scholarly journals The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Xianyan Liu ◽  
Binwei Hao ◽  
Ailing Ma ◽  
Jinxi He ◽  
Xiaoming Liu ◽  
...  
Keyword(s):  
Disease Severity ◽  
Transforming Growth Factor ◽  
Smooth Muscles ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Small Airway ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Functions ◽  
Copd Patients

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factorβ(TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM markerα-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-βin the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-βsignaling in the pathogenesis of COPD, which warrants further investigation.

Inspiratory muscle strength in chronic obstructive pulmonary disease depending on disease severity

2007 ◽  
Vol 113 (5) ◽  
pp. 243-249 ◽  
Author(s):  
Hans-Joachim Kabitz ◽  
Stephan Walterspacher ◽  
David Walker ◽  
Wolfram Windisch
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Muscle Strength ◽  
Pulmonary Disease ◽  
Disease Severity ◽  
Inspiratory Muscle ◽  
Walking Distance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Inspiratory Muscle Strength

Staging criteria for COPD (chronic obstructive pulmonary disease) include symptoms and lung function parameters, but the role of reduced inspiratory muscle strength related to disease severity remains unclear. Therefore the present study tested whether inspiratory muscle strength is reduced in COPD and is related to disease severity according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria and assessed its clinical impact. PImax (maximal inspiratory mouth occlusion pressure), SnPna (sniff nasal pressure) and TwPmo (twitch mouth pressure) following bilateral anterior magnetic phrenic nerve stimulation were assessed in 33 COPD patients (8 GOLD0, 6 GOLDI, 6 GOLDII, 7 GOLDIII and 6 GOLDIV) and in 28 matched controls. Furthermore, all participants performed a standardized 6 min walking test. In comparison with controls, PImax (11.6±2.5 compared with 7.3±3.0 kPa; P<0.001), SnPna (9.7±2.5 compared with 6.9±3.3 kPa; P<0.001) and TwPmo (1.6±0.6 compared with 0.8±0.4 kPa; P<0.001) were markedly lower in COPD patients. TwPmo decreased with increasing COPD stage. TwPmo was correlated with walking distance (r=0.75; P<0.001), dyspnoea (r=−0.61; P<0.001) and blood gas values following exercise (r>0.57; P<0.001). Inspiratory muscle strength, as reliably assessed by TwPmo, decreased with increasing severity of COPD and should be considered as an important factor in rating disease severity and to reflect burden in COPD.

Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

2020 ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Heat Shock ◽  
Lung Function ◽  
Heat Shock Protein ◽  
Disease Severity ◽  
Heat Shock Protein 70 ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

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.

scholarly journals Extracellular adenosine triphosphate is associated with airflow limitation severity and symptoms burden in patients with chronic obstructive pulmonary disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Anita Somborac-Bačura ◽  
Marija Grdić Rajković ◽  
Andrea Vukić Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Disease Severity ◽  
Adenosine Triphosphate ◽  
Quantitative Polymerase Chain Reaction ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Extracellular Adenosine ◽  
Copd Patients

Abstract Extracellular adenosine triphosphate (eATP)-driven inflammation was observed in chronic obstructive pulmonary disease (COPD) but was not investigated in patients’ blood. Therefore, this study aimed to investigate eATP concentration in plasma of COPD patients and its association with disease severity and smoking. Study included 137 patients with stable COPD and 95 control subjects. eATP concentration was determined in EDTA plasma by luminometric method, and mRNA expression of eATP receptors P2X7R and P2Y2R was analysed by quantitative polymerase chain reaction (qPCR). eATP concentration was increased in COPD patients compared to controls (P < 0.001). Moreover, it was increasing with disease severity (GOLD 2–4) as well as symptoms burden and exacerbations history (GOLD A–D) (P < 0.05). eATP in healthy smokers differed from healthy non-smokers (P < 0.05) but was similar to GOLD 2 and GOLD A patients. eATP showed great diagnostic performances (OR = 12.98, P < 0.001) and correctly classified 79% of study participants. It demonstrated association with FEV1 and multicomponent indices (ADO, BODEx, BODCAT, CODEx, DOSE). Regarding gene expression, P2Y2R was increased in the blood of COPD patients. Plasma eATP could become a diagnostic and/or prognostic biomarker in COPD, as it seems to be associated with patients’ condition, quality of life and disease progression.

scholarly journals The CT pulmonary vascular parameters and disease severity in COPD patients on acute exacerbation: a correlation analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tao Yang ◽  
Chihua Chen ◽  
Zhongyuanlong Chen
Keyword(s):  
Acute Exacerbation ◽  
Disease Severity ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Lung Field ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Vessels ◽  
Copd Patients ◽  
Severe Copd

Abstract Background It is necessary to analyze the CT pulmonary vascular parameters and disease severity in chronic obstructive pulmonary disease (COPD) patients to provide evidence support for the management of COPD. Methods COPD patients on acute exacerbation admitted to our hospital from COPD patients from January 2019 to March 2020 was selected. The characteristics and ratio of the cross-sectional area (CSA) of small pulmonary vessels to the total area of the lung field, and the ratio of pulmonary artery and aorta (PA/A) cross-sectional diameter in patients with COPD were analyzed. Results A total of 128 COPD patients were included. There were significant differences in the duration of COPD, smoking history, the PaO2, PaCO2, pH, and FEV1, FVC and FEV1/FVC among COPD patients with different severity (all p < 0.05). The duration of COPD, smoking, PaO2, PaCO2, CSA and PA/A were correlated with the COPD severity (all p < 0.05). Both CSA, PA/A were correlated with post BD FEV1 (all p < 0.05). The cutoff value of CSA and PA/A for the diagnosis of severe COPD was 0.61 and 0.87 respectively, and the AUC of CSA and PA/A for the diagnosis of severe COPD was 0.724 and 0.782 respectively. Conclusions Patients with CSA ≤ 0.61 and PA/A ≥ 0.87 may have higher risks for severe COPD, and more studies are needed in the future to further elucidate the management of COPD.

scholarly journals Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 9 (10) ◽  
pp. 3097 ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Heat Shock ◽  
Lung Function ◽  
Disease Severity ◽  
Heat Shock Protein 70 ◽  
Smoking Status ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Extracellular heat shock protein 70 (eHsp70) might modulate immune responses in chronic obstructive pulmonary disease (COPD). The aim of the study was to explore eHsp70 concentration in stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment. Plasma samples were collected from 137 COPD patients and 95 healthy individuals, and concentration of eHsp70 was assessed by commercially available enzyme-linked immunosorbent assay (ELISA) kit (Enzo Life Science, Farmingdale, NY, USA). COPD patients were subdivided regarding airflow obstruction severity and symptoms severity according to the Global Initiative for COPD (GOLD) guidelines. eHsp70 concentration increased in COPD patients when compared to controls and increased with the severity of airflow limitation as well as symptoms burden and exacerbation history. eHsp70 concentration did not differ among COPD patients based on smoking status, yet it increased in healthy smokers compared to healthy nonsmokers. In addition, eHsp70 negatively correlated with lung function parameters forced expiratory volume in one second (FEV1) and FEV1/ forced vital capacity (FVC), and positively with COPD multicomponent indices BODCAT (BMI, airflow obstruction, dyspnea, CAT score), BODEx (BMI, airflow obstruction, dyspnea, previous exacerbations), CODEx (Charlson’s comorbidity index, airflow obstruction, dyspnea, previous exacerbations) and DOSE (dyspnea, airflow obstruction, smoking status, previous exacerbations) With great predictive value (OR = 7.63) obtained from univariate logistic regression, eHsp70 correctly classified 76% of cases. eHsp70 is associated with COPD prediction and disease severity and might have the potential for becoming an additional biomarker in COPD assessment.

scholarly journals The use of corticosteroids in patients with chronic obstructive pulmonary disease: epidemiological and economic aspects

2009 ◽  
Vol 10 (4) ◽  
pp. 139-148 ◽  
Author(s):  
Pablo M. Katz ◽  
Valeria Pegoraro
Keyword(s):  
Disease Severity ◽  
Systemic Corticosteroid ◽  
Economic Consequences ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Free Treatment ◽  
Inadequate Therapy ◽  
The Difference ◽  
The Cost

Objective: this study aimed at assessing the level of compliance to GOLD guidelines regarding the use of ICS containing drugs for the treatment of patients with COPD in the GPs setting in Italy and at evaluating the economic consequences that the use of corticosteroids may have, specifically in mild and moderate COPD patients where it is inappropriate. Methods: the retrospective GPs database study has analyzed patients with at least one diagnosis of COPD during the period January 2005 – December 2008 who had a report of VEMS and at least one prescription of a drug from ATC R03 class within two months from the date of spirometric exam, who were 40 years or older and that have been followed for at least 9 months. Patients were classified in four disease severity groups according to GOLD (2008). Compliance to GOLD guidelines regarding the use of corticosteroids was evaluated on the basis of the first treatment prescribed after spirometric exam. The analysis evaluated exacerbations as well, assuming their occurrence when one prescription of either antibiotic, oxygen or systemic corticosteroid was found. The cost of the first prescription of treatments containing ICS in mild and moderate patients was calculated. Then the “Hypothetic cost” was built for those patients in order to estimate the cost that would have been created in case the considered treatments had been ICS free. The difference between these two costs represents inappropriate cost that could have been avoided by using an ICS free treatment, more appropriate according to GOLD. Results: a cohort of 2,103 Italian patients with the diagnosis of COPD, followed by 700 GPs all over Italy was analyzed. An ICS-containing treatment was prescribed to more than 50% of patients within each disease severity group. The percentage of patients who experienced an exacerbation within 6 months from the first prescription was not found to be different among patients prescribed with an ICS-free treatment and those treated with an ICS-containing treatment and was independent of the disease severity. In mild and moderate COPD patients respectively, 53% and 48% of the cost generated by the ICS containing prescriptions represent the inappropriate cost for the Health Care System. Moreover, patients are unnecessarily exposed to the risk of inadequate therapy.


scholarly journals Associations Between Sputum Torque Teno Virus Load and Lung Function and Disease Severity in Patients With Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu Xie ◽  
Qing Xue ◽  
Weike Jiao ◽  
Jianhui Wu ◽  
Yan Yu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Viral Load ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Disease Severity ◽  
Torque Teno Virus ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Exacerbation Of Copd

Purpose: Viral load of Torque Teno virus (TTV) is elevated in immunosuppressed patients. The weakened immune response is typical in chronic obstructive pulmonary disease (COPD) patients. However, the relationship between TTV and COPD is still unknown.Patients and Methods: We enrolled 91 patients admitted to hospitals with acute exacerbation of COPD (AECOPD) between January 2017 and August 2017 (ClinicalTrials.gov ID, NCT03236480). Sputum samples were gathered during hospitalization and the 120-day follow-up. TTV distribution and genogroups were assessed, and the associations between viral loads and clinical parameters were analyzed.Results: TTV DNA was detected in 95.6% of COPD patients, and the viral load was nearly invariable at the stable and exacerbation states. Most TTV DNA-positive patients carried four distinct genotypes. Sputum load of TTV was positively associated with RV/TLC (r = 0.378, p = 0.030), and negatively correlated with FEV1/pre and FEV1/FVC (r = −0.484, −0.432, p = 0.011, 0.024, respectively). Neutral correlation between the TTV DNA load and COPD assessment test (CAT) scores (r = 0.258, p = 0.018) was observed.Conclusion: Sputum loads of TTV DNA could be a novel indicator for lung function and disease severity assessment in COPD patients.

scholarly journals Diagnosis of small airway dysfunction in patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 48 (5) ◽  
pp. 307-315
Author(s):  
A. V. Cherniak ◽  
O. I. Savushkina ◽  
T. L. Pashkova ◽  
E. V. Kryukov
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Vital Capacity ◽  
Small Airway ◽  
Diagnostic Methods ◽  
Chronic Obstructive ◽  
Impulse Oscillometry ◽  
Body Plethysmography ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Aim: To assess the prevalence of SAD in COPD patients by various functional diagnostic methods, such as spirometry, body plethysmography, and impulse oscillometry (IOS).Materials and methods: This was an cross-sectional study. Spirometry, body plethysmography and IOS were used in 132 COPD patients in remission under standard anti-COPD treatments. The presence of SAD was confirmed by at least one of the following criteria or their combination: 1) by spirometry: the difference between vital capacity (VC) and forced vital capacity (FVC) > 10%; 2) the presence of air trapping by body plethysmography; 3) identification of the frequency dependence of the resistive resistance at 5 to 20 Hz (R5 - R20 > 0.07 kPa x s/l), as assessed by IOS.Results: Mean forced expiratory volume in 1 s (FEV1) was 42.9% of predicted. Depending on the severity of the obstruction, the patients were divided into 4 groups: 7 patients (group 1) had the obstruction corresponding to GOLD 1 stage, 37 (group 2) to GOLD 2, 49 (group 3) to GOLD 3, and 39 (group 4) to GOLD 4. SAD was found in 96% of COPD patients, whereas in those with severe obstruction (GOLD 3-4), it was present in 100% of the cases. By spirometry, SAD was identified only in 67% of COPD patients, by body plethysmography in 75% of COPD patients (in those with severe obstruction (GOLD 3 and 4) in 88 and 97%, respectively). With IOS, it was possible to identify SAD in 94% of patients and in 100% of those with severe obstruction (GOLD 3-4).Conclusion: With deterioration of obstructive pulmonary ventilation abnormalities in COPD patients, there is a progressive increase in small airway dysfunction. Impulse oscillometry seems to be the most effective method for diagnosis of small airway dysfunction, as it helped to identify SAD in 94% of COPD patients and in 100% of those with severe and very severe obstruction.

scholarly journals Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD

2021 ◽  
Author(s):  
Jonathan R Baker ◽  
Peter S Fenwick ◽  
Carolin K Koss ◽  
Harriet B Owles ◽  
Sarah L Elkin ◽  
...  
Keyword(s):  
Culture Media ◽  
Airway Epithelial Cells ◽  
Small Airway ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Copd Patients ◽  
Agonist And Antagonist ◽  
Underlying Pathophysiology

AbstractCurrent treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating novel therapies. Here, we show that COPD patients have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived mainly from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a novel mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralising antibody could be a promising new therapeutic strategy in the treatment of COPD.

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