Serum angiopoietin-2 and CRP levels during COPD exacerbations.

BACKGROUND AND OBJECTIVE: Angiopoietin-2 (Ang-2) is an important mediator of angiogenesis and has been implicated in many inflammatory diseases. COPD is characterized by systemic inflammation, which is enhanced during exacerbations and may be assessed by measuring serum C-reactive protein (CRP). The aim of the study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh day (D7) of hospitalization due to a COPD exacerbation and to examine possible associations of CRP and Ang-2 levels and kinetics with the length of hospital stay and outcome. METHODS: We conducted a prospective study and evaluated 90 patients admitted to the hospital with a diagnosis of an acute exacerbation of COPD. A venous blood sample was obtained from all patients on D1 and D7 of hospitalization, for the measurement of Ang-2 and CRP. RESULTS: Serum Ang-2 levels were significantly higher on D1 compared to D7 during the course of COPD exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1 compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228, respectively). Patients with unfavorable outcome had significantly higher Ang-2 levels both on D1 (p = 0.04) and D7 (p = 0.01). CONCLUSIONS: Serum Ang-2 levels are elevated at the onset of COPD exacerbations and are positively associated with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could predict the outcome of a COPD exacerbation.

Vitamin D Levels as a Marker of Severe SARS-CoV-2 Infection.

The SARS-CoV-2 virus may cause severe infection, which is associated with diverse clinical manifestations. Vitamin D has immunomodulating properties and may enhance the body's defense system against invading pathogenic organisms. The aim was to assess 25(OH)D3 levels in patients hospitalized for severe infection from the SARS-CoV-2 virus and explore the relationship between 25(OH)D3 and outcomes. In a group of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex, the levels of 25(OH)D3 were analyzed. Levels of 25(OH)D3 were 17.36 ± 8.80 ng/mL (mean ± SD) compared with 24.34 ± 10.34 ng/mL in patients with severe SARS-CoV-2 infection and the control group, respectively, p < 0.001 (Student's t-test). 25(OH)D3 levels were significantly related to outcomes, i.e., survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/mL) and insufficiency (10-20 ng/mL) had a fatal outcome as compared with those with vitamin D sufficiency (p < 0.001, chi-square test, p < 0.001, Fisher's exact test). Levels of 25(OH)D3 were inversely related to C-reactive protein (CRP), ferritin, d-dimer, and fibrinogen levels (p < 0.001, linear regression analysis, beta coefficient of variation, -0.176, -0.160, -0.178, and -0.158, respectively). Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to disease outcomes.

Antioxidants and mucolytics in COPD management: when (if ever) and in whom?

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Oxidative stress is an important mechanism in the pathogenesis of this disease. The oxidant/ antioxidant imbalance occurring in smokers and patients with COPD is well established. Thus, therapeutic strategies targeting oxidative stress with pharmacological antioxidant agents or boosting the endogenous levels of antioxidants is likely to be beneficial as an adjunctive tool in the treatment of COPD patients. Thiol compounts such as N-acetyl-L-cysteine (NAC), carbocysteine, erdosteine, and fudosteine have been extensively studied. Although some results remain controversial, NAC and carbocysteine seem to have beneficial effect in patients not receiving inhaled corticosteroids who suffer from frequent exacerbations. In addition, other antioxidants like superoxide dismutase (SOD) mimetics and nuclear factor-erythroid 2 related factor 2 (Nrf2) are shown to decrease markers of oxidative stress in patients with emphysema, while others like glutathione peroxidase (GPx) mimetics and NO synthase (iNOS) can prevent both inflammation and oxidative stress in clinical trials in vivo (or in mouse models). In this article we review the effectiveness of various antioxidant factors in COPD and their potential beneficial effect in the treatment of the disease.

Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates?

OBJECTIVES: Brain metastases (BMs) often advance the course of non-small cell lung cancer (NSCLC). We performed an observational study in order to investigate the possible correlation of selected clinical and epidemiological factors with BM appearance in patients suffering from different histological subtypes of NSCLC stage I-IV. METHODS: The study included 161 consecutive patients with NSCLC. Analyzed data included patient- and tumor-related characteristics. RESULTS: Thirty-nine patients (24.2%) presented BMs within 12 (0-36) weeks of diagnosis. BMs decreased the mean overall survival significantly (15.6 versus 50.7 weeks, P < 0.001), with hazard ratio (95% confidence interval) 3.60 (2.42-5.35). The age of the patients with BM was significantly lower than that of the patients without BM (60.8 ± 8.9 versus 66.5 ± 8.5, P < 0.001). Patients with BM had significantly higher pack-years consumption (75.9 ± 23.9 versus 58.9 ± 31.9, P = 0.003) and larger tumor size compared with patients without BM (size in mm: 55.1 ± 20.1 versus 45.9 ± 19.3, P = 0.012). The presence of BM was also correlated with the absence of lung (P < 0.001), bone (P = 0.005), and adrenal (P = 0.046) metastases. CONCLUSION: Younger NSCLC patients with high tobacco consumption, large tumor size, and absence of metastases in other organs (lung, bones, adrenal metastases) are at high risk of BM appearance during the course of NSCLC and are candidates for prophylactic cranial irradiation early in the course of the disease.

Mapping EGFR1 mutations in patients with lung adenocarcinoma.

INTRODUCTION: Unselected lung cancer patients seem unable to gain in terms of survival from treatment with epidermal growth factor receptor (EGFR) inhibitors. Screening for specific molecular targets involves detection of EGFR1 mutations. The aim of our study was to develop a simple set of tests to detect mutations at the tyrosine kinase domain of the EGFR1 gene while avoiding expensive DNA sequencing to select patients eligible for treatment. METHODS: DNA samples from 85 adenocarcinoma patients were analyzed. The cohort consisted of 65 female (40 nonsmokers and 25 smokers) and 20 male patients [15 smokers and 5 diagnosed with bronchioloalveolar carcinomas (BAC)]. Different restriction enzymes were identified that recognize mutations at the EGFR1's tyrosine kinase domain. Biocomputing and polymerase chain reaction were used to develop molecular screening tools. RESULTS: Eight mutations were found in 7 patients, of which 5 were female nonsmokers (14.3%), 1 was a male nonsmoker, and 1 a male smoker. Among the mutations that were discovered, 5 (71%) were found at exon 19 and 3 (29%) at exon 20. At exon 19, 4 were deletions found in nonsmoker women, whereas the fifth was a deletion-insertion found in a nonsmoker male patient with BAC. At exon 20, 3 mutations were identified in 2 patients: a duplication (in a nonsmoker woman) and 2 substitutions (in a smoker male with BAC). No mutations were found at exons 18 and 21. Gene copy number was increased in 6 patients (4 female and 2 male) with the highest being found in a smoking female patient diagnosed with BAC. CONCLUSION: Mapping of EGFR1 mutations by alternative methods should be used in the screening of patients with non-small cell lung cancer who are candidates for EGFR inhibitor treatment. Patients with an increased EGFR1 copy number could benefit from the monoclonal antibody therapy.