Mixed Th2 and non-Th2 inflammatory pattern in the asthma-COPD overlap : a network approach

Altres ajuts: The authors are grateful to all the patients who participated in the study. A number of investigators contributed to the study logistics and they are listed in the Supplementary materials. The project was endorsed by the COPD and Asthma Research Board (PII de EPOC y asma) of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR).The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity 10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p =0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p <0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions

Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease

[Background]: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD.[Methods]: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment.[Results]: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3–5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1–1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02–1.3]) were independent risk factors for the progression or development of BE.[Conclusions]: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD

New GOLD classification: longitudinal data on group assignment

Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease

Background and Aim Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs?particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. Methods This was a retrospective population-based cohort study.We selected 900 patients with confirmed COPD aged 35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission.We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1?4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Results Of the patients, 16.4%had 1 severe exacerbations, varying from 9.3%in mild GOLD grade 1 to 44%in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95%confidence interval [CI], 3.53?12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41?17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Conclusions Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality

New GOLD classification: longitudinal data on group assignment

In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

External validation and recalculation of the CODEX index in COPD patients::A 3CIAplus cohort study

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25–75% 426–1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up

Current Challenges in Chronic Bronchial Infection in Patients with Chronic Obstructive Pulmonary Disease

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients.Ye

Asthma-COPD overlap is not a homogeneous disorder : Further supporting data

Asthma-COPD ovelap (ACO) is an umbrella term that encompasses patients with COPD and eosinophilic inflammation (e-COPD) and smoking asthmatics with non-fully reversible airflow obstruction (SA). We compared the clinical characteristics and the inflammatory profile of e-COPD and SA. Patients classified as e-COPD were older and more often male and showed significantly impaired pulmonary function (likely explained by a heavier smoking habit). On the contrary, SA had more atopic features, more reversibility of airflow obstruction and higher IgE levels. The concentrations of IL-5, IL-13, IL-8, IL-6, TNF-α, IL17 in serum were similar between the 2 groups. However, Th2-related biomarkers (periostin, FeNO and blood eosinophils) shower higher median values in e-COPD patients. Our findings reinforce the notion that ACO is a heterogeneous disorder and, as a consequence, it might be unacceptable to offer the same treatment for two related but different conditions

Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL clinical audit.

Current COPD management recommendations indicate that pharmacological treatment can be stepped up or down, but there are no recommendations on how to make this adjustment. We aimed to describe pharmacological prescriptions during a routine clinical visit for COPD and study the determinants of changing therapy. EPOCONSUL is a Spanish nationwide observational cross-sectional clinical audit with prospective case recruitment including 4,508 COPD patients from outpatient respiratory clinics for a period of 12 months (May 2014-May 2015). Prescription patterns were examined in 4,448 cases and changes analyzed in stepwise backward, binomial, multivariate, logistic regression models. Patterns of prescription of inhaled therapy groups were no treatment prescribed, 124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502 (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and triple therapy cases, 2,428 (53.9%) cases. Incorrect prescriptions of inhaled therapies were observed in 261 (5.9%) cases. After the clinical visit was audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307 (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme, 182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified change. Stepping-up strategies were associated with clinical presentation (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive bronchodilator test, and specific inhaled medication groups. Stepping down was associated with lung function impairment, ICS containing regimens, and nonexacerbator phenotype. The EPOCONSUL study shows a comprehensive evaluation of pharmacological treatments in COPD care, highlighting strengths and weaknesses, to help us understand how physicians use available drugs