Airway tree caliber heterogeneity and airflow obstruction

Abstract Background Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV1), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality. Methods MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle–Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality—Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE. Results Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV1) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV1/FVC ratio) (4 studies). Conclusion Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes. PROSPERO registration: CRD42019145747.

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Regulation of Eosinophilia in Asthma—New Therapeutic Approaches for Asthma Treatment

Cells ◽

10.3390/cells10040817 ◽

2021 ◽

Vol 10 (4) ◽

pp. 817

Author(s):

Ruth P. Cusack ◽

Christiane E. Whetstone ◽

Yanqing Xie ◽

Maral Ranjbar ◽

Gail M. Gauvreau

Keyword(s):

Drug Targets ◽

Airflow Obstruction ◽

Chronic Inflammatory Disease ◽

Therapeutic Approaches ◽

Eosinophilic Asthma ◽

Airway Eosinophilia ◽

Gm Csf ◽

New Therapeutic Approaches ◽

Cellular Apoptosis ◽

Reversible Airflow Obstruction

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

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Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study

BMJ Open ◽

10.1136/bmjopen-2020-038360 ◽

2020 ◽

Vol 10 (12) ◽

pp. e038360

Author(s):

Jilles M Fermont ◽

Marie Fisk ◽

Charlotte E Bolton ◽

William MacNee ◽

John R Cockcroft ◽

...

Keyword(s):

Risk Factors ◽

Physical Performance ◽

Risk Prediction ◽

Survival Data ◽

Airflow Obstruction ◽

Secondary Outcome ◽

Chronic Obstructive ◽

Bode Index ◽

Gold Stage ◽

Improved Model

ObjectivesAlthough cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.DesignData from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II–IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.SettingFive UK centres interested in COPD.ParticipantsPopulation-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.InterventionsBaseline measurements included aortic pulse wave velocity (aPWV), carotid intima–media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.Primary and secondary outcome measuresNew occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.ResultsOut of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).ConclusionPoor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.Trial registration numberID 11101.

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Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume

Respiration ◽

10.1159/000513954 ◽

2021 ◽

pp. 1-7

Author(s):

Roberta Pisi ◽

Marina Aiello ◽

Luigino Calzetta ◽

Annalisa Frizzelli ◽

Veronica Alfieri ◽

...

Keyword(s):

Total Lung Capacity ◽

Airflow Obstruction ◽

Diffusing Capacity ◽

Body Plethysmography ◽

Alveolar Volume ◽

Asthmatic Patients ◽

Lung Capacity ◽

Copd Patients ◽

Ventilation Heterogeneity ◽

Patient Groups

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

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Genetic evidence for a causative effect of airflow obstruction on left ventricular filling: a Mendelian randomisation study

Respiratory Research ◽

10.1186/s12931-021-01795-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lars Harbaum ◽

Jan K. Hennigs ◽

Marcel Simon ◽

Tim Oqueka ◽

Henrik Watz ◽

...

Keyword(s):

General Population ◽

Genetic Variants ◽

Airflow Obstruction ◽

Left Ventricular ◽

Sensitivity Analyses ◽

Weighted Regression ◽

Mendelian Randomisation ◽

Effect Estimate ◽

Genome Wide Association Studies ◽

Inverse Variance

Abstract Background Observational studies on the general population have suggested that airflow obstruction associates with left ventricular (LV) filling. To limit the influence of environmental risk factors/exposures, we used a Mendelian randomisation (MR) approach based on common genetic variations and tested whether a causative relation between airflow obstruction and LV filling can be detected. Methods We used summary statistics from large genome-wide association studies (GWAS) on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) measured by spirometry and the LV end-diastolic volume (LVEDV) as assessed by cardiac magnetic resonance imaging. The primary MR was based on an inverse variance weighted regression. Various complementary MR methods and subsets of the instrument variables were used to assess the plausibility of the findings. Results We obtained consistent evidence in our primary MR analysis and subsequent sensitivity analyses that reducing airflow obstruction leads to increased inflow to the LV (odds ratio [OR] from inverse variance weighted regression 1.05, 95% confidence interval [CI] 1.01–1.09, P = 0.0172). Sensitivity analyses indicated a certain extent of negative horizontal pleiotropy and the estimate from biased-corrected MR-Egger was adjusted upward (OR 1.2, 95% CI 1.09–1.31, P < 0.001). Prioritisation of single genetic variants revealed rs995758, rs2070600 and rs7733410 as major contributors to the MR result. Conclusion Our findings indicate a causal relationship between airflow obstruction and LV filling in the general population providing genetic context to observational associations. The results suggest that targeting (even subclinical) airflow obstruction can lead to direct cardiac improvements, demonstrated by an increase in LVEDV. Functional annotation of single genetic variants contributing most to the causal effect estimate could help to prioritise biological underpinnings.

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