Dataset Information

Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

ABSTRACT: A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.

SUBMITTER: Bchir S

PROVIDER: S-EPMC5487915 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

Bchir Sarra S Nasr Hela Ben HB Bouchet Sandrine S Benzarti Mohamed M Garrouch Abdelhamid A Tabka Zouhair Z Susin Santos S Chahed Karim K Bauvois Brigitte B

Journal of cellular and molecular medicine 20161222 7

A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and ...[more]

PMID: 28004483

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Project description:BackgroundObstructive sleep apnea (OSA) is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.MethodsWe prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP), and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.ResultsA total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4%) <5 events/hour (mean AHI-4% = 0.59 +/- 0.60); 33 OSA patients based on an AHI-4% >5 events/hour (mean AHI-4% = 43.3 +/- 28.1). OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005) and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014). The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956). We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148). Furthermore, CPAP therapy did not affect the urinary NGAL-to-creatinine ratio (p = 0.7758 for two-tailed, paired t-test).ConclusionsIn this prospective case-control study comparing patients with severe, hypoxic OSA to control subjects, all with normal serum creatinine, we found no difference between urinary levels of NGAL. Furthermore, CPAP therapy did not change these levels pre- and post-treatment.

Project description:IntroductionNGAL has recently been studied as a biomarker in the diagnostic context of pediatric acute appendicitis (PAA), although existing series are scarce and have limited sample sizes.Materials and methodsA prospective observational study was designed to validate serum NGAL as a diagnostic tool in PAA. This study included 215 patients, divided into 3 groups: (1) patients undergoing major outpatient surgery (n = 63), (2) patients with non-surgical abdominal pain in whom a diagnosis of PAA was excluded (n = 53) and (3) patients with a confirmed diagnosis of PAA (n = 99). Patients in group 3 were divided into complicated or uncomplicated appendicitis. In 201 patients, a serum sample was obtained at the time of diagnosis and NGAL concentration was determined by ELISA. The Kolmogorov-Smirnov test was used to assess normality. Comparative statistical analyses were performed using the Mann-Whitney U test, the Kruskal-Wallis test and the Fisher's exact test. To calculate the discriminative ability of the molecule, the area under the receiver-operating characteristic curves (AUC) was calculated. A p value < 0.05 established statistical significance.ResultsMedian (interquartile range) of serum NGAL values were 38.88 (27.15-48.04) ng/mL (group 1), 51.84 (37.33-69.80) ng/mL (group 2) and 65.06 (50.50-86.60) ng/mL (group 3). The AUC (group 2 vs 3) was 0.642 (95% CI 0.542-0.741) (p < 0.001) and the best cutoff point was found to be at 40.97 ng/mL, with a sensitivity of 89% and a specificity of 34.6%. No statistically significant differences in serum NGAL values were found between patients with uncomplicated PAA and those with complicated PAA.ConclusionsThis prospective validation study with a large sample size confirms that the diagnostic yield of NGAL in the context of PAA is only moderate, and therefore, it should not be used as a unique diagnostic tool. Furthermore, NGAL is not a valid biomarker to discern between uncomplicated and complicated PAA.

Dataset Information

Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

Publications

Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

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