Circulatory Serum Krebs von Den Lungen-6 and Surfactant Protein-D Concentrations Predict Interstitial Lung Disease Progression and Mortality.

There is a need for biomarkers to predict outcomes, including mortality, in interstitial lung disease (ILD). Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are associated with lung damage and fibrosis in all ILDs and are related to important clinical outcomes. Though these two biomarkers have been associated with ILD outcomes, there are no studies that have evaluated their predictive potential in combination. This study aims to determine whether KL-6 and SP-D are linked to poor disease outcomes and mortality. Additionally, we plan to examine whether changes in KL-6 and SP-D concentrations correspond with changes in lung function and whether serial measurements improve their predictive potential to identify disease progression and mortality. Forty-four patients with ILD participated in a prospective 6-month longitudinal observational study. ILD patients who succumbed had the highest KL-6 levels (3990.4 U/mL (3490.0-4467.6)) and highest SP-D levels (256.1 ng/mL (217.9-260.0)), followed by those who deteriorated: KL-6 levels 1357.0 U/mL (822.6-1543.4) and SP-D levels 191.2 ng/mL (152.8-210.5). The generalized linear model (GLM) analysis demonstrated that changes in forced vital capacity (FVC), diffusing capacity of lungs for carbon monoxide (DLCO), forced expiratory volume in 1 s (FEV1), and partial pressure of arterial oxygen (PaO2) were correlated to changes in KL6 (p = 0.016, 0.014, 0.027, 0.047) and SP-D (p = 0.008, 0.012, 0.046, 0.020), respectively. KL-6 (odds ratio (OR): 2.87 (1.06-7.79)) and SPD (OR: 1.76 (1.05-2.97)) were independent predictors of disease progression, and KL-6 (hazard ratio (HR): 3.70 (1.46-9.41)) and SPD (HR: 2.58 (1.01-6.59)) were independent predictors of death by Cox regression analysis. Combined biomarkers (KL6 + SPD + CT + FVC) had the strongest ability to predict disease progression (AUC: 0.797) and death (AUC: 0.961), on ROC analysis. Elevated KL-6 and SPD levels are vital biomarkers for predicting the severity, progression, and outcomes of ILD. High baseline levels or an increase in levels over a six-month follow-up despite treatment indicate a poor prognosis. Combining KL6 and SPD with conventional measures yields a more potent prognostic indicator. Clinical studies are needed to test additional interventions, and future research will determine if this combined biomarker benefits different ethnicities globally.

The Role of Neutrophil-to-Lymphocyte Ratio in Risk Stratification and Prognostication of COVID-19: A Systematic Review and Meta-Analysis.

Several studies have proposed that the neutrophil−lymphocyte ratio (NLR) is one of the various biomarkers that can be useful in assessing COVID-19 disease-related outcomes. Our systematic review analyzes the relationship between on-admission NLR values and COVID-19 severity and mortality. Six different severity criteria were used. A search of the literature in various databases was conducted from 1 January 2020 to 1 May 2021. We calculated the pooled standardized mean difference (SMD) for the collected NLR values. A meta-regression analysis was performed, looking at the length of hospitalization and other probable confounders, such as age, gender, and comorbidities. A total of sixty-four studies were considered, which included a total of 15,683 patients. The meta-analysis showed an SMD of 3.12 (95% CI: 2.64−3.59) in NLR values between severe and non-severe patients. A difference of 3.93 (95% CI: 2.35−5.50) was found between survivors and non-survivors of the disease. Upon summary receiver operating characteristics analysis, NLR showed 80.2% (95% CI: 74.0−85.2%) sensitivity and 75.8% (95% CI: 71.3−79.9%) specificity for the prediction of severity and 78.8% (95% CI: 73.5−83.2%) sensitivity and 73.0% (95% CI: 68.4−77.1%) specificity for mortality, and was not influenced by age, gender, or co-morbid conditions. Conclusion: On admission, NLR predicts both severity and mortality in COVID-19 patients, and an NLR > 6.5 is associated with significantly greater the odds of mortality.

Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia.

Background: There is a paucity of data on biomarkers for the early deterioration and clinical instability of patients in community-acquired pneumonia (CAP), as treatment failure occurs in the first seven days in 90% of patients. Aim: To evaluate serum albumin and copeptin with CURB-65, PSI scoring and ATS/IDSA minor criteria for the prediction of early mortality or ICU-admission (7 days) and clinical instability after 72 h. Methods: In 100 consecutive hospitalized adult CAP patients, PSI-scores, CURB-65 scores, ATS/IDSA 2007 minor criteria, copeptin and albumin on admission were evaluated. Univariate and multivariate Cox regression analysis was performed to assess independent risk factors for early combined mortality or ICU admission. Predictive powers of albumin and copeptin were tested with ROC curves and ICU-free survival probability was tested using Kaplan−Meier analysis. Results: Albumin was lower and copeptin higher in patients with short-term adverse outcomes (p < 0.05). Cox regression analysis showed that albumin [HR (95% CI): 0.41 (0.18−0.94, p = 0.034)] and copeptin [HR (95% CI): 1.94 (1.03−3.67, p = 0.042)] were independent risk factors for early combined mortality or ICU admission (7 days). The Kaplan−Meier analysis observed that high copeptin (>27.12 ng/mL) and low albumin levels (<2.85 g/dL) had a lower (p < 0.001) survival probability. The diagnostic accuracy of albumin was better than copeptin. The inclusion of albumin and copeptin into ATS/IDSA minor criteria significantly improved their predictive power. Conclusions: Both biomarkers serum albumin and copeptin can predict early deterioration and clinical instability in hospitalized CAP patients and increase the prognostic power of the traditional clinical scoring systems.