Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD: A Novel Phenotype

Abstract

BackgroundBecause chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).Methods and FindingsSix inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p<0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.ConclusionsOverall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

Inhaled Corticosteroids Do Not Influence the Early Inflammatory Response and Clinical Presentation of Hospitalized Subjects With COPD Exacerbation

“…First, the baseline inflammation levels and the dosage and time period of inhaled corticosteroid use were not recorded by us; for this reason, we can rule out a possible inflammatory pattern of response related to these factors. 33 Second, in white blood cell counts, data on the number of eosinophils were not collected; new research has found that these blood cells define a specific biologic cluster of patients with COPD exacerbation 34 and directly link corticosteroid treatment to exacerbation. 35 In conclusion, our study suggests that, in COPD patients, chronic use of inhaled corticosteroids does not influence per se the early inflammatory response to COPD exacerbation.…”

Difficulty of Copd Predicting as a Challenge to Modern Clinical Pulmonology

“…Данные фенотипы характери-зуют различия между пациентами, страдающими ХОБЛ, связанные с клинически значимыми прояв-лениями и важными исходами заболевания. При этом различия в выраженности прогрессирования заболевания у пациентов с этими фенотипами вы-явлены не были [3,32,44]. В 2012 году испанское общество пульмонологов и торакальных хирургов усовершенствовало классификацию с использова-нием фенотипов, добавив рекомендации по уче-ту частоты обострений.…”

“…В развитии ХОБЛ большое значение имеют нару-шения защитной системы легких, включающей: клеточные механизмы (инфильтрация провоспа-лительными и эффекторными клетками тканей ре-спираторного тракта); гуморальные механизмы -(цитокиновая дисрегуляция и повышение продук-ции маркеров системного воспаления) и систему свободнорадикальных механизмов (оксидативный и нитрозивный стрессы) [3,13,14,35].…”

“…Воздействие полютантов на эпите-лиальные клетки приводит к выбросу провоспали-тельных цитокинов и молекул адгезии [3,13,17,35], что приводит к поддержанию местного воспаления.…”

Addressing unmet needs in the treatment of COPD

“…COPD is a complex, multicomponent disease in which heterogeneity exists in a range of factors, including lung function decline, exacerbation frequency and the contribution of emphysema and small airways disease to airflow limitation [1,[8][9][10]98]. Addressing this heterogeneity is an unmet need in COPD management.…”