Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

George, Lauren; Brightling, Christopher E.

doi:10.1177/2040622315609251

Cited by 244 publications

(191 citation statements)

References 142 publications

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“…Of special importance with respect to the current findings, is that both type VI collagen formation (Pro-C6) and degradation (C6M) were correlated to eosinophil blood count. This is an interesting finding as in both asthma and COPD, sputum eosinophilia is associated with response to therapy and has been used for tailored strategies for normalization of sputum eosinophils in order to reduce exacerbation frequency and severity [72]. This may reflect a disruption of the integrity between the interstitial matrix and basement membrane, and inflammation by eosinophils and neutrophils, resulting in the destruction of type VI collagen and a repair response associated with more type VI collagen formation.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

et al. 2017

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BackgroundChronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study.MethodsThe COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed.ResultsThe circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV1) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015). In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36. C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively).ConclusionsThese data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.

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Section: Discussionmentioning

confidence: 99%

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

et al. 2017

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“…The importance of eosinophils in asthma has been known for decades, and assessment of sputum eosinophil content has significant utility in treatment choice for asthmatic patients (150). Eosinophils have both inflammatory and tissue remodeling effects, and their derived mediators can damage epithelial cells, stimulate EMT, activate or suppress sensory nerves, modulate the activity of stem cells and plasma cells, and alter mechanical responses of airways (151–153). Tan and colleagues (154) took biopsies from the superior meatus, where the olfactory zone resides, and found a strong correlation between eosinophils in that area and anosmia.…”

Section: Race Eosinophilia and Crs: What Are The Roles Of Genes Andmentioning

confidence: 99%

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Schleimer

2017

Annu. Rev. Pathol. Mech. Dis.

365

381

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Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.

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“…In COPD, there is infiltration of neutrophils and macrophages driven by T h 1, T h 17, and CD8 + T cells, and typically no mast-cell activation, which accounts for the lack of reversibility. Nevertheless, eosinophil might play an important role in 10%–40% of patients with COPD 11. Furthermore, patients with severe asthma may have prominent neutrophilia in biopsy specimens, although these patients are steroid-dependent and demonstrate more severe disease when compared to patients in whom bronchoalveolar lavage eosinophilia is evident 12…”

Section: How To Differentiate Asthma From Copdmentioning

confidence: 99%

Airflow obstruction: is it asthma or is it COPD?

Rogliani¹,

Ora²,

Puxeddu³

et al. 2016

COPD

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Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction. However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction. Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition. The association of asthma and COPD in the same patient has been designated mixed asthma–COPD phenotype or overlap syndrome. However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population. We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy. Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject.

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Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

Cited by 244 publications

References 142 publications

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Airflow obstruction: is it asthma or is it COPD?

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