Mental health, serum biomarkers and survival in severe COPD: a pilot study

Background: Chronic obstructive pulmonary disease (COPD) impairs physical status and impacts on mental health. This prospective study was designed to assess associations between mental health and systemic biomarkers, and their combined relationship with long-term survival in stable severe COPD. Methods: Forty-five patients with severe but stable COPD (forced expiratory volume in 1 s of 29.8 (quartiles: 22.6;41.4) % predicted) were assessed using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), St. George's Respiratory Questionnaire and the State-Trait Anxiety Inventory (STAI). The following serum biomarkers were measured: 25-OH-cholecalciferol, C-reactive protein, erythrocyte sedimentation rate, leucocyte number, serum amyloid-A (SA-A), N-terminal pro-brain natriuretic peptide, troponin I, glycosylated haemoglobin, haemoglobin (Hb), haematocrit (Hc), creatinine and thyroid-stimulating hormone. Patients were followed-up for 36 months. Associations between aspects of mental health and biomarkers, and their utility as predictors of 3-year survival were evaluated by regression analyses. Results: The prevalence of anxiety (HADS-A: 89.9 %), depression (HADS-D: 58.8 %;PHQ: 60.6 %), somatisation (PHQ-15: 81.8 %) and psychosocial stress (PHQ-stress: 60.6 %) was high. There was a significant positive association between the leucocyte count and SA-A level with STAI-trait anxiety (p = 0.03 and p = 0.005, respectively), and between leucocytes and PHQ-stress (p = 0.043). Hb and Hc were significantly negatively associated with HADS-depression (p = 0.041 and p = 0.031, respectively). Univariate Cox regression analyses revealed that leucocyte count (hazard ratio (HR) 2.976, 95 % CI 1.059-8.358;p = 0.038), and stress (HR 4.922, 95 % CI 1.06-22.848;p = 0.042) were linked to long-term survival. In multivariate Cox regression analyses, including known risk factors for survival in COPD, PHQ-stress (HR 45.63, 95 % CI 1.72-1,208.48;p = 0.022) remained significantly associated with survival. Conclusion: In this pilot study different dimensions of mental health were correlated to serum biomarkers, probably reflecting systemic effects of COPD. While leucocyte number and PHQ-stress were associated with long-term survival in univariate analyses, PHQ-stress remained in multivariate analyses as independent prognostic factor

Extensively drug resistant tuberculosis in a high income country: A report of four unrelated cases

<p>Abstract</p> <p>Background</p> <p>Multi drug resistance <it>of Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) remains a major threat to public health, reinforced by recent reports about the clinical course of patients infected with extensively drug resistant (XDR) strains in South Africa. There is little information about the clinical course of XDR tuberculosis patients in industrialised countries.</p> <p>Methods</p> <p>We evaluated all isolates of <it>M. tuberculosis</it>, in which drug susceptibility testing was performed at our institution since 1997, for multi and extensive drug resistance. Clinical courses of patients infected by strains fulfilling the recently revised criteria for XDR tuberculosis were analysed.</p> <p>Results</p> <p>Four XDR <it>M. tuberculosis </it>isolates were identified. All patients had immigrated to Germany from Russia, Georgia, and former Yugoslavia and none were infected by the human immunodeficiency virus. All patients where treated for tuberculosis for 5.5 to 15 years and for XDR tuberculosis for 1.9 to 2.5 years. They received inhospital treatment in Germany for 11 months, 4.5 years and twice for 6 years. Non-compliance was an important factor in all four patients, three patients had to be treated in Germanys only locked facility for tuberculosis treatment. One patient with XDR tuberculosis died, one patient had still open pulmonary tuberculosis at last contact and 2 patients were cured.</p> <p>Conclusion</p> <p>Cases of XDR tuberculosis have been treated in our region for several years. Even in a high income setting, XDR tuberculosis has a tremendous impact on quality of live, outcome and the total cost. All reasonable efforts to prevent the spread of XDR tuberculosis must be made and maintained.</p

Scorpionfish BPI is highly active against multiple drug-resistant Pseudomonas aeruginosa isolates from people with cystic fibrosis

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa (Pa) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA

Cardiopulmonary exercise pattern in patients with persistent dyspnoea after recovery from COVID-19

Cause and mechanisms of persistent dyspnoea after recovery from COVID-19 are not well described. The objective is to describe causal factors for persistent dyspnoea in patients after COVID-19. We examined patients reporting dyspnoea after recovery from COVID-19 by cardiopulmonary exercise testing. After exclusion of patients with pre-existing lung diseases, ten patients (mean age 50±13.1 years) were retrospectively analysed between May 14th and September 15th, 2020. On chest computed tomography, five patients showed residual ground glass opacities, and one patient showed streaky residua. A slight reduction of the mean diffusion capacity of the lung for carbon monoxide was noted in the cohort. Mean peak oxygen uptake was reduced with 1512±232 ml/min (72.7% predicted), while mean peakwork rate was preserved with 131±29 W (92.4% predicted). Mean alveolar-arterial oxygen gradient (AaDO2) at peak exercise was 25.6±11.8 mmHg. Mean value of lactate post exercise was 5.6±1.8 mmol/l. A gap between peak work rate in (92.4% predicted) to peak oxygen uptake (72.3% pred.) was detected in our study cohort. Mean value of lactate post exercise was high in our study population and even higher (n.s.) compared to the subgroup of patients with reduced peak oxygen uptake and other obvious reason for limitation. Both observations support the hypothesis of anaerobic metabolism. The main reason for dyspnoea may therefore be muscular

Lipopolysaccharide Binding Protein and Bactericidal/Permeability-Increasing Protein as Biomarkers for Invasive Pulmonary Aspergillosis

Early diagnosis of invasive pulmonary aspergillosis (IPA) is crucial to prevent lethal disease in immunocompromized hosts. So far, lipopolysaccharide binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) levels have not been evaluated as biomarkers for IPA. IL-8, previously introduced as a biomarker for IPA, was also included in this study. Bronchoalveolar lavage fluid (BALF) of IPA patients and control patients with non-infectious lung disease was collected according to clinical indications. Measurements in BALF displayed significantly higher levels of LBP (p < 0.0001), BPI (p = 0.0002) and IL-8 (p < 0.0001) in IPA compared to control patients. Receiver operating characteristic curve analysis revealed higher AUC for LBP (0.98, 95% CI 0.95-1.00) than BPI (0.84, 95% CI 0.70-0.97; p = 0.0301). Although not significantly different, AUC of IL-8 (0.93, 95% CI 0.85-1.00) also tended to be higher than AUC for BPI (p = 0.0624). When the subgroup of non-hematological patients was analyzed, test performance of LBP (AUC 0.99, 95% CI 0.97-1.00), BPI (AUC 0.97, 95% CI 0.91-1.00) and IL-8 (AUC 0.96, 95% CI: 0.90-1.00) converged. In conclusion, LBP and-to a lesser extend-BPI displayed high AUCs that were comparable to those of IL-8 for diagnosis of IPA in BALF. Further investigations are worthwhile, especially in non-hematological patients in whom sensitive biomarkers for IPA are lacking

Selective Modulation of Hedgehog/GLI Target Gene Expression by Epidermal Growth Factor Signaling in Human Keratinocytes

Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that epidermal growth factor receptor (EGFR) signaling modulates the target gene expression profile of GLI transcription factors in epidermal cells. Using expression profiling and quantitative reverse transcriptase PCR, we identified a set of 19 genes whose transcription is synergistically induced by GLI1 and parallel EGF treatment. Promoter studies of a subset of GLI/EGF-regulated genes, including the genes encoding interleukin-1 antagonist IL1R2, Jagged 2, cyclin D1, S100A7, and S100A9, suggest convergence of EGFR and HH/GLI signaling at the level of promoters of selected direct GLI target genes. Inhibition of EGFR and MEK/ERK but not of phosphatidylinositol 3-kinase/AKT abrogated synergistic activation of GLI/EGF target genes, showing that EGFR can signal via RAF/MEK/ERK to cooperate with GLI proteins in selective target gene regulation. Coexpression of the GLI/EGF target IL1R2, EGFR, and activated ERK1/2 in human anagen hair follicles argues for a cooperative role of EGFR and HH/GLI signaling in specifying the fate of outer root sheath (ORS) cells. We also show that EGF treatment neutralizes GLI-mediated induction of epidermal stem cell marker expression and provide evidence that EGFR signaling is essential for GLI-induced cell cycle progression in epidermal cells. The results suggest that EGFR signaling modulates GLI target gene profiles which may play an important regulatory role in ORS specification, hair growth, and possibly cancer

Bronchoscopic Coil Treatment for Patients with Severe Emphysema: A Meta-Analysis

Background: Bronchoscopic coil treatment has been shown to improve pulmonary function, exercise capacity, and quality of life in patients with severe emphysema. Objectives: To perform a meta-analysis of the results of four independent European clinical trials investigating this coil therapy for emphysema. Methods: Data on all patients included in the four European clinical trials were analyzed for efficacy and safety outcomes. Results: A total of 2,536 coils were placed during 259 procedures in 140 patients. A total of 37 chronic obstructive pulmonary disease exacerbations and 27 pneumonias were recorded as serious adverse events up to 1 year after treatment. The pneumothorax rate was 6.4%. Both 6 and 12 months after treatment, significant (all p <0.001) improvements were observed for: forced expiratory volume in 1 s [+0.08 liters (+/- 0.19) and +0.08 liters (+/- 0.21)], residual volume [RV; -510 ml (+/- 850) and -430 ml (+/- 720)], 6-min walking distance [6MWD; +44.1 m (+/- 69.8) and +38.1 m (+/- 71.9)], and St. George's Respiratory Questionnaire score [SGRQ; -9.5 points (+/- 14.3) and -7.7 points (+/- 14.2)]. No differences in any outcome measures were observed between heterogeneous and homogeneous emphysema patients. Only a high baseline RV was found to be an independent predictor of successful treatment. Conclusions: Bronchoscopic coil treatment improves pulmonary function, 6MWD, and quality of life in patients with severe emphysema up to 1 year after treatment, independent of the distribution of the disease. (C) 2015 S. Karger AG, Base