COPD Subjects Research Articles

Dissociation between physical capacity and daily physical activity in COPD patients. A population-based approach

BadkgroundPhysical capacity (PC) and daily physical activity (PA) are two crucial factors in the clinical course of COPD, although they do not always maintain a close relationship. The objectives were to evaluate the frequency of PC-PA dissociation in patients with COPD and subjects without airflow limitation (AL) and to identify its risk factors. MethodsA sample of 319 COPD patients and 399 subjects without AL was consecutively obtained from a population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, lung function testing, blood analysis and low-dose computed tomography (CT) scan with evaluation of lung density and airway wall thickness. A distance walked in 6 min > 70% predicted was considered an indicator of normal PC, while a Yale Physical Activity Survey summary index score <51 was used to identify with sedentary lifestyle. Results166 COPD patients (52.0%) reported a sedentary lifestyle with evidence of preserved PC, while this phenomenon was present in 188 (47.1%) subjects without AL. In the COPD group, symptoms of chronic bronchitis, depression and elevated hematocrit and blood eosinophil count were identified as independent risk factors for PC-PA dissociation. In turn, in the subjects without AL, the risk factors for PC-PA dissociation were low fat-free mass, obesity and anxiety, as well as reduced levels of HDL-cholesterol and the absence of osteoporosis. ConclusionsAlmost half of COPD patients and subjects without airflow limitation with preserved PC maintain a sedentary lifestyle, with different risk factors for sedentarism between both groups.

Abdominal obesity in COPD is associated with specific metabolic and functional phenotypes

BackgroundAbdominal obesity (AO) is linked to reduced health status and mortality. While it is known that AO is prevalent in chronic obstructive pulmonary disease (AO-COPD), the specific metabolic and functional consequences associated with AO-COPD remain understudied.MethodsWe studied 199 older adults with COPD and 168 control subjects with and without AO and assessed visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry. VAT > 70th percentile of the control group qualified a subject as AO in a sex specific manner. We measured plasma concentrations and whole body production (WBP) rates of multiple amino acids to assess the metabolic profile. We assessed medical history, body composition by Dual-Energy X-ray Absorptiometry, muscle strength, and cognitive function. We performed statistics by analysis of covariance (p) and FDR (q) for multiple comparisons.ResultsAO-COPD subjects had 27% more VAT (q < 0.01) than AO-Control subjects despite correction for BMI. Branched-chain amino acid concentrations and WBP rates were generally elevated in AO-COPD but whole body clearance rate was only elevated in COPD. Metabolic syndrome comorbidities (p < 0.01) and systemic inflammation (P < 0.05) were most prevalent in the AO-COPD group. Muscle strength was reduced in COPD subjects (p < 0.001), but partially preserved when combined with AO. Cognitive dysfunction and mood disturbances were present in COPD subjects (p < 0.001) with worst performers in AO-COPD (q < 0.05).ConclusionThe presence of AO is associated with specific metabolic and functional phenotypes in COPD.Clinical trial registry Trial registration ClinicalTrials.gov. In the present paper, we report an analysis of the baseline measurements of COPD subjects and healthy controls from the study numbers: NCT01787682, NCT01787682, NCT02157844, NCT02082418, NCT02065141, NCT02770092, NCT02908425, NCT03159390, NCT02780219, NCT03327181, NCT03796455, NCT04928872, NCT04461236, NCT01173354, NCT01154400.

Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD.

Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD versus controls (log2 fold change (log2FC) -2.0, -2.2, -1.5, -0.5, -0.7 and -0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= -0.56, r= -0.58, r= -0.45, r= -0.36, r= -0.44, r= -0.37, r= -0.40 and r= -0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= -0.55, r= -0.61, r= -0.48, r= -0.51, r= -0.41, r= -0.31 and r= -0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPD versus controls (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPD versus healthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85). Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.

Outdoor air pollution impacts chronic obstructive pulmonary disease deaths in South Asia and China: a systematic review and meta-analysis

Background: Chronic obstructive lung disease is among leading causes of death globally. Exposure to outdoor pollution is an important cause for increased mortality and morbidity. Objective: To present a systemic synthesis evidence regarding impact of outdoor pollution on COPD mortality in south asia and china. Methods: A systematic search on studies with statistical power has been conducted from 1990 - June 30th 2021, in English electronic databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from MEDLINE and PUBMED databases with terms: Chronic Obstructive Pulmonary disease OR COPD OR Chronic Bronchitis OR Emphysema OR COPD Deaths OR Chronic Obstructive Lung Disease OR Airflow Obstruction OR Chronic Airflow Obstruction OR Airflow Obstruction, Chronic OR Bronchitis, Chronic AND Mortality OR Death OR Deceased AND Outdoor pollution, ambient pollution was conducted. Results: Out of 1899 papers screened only 16 found eligible to be included in the study. Subjects with COPD exposed to higher levels of outdoor air pollution had a 49 % higher risk of death as compared to COPD subjects exposed to lower levels of outdoor air pollution. When taken individual pollutants into consideration, common air pollutants like PM10 had an OR of 1.06 at CI 95%, where as SO2 had OR of 0.66 at 95% CI , and NO2 with 1.01 OR at 95% CI. These values suggest that there is an effect of outdoor pollution on COPD but not to a significant level. Conclusion: Despite heterogeneity across selected studies, exposure to outdoor pollutants found to have risk of COPD mortality. Though it appears to have risk, COPD mortality was not significantly associated with outdoor pollutants. Controlling air pollution can substantially decrease the risk of COPD in South Asia and China. Further research including more prospective and longitudinal studies are urgently needed in COPD sub-groups.

Effect of barometric pressure on single-breath carbon monoxide diffusing capacity

BackgroundSingle-breath diffusing capacity for carbon monoxide (DLCO) quantifies gas transfer in the lungs. DLCO measurement is affected by barometric pressure (Pb) and alveolar partial pressure of oxygen (PAO2). The current equations for adjusting DLCO for Pb and PAO2 may not be accurate given advances in test performance and technology. We quantify changes in DLCO with alterations in Pb in normal and COPD subjects, determine the accuracy of the current Pb and PAO2 adjustment equations and develop updated adjustment equations. MethodsWe measured DLCO in 13 normal and 10 COPD subjects at 1330 m altitude and in a hypobaric/hyperbaric chamber at altitudes of sea-level and 2500 m; six normal subjects were tested at 3600 m. We determined if there were significant differences in DLCO between altitudes. We developed an equation for adjusting DLCO for changes in Pb from sea-level. We compared this equation with the existing Pb adjustment equation in normal and COPD subjects. We determined the accuracy of the current PAO2 adjustment equation and developed a new PAO2 adjustment equation. ResultsDLCO significantly increased with decreasing Pb. We developed a Pb adjustment equation that adjusts DLCO measured at altitudes between 1330 m and 3600 m to sea-level values. This Pb adjustment equation yields DLCO results that are not significantly different than the currently recommended equation. We developed a more accurate PAO2 adjustment equation. ConclusionDLCO measurement is significantly affected by altitude. We developed equations that accurately adjust DLCO for changes in Pb and PAO2 in normal and COPD subjects.

Efficacy of Nasal High-Flow Oxygen Therapy in Chronic Obstructive Pulmonary Disease Patients in Long-Term Oxygen and Nocturnal Non-Invasive Ventilation during Exercise Training.

High-flow oxygen therapy (HFOT) improves gas exchange and dead space washout and reduces the level of work required for breathing. This study aimed to evaluate pulmonary rehabilitation (PR) combined with HFOT in COPD patients treated with nocturnal non-invasive ventilation (NIV) and long-term oxygen therapy (LTOT). In particular, we sought to discover whether the addition of HFOT during exercise training could improve patients’ performance, mainly with regard to their Six-Minute Walking Test (6MWT) outcomes, and reduce the exacerbation rates, periods of rehospitalization or need to resort to unscheduled visits. Thirty-one COPD subjects (13 female) who used nocturnal NIV were included in a randomized controlled trial and allocated to one of two groups: the experimental group (EG), with 15 subjects, subjected to PR with HFOT; and the control group (CG), with 16 subjects, subjected to PR without HFOT. The primary outcome of the study was the observation of changes in the 6MWT. The secondary outcome of the study was related to the rate of exacerbation and hospitalization. Data were collected at baseline and after one, two and three cycles of cycle-ergometer exercise training performed in 20 supervised sessions of 40 min thrice per week, with a washout period of 3 months between each rehabilitation cycle. Statistical significance was not found for the 6MWT distance (W = 0.974; p = 0.672) at the last follow-up, but statistical significance was found for the Borg scale in regard to dyspnea (W = 2.50; p < 0.001) and fatigue (W = 2.00; p < 0.001). HFOT may offer a positive option for dyspnea-affected COPD patients in the context of LTOT and nocturnal NIV.

Pulmonary Arterial Pressure Changes Under Dobutamine Stress Echocardiography in Non-Anemic Iron Deficient COPD Subjects.

PurposeNon-anemic iron deficiency (NAID) is common in COPD, and could induce functional/structural changes in the pulmonary vascular bed. Thus, we aimed to study, during resting and ambient oxygen conditions, the systolic pulmonary arterial pressure (sPAP) changes during dobutamine stress echocardiography (DSE) for NAID+ compared to NAID- subjects with COPD.Patients and MethodsWe analyzed 24 patients with COPD and evaluated their clinical parameters, including lung function and serum iron profile, followed by the changes in the sPAP under DSE.ResultsTen subjects with NAID+ were compared with fourteen NAID- subjects for sPAP measurement. At baseline, only left atrial volume was significantly different between groups (30±4 vs 23±5 mL*m2), respectively (p-value=0.002). For the right side, tricuspid annular plane systolic excursion (TAPSE) was similar between-groups (22±2 vs 20±4, p-value >0.05), at baseline. The sPAP (mmHg) changes were also not significantly different between groups (pre 32±14 vs peak 48±14 for NAID+ and pre 29±7 vs peak 43±10 for NAID-, Group p-value=0.400, Time p-value <0.0001, and Interaction p-value=0.606).ConclusionCOPD subjects with NAID do not show increased sPAP responses during DSE, compared with iron-replete subjects.

Embedded system design for classification of COPD and pneumonia patients by lung sound analysis.

Chronic obstructive pulmonary disease (COPD) and pneumonia are lethal pulmonary illnesses with equivocal nature of abnormal pulmonic acoustics. Using lung sound signals, the classification of pulmonary abnormalities is a difficult task. A standalone system was conceived for screening COPD and Pneumonia patients through signal processing and machine learning methodologies. The proposed system will assist practitioners and pulmonologists in the accurate classification of disease. In this research work, ICBHI's and self-collected lung sound (LS) databases are used to investigate COPD and pneumonia patient. In this scheme, empirical mode decomposition (EMD), discrete wavelet transform (DWT), and analysis of variance (ANOVA) techniques are employed for segmentation, noise elimination, and feature selection, respectively. To overcome the inherent limitation of ICBHI's LS database, the adaptive synthetic (ADASYN) sampling technique is used to eradicate class imbalance. Lung sound features are used to train fine Gaussian support vector machine (FG-SVM) for classification of COPD, pneumonia, and heathy healthy subjects. This machine learning scheme is implemented on low cost and portable Raspberry pi 3 model B+ (Cortex-A53 (ARMv8) 64-bit SoC @ 1.4GHz through hardware-supported language. Resultant hardware is capable of screening COPD and pneumonia patients accurately and assist health professionals.

The Relationship of Partial Pressure of Carbon Dioxide (PaCO2) with Disease Severity Indicators Such as BODE and GOLD in Hospitalized COPD Patients.

Purpose This study aimed to investigate the relationship of partial pressure of carbon dioxide (PaCO2) with BODE and GOLD in stable COPD subjects and to explore the predictive value of PaCO2 for severe COPD (BODE index score ≥5 or GOLD index score ≥3). Patients and Methods. In total, 80 participants with COPD and free from other conditions affecting PaCO2 were recruited. Arterial blood gases, BODE, GOLD, SGRQ, lung function, and other data were collected. The BODE index was calculated, and patients were divided into two groups according to the BODE index and PaCO2 median, respectively. We used Pearson's correlation test and the receiver operating characteristic curves to evaluate the utility of PaCO2. Besides, the univariate and multivariate logistic regression analyses were conducted to verify whether PaCO2 was an independent factor associated with BODE grades. Results COPD subjects with BODE ≥5 and GOLD ≥3 had significantly higher levels of PaCO2 (p = 0.004, p = 0.001, respectively). In the high PaCO2 group, patients underwent poorer outcomes than the low PaCO2 group. PaCO2 was negatively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = −0.612, p < 0.001). The performance of PaCO2 levels in predicting BODE ≥5 and GOLD ≥3 was 0.748 and 0.755, respectively. The logistic regression analyses proved that PaCO2 was associated with BODE ≥5 in COPD patients (odds ratio = 1.160, 95% CI: 1.025–1.313, p = 0.019). Conclusions A higher level of PaCO2 was associated with a higher index for BODE or GOLD in COPD and had the predictive value for severe COPD.

Circulating Complement C1q as a Novel Biomarker is Associated with the Occurrence and Development of COPD.

PurposeIncreasing evidence has shown that the immune response interacts with the chronic inflammatory response and gives rise to the occurrence and development of COPD. Complement component 1q (C1q), as a subcomponent of the C1 complex, could be involved in innate and adaptive immunity. Our study aimed to investigate the relationship between C1q and the clinical characteristics of COPD subjects.Patients and MethodsSerum C1q levels were measured in 203 COPD subjects and 191 non-COPD controls. Correlations between C1q and the characteristics of COPD were analyzed using Spearman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. All 203 COPD subjects were followed up for 1 year for future acute exacerbations.ResultsThere were significant reductions in serum C1q levels in COPD subjects compared to non-COPD controls. Moreover, serum C1q levels were obviously positively correlated with the FEV1/FVC ratio and predicted FEV1% but had a weakly negative correlation with the %LAA-950 and the percentage of neutrophils in peripheral blood. Using a cutoff value of 137.150 mg/l as the boundary in ROC analysis, the sensitivity and specificity were 65.9% and 76.0%, respectively. The 1-year follow-up results showed that C1q levels less than 137.150 mg/l were negatively related to the time to the next severe exacerbation and the time to death.ConclusionCirculating C1q levels may be a novel biomarker not only related to the pulmonary function of COPD but also having great potential to predict the risk of COPD deterioration in the future. However, further prospective trials are needed to clarify the influences of C1q on the pathogenesis of COPD.

Integrated analysis reveals lung fibrinogen gamma chain as a biomarker for chronic obstructive pulmonary disease.

BackgroundChronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable airway disease. This study aimed to identify key genes related to COPD pathogenesis through an integrated transcriptomic and proteomic analysis of lung tissue from COPD subjects undergoing lung resection for malignancy.MethodsWe performed RNA sequencing, gene expression analysis, and gene set enrichment analysis (GSEA) on lung tissue in 13 non-smokers, 16 smokers, and 16 COPD patients. Key genes were verified by RT-qPCR, immunohistochemistry and Western blot in human lung tissues, cigarette smoke extract (CSE)-exposed human bronchial epithelial cell line (BEAS-2B cells), and a cigarette smoke (CS)-induced mouse model.ResultsThere were 521 differentially expressed genes between non-smokers and smokers, 57 genes between smokers and COPD patients, and 860 genes between non-smokers and COPD patients. Fibrinogen gamma chain (FGG) was highly expressed in COPD patients versus smokers and in COPD patients versus healthy controls. GSEA of the COPD patients with the highest FGG expression were enriched in the B cell receptor signaling pathway, pantothenate and CoA biosynthesis, Fc epsilon RI signaling pathway, and the Toll-like receptor (TLR) signaling pathway. RT-PCR analysis confirmed enhanced FGG mRNA levels in the lungs of both smokers and COPD patients compared to non-smokers and in CSE-exposed cells compared to control cells. FGG protein levels were elevated in the lungs of COPD patients and smokers compared to non-smokers and in the lungs of CS-exposed mice compared to control mice.ConclusionsFGG may serve as a biomarker for COPD and may play an important role in its pathogenesis.

Correlation between Measurement of Lung Diffusion Capacity Using Single Breath Methods (DLCO-SB) and COPD Group in Persahabatan Hospital Jakarta

Background: This was a preliminary study to measure DLCO-SB on COPD patients in Persahabatan Hospital to understand the prevalence of DLCO reduction among COPD patients.Methods: This was a cross sectional study of COPD patients who attended COPD-Asthma clinic in Persahabatan Hospital Jakarta. Spirometry and DLCO-SB were performed consecutively during May–July 2015. Comorbidities were also recorded.Results: Spirometry and DLCO-SB measurements were conducted on 65 COPD subjects of which 10.8% subjects were in COPD Group A, 29.2% Group B, 32.3% Group C and 27.7% Group D. The mean age was 64.15; mean FEV1% was 46.05%, mean DLCO measured was 19.42 ml/min/mmHg and the mean DLCO% was 72.00%. The proportion of DLCO decline among COPD patients was 56.92%. There were significant correlations between COPD group, GOLD COPD grade, FEV1, BMI and comorbidities with the DLCO value results. There were no significant correlation between DLCO value with sex, age, smoking history, Brinkmann Index, obstructive-restrictive criteria, comorbidities and length of COPD period. Conclusion: The proportion of DLCO decline among COPD patients was 56.92%. There were significant correlations between COPD group, GOLD COPD grade, FEV1, BMI and previous TB history with the results of DLCO.

Relation between Chronic Obstructive Pulmonary Disease and Peripheral Arterial Disease among Construction Workers

Introduction: PAD was asymptomatic in a large proportion of COPD patients and was associated with more severe lung disease than in COPD subjects without PAD. Materials and Methods: This was a Cross-sectional study conducted at Department of Physiology, Santosh Medical College diagnosed with COPD using Spirometry was recruited for the study with a Sample size of 130 patients. Results: The characteristics of the population for follow-up (n=130) are presented in table 1. The mean Mean±SD was 51.73±6.1 years. The prevalence of never smokers was 21.5%, former smokers were 51.5% and current smokers were 26.9%. In total, 41 out of 130 individuals (31.5%) had PAD based on an ABI of less than 0.6. A statistically significant association was found between COPD and newly diagnosed PAD during follow-up. The association between COPD and incident PAD was stronger (adjusted OR 1.91, 95% CI 1.14–3.21). Stratified analysis by smoking status revealed that the overall association between COPD and newly developed PAD was driven by the ever smoker group. Conclusion: Subjects with COPD have a higher risk of developing PAD. People with both COPD and PAD have a substantially increased risk of death. Consequently, early detection of PAD and preventive actions in people with COPD should receive more attention in clinical respiratory care. Keywords: Peripheral Arterial Disease, Chronic Obstructive Pulmonary Disease, Ankle-brachial index.

Eosinophilia and fractional exhaled nitric oxide levels in chronic obstructive lung disease

IntroductionCOPD is a heterogeneous disorder with varied phenotypes. We aimed to determine the prevalence of asthma history, peripheral eosinophilia and elevated FeNO levels along with the diagnostic utility of peripheral...

Risk Factors for Development and Severity of COVID-19 in COPD Patients.

The impact that COVID-19 could have on patients with COPD is a real concern. In this study we evaluated, in a cohort of longitudinally followed COPD subjects, the incidence of COVID-19, seeking for possible risk factors and prognostic factors predicting the clinical outcome. In our cohort of 370 patients (followed for 5.3 ± 2.7 years), 22 developed COVID-19 (COPD/COVID-19+) between February/November 2020 (5.9%). Cardio-metabolic conditions (hypertension, dyslipidemia, obesity, diabetes) but not respiratory abnormalities (FEV1, DLCO, emphysema and exacerbation history), were risk factors for development of COVID-19 in COPD patients. Out of the 22 COPD/COVID-19+ patients, 10 needed intensive care. Low DLCO and emphysema, but also metabolic comorbidities, were related to the need for intensive care.

Relationship between echocardiographic tricuspid annular plane systolic excursion and mortality in COVID-19 patients: A Meta-analysis.

BackgroundThe evaluation of the tricuspid annular plane systolic excursion (TAPSE) is recommended to assess the right ventricular (RV) systolic function. We performed an updated meta‐analysis of the association between TAPSE and short‐term mortality in COVID‐19 patients.MethodsMEDLINE and Scopus databases were searched to locate all the articles published up to May 1, 2021, reporting data on TAPSE among COVID‐19 survivors and non‐survivors. The difference of TAPSE between the two groups was expressed as mean difference (MD) with the corresponding 95% confidence interval (CI) using the Mantel‐Haenszel random effects model. Both Q value and I2 statistics were used to assess heterogeneity across studies. Sensitivity analysis, meta‐regression, and evaluation of bias were performed.ResultsTwelve studies, enrolling 1272 COVID‐19 patients (778 males, mean age 69.3 years), met the inclusion criteria and were included in the final analysis. Non‐survivors had a lower TAPSE compared to survivors (MD = −3.089 mm, 95% CI = −4.087 to −2.091, p < 0.0001, I2 = 79.0%). Both the visual inspection of the funnel plot and the Egger's tests (t = 1.195, p = 0.259) revealed no evidence of publication bias. Sensitivity analysis confirmed yielded results. Meta‐regression analysis evidenced that the difference in TAPSE between the two groups was only influenced by pre‐existing chronic obstructive pulmonary disease (COPD, p = 0.02).ConclusionCOVID‐19 non‐survivors have a lower TAPSE when compared to survivors, especially in COPD subjects. Current data suggest that the TAPSE assessment may provide useful information regarding the short‐term prognosis of COVID‐19 patients during the infection.

Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive ‘gas-distribution’ type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on ‘GOLD’ classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ({R}^{2}=0.42). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Dysregulation of COVID-19 related gene expression in the COPD lung

BackgroundChronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.MethodsWe quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.ResultsACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of –0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES.Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).ConclusionThis study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.

Eicosanoids and Eosinophilic Inflammation of Airways in Stable COPD.

PurposeLipid mediators, particularly eicosanoids, are associated with airway inflammation, especially with the eosinophilic influx. This study aimed to measure lipid mediators and cells in induced sputum, that could possibly reflect the inflammatory process in the bronchial tree of COPD subjects.Patients and MethodsEighty patients diagnosed with COPD and 37 healthy controls participated in the study. Induced sputum samples were ascertained for differential cell count and induced sputum supernatant concentrations of selected eicosanoids by the means of gas chromatography/mass spectrometry and high-performance liquid chromatography/tandem mass spectrometry.ResultsIncreased sputum eosinophilia was associated with higher concentrations of selected proinflammatory eicosanoids. In COPD subjects prostaglandin D2 and 11-dehydro-thromboxane B2 correlated negatively with airway obstruction measured by FEV1 and FEV1/FVC values. COPD subjects with disease exacerbations during past 12 months had significantly higher concentrations of prostaglandin D2, 12-oxo-eicosatetraenoic acid and 5-oxo-eicosatetraenoic acid.ConclusionStable COPD is often associated with eosinophil influx in the lower airways and elevated concentrations of eicosanoids that is reflected by some disease characteristics.

Predictors of post discharge home oxygen therapy and Bilevel positive airway pressure therapy in stable hypercapnoea

Background: Hospital admission for acute exacerbation of COPD (AE-COPD) accounts for 70% of total costs of COPD treatment, and treatment cost is related to the duration of hospital stay. If post-discharge supportive care is required an extra cost will be added. The objectives of this study are to determine the predictive factors of post-discharge supportive care (Domiciliary oxygen, Bi-level positive airway pressure) in known COPD patients who got admitted with acute exacerbation. This is likely to help the treating physician to prime the family and plan an early discharge of the patient with supportive care instead of waiting for the patient to be off oxygen or BiPAP support. Methods: This is a retrospective study done at the pulmonology department of tertiary care hospital from January 2018-Jan 2019. Data sources were electronic medical records and the hospital discharge minimum data set. This study included 89 known COPD subjects who were not on prior supportive care (Long term oxygen therapy or home BIPAP) and were admitted for the management of acute exacerbation. Clinical parameters like symptoms at onset and the duration of symptoms (cough, fever, breathlessness, sputum production),comorbidities, initial blood investigations(complete blood counts, serum creatinine, arterial blood gas analysis, sputum culture reports)radiological findings, treatment details, pulmonary function test were evaluated with appropriate statistical tests. Parameters associated with post-discharge supportive care were evaluated. Results: A total of 89 patients were included in the study. Four patients were excluded because of the death. Presence of type II respiratory failure related findings like respiratory acidosis PH (P=0.02), elevated bicarbonate HCO3 (P=0.01), elevated carbon dioxide level PCO2 (p=0.007) in the ABG, and the requirement of non-invasive ventilation (P=0.00), Chest X-ray finding of hyperinflation (P=0.03) and treatment-related variables like prolonged duration of hospitalization (P&lt;0.01) were associated with post-discharge supportive care (Home oxygen therapy and BiPAP support) in univariate analysis. In the multivariate analysis hyperinflation (Odds ratio OR-4.73; 95% confidence interval; 1.37-16.33), noninvasive ventilation (OR-4.9; 95% CI: 1.29-18.47), and prolonged duration of hospitalization (OR-1.32; 95% CI: 1.05-1.66) remained significantly associated with post-discharge home oxygen therapy and home BiPAP therapy. Conclusion: This study results conclude that severe disease as marked by hyperinflation on Chest X-ray, presence of type II respiratory failure related changes in the ABG and requirement of non-invasive ventilation, and longer duration of hospitalization predicts the post-discharge supportive care. These findings can help the clinician to prepare for earlier discharge with post-discharge supportive care.