scholarly journals Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Iwona Gilowska ◽  
Łukasz Kasper ◽  
Katarzyna Bogacz ◽  
Jan Szczegielniak ◽  
Teresa Szymasek ◽  
...  

Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9.

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yongchun Shen ◽  
Ting Yang ◽  
Shujin Guo ◽  
Xiao'ou Li ◽  
Lei Chen ◽  
...  

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation. However, no data on the possible relationship between COPD and ox-LDL are available. This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress. Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62±7.56versus12.57±5.90 mU/L,P<0.05). Serum levels of CRP and ROS were also significantly higher in COPD patients. Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r=−0.347,P=0.016), while they correlated positively with CRP and ROS levels. These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD. Future studies are needed to determine whether and how ox-LDL plays a role in COPD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.


2021 ◽  
Vol 162 (5) ◽  
pp. 185-191
Author(s):  
Mónika Fekete ◽  
Vince Fazekas-Pongor ◽  
Gergő Szőllősi ◽  
János Tamás Varga

Összefoglaló. Bevezetés: Krónikus obstruktív tüdőbetegségben (COPD) az obesitas mellett a csökkent fizikai aktivitás nagymértékben fokozza a metabolikus szindróma kialakulásának valószínűségét. Célkitűzés: Kutatásunk célja volt felmérni a metabolikus szindróma prevalenciáját COPD-ben, valamint azt, hogy milyen mértékben függ össze az életkorral, a nemmel, a társbetegségekkel, a tüdőfunkció károsodásának mértékével, a tápláltsági állapottal, a fizikai terhelhetőséggel és az életminőséggel. Módszer: Keresztmetszeti vizsgálatot végeztünk az Országos Korányi Pulmonológiai Intézet Légzésrehabilitációs Osztályán fekvő betegek körében 2019. július 1. és december 31. között. A véletlenszerűen kiválasztott 300, 40 év feletti betegnek ismertük az antropometriai, légzésfunkciós vizsgálati eredményét és laboratóriumi paramétereit. Adatokat gyűjtöttünk a dohányzási szokásokról, az előző évi exacerbatiók számáról és a kortikoszteroidok használatáról is. Az életminőség mérésére a betegségspecifikus Szent György-féle Légzési Kérdőív magyar nyelvre validált változatát használtuk. A metabolikus szindrómát a Nemzetközi Diabetes Szövetség kritériumai alapján határoztuk meg. Eredmények: A metabolikus szindróma a betegek 72%-ánál fordult elő, férfi: 65,9% nő: 77,2% (p = 0,031). A metabolikus szindrómás betegek esetében rövidebb 6 perces sétatávolságot mértünk ([m] 250 [150–330] vs. 295 [162–360]; p = 0,384), és szignifikánsan több volt az előző évi exacerbatiók száma (3 [0–6] vs. 1 [1–2]; p<0,001) a nem metabolikus szindrómás betegekhez képest. A BMI-re történő stratifikáció után a metabolikus szindróma jelenléte nagyobb volt BMI≥25 kg/m2 esetén. A hasi elhízás, a magas vérnyomás, a hyperlipidaemia és a hyperglykaemia szignifikánsan gyakoribb volt BMI≥25 kg/m2 esetén (p<0,001). Következtetés: Eredményeink azt sugallják, hogy a metabolikus szindrómás betegekben megnő az együttes morbiditási index, különösen azok körében, akik túlsúlyosak vagy elhízottak. Ezért a COPD-s betegekben nagyon fontos időben felismerni és megfelelően kezelni a metabolikus szindrómát. Orv Hetil. 2021; 162(5): 185–191. Summary. Introduction: Both obesity and the lack of physical activity among chronic obstructive pulmonary disease (COPD) patients increase the risk of developing metabolic syndrome. Objective: The goal of our study was to assess the prevalence of metabolic syndrome among COPD patients and to examine its correlation with age, gender, comorbidities, lung function values, nutritional status, exercise capacity, and quality of life. Method: A cross-sectional study was performed at the Department of Pulmonary Rehabilitation of the Hungarian National Korányi Institute for Pulmonology between July 1st and December 31st, 2019. A total of 300 patients aged over 40 were selected at random. Anthropometric data were collected along with lung function values, laboratory parameters, smoking status, the number of exacerbations in the previous year, and the use of corticosteroids. Quality of life was measured by the validated Hungarian, COPD-specific Saint George Respiratory Questionnaire. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Results: Metabolic syndrome affected 72% of COPD patients (male: 65.9%, female 77.2%; p = 0.031). In patients with metabolic syndrome, shorter 6-minute walking distance was measured ([m] 250 [150–330] vs. 295 [162–360]; p = 0.384) and the number of exacerbations in the previous year was significantly higher (3 [0–6] vs. 1 [1–2]; p<0.001) compared to patients with no metabolic syndrome. After stratification for BMI, metabolic syndrome was more frequent in the case of BMI≥25 kg/m2. Central adiposity, hypertension, hyperlipidemia, and hyperglycemia were also significantly more frequent among patients with BMI≥25 kg/m2 (p<0.001). Conclusion: Our results suggest that the co-morbidity index increases in patients with metabolic syndrome, especially in overweight or obese patients. Therefore, early detection and appropriate treatment of metabolic syndrome in patients with COPD is very important. Orv Hetil. 2021; 162(5): 185–191.


2020 ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
...  

Abstract Background: Extracellular heat shock protein 70 (eHsp70) acts like a damage-associated molecular pattern (DAMP) and it might modulate immune responses in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore plasma eHsp70 concentration in patients with stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment.Methods: Blood samples were collected from 137 COPD patients and 95 healthy individuals. COPD patients were subdivided into GOLD 2-4 stages based on airflow obstruction severity and GOLD A-D groups regarding symptoms and exacerbations. Concentration of eHsp70 was assessed in EDTA plasma by the commercially available ELISA kit. Statistic analysis was performed by MedCalc statistical software.Results: eHsp70 concentration was increased in COPD patients when compared to controls and was increasing with the severity of airflow limitation as well as symptoms burden and exacerbation history. There were no differences in eHsp70 concentrations among COPD patients based on smoking status, yet eHsp70 was increased in healthy smokers compared to healthy non-smokers. Interestingly, healthy smokers had similar eHsp70 level as COPD patients in GOLD 2 stage and those in GOLD A group. In addition, eHsp70 showed significant negative correlation with lung function parameters FEV1 and FEV1/FVC and positive correlation with COPD multicomponent indices BODCAT, BODEx, CODEx and DOSE. Finally, eHsp70 showed great predictive value (OR=7.63) and correctly classified 76% of cases.Conclusions: Plasma eHsp70 is associated with COPD prediction and disease severity and might have a potential of becoming an additional biomarker in COPD assessment.


2017 ◽  
Vol 10 (3) ◽  
pp. 114-127 ◽  
Author(s):  
Alireza Shahriary ◽  
Mostafa Ghanei ◽  
Hossein Rahmani

AbstractSulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas inhalation is mustard lung which is discussed as a phenotype of chronic obstructive pulmonary disease (COPD). In this complication, there are clinical symptoms close to COPD with common etiologies, such as in smokers. Based on information gradually obtained by conducting the studies on mustard lung patients, systemic symptoms along with pulmonary disorders have attracted the attention of researchers. Changes in serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), matrix metalloproteinases (MMPs), interleukin (IL), chemokines, selectins, immunoglobulins, and signs of imbalance in oxidant-antioxidant system at serum level, present the systemic changes in these patients. In addition to these, reports of extra-pulmonary complications, such as osteoporosis and cardiovascular disease are also presented. In this study, the chance of developing the systemic nature of this lung disease have been followed on using the comparative study of changes in the mentioned markers in mustard lung and COPD patients at stable phases and the mechanisms of pathogenesis and phenomena, such as airway remodeling in these patients.


2019 ◽  
Vol 8 (4) ◽  
pp. 562
Author(s):  
Hung-Yu Huang ◽  
Chun-Yu Lo ◽  
Lan-Yan Yang ◽  
Fu-Tsai Chung ◽  
Te-Fang Sheng ◽  
...  

Negative pressure ventilation (NPV), when used as an adjuvant to pulmonary rehabilitation, improves lung function, increases exercise capacity, and reduces exacerbations. The aim of this study was to determine whether maintenance NPV improves long-term clinical outcomes and reduces mortality in patients with chronic obstructive pulmonary disease (COPD). Between 2003 and 2009, 341 patients were treated for COPD either with or without hospital-based NPV. We measured forced expiratory volume in one second (FEV1), 6-min walking distance (6MWD), and oxygen saturation by pulse oximetry (SpO2) during a 6-min walk test (6MWT) every 3–6 months. Desaturation (D) during the 6MWT was defined as a reduction in SpO2 of ≥10% from baseline. The NPV group had a better survival outcome than the Non-NPV group. The 8-year survival probabilities for the NPV and Non-NPV groups were 60% and 20%, respectively (p < 0.01). Baseline desaturation was a significant risk factor for death, and the risk of death increased with desaturation severity (SpO2 80~89: hazard ratios (HR) 2.7, 95% confidence interval (CI) 1.4–5.3; SpO2 < 80: HR 3.1, 95% CI 1.3–7.4). The NPV group had a slower decline in lung function and 6MWD. The NPV + D and Non-NPV+D had a threefold and fourfold increase in the risks of all-cause mortality compared with the NPV-ND, respectively. Maintenance non-invasive NPV reduced long-term mortality in COPD patients. The desaturating COPD patients had an increased mortality risk compared with non-desaturating COPD patients.


1970 ◽  
Vol 6 (2) ◽  
pp. 22-30 ◽  
Author(s):  
R Shrestha ◽  
R Shakya

Introduction : Chronic Obstructive Pulmonary Disease (COPD) is one of the leading problems affecting majority of population all over the world which diminishes the quality of life of the individual and create extra burden to the society as well as country. Inhaled bronchodilator therapy is the mainstay of treatment in the management of COPD. Various inhaled [e.g. metered dose inhaler (MDI) /dry powder inhaler (DPI)] formulations are available and are widely used among the COPD patients in Nepal. Methodology : This is cross sectional prospective study, designed to compare the bronchodilating effect produced when salbutamol is delivered via two devices: MDI (Asthalin® from Cipla) and DPI (Asthalin® rotacap delivered via Rotahaler® from Cipla), in patients with stable COPD. It is proven by previous studies that intervention is necessary to improve the compliance of the patients; all subjects (total n=60; 30 in each group) are counseled and trained to follow correct inhaling technique through particular device. Then their improvements in lung function were measured with reference to the pulmonary function test based on spirometry. Results : Patients enrolled in each group were not statistically different regarding to age (P=0.318), weight (P=0.324) & BMI (P=0.836). Among the total subjects 87% had smoking history and 2% were still smoking and there was no signifi cant difference in smoking habit between the two groups (p-value 0.544 > 0.05). Similarly 91.6 % of the total had exposure to indoor air pollution which had been the major risk factor for COPD. Most of the patients were on stage II COPD (62%). Salbutamol was found to have no effect on vital statistics of patients. Study showed there was no significant difference in the improvement of forced expiratory volume in one second (FEV1) (p=0.802), FVC (p= 0.693), FEV1 % (p=1) and PEF (p=0.448) between MDI and Rotahaler groups. Major side effect associated with the MDI users is headache (79%) while those among Rotahaler users were muscle cramps (79%). Even though intervention improved the inhaler using technique among the patients in both the groups, it was found even after counseling, DPI seemed to be better understood by the patients in comparison to MDI (p=0.003 & 0.00). In addition DPI was preferred by most of the patients who were familiar with both delivery systems. It was also found to be cheaper than the MDI. Conclusion : Overall evidence suggests that although both MDI & DPI improve the lung function of COPD patients to similar extent, DPI is cheaper and more preferred and can be easily handled by the patients which can result in reduction of non-compliance. Keyword : COPD; Salbutamol; DPI; MDI; Spirometry DOI: 10.3126/saarctb.v6i2.3054 SAARC J. Tuber. Lung Dis. HIV/AIDS 2009 VI (2) 22-30


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Nailya Kubysheva ◽  
Larisa Postnikova ◽  
Svetlana Soodaeva ◽  
Viкtor Novikov ◽  
Tatyana Eliseeva ◽  
...  

The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.


Medicina ◽  
2010 ◽  
Vol 46 (5) ◽  
pp. 315 ◽  
Author(s):  
Agnė Babušytė ◽  
Jolanta Jeroch ◽  
Rimantas Stakauskas ◽  
Kristina Stravinskaitė ◽  
Kęstutis Malakauskas ◽  
...  

Objective. The aim of study was to investigate a chemotactic effect of induced sputum and bronchoalveolar lavage fluid on blood neutrophils in patients with chronic obstructive pulmonary disease (COPD) and healthy individuals. Material and methods. Forty-three smokers with COPD, 19 ex-smokers with COPD, 13 healthy smokers, and 17 healthy nonsmokers were recruited to the study. Neutrophils were isolated from peripheral blood of study individuals. For the same experimental conditions, pooled induced sputum and bronchoalveolar lavage fluid of 20 COPD patients were used. Neutrophil chemotaxis in vitro was performed in cell-transmigration chamber. Substances tested for chemoattraction (interleukin-8, induced sputum, bronchoalveolar lavage fluid directly or in addition to interleukin-8) were added to lower wells. Upper wells were filled with 2.5×106/mL of neutrophil culture and incubated for 2 hours. Migration was analyzed by flow cytometry. Results. Interleukin-8 (10–100 ng/mL) induced a dose-dependant neutrophil migration in all the groups. Only 100 ng/L of interleukin-8 induced more intensive chemotaxis of neutrophils from COPD smokers as compared to ex-smokers (P<0.05). Such difference between healthy individuals was obtained using 30 ng/mL of interleukin-8 (P<0.05). Induced sputum/interleukin-8 (10–100 ng/mL), as well as induced sputum directly, induced neutrophil migration (P<0.05). Chemotaxis of neutrophils isolated from COPD patients and healthy nonsmokers did not depend on additional interleukin-8 concentration. Bronchoalveolar lavage fluid/interleukin-8 (30–100 ng/mL) induced more intensive migration of neutrophils from COPD patients than bronchoalveolar lavage fluid (P<0.05) alone. Conclusions. Migration of neutrophils isolated from patients with COPD was more intensive compared to healthy individuals. Induced sputum and bronchoalveolar lavage fluid directly and with addition of interleukin-8 stimulated chemotaxis, and it was higher in neutrophils from COPD patients. Migration of neutrophils did not depend on smoking status.


2021 ◽  
Author(s):  
Jie Liu ◽  
Wenjing Zhu

Abstract Background: Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease which is expected to become the third leading cause of death worldwide in 2030. Series of susceptibility genes and single nucleotide polymorphism (SNPs) play an important role in the occurrence and development of COPD.Methods: In our study, 98 COPD patients and 90 healthy volunteers were enrolled. The +869 SNP (SNP, Single Nucleotide Polymorphisms) of TGF-β1 was detected in 98 COPD patients and 90 healthy volunteers by PCR-DNA sequencing. The effects of different genotypes of +869 locus on the susceptibility of COPD, pulmonary function and airflow limitation of COPD patients were analyzed.Results: Allele C of +869 locus was associated with the susceptibility of COPD (OR:1.913, 95% CI: 1.251-2.926). The predicted value of FEV1% (FEV1, Forced Expiratory Volume in One Second) in patients with CC of +869 locus was significantly lower than that in patients with TT (P < 0.05). The genotype frequencies of CC, CT and TT were 6.5%, 58.7% and 34.8% in Mild-to-Moderate airflow restriction patients. In severe airflow restriction patients, the genotype frequencies were CC 23.1%, CT 57.7% and TT 19.2%. The distribution of CC genotype in severe airflow restriction COPD patients was significantly higher than that in Mild-to-Moderate airflow restriction COPD patients (P = 0.037). Moreover, the frequency of C allele was significantly higher in patients with severe airflow restriction than that patients with Mild-to-Moderate airflow restriction (P = 0.024).Conclusions: The SNP of +869 T/C in TGF-β1 is closely related to the susceptibility of COPD and the airflow restriction of COPD patients.


Sign in / Sign up

Export Citation Format

Share Document