P184 Macrophage phagocytosis in COPD patients at exacerbation compared to stable state

Abstract Background Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters. Methods Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR. Results Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state. Conclusion Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.

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Antiviral immunity is impaired in COPD patients with frequent exacerbations

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00253.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. L893-L903 ◽

Cited By ~ 12

Author(s):

Aran Singanayagam ◽

Su-Ling Loo ◽

Maria Calderazzo ◽

Lydia J. Finney ◽

Maria-Belen Trujillo Torralbo ◽

...

Keyword(s):

Epithelial Cells ◽

Treatment Options ◽

Stable State ◽

Innate Immune ◽

Chronic Obstructive ◽

Type I ◽

Obstructive Pulmonary Disease ◽

Immune Mediators ◽

Copd Patients

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.

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Stable state fibrinogen is additive to MR-proADM as a predictor of mortality in COPD patients

10.1183/13993003.congress-2015.pa3362 ◽

2015 ◽

Author(s):

Maaike Zuur-Telgen ◽

Paul Van der Valk ◽

Bram Zuur ◽

Job Van der Palen ◽

Huib Kerstjens ◽

...

Keyword(s):

Stable State ◽

Copd Patients

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Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

Frontiers in Microbiology ◽

10.3389/fmicb.2021.781797 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anaëlle Muggeo ◽

Jeanne-Marie Perotin ◽

Audrey Brisebarre ◽

Sandra Dury ◽

Valérian Dormoy ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Clinical Symptoms ◽

Bacterial Load ◽

Stable State ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Mass Spectrometry Identification

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.

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Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Journal of Clinical Medicine ◽

10.3390/jcm9082670 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2670

Author(s):

Keiji Oishi ◽

Kazuto Matsunaga ◽

Toshihiro Shirai ◽

Keita Hirai ◽

Yasuhiro Gon

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Stable State ◽

Epidemiologic Studies ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Blood Eosinophils ◽

The Relationship

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

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Changes of Respiratory Mechanics in COPD Patients from Stable State to Acute Exacerbations with Respiratory Failure

COPD Journal of Chronic Obstructive Pulmonary Disease ◽

10.1080/15412555.2016.1254173 ◽

2016 ◽

Vol 14 (2) ◽

pp. 150-155 ◽

Cited By ~ 8

Author(s):

Piero Ceriana ◽

Michele Vitacca ◽

Annalisa Carlucci ◽

Mara Paneroni ◽

Lara Pisani ◽

...

Keyword(s):

Respiratory Failure ◽

Respiratory Mechanics ◽

Stable State ◽

Copd Patients ◽

Acute Exacerbations

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Lung and respiratory muscle function at discharge from a respiratory intensive care unit

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2005.631 ◽

2005 ◽

Vol 63 (3) ◽

Cited By ~ 4

Author(s):

M. Vitacca ◽

L. Bianchi ◽

L. Barbano ◽

N. Ambrosino

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Muscle Function ◽

Respiratory Muscle ◽

Stable State ◽

Study Group ◽

Arterial Blood ◽

Respiratory Muscle Function ◽

Copd Patients ◽

Respiratory Intensive Care Unit

Background. The purpose of this prospective observational study was to describe lung and respiratory muscle function at Respiratory Intensive Care Unit (RICU) discharge after a severe exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods. The study was conducted in 42 consecutive COPD patients in whom arterial blood gases, dynamic and static lung volumes, maximal inspiratory pressure (MIP) were assessed at discharge from the RICU and compared with values measured 6 months previously when they were in a stable state. The same measurements were performed at 6-month interval in 42 comparable stable COPD patients not requiring any hospitalisation for at least 6 months used as controls. Results. 24% of patients in the study group were discharged with hypercapnia whereas they were normocapnic before the acute episode. Compared to prior to exacerbation, patients of study group showed a significant worsening in mean values of PaCO2 (p=0.005), MIP (p=0.005) and FEV1 (p=0.041). Predefined criteria of worsening in PaCO2, MIP and FEV1 were observed in 47%, 33% and 28% of patients in study respectively. Neither lung nor respiratory muscle function in last stable state did predict post RICU functional worsening. In a period of 6 months controls showed no change in the studied parameters. Conclusions. After a severe acute exacerbation requiring admission to a RICU and immediately before discharge 1) a large proportion of COPD patients still show preserved lung and respiratory muscle function 2) more than one third of them would require further care and rehabilitative attempts to restore functional derangements.

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Stable State Proadrenomedullin Level in COPD Patients: A Validation Study

COPD Journal of Chronic Obstructive Pulmonary Disease ◽

10.1080/15412555.2016.1250254 ◽

2016 ◽

Vol 14 (2) ◽

pp. 219-227 ◽

Cited By ~ 2

Author(s):

Maaike Zuur-Telgen ◽

Paul VanderValk ◽

Job van der Palen ◽

Huib A. M. Kerstjens ◽

Marjolein Brusse-Keizer

Keyword(s):

Validation Study ◽

Stable State ◽

Copd Patients

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Association of exacerbation phenotype with the sputum microbiome in chronic obstructive pulmonary disease patients during the clinically stable state

Journal of Translational Medicine ◽

10.1186/s12967-021-02788-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chia-Yu Yang ◽

Shiao-Wen Li ◽

Chia-Yin Chin ◽

Chia-Wei Hsu ◽

Chi-Ching Lee ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Bacterial Diversity ◽

Pulmonary Disease ◽

Stable State ◽

Physiological Role ◽

Cooperative Networks ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Abstract Background Chronic obstructive pulmonary disease (COPD) is a progressive, life-threatening lung disease with increasing prevalence and incidence worldwide. Increasing evidence suggests that lung microbiomes might play a physiological role in acute exacerbations of COPD. The objective of this study was to characterize the association of the microbiota and exacerbation risk or airflow limitation in stable COPD patients. Methods The sputum microbiota from 78 COPD outpatients during periods of clinical stability was investigated using 16S rRNA V3-V4 amplicon sequencing. The microbiome profiles were compared between patients with different risks of exacerbation, i.e., the low risk exacerbator (LRE) or high risk exacerbator (HRE) groups, and with different airflow limitation severity, i.e., mild to moderate (FEV1 ≥ 50; PFT I) or severe to very severe (FEV1 < 50; PFT II). Results The bacterial diversity (Chao1 and observed OTUs) was significantly decreased in the HRE group compared to that in the LRE group. The top 3 dominant phyla in sputum were Firmicutes, Actinobacteria, and Proteobacteria, which were similar in the HRE and LRE groups. At the genus level, compared to that in the LRE group (41.24%), the proportion of Streptococcus was slightly decreased in the HRE group (28.68%) (p = 0.007). However, the bacterial diversity and the proportion of dominant bacteria at the phylum and genus levels were similar between the PFT I and PFT II groups. Furthermore, the relative abundances of Gemella morbillorum, Prevotella histicola, and Streptococcus gordonii were decreased in the HRE group compared to those in the LRE group according to linear discriminant analysis effect size (LEfSe). Microbiome network analysis suggested altered bacterial cooperative regulation in different exacerbation phenotypes. The proportions of Proteobacteria and Neisseria were negatively correlated with the FEV1/FVC value. According to functional prediction of sputum bacterial communities through Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis, genes involved in lipopolysaccharide biosynthesis and energy metabolism were enriched in the HRE group. Conclusion The present study revealed that the sputum microbiome changed in COPD patients with different risks of exacerbation. Additionally, the bacterial cooperative networks were altered in the HRE patients and may contribute to disease exacerbation. Our results provide evidence that sputum microbiome community dysbiosis is associated with different COPD phenotypes, and we hope that by understanding the lung microbiome, a potentially modifiable clinical factor, further targets for improved COPD therapies during the clinically stable state may be elucidated.

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The different phenotypes of COPD

British Medical Bulletin ◽

10.1093/bmb/ldaa043 ◽

2021 ◽

Author(s):

Ahmed Yousuf ◽

Hamish McAuley ◽

Omer Elneima ◽

Christopher E Brightling

Keyword(s):

Biologic Therapy ◽

Stable State ◽

Symptom Burden ◽

Chronic Obstructive ◽

Blood Eosinophil ◽

Eosinophilic Inflammation ◽

Significant Morbidity ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Eosinophil Counts

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. To improve the health status and reduce symptom burden, it is important to identify a group of patients with similar characteristics and prognosis, called clinical phenotypes. Herein we shall review the different phenotypes of COPD. Sources of data Keywords (COPD, phenotype, acute exacerbation) search was conducted in PubMed, Google Scholar. Areas of agreement Those with raised blood eosinophil counts respond better to steroid therapy at stable state and exacerbation. Areas of controversy There is no universally accepted blood eosinophil cut-off value that will indicate favourable response to corticosteroids and potentially for future biologic therapy. Growing points There is an urgent need for further therapeutic options for COPD patients with non-eosinophilic inflammation. Areas timely for developing research Well-designed COPD trials with identification of phenotypes for more personalization of the treatment of COPD.

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