Progressive fibrosing interstitial lung disease: treatable traits and therapeutic strategies.

PURPOSE OF REVIEW: In this review, the authors describe therapeutic strategies for a disease group called progressive fibrosing interstitial lung disease (PF-ILD) and highlight the importance of the definition of progression, prognosis, and treatment response. RECENT FINDINGS: Although it is a relatively new concept, the term PF-ILD has been increasingly applied in clinical research and practice. Three domains commonly used to detect the disease progression include clinical symptoms, rate of forced vital capacity (FVC) decline and the extent of fibrosis on imaging. Although details of the pathogenesis of PF-ILD are still unclear, it has become apparent that genetic predisposition and an abnormal tissue microenvironment and host response are involved in the nature of the disease. Antifibrotic agents recently showed their efficacy on the treatment of PF-ILD. Both nintedanib and pirfenidone can slow the disease progression, as defined by a decline of FVC from baseline, of PF-ILD whenever compared with placebo, similar to the results in idiopathic pulmonary fibrosis (IPF) trials. This effect seems consistent irrespective of the underlying ILD diagnosis. SUMMARY: Recent evidence supports the use of antifibrotic therapy in the management of the phenotype progressive non-IPF ILD. Ongoing studies exploring genetic and other molecular biomarkers could identify at-risk individuals or predict treatment response and prognosis (endotypes). This would support the concept of 'treatable traits' in the field of ILD.

Treatment of idiopathic pulmonary fibrosis with Nintedanib: an update.

Introduction: Idiopathic pulmonary fibrosis (IPF) is an incurable, progressive and debilitating disease. Nintedanib is one of two anti-fibrotic therapies available for the treatment of IPF and has been approved since 2014. Together with pirfenidone and antacid medications it has received a conditional recommendation for the treatment for IPF by international clinical practice guidelines.Areas covered: The authors review the mechanisms of action, pharmacological profile and update scientific data and our opinions on efficacy, safety profile and tolerability of nintedanib.Expert opinion: Nintedanib significantly slows disease progression in IPF patients with tolerable and manageable side effects. Its potential future role in the treatment of progressive fibrosing interstitial lung diseases other than IPF is challenging.

Urine neutrophil gelatinase-associated lipocalin: a diagnostic and prognostic marker for acute kidney injury (AKI) in hospitalized cirrhotic patients with AKI-prone conditions.

BACKGROUND: Acute kidney injury (AKI) is known to increase mortality in hospitalized cirrhotic patients; therefore early identification is utmost significance. There are only a few studies evaluating the cut-off level of urine neutrophil gelatinase-associated lipocalin (uNGAL) for diagnosing AKI and its prognostic value in cirrhotic patients. We aimed to determine the accuracy of uNGAL as a biomarker for early identification of AKI and to determine the cut-off level of uNGAL for diagnosing AKI in hospitalized cirrhotic patients; and (2) to explore the association of 30-day liver-related mortality with uNGAL level. METHODS AND MATERIAL: We prospectively enrolled cirrhotic patients admitted at the King Chulalongkorn Memorial Hospital during May 1, 2011 to Dec 31, 2013. UNGAL levels were measured within 24 h after admission. Clinical and laboratory data were obtained. Patients were followed up to 30 days. RESULTS: Of 137 cirrhotic hospitalized patients, 121 cirrhotic patients (88.3 %) with AKI-prone conditions were included with mean age of 57.3 ± 14.7 years. Thirty-five patients (29 %) developed AKI within 72 h of admission. The causes of AKI were prerenal azotemia (68.6 %), acute tubular necrosis (25.7 %), hepatorenal syndrome (5.7 %), respectively. The mean uNGAL level was significantly higher in the patients who developed AKI compared with those who did not (290.6 ± 356.3 vs. 54.4 ± 73.7 ng/mL; P = 0.0001). The AUC of uNGAL for diagnosing AKI was 0.83 (95 % [CI]: 0.76-0.91) with the optimal cut-off level of 56 ng/mL, providing 77.1 % sensitivity and 73.3 % specificity. Fourteen percent of subjects died during the 30-day follow-up period. The mean uNGAL levels were significantly higher in the mortality group. The AUC of uNGAL in predicting mortality was 0.75 (95 % [CI]: 0.66-0.85), with a best cut-off level of 72 ng/mL providing 70.6 % sensitivity and 69.2 % specificity. However, in multivariate logistic regression analysis, uNGAL is not an independent factor for 30-day liver-related mortality prediction. CONCLUSIONS: uNGAL is a valid marker for the early detection of AKI in hospitalized cirrhotic patients with AKI-prone conditions; however, its level could not independently predict 30-day liver-related mortality.