Background Biomarkers reflective of disease activity in cystic fibrosis (CF) have the potential to improve patient care, particularly during CF pulmonary exacerbations (CFPEs). Although blood-based ...biomarkers have been studied in CFPE for nearly 3 decades, none have been integrated into routine clinical practice. To facilitate progress in this area, we performed a systematic review evaluating blood-based biomarkers during CFPE. Methods MEDLINE, EMBASE, and CENTRAL were searched to identify relevant studies published from January 1995 to August 2012. We included all full-text studies examining systemic (blood-based) biomarkers to aid in the diagnosis of CFPE, predict outcomes of CFPE, and/or monitor the response to CFPE treatment. Results Seventy-eight unique blood-based biomarkers have been studied to date, mainly inflammatory cytokines, acute phase reactants, and markers of oxidative stress. C-reactive protein (CRP) consistently correlated with disease activity, with a statistically significant increase from stable to exacerbation state in five of six studies, and changes in response to CFPE treatment, with a statistically significant decrease from the beginning to the end of CFPE treatment in 18 of 20 studies. Other promising biomarkers of CFPE disease activity include neutrophil elastase antiproteinase complex, IL-6, myeloperoxidase (MPO), lactoferrin, and calprotectin. Conclusions Although there are several blood-based biomarkers with evidence for application within the CFPE setting, CRP has been the most widely studied biomarker demonstrating the potential for clinical usefulness. Further validation studies and clinical trials are required to determine whether blood-based biomarkers can be used to ultimately improve health outcomes in the setting of a CFPE.
BACKGROUND Mortality risk prediction tools have been developed in idiopathic pulmonary fibrosis, however, it is unknown whether these models accurately estimate mortality in systemic ...sclerosis-associated interstitial lung disease (SSc-ILD). Methods: Four baseline risk prediction models—the Composite Physiologic Index, the Interstitial Lung Disease-Gender, Age, Physiology Index, the du Bois index, and the modified du Bois index—were calculated for patients recruited from a specialized SSc-ILD clinic. Each baseline model was assessed using logistic regression analysis with 1-year mortality as the outcome variable. Discrimination was quantified using the area under the receiver operating characteristic curve. Calibration was assessed using the goodness-of-fit test. The incremental prognostic ability of additional predictor variables was determined by adding prespecified variables to each baseline model. Results: The 156 patients with SSc-ILD completed 1,294 pulmonary function tests, 725 6-min walk tests, and 637 echocardiograms. Median survival was 15.0 years from the time of SSc-ILD diagnosis. All baseline models were significant predictors of 1-year mortality in SSc-ILD. The modified du Bois index had an area under the receiver operating characteristic curve of 0.84, compared with 0.77 to 0.81 in the other models. Calibration was acceptable for the modified du Bois index, but was poor for the other models. All baseline models include FVC and 6-min walk distance was identified as an additional independent predictor of 1-year mortality. Conclusions The modified du Bois index has good discrimination and calibration for the prediction of 1-year mortality in SSc-ILD. FVC and 6-min walk distance are important independent predictors of 1-year mortality in SSc-ILD. CHEST 2015; 148(5):1268-1275
BACKGROUND Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains ...challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.
