The association of elevated circulating endocan levels with lung function decline in COPD patients

AbstractBackgroundThe remodeling mechanism and cellular players causing persistent airflow limitation in chronic obstructive pulmonary disease (COPD) remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. It remains, however, unclear, whether fibrocytes are present in bronchial tissue of COPD patients.ObjectiveWe aimed to quantify fibrocytes density in bronchial specimens from both control subjects and COPD patients, and to define associations with clinical, functional and computed tomography relevant parameters.Methods17 COPD patients and 25 control subjects with normal lung function testing and no chronic symptoms, all of them requiring thoracic surgery, were recruited. LFT and CT-scan were performed before surgery. Using co-immunostaining and image analysis, we identify CD45+ FSP1+ cells as tissue fibrocytes and quantify their density in distal and proximal bronchial specimens from the whole series.ResultsHere, we demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients, compared to those of controls. The density of fibrocytes is negatively correlated with lung function parameters, such as FEV1 and FEV1/FVC, and positively with bronchial wall thickness assessed by CT scan. High density of distal bronchial fibrocytes predicts presence of COPD with a sensitivity of 83% and a specificity of 70%.ConclusionsOur results thus suggest that recruitment of fibrocytes in the bronchi may participate to lung function decline during COPD progression.Clinical ImplicationsHigh density of tissue fibrocytes is associated with a deteriorated lung function and an increase in airway wall thickness. A low density tissue fibrocytes virtually eliminates the presence of COPD.Capsule summaryBlood fibrocytes assessed during exacerbation is a predictor of mortality in COPD. This study shows an increase of bronchial fibrocytes, that is associated with lower lung function, increased bronchial thickness and air trapping in COPD.

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Follow-up desaturation in 6 minute walk tests and lung function decline in COPD patients

10.1183/13993003.congress-2018.pa2275 ◽

2018 ◽

Author(s):

Marie Waatevik ◽

Tomas Eagan ◽

Francisco Real ◽

Jon Hardie ◽

Per Bakke ◽

...

Keyword(s):

Lung Function ◽

Lung Function Decline ◽

Copd Patients ◽

Minute Walk ◽

Walk Tests

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Predictors of lung function decline: a retrospective study in COPD patients

10.1183/13993003.congress-2018.pa4098 ◽

2018 ◽

Author(s):

Francesco Spelta ◽

Michela Pizzini ◽

Lucia Cazzoletti ◽

Valentina Rigoni ◽

Francesco Zamboni ◽

...

Keyword(s):

Retrospective Study ◽

Lung Function ◽

Lung Function Decline ◽

Copd Patients

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Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD

Respiratory Research ◽

10.1186/s12931-021-01718-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

R. Singh ◽

◽

K. B. R. Belchamber ◽

P. S. Fenwick ◽

K. Chana ◽

...

Keyword(s):

Lung Function ◽

Inhaled Corticosteroids ◽

Stable State ◽

Smoking History ◽

Lower Airway ◽

Lung Function Decline ◽

Bacterial Colonisation ◽

Exacerbation Frequency ◽

Macrophage Phagocytosis ◽

Copd Patients

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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Assessment of risk factors responsible for rapid deterioration of lung function over a period of one year in patients with chronic obstructive pulmonary disease

Scientific Reports ◽

10.1038/s41598-021-92968-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anees ur Rehman ◽

Shahid Shah ◽

Ghulam Abbas ◽

Sabariah Noor Harun ◽

Sadia Shakeel ◽

...

Keyword(s):

Risk Factors ◽

Lung Function ◽

Hospital Admission ◽

Significant Risk ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Rapid Deterioration ◽

Copd Patients ◽

One Year

AbstractCompromised lung function is a common feature of COPD patients, but certain factors increase the rate of lung function decline in COPD patients. The objective of the current study was to investigate the effect of different clinically important factors responsible for rapid deterioration of lung function quantified as ≥ 60 ml decline in FEV1 over a period of one year. COPD patients recruited from the chest clinic of Penang hospital were followed-up for one year from August 2018 to August 2019. Rapid deterioration of lung function was defined as greater than 60 ml/year decline in force expiratory volume in one second. Among 367 included patients 73.84% were male, with mean age 65.26 (9.6) years and % predicted FEV1 51.07 (11.84). 30.27% patients showed mean decline of ≥ 60 ml in FEV1. The regression analysis showed that current smoking relative risk (RR) = 2.38 (1.78–3.07), p < 0.001); GOLD Stage III& IV RR = 1.43 (1.27–1.97), p < 0.001); mMRC score 3 to 4 RR = 2.03 (1.74–2.70), p < 0.01); SGRQ-C score ≥ 10 points difference RR = 2.01 (1.58–2.73), p < 0.01); SGRQ-C symptoms Score ≥ 10 points difference RR = 1.48 (1.23–2.29), p < 0.001); 6MWT < 350 m RR = 2.29 (1.87–3.34), p < 0.01); ≥ 3 exacerbation in study year RR = 2.28 (1.58–2.42, p < 0.001); 8 or more hospital admission days (RR = 3.62 (2.66–4.20), p < 0.001); Charlson comorbidity index ≥ 3 RR = 3.18 (2.23–3.76), p < 0.01) and emphysema RR = 1.31 (1.15–1.79), p < 0.01) were significant risk factors for the rapid deterioration of lung function (FEV1 decline ≥ 60 ml). Among different factors CCI score ≥ 3, abrupt decline in health status, exacerbation frequency ≥ 3, hospital admission days ≥ 8 and emphysema were reported as risk factors for rapid deterioration of lung function.

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