Idiopathic pulmonary fibrosis: 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: 39.21). 08/2012; 380(9842):699-701. DOI: 10.1016/S0140-6736(12)61256-2
Source: PubMed
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF), the etiopathogeny of which is still unknown, is the most frequent and severe of idiopathic interstitial pneumonias. It progressively leads, sometimes more acutely when exacerbations occur, to a restrictive respiratory insufficiency. Its prognosis is very dark with a median survival of 3-5 years. No treatment so far has been curative. Its diagnostic and therapeutic management has been greatly improved due to the technical progress in terms of high-resolution tomodensitometry, to the availability of new drugs with a real antifibrotic potential and to the production of international recommendations. The diagnosis is reached in 2/3 of IPF patients presenting with a typical usual interstitial pneumonitis (UIP) CT-scan pattern. It requires a videothoracoscopic biopsy in the remaining patients. Multidisciplinary discussions are key to a proper diagnosis of IPF. Pirfenidone is presently the only drug with a real antifibrotic potential in mild to moderate forms of the disease (FVC>50% and DLCO>35% predicted). The other ones have proved either inefficient or toxic. It is highly recommended to include patients in innovative targeted protocols. Non-pharmacological management of these patients comprises long-term oxygen therapy, pulmonary rehabilitation and overall lung transplantation. Pulmonary hypertension, to be detected regularly during the follow-up, is associated to a dark prognosis. No specific treatment is efficient in this context. Several comorbidities, particularly frequent in IPF, should be treated when present: gastro-oesophageal reflux, obstructive sleep apnea, emphysema. The particular high frequency of bronchopulmonary cancer should be highlighted.
    Revue de Pneumologie Clinique 02/2014; · 0.19 Impact Factor
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    ABSTRACT: Abnormal acid gastro-oesophageal reflux is common in patients with idiopathic pulmonary fibrosis (IPF) and is considered a risk factor for development of IPF. Retrospective studies have shown improved outcomes in patients given anti-acid treatment. The aim of this study was to investigate the association between anti-acid treatment and disease progression in IPF. In an analysis of data from three randomised controlled trials, we identified patients with IPF assigned to receive placebo. Case report forms had been designed to prospectively obtain data about diagnosis and treatment of abnormal acid gastro-oesophageal reflux in each trial. The primary outcome was estimated change in forced vital capacity (FVC) at 30 weeks (mean follow-up) in patients who were and were not using a proton-pump inhibitor or histamine-receptor-2 (H2) blocker. Of the 242 patients randomly assigned to the placebo groups of the three trials, 124 (51%) were taking a proton-pump inhibitor or H2 blocker at enrolment. After adjustment for sex, baseline FVC as a percentage of predicted, and baseline diffusing capacity of the lung for carbon monoxide as a percentage of predicted, patients taking anti-acid treatment at baseline had a smaller decrease in FVC at 30 weeks (-0·06 L, 95% CI -0·11 to -0·01) than did those not taking anti-acid treatment (-0·12 L, -0·17 to -0·08; difference 0·07 L, 95% CI 0-0·14; p=0·05). Anti-acid treatment could be beneficial in patients with IPF, and abnormal acid gastro-oesophageal reflux seems to contribute to disease progression. Controlled clinical trials of anti-acid treatments are now needed. National Institutes of Health.
    The Lancet Respiratory Medicine 07/2013; 1(5):369-76. DOI:10.1016/S2213-2600(13)70105-X
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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