Association of ET-1 gene polymorphisms with COPD phenotypes in a Caucasian population

Background and Aim. The phenotypic expression of COPD consists of pulmonary emphysema and chronic bronchitis. An imprecise phenotypic definition may result in inconsistencies among genetic studies regarding COPD pathogenesis. Endothelin-1 gene polymorphisms have been linked to increased susceptibility of COPD development. The present study examined the involvement of +138 insA/delA and G198T ET-1 polymorphisms with emphysematous and bronchitic COPD phenotypes. Methods. In order to narrow down the phenotypic choices to either COPD-associated pulmonary emphysema or chronic bronchitis, a DLCO<60% predicted threshold was chosen as an indicator of severe emphysema.116 COPD smokers and 74 non-related, non-COPD smokers were evaluated. Results. Statistical analysis showed that the 4A allele of the +138insA/delA SNP and the 4A:T haplotype were associated predominantly with a chronic bronchitis phenotype, whereas the TT genotype of the G198T SNP was found to be protective from emphysema development. Conclusions. The presence of both the 4A and T allele seems to modify the final expression of COPD towards a chronic bronchitis phenotype, since the G:3A haplotype was associated with a predominantly emphysematous phenotype in our study

Risk factors for early mortality in haematological malignancy patients with pulmonary mucormycosis

Pulmonary mucormycosis (PM) is a life-threatening opportunistic mycosis with a variable clinical evolution and few prognostic markers for outcome assessment. Several clinical risk factors for poor outcome present at the diagnosis of PM were analyzed in 75 consecutive hematology patients from 2000-2012. Significant variables (P 22 was associated with 8-fold high rates of mortality (P < 0.0001) within 28 days of diagnosis and median survival of 7 days versus 6528 days in patients with risk scores 6422. We found that APACHE II score, severe lymphocytopenia and high LDH levels at the time of PM diagnosis were independent markers for rapid disease progression and deat

Expression of intracellular components of the NF-κB alternative pathway (NF-κB2, RelB, NIK and Bcl3) is associated with clinical outcome of NSCLC patients

A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P < 0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes

High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis

Introduction: High-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC). Methods: We performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis. Results: Six randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure. Conclusion: The high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications. Copyright © 2022 Sampsonas, Karamouzos, Karampitsakos, Papaioannou, Katsaras, Lagadinou, Zarkadi, Malakounidou, Velissaris, Stratakos and Tzouvelekis

SH2 Domain-Containing Phosphatase-SHP2 Attenuates Fibrotic Responses through Negative Regulation of Mitochondrial Metabolism in Lung Fibroblasts

Background: We have previously shown that SHP2 downregulation may predispose fibroblasts to differentiate into myofibroblasts and proposed a role for SHP2 downregulation in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent data have shown that SHP2 localizes to the mitochondrial intercristae, and its overexpression enhances mitochondrial metabolism leading to oxidative stress and senescence. Objective: To determine the effect of SHP2 on fibrotic responses. Methods and Results: Primary mouse lung fibroblasts derived from mice carrying a conditional knock-in mutation (D61G/+), rendering the SHP2 catalytic domain constitutively active, had reduced proliferation (1.6-fold, p &amp;lt; 0.05), migration (2-fold, p &amp;lt; 0.05), as well as reduced responsiveness of TGFB-1 induced fibroblasts-to-myofibroblasts differentiation, compared to wild-type ones. Electron microscope analysis revealed that SHP2 D61G/+ mouse lung fibroblasts were characterized by mitochondrial abnormalities, including swollen mitochondria with disrupted electron-lucent cristae and an increased number of autophagosomes compared to wild-type ones. SHP2 D61G/+ MLFs exhibited increased protein levels of autophagy markers, including LC3B-II and p-62, evidence that was confirmed by immunofluorescence analysis. Mitochondrial function analysis revealed that stable (genotype D61G/+) overexpression of SHP2 led to impaired mitochondrial function, as assessed by decreased mitochondrial membrane potential (1.29-fold, p &amp;lt; 0.05), coupling efficiency (1.82 fold, p &amp;lt; 0.05), oxygen consumption rate (1.9-fold, p &amp;lt; 0.05), and increased reactive oxygen species production both at baseline (1.75-fold, p &amp;lt; 0.05) and following H2O2 stimulation (1.63-fold, p &amp;lt; 0.05) compared to wild-type ones (SHP2+/+). SHP2 D61G/+ mouse lung fibroblasts showed enhanced AMPK activity, as well as decreased activation of the mTORC1 signaling pathway, potentially leading to ineffective mitochondrial metabolism and increased autophagy. Conclusions: SHP2 attenuates fibrotic responses in fibroblast cell lines through negative regulation of mitochondrial metabolism and induction of autophagy. SHP2 activation may represent a promising therapeutic strategy for patients with fibrotic lung diseases. © 2023 by the authors

Reduced immunogenicity of the mRNA vaccine BNT162b2 in patients with idiopathic pulmonary fibrosis

[No abstract available

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2–79.2) vs. 78.3, (95% CI 76.0–81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5–41.1) vs. 45.5, (95% CI 41.9–49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4–40.7) vs. 44.4, (95% CI 41.5–48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (< 0.60 K/μL) [HR 2.05, (95% CI 1.19–3.53), (P = 0.01)]. Conclusions: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF. © 2021, The Author(s)