk of developing ILD, (2) diagnose the condition at an earlier stage, (3) identify novel mechanisms that cause ILD, and (4) eventually develop personalized therapeutic strategies for intervention.