scholarly journals Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial

2019 ◽  
Vol 6 (1) ◽  
pp. e000431 ◽  
Author(s):  
Bartolome R Celli ◽  
Julie A Anderson ◽  
Robert Brook ◽  
Peter Calverley ◽  
Nicholas J Cowans ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Forced Expiratory Volume ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Mortality And Morbidity ◽  
Copd Exacerbations ◽  
Club Cell ◽  
Risk Of Death ◽  
Increased Risk

RationaleSystemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts.ObjectivesRelate systemic levels of those proteins to forced expiratory volume in 1 s (FEV1) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV1 of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial.MethodsParticipants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV1 decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender.ResultsSystemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV1, FEV1 decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months.ConclusionsIn COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV1 decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD.Trial registration numberNCT01313676.

scholarly journals Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype

2018 ◽  
Vol 51 (2) ◽  
pp. 1702146 ◽  
Author(s):  
Bartolome R. Celli ◽  
Nicholas Locantore ◽  
Ruth Tal-Singer ◽  
John Riley ◽  
Bruce Miller ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Forced Expiratory Volume ◽  
Fat Free Mass ◽  
Tissue Loss ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Club Cell ◽  
Body Compartments

We tested whether emphysema progression accompanies enhanced tissue loss in other body compartments in 1817 patients from the ECLIPSE chronic obstructive pulmonary disease (COPD) cohort.Clinical and selected systemic biomarker measurements were compared in subjects grouped by quantitative tomography scan emphysema quartiles using the percentage of low attenuation area (LAA%). Lowest and highest quartile patients had amino-acid metabolomic profiles. We related LAA% to 3 years decline in lung function (forced expiratory volume in 1 s (FEV1)), body mass index (BMI), fat-free mass index (FFMI) and exacerbations, hospitalisations and mortality rates.Participants with more baseline emphysema had lower FEV1, BMI and FFMI, worse functional capacity, and less cardiovascular disease but more osteoporosis. Systemic C-reactive protein and interleukin-6 levels were similar among groups, but club cell protein 16 was higher and interleukin-8, surfactant protein D and soluble receptor for advanced glycation end product were lower with more emphysema. Metabolomics differed between extreme emphysema quartiles. Patients with more emphysema had accelerated FEV1, BMI and FFMI decline and more exacerbations, hospitalisations and mortality.COPD patients with more emphysema undergo excessive loss of pulmonary and extrapulmonary tissue, which is probably related to abnormal tissue maintenance. Because of worse clinical outcomes, we propose this subgroup be named the multi-organ loss of tissue (MOLT) COPD phenotype.

scholarly journals Pneumoproteins in Offshore Drill Floor Workers

2019 ◽  
Vol 16 (3) ◽  
pp. 300 ◽  
Author(s):  
Niels E. Kirkhus ◽  
Bente Ulvestad ◽  
Lars Barregard ◽  
Øivind Skare ◽  
Raymond Olsen ◽  
...  
Keyword(s):  
Strong Association ◽  
Surfactant Protein ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Drilling Mud ◽  
Air Concentration ◽  
Work Period ◽  
Club Cell ◽  
Before And After ◽  
Oil Mist

The aim was to assess pneumoproteins and a certain biomarker of systemic inflammation in drill floor workers exposed to airborne contaminants generated during drilling offshore, taking into consideration serum biomarkers of smoking, such as nicotine (S-Nico) and cotinine. Blood samples of club cell protein 16 (CC-16), surfactant protein D (SP-D) and C-reactive protein (CRP) were collected before and after a 14-day work period from 65 drill floor workers and 65 referents. Air samples of oil mist, drilling mud components and elemental carbon were collected in person. The drill floor workers were exposed to a median air concentration of 0.18 mg/m3 of oil mist and 0.14 mg/m3 of airborne mud particles. There were no differences in the concentrations of CC-16 and SP-D across the 14-day work period and no difference between drill floor workers and referents at baseline after adjusting for differences in sampling time and smoking. CRP decreased across the work period. There was a strong association between the CC-16 concentrations and the time of sampling. Current smokers with S-Nico > detection limit (DL) had a statistically significantly lower CC-16 concentration, while smokers with S-Nico <DL had CC-16 concentrations similar to that of the non-smokers. Fourteen days of work offshore had no effect on serum pneumoprotein and CRP concentrations. However, the time of blood sampling was observed to have a strong effect on the measured concentrations of CC-16. The effect of current smoking on the CC-16 concentrations appears to be dependent on the S-Nico concentrations.

scholarly journals Biomarkers in Airway Diseases

2013 ◽  
Vol 20 (3) ◽  
pp. 180-182 ◽  
Author(s):  
Janice M Leung ◽  
Don D Sin
Keyword(s):  
Clinical History ◽  
Surfactant Protein ◽  
Secretory Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Club Cell ◽  
Disease Phenotypes ◽  
Airway Diseases ◽  
Steroid Responsiveness

The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs

Thorax ◽  
2020 ◽  
Vol 75 (8) ◽  
pp. 640-647 ◽  
Author(s):  
Min Hyung Ryu ◽  
Kevin Soon-Keen Lau ◽  
Denise Jill Wooding ◽  
Shuyu Fan ◽  
Don D Sin ◽  
...  
Keyword(s):  
Air Pollution ◽  
Diesel Exhaust ◽  
Surfactant Protein ◽  
Systemic Circulation ◽  
Regulatory Proteins ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Asthma Morbidity ◽  
Club Cell ◽  
Human Airways

RationaleExposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways.MethodsFourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators.ResultsIn human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV1.ConclusionShort-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion.Trial registration numberNCT02017431.

scholarly journals Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

2009 ◽  
Vol 27 (6) ◽  
pp. 287-294 ◽  
Author(s):  
Tania Ahmed Shakoori ◽  
Don D. Sin ◽  
Farkhanda Ghafoor ◽  
Saira Bashir ◽  
S. Nazim Hussain Bokhari
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Stable Disease ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Control Subjects ◽  
Acute Exacerbations

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations.Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease.Study design: case control study.Methods: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n= 13) and in control subjects (n= 54) using a specific immunoassay and compared the levels using analysis of variance.Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL;p= 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted.Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

scholarly journals Preoperative pulmonary function in all comers for cardiac surgery predicts mortality

2019 ◽  
Vol 29 (2) ◽  
pp. 244-251
Author(s):  
Emilie C Risom ◽  
Katrine B Buggeskov ◽  
Ulla B Mogensen ◽  
Martin Sundskard ◽  
Jann Mortensen ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Lung Function ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Clinical Trial Registration ◽  
Obstructive Pulmonary Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

Abstract OBJECTIVES Although reduced lung function and chronic obstructive pulmonary disease (COPD) is associated with higher risk of death following cardiac surgery, preoperative spirometry is not performed routinely. The aim of this study was to investigate the relationship between preoperative lung function and postoperative complications in all comers for cardiac surgery irrespective of smoking or COPD history. METHODS Preoperative spirometry was performed in elective adult cardiac surgery patients. Airflow obstruction was defined as the ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio below the lower limit of normal (LLN) and reduced forced ventilatory capacity defined as FEV1 <LLN. RESULTS A history of COPD was reported by 132 (19%) patients; however, only 74 (56%) had spirometry-verified airflow obstruction. Conversely, 64 (12%) of the 551 patients not reporting a history of COPD had spirometry-verified airflow obstruction. The probability of death was significantly higher in patients with airflow obstruction (8.8% vs 4.5%, P = 0.04) and in patients with a FEV1 <LLN (8.7% vs 3.7%, P = 0.007). In the multivariate analysis were age [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.0–2.5; P = 0.04], prolonged cardiopulmonary bypass time (HR 1.2, 95% CI 1.02–1.3; P = 0.03), reduced kidney function (HR 2.5, 95% CI 1.2–5.6; P = 0.02) and FEV1 <LLN (HR 2.4, 95% CI 1.1–5.2; P = 0.03) all independently associated with an increased risk of death. CONCLUSIONS Preoperative spirometry reclassified 18% of the patients. A reduced FEV1 independently doubled the risk of death. Inclusion of preoperative spirometry in routine screening of cardiac surgical patients may improve risk prediction and identify high-risk patients. Clinical trial registration number NCT01614951 (ClinicalTrials.gov).

scholarly journals Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

2016 ◽  
Vol 1 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Alexandra Comes ◽  
Edith Simona Ianoşi ◽  
Gabriela Jimborean
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Inflammatory Biomarkers ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Additional Tool ◽  
Copd Exacerbations ◽  
Increased Risk

AbstractChronic obstructive lung disease (COPD) is a severe progressive disease associated with high morbidity and mortality. Early diagnosis and correct treatment improve the symptoms, quality of life and survival in COPD. Exacerbations of the disease are acute events that cause worsening of COPD symptoms (dyspnea, cough and/or sputum) and may require modification of stable COPD therapy. COPD exacerbations add inflammation, damage the quality of life, deteriorate the lung function, increase mortality and associate high socio-economic costs. Accurate early prediction of exacerbation and mortality risk facilitates patient selection upon risk, in order to provide appropriately targeted early treatment. The risk of having frequent exacerbations is clearly demonstrated by recognized studies in patients with specific criteria: previous exacerbation in the last year, decrease in FEV1s, increase in the score of St. George Questionnaire (life quality decline), high levels of several inflammatory biomarkers, such as neutrophils, C-reactive protein (CRP), fibrinogen, pro-calcitonin, eosinophils, IL-6, IL-8, chemokine ligand 18 (CCL-18/PARC), surfactant protein D (SP-D). Simultaneously elevated levels of CRP, fibrinogen and leukocyte count in COPD patients were associated with an increased risk for exacerbations. At the same time, elevated levels of the three biomarkers are associated with an increased risk of major comorbidities in COPD. Biomarker detection may be an additional tool for assessment and management of COPD comorbidities. Detection of pathologic levels of inflammatory biomarkers improves the ability to predict the risk mortality in COPD alongside with BODE index (BMI, obstruction in lung function, dyspnea scale, 6-minute walk test) and may provide a targeted treatment.

scholarly journals Association between cardiovascular disease- and inflammation-related serum biomarkers and poor lung function in elderly

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
K. Egervall ◽  
A. Rosso ◽  
S. Elmståhl
Keyword(s):  
Cardiovascular Disease ◽  
Lung Function ◽  
Pulmonary Function ◽  
Serum Levels ◽  
Forced Expiratory Volume ◽  
Serum Biomarkers ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Geriatric Population ◽  
Increased Risk

Abstract Background Cardiovascular disease (CVD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and reduced lung function is an important risk factor for CVD and CVD-related death. However, the mechanisms behind the increased risk for CVD in COPD patients are not fully understood. Methods We examined the association between CVD- and inflammation-related serum biomarkers, and pulmonary function in a geriatric population. 266 biomarkers related to CVD and inflammation were analyzed in blood samples from 611 subjects aged 66–86 years who participated in the Good Aging in Skåne study. Serum levels were assessed by a proximity extension assay. Pulmonary function was measured using the lower limit of normality (LLN) spirometry criteria, i.e., forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)  <  LLN. Logistic regression models were implemented and multiple comparisons were accounted for. Results 10.3% of the study participants fulfilled pulmonary function decline criteria according to LLN. Out of the 266 biomarkers, only plasminogen activator, urokinase receptor (PLAUR) was statistically significantly associated with decreased pulmonary function. We could not find a statistically significant association between pulmonary function decline and other biomarkers previously linked to COPD, such as interleukin 6, tumor necrosis factor and surfactant protein D. Conclusion We found that serum levels of PLAUR are associated with pulmonary function decline in older adults. PLAUR is activated following inflammation and promotes matrix metallopeptidase (MMP) activation and extracellular matrix (ECM) degradation. This implies that PLAUR could play a role in the early phase of COPD pathogenesis.

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