Bone marrow characterization in COPD: a multi-level network analysis

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-β, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils

Gut epithelial barrier markers in patients with obstructive sleep apnea

Background: obstructive sleep apnea (OSA) is now being recognized as an additional contributing factor to the pathogenesis of obesity-related comorbidities. At the same time, there is now increasing evidence to suggest that intestinal wall permeability plays a role in the development of metabolic syndrome. In the present study, circulating zonulin and fatty acid binding protein (I-FABP) were measured in association with metabolic, hepatic, and inflammatory parameters. Results: compared with controls, plasma I-FABP levels were significantly higher in patients with OSA (571 pg/mL [IQR 290-950] vs 396 pg/mL [IQR 234-559], p = 0.04). Zonulin levels were similar between groups. Significant relationships were observed between zonulin levels and waist circumference (p < 0.05), glucose (p < 0.05), and insulin (p < 0.05). In addition, in the OSA group, zonulin levels correlated negatively with the mean nocturnal oxygenation saturation (p < 0.05) and positively with total cholesterol (p < 0.05), alanine aminotransferase (ALT) (p < 0.005), aminotransferase (AST) (p < 0.01), gamma glutamyltransferase (GGT) (p < 0.005), and high-sensitivity C-reactive protein (hs-CRP) (p < 0.05). Multivariate analysis showed that associations between zonulin and ALT, AST, and hs-CRP were attenuated, but not eliminated, after adjustment for other variables. Conclusions: the results of this study suggest that OSA is a risk factor for intestinal damage, regardless of metabolic profile, and that intestinal permeability might be a possible contributor to nonalcoholic fatty liver disease in patients with OSA

Impact of Blood Eosinophil Variability in Asthma:A Real-Life Population Study

RATIONALE: Blood eosinophil count predicts response to inhaled corticosteroids and specific biologic therapies in selected asthma patients. Despite this important role, fundamental aspects of eosinophil behavior in asthma have not been studied. Objectives To investigate the behavior of blood eosinophils in a population comparing their distribution with the general population and studying their intra-individual variability over time in relation to hospital episodes (emergency department visits and hospitalizations) in clinical practice. METHODS: The distribution and variability of 35,703 eosinophil determinations in 10,059 stable asthma patients were investigated in the Majorca Real-Life Investigation in COPD and Asthma cohort (MAJORICA). Eosinophil distribution in the asthma population was compared with a control sample from the general population of 8,557 individuals. Eosinophil variability and hospital episodes were analyzed using correlations, ROC curves and multiple regression analysis. We defined the Eosinophil Variability Index (EVI) as (Eosmax-Eosmin/Eosmax) x 100%. The findings of the asthma population were re-tested in an external well-characterized asthma cohort. RESULTS: The eosinophil count values and variability were higher in the asthma population than in the general population (p-value<0.001). Variability data showed a better association with hospital episodes than the counting values. An EVI≥50% was more strongly associated with hospital episodes than any of the absolute counting values. These results were validated in the external cohort. CONCLUSION: The eosinophil variability in asthma patients better identifies the risk of any hospital episode than the absolute counting values currently used to target specific treatments

LATE-BREAKING ABSTRACT: Prevalence of comorbidities in patients with asthma-COPD overlap syndrome (ACOS) in primary care

Introduction: Comorbidities are known to be frequent in COPD patients. However, less is known about the prevalence of comorbidities in patients with the asthma-COPD overlap syndrome (ACOS). Aims: To estimate the prevalence of comorbidities in patients with ACOS in comparison with patients with COPD. Methods: Data were extracted from the MAJOrca Real-life Investigation in COPD and Asthma (MAJORICA) database of primary care in Spain. Patients with a physician-confirmed diagnosis of both asthma and COPD were identified as ACOS cases and compared with a population that had a COPD diagnosis only. Baseline characteristics (age, gender, smoking status) were compared using Chi-square and student's t -tests, where appropriate. Prevalence of comorbidities was compared using multivariate logistic regression. Results: We identified 5,093 ACOS patients and compared them with 22,778 COPD patients. Patients with COPD were more frequently men (69.2%) than ACOS patients (46.6%), were older (COPD: 65.8 years; ACOS: 64.0 years) and differed by non-smoking status (COPD: 22.1%; ACOS: 45.8%) (all, p<0.001). In adjusted analyses, allergic rhinitis (OR: 1.81, 95%CI: 1.63-2.00), anxiety (OR: 1.18, 95%CI: 1.10-1.27), GERD (OR: 1.18, 95%CI: 1.04-1.33) and osteoporosis (OR: 1.14, 95%CI: 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR: 0.79, 95%CI: 0.66-0.95) and ischaemic heart disease (OR: 0.88, 95%CI: 0.79-0.98) were less frequent. Conclusions: In our population of ACOS patients, allergic rhinitis, anxiety, GERD and osteoporosis are more prevalent than in COPD patients, while ischaemic heart disease and chronic kidney disease are less frequent

Comorbidome, pattern and impact of asthma-COPD overlap syndrome (ACOS) in real-life

BACKGROUND: Asthma-COPD overlap syndrome (ACOS) has been described and acknowledged as a distinct clinical entity; however, its characteristics in daily clinical practice are largely unknown. The aim of this study was to identify the prevalence of ACOS in the real-life population, its pattern of comorbidities, and its impact on hospitalization risk. METHODS: Data for this retrospective cohort study were extracted from the Majorca Real-Life Investigation in COPD and Asthma cohort, including primary care, hospitalization, and pharmacy data from the Balearic Islands, Spain. Patients who had received a physician-confirmed diagnosis of both asthma and COPD were identified as having ACOS and compared with a COPD-only population. In subanalyses, more stringent diagnostic criteria (Global Initiative for Asthma-Global Initiative for Chronic Obstructive Lung Disease) were applied. The pattern and impact of comorbidities on all-cause hospitalization were compared by multivariate logistic regression. RESULTS: In total, 5,093 patients with ACOS (prevalence, 5.55 per 1,000 inhabitants) were compared with 22,778 patients with COPD (30.40 per 1,000 inhabitants). Patients with ACOS were more frequently female (53.4%) than were patients with COPD (30.8%), younger (ACOS, 64.0 years; COPD, 65.8 years), and differed by nonsmoking status (ACOS, 41.4%; COPD, 22.1%) (all, P <.001). In adjusted analyses, allergic rhinitis (OR, 1.81; 95% CI, 1.63-2.00), anxiety (OR, 1.18; 95% CI, 1.10-1.27), gastroesophageal reflux disease (OR, 1.18; 95% CI, 1.04-1.33), and osteoporosis (OR, 1.14; 95% CI, 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR, 0.79; 95% CI, 0.66-0.95) and ischemic heart disease (OR, 0.88; 95% CI, 0.79-0.98) were less frequent. In patients with ACOS, cardiovascular diseases showed the strongest association with hospitalization. CONCLUSIONS: ACOS is prevalent in the general population, and it affects to a large extent females with less smoking exposure compared with patients with COPD only. Cardiovascular comorbidities in particular contribute most to overall hospitalization risk of patients with ACOS