Neutrophil-Mediated Lung Damage: A New COPD Phenotype?

Sin, Don D.; Eeden, Stephan F. van

doi:10.1159/000334178

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…54 The activation of neutrophils provokes dissolution of the alveolar wall, injury to the ciliated epithelium and connective tissue matrix, mucus hypersecretion, and squamous metaplasia in epithelial cells, thereby leading to emphysema and fibrotic repair in the small airways. 54,59 Natural Killer T Cells Rijavec et al 60 demonstrated that in induced sputum, bronchoalveolar lavage fluid, and bronchial-biopsy specimens, the proportion of natural killer T (NKT) cells in the airway is low, but slightly increased in COPD. The NKT cells play a supplementary role in the pathogenesis of COPD.…”

Section: Neutrophilsmentioning

confidence: 99%

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

Bu¹,

Wang²,

Yin³

2020

COPD

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Recently, the therapeutic potential of immune-modulation during the progression of chronic obstructive pulmonary disease (COPD) has been attracting increasing interest. However, chronic inflammatory response has been oversimplified in descriptions of the mechanism of COPD progression. As a form of first-line airway defense, epithelial cells exhibit phenotypic alteration, and participate in epithelial layer disorganization, mucus hypersecretion, and extracellular matrix deposition. Dendritic cells (DCs) exhibit attenuated antigen-presenting capacity in patients with advanced COPD. Immature DCs migrate into small airways, where they promote a pro-inflammatory microenvironment and bacterial colonization. In response to damageassociated molecular patterns (DAMPs) in lung tissue affected by COPD, neutrophils are excessively recruited and activated, where they promote a proteolytic microenvironment and fibrotic repair in small airways. Macrophages exhibit decreased phagocytosis in the large airways, while they demonstrate high pro-inflammatory potential in the small airways, and mediate alveolar destruction and chronic airway inflammation. Natural killer T (NKT) cells, eosinophils, and mast cells also play supplementary roles in COPD progression; however, their cellular activities are not yet entirely clear. Overall, during COPD progression, "exhausted" innate immune responses can be observed in the large airways. On the other hand, the innate immune response is enhanced in the small airways. Approaches that inhibit the inflammatory cascade, chemotaxis, or the activation of inflammatory cells could possibly delay the progression of airway remodeling in COPD, and may thus have potential clinical significance.

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Section: Neutrophilsmentioning

confidence: 99%

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

Bu¹,

Wang²,

Yin³

2020

COPD

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“…Finally, the "chronic bronchitis phenotype" is characterized by frequent exacerbations, greater airway obstruction and more frequent cardiovascular comorbidities, which are all characteristics that closely resemble our neutrophil phenotype. It is worth remembering that a neutrophil phenotype for COPD was proposed by Sin who hypothesized neutrophil mediated lung damage [26].…”

Section: Discussionmentioning

confidence: 99%

What Role Do Immunological and Inflammatory Biomarkers Play on Mortality and Exacerbations in COPD Patients?

Romanelli¹,

Raciti²,

Papa³

et al. 2022

J Biomed Res Environ Sci

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Background: COPD phenotypes have been identified according to patient clinical characteristics and, more recently, to their immunological markers. However, the role of these biomarkers in relation to exacerbations in different COPD phenotypes is not yet clear. Thus it is important to continue investigating this topic to plan the most appropriate treatment, to contrast the decline of respiratory function and to reduce subsequent exacerbations in COPD patients. Therefore the aim of this study was to assess whether biomarkers are only predictors of exacerbations and mortality in COPD patients or instead play a causal role in these adverse COPD developments. Methods: COPD phenotypes were identified according to patient clinical characteristics or immunological markers. Immunological and inflammatory biomarkers were identified as predictors of mortality and exacerbations. COPD patients were identified from the hospital discharge register of Pisa (Italy) in 2000-2006, on the basis of diagnoses and a FEV1/FVC < 0.70, and enrolled in 2003-2006 according to a longitudinal approach. They were characterized at enrollment by age, sex, comorbidities, immunological and inflammatory biomarkers. The phenotype was assigned at enrollment as eosinophilic (eosinophils>2%) or neutrophilic (leukocytes>11.0x109/L and/or neutrophils>65%). Mortality and exacerbations registered in the period 2003-2012 were assessed by phenotype and other possible predictors in regression models. Results: Mortality rates reached 43.3% in COPD patients: 69.1% and 36.5% in neutrophilic and eosinophilic, respectively. The exacerbation rate was higher in neutrophilic (54.4%) than in eosinophilic patients (48.4%). Uni-variable regression confirmed that mortality was related to age, Congestive Heart Failure (CHF), Ischemic Heart Disease (IHD), elevated neutrophil count and Neutrophil to Lymphocyte Ratio (NLR). At multivariable analysis only age was associated with mortality, whereas inflammatory biomarkers induced exacerbations. Conclusion: Mortality was influenced by phenotype and age, exacerbations by COPD severity and NLR to suggest that an appropriate treatment and the biomarker’s monitoring might help prevent exacerbations.

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Prospects of neutrophilic implications against pathobiology of chronic obstructive pulmonary disease: Pharmacological insights and technological advances

Liao,

Wang,

Sun

et al. 2025

International Immunopharmacology

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Neutrophil-Mediated Lung Damage: A New COPD Phenotype?

Cited by 5 publications

References 26 publications

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

What Role Do Immunological and Inflammatory Biomarkers Play on Mortality and Exacerbations in COPD Patients?

Prospects of neutrophilic implications against pathobiology of chronic obstructive pulmonary disease: Pharmacological insights and technological advances

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