scholarly journals Drug Metabolism in Severe Chronic Obstructive Pulmonary Disease: A Phenotyping ‘Cocktail’ Study

2020 ◽  
Author(s):  
Richard McNeill ◽  
Mei Zhang ◽  
Michael Epton ◽  
Matthew Doogue
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Drug Metabolism ◽  
Pulmonary Disease ◽  
Fold Increase ◽  
Drug Clearance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Clinically Significant ◽  
Healthy Participants ◽  
Severe Copd

Aims To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified ‘Inje’ drug cocktail. Methods This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg, and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. Results The oral clearance (95% CI) in participants with COPD relative to controls was: midazolam 63% (60-67%), dextromethorphan 72% (40-103%), losartan 53% (52-55%), omeprazole 35% (31-39%), caffeine 52% (50-53%), and paracetamol 73% (72-74%). There was a five-fold increase in AUC for omeprazole and approximately two-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. Conclusion Severe COPD is associated with a clinically significant reduction in drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.

scholarly journals Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease

2015 ◽  
Vol 93 (6) ◽  
pp. 541-547 ◽  
Author(s):  
Marwa F. Abd El-Fatah ◽  
Mohamed A. Ghazy ◽  
Mohamed S. Mostafa ◽  
May M. El-Attar ◽  
Ahmed Osman
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Fold Increase ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Metalloproteinase 9 ◽  
Severe Copd

Chronic obstructive pulmonary disease (COPD) is a complex immunological disease with multiple pathological features that is primarily induced by smoking together with additional genetic risk factors. COPD is frequently underdiagnosed; forced expiratory volume in the first second (FEV1) is considered to be the main diagnostic measure for COPD, yet it is insufficiently sensitive to monitor disease progression. Biomarkers capable of monitoring COPD progression and severity are needed. In this report, we evaluated matrix metalloproteinase-9 (MMP-9) as an early marker for the detection and staging of COPD, by assessing the mRNA levels of MMP-9 in peripheral blood samples collected from 22 COPD patients, 6 asymptomatic smokers, and 5 healthy controls. Our results demonstrate that the mRNA levels of MMP-9 increased more than two-fold in severe COPD relative to non-COPD smokers or moderate COPD groups. Moreover, in the very severe COPD group, MMP-9 mRNA levels showed a 4-fold increase relative to the non-COPD smokers or the moderate COPD groups, while there was a mild increase (∼40%) when compared to the severe COPD group. Taken together, our results suggest that MMP-9 serves as a biomarker for the grade and severity of COPD.

scholarly journals Diagnostic performance of lung volumes in assessment of reversibility in chronic obstructive pulmonary disease

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Gamal Agmy ◽  
Manal A. Mahmoud ◽  
Azza Bahaa El-Din Ali ◽  
Mohamed Adam
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cutoff Point ◽  
Whole Body ◽  
Significant Response ◽  
Chronic Obstructive ◽  
Lung Volumes ◽  
Obstructive Pulmonary Disease ◽  
Gold Stage ◽  
Clinically Significant

Abstract Background Reversibility measured by spirometry in chronic obstructive pulmonary disease (COPD) is defined as an increase in forced expiratory volume in first second (FEV1) that is both more than 12% and 200 mL above the pre-bronchodilator value in response to inhaled bronchodilators. FEV1 only may not fully reverberate the changes caused by reduction in air trapping or hyperinflation. To date, the studies that examined the effect of inhaled bronchodilators (BD) on residual volume (RV) and total lung capacity (TLC) are limited. This study was carried out to assess the differences between flow and volume responses after bronchodilator reversibility testing in patients with different COPD GOLD stages (GOLD stage I to stage IV). Spirometry and whole body plethysmography were done before and 15 min after inhalation of 400 μg salbutamol. Results Majority (53.3%) of cases were volume responders, 18.7% were flow responders, 20% were flow and volume responders, and 8% were non responders. Significant increase in Δ FEV1% was found in 15% of cases while 55% showed a significant increase in Δ FVC (P= < 0.001). Mean difference of Δ FVC (L) post BD was significantly increased with advancing GOLD stage (P= 0.03). A cutoff point > 20% for Δ RV% had 70% sensitivity and 60% specificity and > 12% for Δ TLC% showed 90% sensitivity and 45% specificity for prediction of clinically significant response to BD based on FEV1. A cutoff point > 18% for Δ RV% had 78% sensitivity and 29% specificity and > 14% for Δ TLC% had 50% sensitivity and 70% specificity for prediction of clinically significant response to BD based on FVC. Conclusion ΔFEV1 underestimates the true effect of bronchodilators with advancing GOLD stage. Measurement of lung volumes in addition to the standard spirometric indices is recommended when determining bronchodilator response in COPD patients.

scholarly journals Paraoxonase 1 and Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1891
Author(s):  
Jun Watanabe ◽  
Kazuhiko Kotani ◽  
Alejandro Gugliucci
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease ◽  
Paraoxonase Activity ◽  
Severe Copd

Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted.

scholarly journals Prevalence of obstructive sleep apnea among patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Osama Ibrahim Mohammad ◽  
Ahmed Gouda Elgazzar ◽  
Shymaa Mohammad Mahfouz ◽  
Marwa Elsayed Elnaggar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obese Patients ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Obstructive Sleep ◽  
Severe Copd

Abstract Background The conjunction of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is known as overlap syndrome (OS). The coexistence of these diseases has cardiovascular morbidity and mortality. The aim of this study is to assess the prevalence of OSA in COPD patients. One hundred COPD patients (obese and non-obese) performed sleep questionnaires and polysomnograms. Results OSA prevalence in COPD was 50% and it increases with increasing disease severity (P < 0.001). The highest prevalence of OSA was found in obese patients with severe COPD; 90.5% of these patients have OSA. In the OSA group, obese patients were found to have significantly higher STOP-Bang Questionnaire (SBQ), Epworth Sleep Scale (ESS), modified medical research council (mMRC) dyspnea scale, apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI). Both obese and non-obese COPD patients showed significant positive correlations between AHI and smoking index (SI), SBQ, ESS, mMRC, ODI, and neck circumference (NC). Conclusions From this study, it can be concluded that moderate and severe COPD patients had a higher diagnosis of sleep-disordered breathing. Also, obese-COPD patients are more susceptible to develop OSA. Trial registration Name of the registry: Benha University Protocol Record Benha U123, Obstructive Sleep Apnea Prevalence in Patients With Chronic Obstructive Pulmonary Diseases. Trial registration number: NCT04903639. Date of registry: 5/22/2021 (retrospective study).

scholarly journals Decreased plasma epidermal growth factor (EGF) levels in patients with severe chronic obstructive pulmonary disease

Pneumologia ◽  
2019 ◽  
Vol 68 (1) ◽  
pp. 21-26
Author(s):  
Retno AS Soemarwoto ◽  
Andika Chandra Putra ◽  
Syazili Mustofa ◽  
◽  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Pulmonary Disease ◽  
Plasma Levels ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Epidermal Growth ◽  
Severe Copd

Abstract Background Chronic mucus hypersecretion is a common feature in chronic obstructive pulmonary disease (COPD) and is associated with epidermal growth factor (EGF) activity. Aberrant EGF and its receptor signalling can cause airway hyperproliferation, increase in mucous cell differentiation and mucus hyperproduction. Furthermore, it can also promote subepithelial fibrosis and excessive collagen deposition in COPD. The objective of this research was to investigate the plasma levels of EGF in smokers with COPD in comparison with clinically healthy smokers. In addition, the relationship between the plasma levels of EGF and clinical features was investigated. Methods A cross-sectional study included 82 clinically stable male patients with mild-to-very severe COPD (mean age: 64.5±8.6 years), and the control group consisted of 86 healthy male smokers (mean age: 61.6±9.5 years). To define COPD, we performed spirometry and classified COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. We analyzed the levels of EGF by enzyme-linked immunosorbent assay in plasma. Results The mean serum levels of EGF were significantly lower in smokers with COPD than those in controls (69.30 and 83.82 pg/mL, respectively, p = 0.046). The plasma levels of EGF were significantly different (p = 0.004) between mild COPD and moderate-to-very severe COPD. There were no significant differences between the levels of EGF in plasma of spontaneous sputum producers (COPD patients) vs. nonsputum producers (p = 0.101) and between nonexacerbated COPD and exacerbated COPD patients(p = 0.138). Conclusions There is a significant difference in the plasma levels of EGF in male smokers with COPD as compared with male healthy smokers. Our findings suggest that the plasma levels of EGF may contribute to the pathogenesis of COPD.

scholarly journals The Burden of Illness in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease in Canada

2012 ◽  
Vol 19 (5) ◽  
pp. 319-324 ◽  
Author(s):  
M Reza Maleki-Yazdi ◽  
Suzanne M Kelly ◽  
Sy S Lam ◽  
Mihaela Marin ◽  
Martin Barbeau ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Burden Of Illness ◽  
Patient Survey ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Global Initiative ◽  
One Year ◽  
Severe Copd

INTRODUCTION: No recent Canadian studies with physician- and spirometry-confirmed diagnosis of chronic obstructive pulmonary disease (COPD) that assessed the burden of COPD have been published.OBJECTIVE: To assess the costs associated with maintenance therapy and treatment for acute exacerbations of COPD (AECOPD) over a one-year period.METHODS: Respirologists, internists and family practitioners from across Canada enrolled patients with an established diagnosis of moderate to severe COPD (Global initiative for chonic Obstructive Lung Disease stages 2 and 3) confirmed by postbronchodilator spirometry. Patient information and health care resources related to COPD maintenance and physician-documented AECOPD over the previous year were obtained by chart review and patient survey.RESULTS: A total of 285 patients (59.3% male; mean age 70.4 years; mean pack years smoked 45.6; mean duration of COPD 8.2 years; mean postbronchodilator forced expiratory volume in 1 s 58.0% predicted) were enrolled at 23 sites across Canada. The average annual COPD-related cost per patient was $4,147. Across all 285 patients, maintenance costs were $2,475 per patient, of which medications accounted for 71%. AECOPD treatment costs were $1,673 per patient, of which hospitalizations accounted for 82%. Ninety-eight patients (34%) experienced a total of 157 AECOPD. Treatment of these AECOPD included medications and outpatient care, 19 emergency room visits and 40 hospitalizations (mean length of stay 8.9 days). The mean cost per AECOPD was $3,036.DISCUSSION: The current costs associated with moderate and severe COPD are considerable and will increase in the future. Appropriate use of medications and strategies to prevent hospitalizations for AECOPD may reduce COPD-related costs because these were the major cost drivers.

Preserved muscle metaboreflex in chronic obstructive pulmonary disease

2011 ◽  
Vol 36 (6) ◽  
pp. 821-830 ◽  
Author(s):  
Megan F.B. Sherman ◽  
Jeremy D. Road ◽  
Donald C. McKenzie ◽  
A. William Sheel
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Heart Rate ◽  
Blood Flow ◽  
Pulmonary Disease ◽  
Exercise Capacity ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease ◽  
Muscle Metaboreflex ◽  
Severe Copd

The objective of this study was to measure the magnitude of the muscle metaboreflex in people with chronic obstructive pulmonary disease (COPD) compared with healthy controls and to assess the relationships between disease severity, exercise capacity, and the magnitude of the muscle metaboreflex. Nine people with mild-to-severe COPD and 11 age- and gender-matched healthy controls performed isometric handgrip exercise (IHG), followed by postexercise circulatory occlusion (PECO) while hemodynamic changes were measured. Continuous measures of heart rate, arterial pressure, leg blood flow, leg vascular resistance, and total peripheral resistance were obtained. Participants then performed a cycle test to exhaustion. Heart rate, blood pressure, and blood flow responses during IHG and PECO were similar between the COPD group and healthy controls (p > 0.05). There was no association between disease severity or exercise capacity and the magnitude of the muscle metaboreflex. We observed a preserved muscle metaboreflex in mild-to-severe COPD, suggesting the metaboreflex is not a contributing factor to the development of exercise intolerance in this population.

scholarly journals Meal Induced Oxygen Desaturation and Dyspnea in Chronic Obstructive Pulmonary Disease

1998 ◽  
Vol 5 (5) ◽  
pp. 361-365 ◽  
Author(s):  
Norman Wolkove ◽  
Li Yi Fu ◽  
Ashok Purohit ◽  
Antoinette Colacone ◽  
Harvey Kreisman
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Arterial Oxygen Saturation ◽  
Care Facility ◽  
Forced Expiratory Volume ◽  
Oxygen Desaturation ◽  
Arterial Oxygen ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Severe Copd

OBJECTIVE: To study arterial oxygen saturation (SpO2) obtained by pulse oximetry and dyspnea during active eating (AE) and passive eating (PE) in patients with severe chronic obstructive pulmonary disease (COPD).DESIGN: Patients were studied on two consecutive days with AE and PE, which occurred in random order. SpO2was recorded for 20 mins before and during eating, and dyspnea was recorded by the patient using a 10 cm visual analogue scale before and upon completion of eating.SETTING: Subjects were in-patients at an intermediate care facility who were hospitalized for pulmonary rehabilitation or for convalescence after an exacerbation of COPD.POPULATION STUDIED: Thirty-five patients with severe COPD (forced expiratory volume in 1 s [FEV1] less than 50% predicted, FEV1to forced vital capacity ratio less than 65%) were studied. Mean age was 70.5±7.1 years.MAIN RESULTS: Mean SpO2decreased significantly (P<0.05) from 91.7±3.4% to 90.1±4.0% during AE, and 91.7±3.2% to 90.8±3.6% during PE. Mean lowest SpO2was lower and percentage of time with SpO2less than 90% was greater during eating compared with corresponding control periods during both AE and PE. Dyspnea increased significantly (P<0.05) from 1.4±1.2 to 3.3±2.3 cm during AE, and from 1.5±1.5 to 2.4±2.2 cm during PE. The increase in dyspnea was significantly greater during AE than PE.CONCLUSIONS: Eating is an activity that can adversely affect SpO2and increase dyspnea in patients with severe COPD. Oxygen desaturation and particularly increased dyspnea may at least in part relate to the recruitment of upper extremity muscles during eating.

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