Treatment of idiopathic pulmonary fibrosis: Is there anything new?

Abstract

Treatment of idiopathic pulmonary fibrosis: Is there anything new?ABDELAZIZ MM, SAMMAN YS, WALI SO, HAMED MMA. Respirology 2005; 10 : 284-289 Abstract: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia of unknown aetiology and is associated with the histological picture of usual interstitial pneumonia. Treatment in most cases is unsatisfactory and the prognosis remains poor. There is insufficient evidence to suggest that any treatment, apart from lung transplantation, improves survival or halts disease progression for IPF patients. Data on treatment response are limited by the paucity of clinical trails, the lack of homogenous clinical features, the small number of patients, and the absence of histological and radiological documentation in many cases. Anti-inflammatory medications such as corticosteroids, azathioprine and cyclophosphamide remain the commonly used medications. More recently, it has been proposed that IPF is a primary fibrotic disease rather than an inflammatory condition. Antifibrotic agents such as colchicine, pirfenidone and interferon-gamma (IFN-g ) have been tried. However, a recent placebo-controlled trial has failed to demonstrate a significant effect of IFN-g on disease progression, lung function or quality of life in IPF patients, though a clinically significant survival benefit of the drug could not be ruled out.

Oncostatin M overexpression induces matrix deposition, STAT3 activation, and SMAD1 Dysregulation in lungs of fibrosis-resistant BALB/c mice

“…This suggests that OSM can induce ECM accumulation without proinflammatory cytokine elevation in BALB/c mice, and this may have relevance in human disease in the context of the recent de-emphasis of the role of classic inflammatory mediators in IPF pathogenesis. 41,42 In addition, IL-4 and IL-5 were not regulated at the protein or mRNA level, indicating a lack of Th2-skewed cytokine response in BALB/c mice in contrast to expectations. 13 It is unclear why there is such a differential gene response to the same cytokine and this may be related to differences in strain responses to adenovirus vector, or that OSM overexpression may engage feedback mechanisms differently in these two strains.…”

Endothelin-1 Induces Alveolar Epithelial–Mesenchymal Transition through Endothelin Type A Receptor–Mediated Production of TGF-β1

“…Classically it was believed that resident pulmonary fibroblasts differentiate into myofibroblasts in response to inflammation. However, anti-inflammatory treatments have been unsuccessful in treating diseases such as IPF, suggesting that alternative mechanisms may be involved (11). Recently new hypotheses regarding the origin of pulmonary myofibroblasts have been raised (12).…”

New Insights into the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis: A Potential Role for Stem Cells in the Lung Parenchyma and Implications for Therapy

“…The reason for patients_ failure to respond to anti-inflammatory therapy with corticosteroids may be that the lung is in a stage of fibrosis rather than inflammation at the time of diagnosis. Thus, anti-fibrotic drugs that interfere with or modulate further progression of lung fibrosis may have potential to improve respiratory function (176,182,186). Anti-cytokine therapeutic strategies are directed at abrogating the activities of the targeted cytokines that have diverse regulatory activities in several processes that comprise fibrosis.…”

“…The most promising potential anti-fibrotic agents, have been recently reviewed (3,176,182,185,187) and are either recommended for consideration in clinical trials, or will require additional evaluation prior to a trial. The major anti-fibrotic and anti-cytokine agents that have been used in the treatment of IPF include: colchicine, penicillamine, pirfenidone, TGFb antagonist, anti-tumor necrosis factor a (TNFa) interferon-g (IFN-g) and connective tissue growth factor antagonist, (188Y197) ( Table II).…”