Maximal Voluntary Ventilation Should Not Be Estimated From the Forced Expiratory Volume in the First Second in Healthy People and COPD Patients

Abstract Background We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels. Methods Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels. Results In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups. Conclusion In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases. Trial registration: Clinicaltrials.gov NCT00683722.

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Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10020269 ◽

2021 ◽

Vol 10 (2) ◽

pp. 269

Author(s):

Elisabetta Zinellu ◽

Alessandro G. Fois ◽

Elisabetta Sotgiu ◽

Sabrina Mellino ◽

Arduino A. Mangoni ◽

...

Keyword(s):

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Serum Albumin ◽

Pulmonary Disease ◽

Meta Analysis ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Standard Mean Difference ◽

Copd Patients

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.

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Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD

npj Primary Care Respiratory Medicine ◽

10.1038/s41533-021-00241-z ◽

2021 ◽

Vol 31 (1) ◽

Author(s):

Sandeep Bansal ◽

Martin Anderson ◽

Antonio Anzueto ◽

Nicola Brown ◽

Chris Compton ◽

...

Keyword(s):

Health Status ◽

Triple Therapy ◽

Treatment Guidelines ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Fluticasone Furoate ◽

Double Blind ◽

Once Daily ◽

Copd Patients ◽

Severe Copd

AbstractChronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.

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Angiogenesis-related factors in skeletal muscles of COPD patients: roles of angiopoietin-2

Journal of Applied Physiology ◽

10.1152/japplphysiol.00954.2012 ◽

2013 ◽

Vol 114 (9) ◽

pp. 1309-1318 ◽

Cited By ~ 6

Author(s):

Mahroo Mofarrahi ◽

Ioanna Sigala ◽

Theodoros Vassilokopoulos ◽

Sharon Harel ◽

Yeting Guo ◽

...

Keyword(s):

Vastus Lateralis ◽

Interferon Γ ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Mrna Levels ◽

Gene Expressions ◽

Related Factors ◽

Control Subjects ◽

Copd Patients ◽

Angiopoietin 2

The role of angiogenesis factors in skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is unknown. The first objective of this study was to assess various pro- and antiangiogenic factor and receptor expressions in the vastus lateralis muscles of control subjects and COPD patients. Preliminary inquiries revealed that angiopoietin-2 (ANGPT2) is overexpressed in limb muscles of COPD patients. ANGPT2 promotes skeletal satellite cell survival and differentiation. Factors that are involved in regulating muscle ANGPT2 production are unknown. The second objective of this study was to evaluate how oxidants and proinflammatory cytokines influence muscle-derived ANGPT2 expression. Angiogenic gene expressions in human vastus lateralis biopsies were quantified with low-density real-time PCR arrays. ANGPT2 mRNA expressions in cultured skeletal myoblasts were quantified in response to proinflammatory cytokine and H2O2 exposure. Ten proangiogenesis genes, including ANGPT2, were significantly upregulated in the vastus lateralis muscles of COPD patients. ANGPT2 mRNA levels correlated negatively with forced expiratory volume in 1 s and positively with muscle wasting. Immunoblotting confirmed that ANGPT2 protein levels were significantly greater in muscles of COPD patients compared with control subjects. ANGPT2 expression was induced by interferon-γ and -β and by hydrogen peroxide, but not by tumor necrosis factor. We conclude that upregulation of ANGPT2 expression in vastus lateralis muscles of COPD patients is likely due to oxidative stress and represents a positive adaptive response aimed at facilitating myogenesis and angiogenesis.

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Randomised controlled trial to investigate the use of high-frequency airway oscillations as training to improve dyspnoea (TIDe) in COPD

Thorax ◽

10.1136/thoraxjnl-2021-217072 ◽

2021 ◽

pp. thoraxjnl-2021-217072

Author(s):

Enya Daynes ◽

Neil Greening ◽

Sally J Singh

Keyword(s):

Muscle Weakness ◽

High Frequency ◽

Controlled Trial ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Registration Number ◽

Randomised Controlled ◽

Double Blinded

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by symptomatic dyspnoea and reduced exercise tolerance, in part as a result muscle weakness, for which inspiratory muscle training (IMT) may be useful. Excess mucus hypersecretion commonly coexists in COPD and may lead to reduce ventilation, further impacting on breathlessness. Devices for sputum clearance may be employed to aid mucus expectoration. This trial aimed to explore the effectiveness of a combined IMT and high-frequency airway oscillating (HFAO) device in the management of dyspnoea.MethodsThis was a double-blinded, randomised sham-controlled trial which recruited symptomatic patients with COPD. Patients were randomised to either a HFAO device (Aerosure) or sham device for 8 weeks, three times a day. The primary outcome was the Chronic Respiratory Questionnaire dyspnoea (CRQ-D) domain. Pre-specified subgroup analyses were performed including those with respiratory muscle weakness, excessive sputum and frequent exacerbators.Results104 participants (68% men, mean (SD) age 69.75 years (7.41), forced expiratory volume in 1 s per cent predicted 48.22% (18.75)) were recruited to this study with 96 participants completing. No difference in CRQ-D was seen between groups (0·28, 95% CI −0.19 to 0.75, p=0.24), though meaningful improvements were seen over time in both groups (mean (SD) HFAO 0.45 (0.78), p<0.01; sham 0.73 (1.09), p<0.01). Maximal inspiratory pressure significantly improved in the HFAO group over sham (5.26, 95% CI 0.34 to 10.19, p=0.05). Similar patterns were seen in the subgroup analysis.ConclusionThere were no statistical differences between the HFAO and the sham group in improving dyspnoea measured by the CRQ-D.Trial registration numberISRCTN45695543.

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Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Metabolites ◽

10.3390/metabo9080157 ◽

2019 ◽

Vol 9 (8) ◽

pp. 157 ◽

Cited By ~ 2

Author(s):

Eitan Halper-Stromberg ◽

Lucas Gillenwater ◽

Charmion Cruickshank-Quinn ◽

Wanda Kay O’Neal ◽

Nichole Reisdorph ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Cell Metabolism ◽

Lavage Fluid ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

False Discovery ◽

Copd Patients ◽

Clinical Covariates

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography–mass spectrometry (LC–MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10−4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

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Maintenance Negative Pressure Ventilation Improves Survival in COPD Patients with Exercise Desaturation

Journal of Clinical Medicine ◽

10.3390/jcm8040562 ◽

2019 ◽

Vol 8 (4) ◽

pp. 562

Author(s):

Hung-Yu Huang ◽

Chun-Yu Lo ◽

Lan-Yan Yang ◽

Fu-Tsai Chung ◽

Te-Fang Sheng ◽

...

Keyword(s):

Lung Function ◽

Negative Pressure ◽

Significant Risk ◽

Forced Expiratory Volume ◽

Walking Distance ◽

Chronic Obstructive ◽

Negative Pressure Ventilation ◽

Risk Of Death ◽

Copd Patients

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.

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Cost-Effectiveness of Combination Therapy for Chronic Obstructive Pulmonary Disease

Canadian Respiratory Journal ◽

10.1155/2008/257618 ◽

2008 ◽

Vol 15 (8) ◽

pp. 437-443 ◽

Cited By ~ 15

Author(s):

Anderson Chuck ◽

Philip Jacobs ◽

Irvin Mayers ◽

Darcy Marciniuk

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Cost Effectiveness ◽

Combination Therapy ◽

Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Life Years

BACKGROUND: There is evidence that combination therapy (CT) in the form of long-acting beta2-agonists (LABAs) and inhaled corticosteroids can improve lung function for patients with chronic obstructive pulmonary disease (COPD).OBJECTIVE: To determine the cost-effectiveness of using CT in none, all or a selected group of COPD patients.METHODS: A Markov model was designed to compare four treatment strategies: no use of CT regardless of COPD severity (patients receive LABA only); use of CT in patients with stage 3 disease only (forced expiratory volume in 1 s [FEV1] less than 35% of predicted); use of CT in patients with stages 2 and 3 disease only (FEV1less than 50% of predicted); and use of CT in all patients regardless of severity of COPD. Estimates of mortality, exacerbation and disease progression rates, quality-adjusted life years (QALYs) and costs were derived from the literature. Three-year and lifetime time horizons were used. The analysis was conducted from a health systems perspective.RESULTS: CT was associated with a cost of $39,000 per QALY if given to patients with stage 3 disease, $47,500 per QALY if given to patients with stages 2 and 3 disease, and $450,333 per QALY if given to all COPD patients. Results were robust to various assumptions tested in a Monte Carlo simulation.CONCLUSION: Providing CT for COPD patients in stage 2 or 3 disease is cost-effective. The message to family physicians and specialists is that as FEV1worsens and reaches 50% of predicted values, CT is recommended.

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Serum Vitamin A and Inflammatory Markers in Individuals with and without Chronic Obstructive Pulmonary Disease

Mediators of Inflammation ◽

10.1155/2015/862086 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

L. M. O. Caram ◽

R. A. F. Amaral ◽

R. Ferrari ◽

S. E. Tanni ◽

C. R. Correa ◽

...

Keyword(s):

Vitamin A ◽

Inflammatory Markers ◽

Smoking Status ◽

Serum Vitamin ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Serum Retinol ◽

Lower Serum ◽

Necrosis Factor Alpha ◽

Copd Patients

Background.Vitamin A is essential for the preservation and integrity of the lung epithelium and exerts anti-inflammatory effects.Objective.Evaluating vitamin A in the serum and sputum and testing its correlation with inflammatory markers in individuals with or without COPD.Methods.We evaluated dietary intake, serum and sputum vitamin A, tumor necrosis factor alpha, interleukin- (IL-) 6, IL-8, and C-reactive protein in 50 COPD patients (age = 64.0 ± 8.8 y; FEV1(forced expiratory volume in the first second) (%) = 49.8 ± 16.8) and 50 controls (age = 48.5 ± 7.4 y; FEV1(%) = 110.0 ± 15.7).Results.COPD exhibited lower serum vitamin A (1.8 (1.2–2.1) versus 2.1 (1.8–2.4)μmol/L,P<0.001) and lower vitamin A intake (636.9 (339.6–1349.6) versus 918.0 (592.1–1654.6) RAE,P=0.05) when compared with controls. Sputum concentration of vitamin A was not different between groups. Sputum vitamin A and neutrophils were negatively correlated (R2=-0.26;P=0.03). Smoking (0.197,P=0.042) exhibited positive association with serum vitamin A. COPD was associated with lower serum concentrations of vitamin A without relationship with the systemic inflammation.Conclusions.Serum concentration of vitamin A is negatively associated with the presence of COPD and positively associated with smoking status. Sputum retinol is quantifiable and is negatively influenced by neutrophils. Although COPD patients exhibited increased inflammation it was not associated with serum retinol.

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Maximal voluntary ventilation should not be estimated from FEV1 in COPD patients and healthy

10.1183/13993003.congress-2019.pa1254 ◽

2019 ◽

Author(s):

Matías Otto ◽

Antonio Sarmento ◽

Palomma Russelly Saldanha Araújo ◽

Catherinne Farías ◽

Rodrigo Torres-Castro ◽

...

Keyword(s):

Copd Patients ◽

Maximal Voluntary Ventilation

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