Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10(-11)]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10(-4)] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10(-5)]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.
- Klíčová slova
- MUC2, MUC5B, association study, cytokines, idiopathic pulmonary fibrosis, network analysis, sequenom MassARRAY, single nucleotide polymorphism,
- Publikační typ
- časopisecké články MeSH
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation associated with chronic inflammation. Matrix metalloproteinases (MMPs) are proteolytic enzymes that contribute to the inflammatory response in COPD and degrade extracellular matrix components. Their enzymatic activity is inhibited by a four-member family of tissue inhibitors of metalloproteinases (TIMPs). In COPD, the MMP/TIMP network, mainly MMP-9, has been repeatedly observed to be dysregulated at both the local (lung) and systemic levels. Here, we review the findings reported in numerous cross-sectional studies with our primary focus on longitudinal observations in human COPD studies. The data from longitudinal prospective studies on the MMP/TIMP network may lead to the introduction of novel prognostic biomarkers into clinical management of COPD. We address the relationship between the systemic and local lung MMP/TIMP network in COPD patients and briefly describe the involvement of microRNAs. Finally, the role of the MMP/TIMP network in COPD treatment is discussed.
- Klíčová slova
- Biomarker, Chronic obstructive pulmonary disease, Local and systemic response, Matrix metalloproteinases, MicroRNAs, Tissue inhibitors of metalloproteinases,
- MeSH
- biologické markery metabolismus MeSH
- chronická obstrukční plicní nemoc enzymologie MeSH
- fenotyp MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 metabolismus MeSH
- matrixové metaloproteinasy metabolismus MeSH
- mikro RNA metabolismus MeSH
- plíce metabolismus MeSH
- prognóza MeSH
- průřezové studie MeSH
- regulace genové exprese enzymů * MeSH
- tkáňové inhibitory metaloproteinas metabolismus MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- matrixová metaloproteinasa 9 MeSH
- matrixové metaloproteinasy MeSH
- mikro RNA MeSH
- MMP9 protein, human MeSH Prohlížeč
- tkáňové inhibitory metaloproteinas MeSH
Sandblasting is traditionally known as a high-risk profession for potential development of lung silicosis. Reported is a case of a sandblaster with confirmed accelerated silicosis, a condition rather rarely diagnosed in the Czech Republic. Initially, the patient presented with progressive dry cough and exertional dyspnoea. In the early diagnostic process, a possible occupational aetiology was considered given his occupational history and known high-risk exposure to respirable silica particles confirmed by industrial hygiene assessment at the patient's workplace. The condition was confirmed by clinical, histological and autopsy findings. The patient died during lung transplantation, less than five years from diagnosis.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- hutnictví * MeSH
- lidé MeSH
- nemoci z povolání diagnóza etiologie MeSH
- oxid křemičitý toxicita MeSH
- pracovní expozice škodlivé účinky MeSH
- progrese nemoci MeSH
- silikóza diagnóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- oxid křemičitý MeSH
BACKGROUND: AECOPD is a life threatening condition for patients with chronic obstructive pulmonary disease (COPD) and lack of specific biomarker hinders effective management. Sputum, blood, breath and urinary biomarkers have all been investigated. We measured maximum respiratory pressure post exacerbation once the patient was compliant with the test and after 6 weeks, to assess any correlations. METHODS AND RESULTS: The maximum pressures were measured using a closed circuit spirometer with a clean rubber mouthpiece properly placed with the patients lips sealed around it. Patients were properly instructed to exhale slowly and completely, then inspire with maximum possible effort and advised to keep it for nearly 1.5 s for maximum inspiratory pressure (MIP). For maximum expiratory pressures (MEP) patients were instructed to inspire slowly and completely, then expire forcefully with maximum effort. With the recorded values TTI (time tension index) was calculated. This was repeated again after 6 weeks. Using Pearsons correlation coefficient we found that MIP had a negative correlation with TTI and a positive correlation with FEV1. FEV1 had a positive correlation with FVC. MEP showed no significant correlation with TTI, but a positive correlation with FEV1. CONCLUSION: Acute exacerbations of COPD has a profound effect on the respiratory musculature especially the expiratory muscles but the maximum pressures are not specific enough to be prognostic markers. It might be worthwhile studying transformations of the respiratory musculature at the molecular level. More studies must be conducted to find a specific marker to aid in the management of the condition.
- MeSH
- chronická obstrukční plicní nemoc diagnóza patofyziologie MeSH
- dýchací svaly MeSH
- lidé MeSH
- spirometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
