Prognostic significance of Glasgow prognostic score in patients with acute exacerbation of idiopathic pulmonary fibrosis : Glasgow prognostic score and IPF-AE

Since the initial work, a decade ago that the combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with cancer, there have been more than 60 studies (>30,000 patients) that have examined and validated the use of the GPS or the modified GPS (mGPS) in a variety of cancer scenarios. The present review provides a concise overview of these studies and comments on the current and future clinical utility of this simple objective systemic inflammation-based score. The GPS/mGPS had independent prognostic value in (a) unselected cohorts (4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients). Association studies (15 studies, >2,000 patients) pointed to an increased GPS/mGPS being associated with increased weight and muscle loss, poor performance status, increased comorbidity, increased pro-inflammatory and angiogenic cytokines and complications on treatment. These studies have originated from 13 different countries, in particular the UK and Japan. A chronic systemic inflammatory response, as evidenced by the GPS/mGPS, is clearly implicated in the prognosis of patients with cancer in a variety of clinical scenarios. The GPS/mGPS is the most extensively validated of the systemic inflammation-based prognostic scores and therefore may be used in the routine clinical assessment of patients with cancer. It not only identifies patients at risk but also provides a well defined therapeutic target for future clinical trials. It remains to be determined whether the GPS has prognostic value in other disease states. Copyright © 2012 Elsevier Ltd. All rights reserved.

Idiopathic pulmonary fibrosis is a progressive and usually fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture. Although the pathogenetic mechanisms remain to be determined, the prevailing hypothesis holds that fibrosis is preceded and provoked by a chronic inflammatory process that injures the lung and modulates lung fibrogenesis, leading to the end-stage fibrotic scar. However, there is little evidence that inflammation is prominent in early disease, and it is unclear whether inflammation is relevant to the development of the fibrotic process. Evidence suggests that inflammation does not play a pivotal role. Inflammation is not a prominent histopathologic finding, and epithelial injury in the absence of ongoing inflammation is sufficient to stimulate the development of fibrosis. In addition, the inflammatory response to a lung fibrogenic insult is not necessarily related to the fibrotic response. Clinical measurements of inflammation fail to correlate with stage or outcome, and potent anti-inflammatory therapy does not improve outcome. This review presents a growing body of evidence suggesting that idiopathic pulmonary fibrosis involves abnormal wound healing in response to multiple, microscopic sites of ongoing alveolar epithelial injury and activation associated with the formation of patchy fibroblast-myofibroblast foci, which evolve to fibrosis. Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies.

Although acute exacerbation of idiopathic pulmonary fibrosis (IPF) has become well recognised, the reported incidence and outcomes are highly variable, and risk factors are unknown. The aim of this study was to estimate the incidence, risk factors and impact of acute exacerbations, and other known causes of rapid deterioration. This was a retrospective review of 461 patients with IPF (269 cases were biopsy-proven). The median follow-up period was 22.9 months. Rapid deterioration requiring hospitalisation occurred in 163 (35.4%) patients, with multiple episodes in 42 patients. Acute exacerbation was the most frequent cause (55.2%), followed by infection. The 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low forced vital capacity (FVC) were significant risk factors. The in-hospital mortality rate was 50.0%, and the 1- and 5-yr survival rates from the initial diagnosis were 56.2 and 18.4%, respectively. Acute exacerbation was a significant predictor of poor survival after the initial diagnosis, along with increased age, low FVC and diffusing capacity of the lung for carbon monoxide, and steroid use with or without cytotoxic therapy. 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low FVC were risk factors. Acute exacerbation had a serious impact on the overall survival of the patients with IPF.