Idiopathic pulmonary fi brosis: New evidence and an improved standard of care in 2012

Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, University of Washington, Seattle, WA 98195, USA.
The Lancet (Impact Factor: 45.22). 08/2012; 380(9842):699-701. DOI: 10.1016/S0140-6736(12)61256-2
Source: PubMed
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    ABSTRACT: This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.
    European Respiratory Review 03/2013; 22(127):26-32. DOI:10.1183/09059180.00006812
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    ABSTRACT: We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (Pmeta = 2.4 × 10(-8) to 1.1 × 10(-19)), including FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13) and chromosomal regions 7q22 and 15q14-15. Our results suggest that genes involved in host defense, cell-cell adhesion and DNA repair contribute to risk of fibrotic IIPs.
    Nature Genetics 04/2013; 45(6). DOI:10.1038/ng.2609 · 29.35 Impact Factor
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    ABSTRACT: A r t i c l e s IIPs represent a group of lung diseases commonly characterized by pulmonary fibrosis or progressive scarring of the alveolar intersti-tium that can lead to significant morbidity and mortality due to hypoxemic respiratory insufficiency 1 . Although some forms of pul-monary fibrosis are associated with known environmental expo-sures (for example, asbestos), drug toxicity 2 , radiation exposure or collagen vascular diseases (for example, scleroderma), IIPs have no known etiology. The most common and severe IIP is idiopathic pulmonary fibrosis (IPF) 1 , which has a median survival time of 2–3 years after diagnosis. There are no IPF pharmacological thera-pies approved for use in the United States, and lung transplantation is the only intervention known to prolong life 3 . Although all IIPs have a variable clinical course, they often progress to end-stage lung disease and death. It seems likely that risk of IIP is determined by multiple genetic variants and environmental toxins, but the specific causes of IIP are only beginning to emerge. The evidence for a genetic component to the risk of IIP is substan-tial and includes familial clustering of disease, the occurrence of pul-monary fibrosis as part of systemic genetic syndromes, considerable variability in the risk of pulmonary fibrosis among those with similar exposures to known environmental agents, such as asbestos, and the identification of genetic risk loci for IIP. Rare mutations in the TERT, TERC, SFTPC and SFTPA2 genes have been associated with familial interstitial pneumonia (FIP; defined as two or more family members with IIP) and IPF 4–9 , and a common polymorphism in TERT has been associated with IPF 10 . Recently, we identified a promoter vari-ant in the MUC5B gene (rs35705950) that is present in approximately 50–60% of individuals with FIP or IPF and is estimated to increase risk by 6-fold for heterozygotes and by 20-fold for homozygotes 11 . The identification of MUC5B as a common risk factor has altered our view of the pathogenesis of pulmonary fibrosis from focusing primarily on alveolar epithelia and the lung matrix to inclusion of Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
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