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Macrophage chitinase 1 stratifies chronic obstructive lung disease.

ABSTRACT: Diagnosis and therapy of chronic inflammatory lung disease is limited by the need for individualized biomarkers that provide insight into pathogenesis. Herein we show that mouse models of chronic obstructive lung disease exhibit an increase in lung chitinase production but cannot predict which chitinase family member may be equivalently increased in humans with corresponding lung disease. Moreover, we demonstrate that lung macrophage production of chitinase 1 is selectively increased in a subset of subjects with severe chronic obstructive pulmonary disease, and this increase is reflected in plasma levels. The findings provide a means to noninvasively track alternatively activated macrophages in chronic lung disease and thereby better differentiate molecular phenotypes in heterogeneous patient populations.

SUBMITTER: Agapov E

PROVIDER: S-EPMC2746984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Summit Score Stratifies Mortality and Morbidity in Chronic Obstructive Pulmonary Disease.

Project description:IntroductionTobacco use and other cardiovascular risk factors often accompany chronic obstructive pulmonary disease (COPD). This study derived and validated the Summit Score to predict mortality in people with COPD and cardiovascular risks.MethodsSUMMIT trial subjects (N=16,485) ages 40-80 years with COPD were randomly assigned 50%/50% to derivation (N=8181) and internal validation (N=8304). Three external COPD validations from Intermountain Healthcare included outpatients with cardiovascular risks (N=9251), outpatients without cardiovascular risks (N=8551), and inpatients (N=26,170). Cox regression evaluated 40 predictors of all-cause mortality. SUMMIT treatments including combined fluticasone furoate (FF) 100μg/vilanterol 25μg (VI) were not included in the score.ResultsMortality predictors were FEV1, heart rate, systolic blood pressure, body mass index, age, smoking pack-years, prior COPD hospitalizations, myocardial infarction, heart failure, diabetes, anti-thrombotics, anti-arrhythmics, and xanthines. Combined in the Summit Score (derivation: c=0.668), quartile 4 vs 1 had HR=4.43 in SUMMIT validation (p<0.001, 95% CI=3.27, 6.01, c=0.662) and HR=8.15 in Intermountain cardiovascular risk COPD outpatients (p<0.001, 95% CI=5.86, 11.34, c=0.736), and strongly predicted mortality in the other Intermountain COPD populations. Among all SUMMIT subjects with scores 14-19, FF 100μg/VI 25μg vs placebo had HR=0.76 (p=0.0158, 95% CI=0.61, 0.95), but FF 100μg/VI 25μg was not different from placebo for scores <14 or >19.ConclusionIn this post hoc analysis of SUMMIT trial data, the Summit Score was derived and validated in multiple Intermountain COPD populations. The score was used to identify a subpopulation in which mortality risk was lower for FF 100μg/VI 25μg treatment.Trial registrationThe SUMMIT trial is registered at ClinicalTrials.gov as number NCT01313676.

| S-EPMC7381787 | biostudies-literature

Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease.

Project description:RationaleInteractions of nontypeable Haemophilus influenzae (NTHI) with macrophages are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-macrophage inflammation are poorly understood. Outer membrane protein (OMP) P6 and lipooligosaccharide (LOS) of NTHI are potent immunomodulators. We theorized that alveolar macrophages in COPD possess fundamental immune defects that permit NTHI to evade host responses.ObjectiveTo test this hypothesis, we obtained human alveolar and blood macrophages from exsmokers with COPD, exsmokers without COPD, and nonsmokers.MethodsAlveolar and blood macrophages from each donor were incubated with purified LOS and OMP P6 and with OMP P2 and the total outer membrane preparation (0.1-1 microg/ml).MeasurementsSupernatants (24 h) were assayed for IL-1beta, TNF-alpha, IL-10, IL-12, and IL-8 by multianalyte multiplexed flow cytometry.ResultsComparative induction of COPD and non-COPD alveolar macrophages by LOS and OMP P6 revealed diminished IL-8, TNF-alpha, and IL-1beta responses of COPD alveolar macrophages (p < or = 0.03 for each). COPD alveolar macrophages also had diminished responses to total outer membrane (p < or = 0.03 for each). In contrast, COPD blood macrophages had no significant differences among donor groups in IL-8, TNF-alpha, or IL-1beta responsiveness to NTHI antigens. Diminished IL-12 responses of COPD blood macrophages to NTHI antigens, compared with nonsmokers, could not be independently dissociated from group differences in age and pack-years.ConclusionsThese findings support a paradigm of defective immune responsiveness of alveolar macrophages, but not blood macrophages, in COPD.

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Alveolar Macrophage Immunometabolism and Lung Function Impairment in Smoking and Chronic Obstructive Pulmonary Disease.

Project description: Not available

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Alveolar macrophage immunometabolism and lung function impairment in smoking and chronic obstructive pulmonary disease

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2020-04-17 | GSE130928 | GEO

Lung proteomic biomarkers associated with chronic obstructive pulmonary disease

Project description:Identifying protein biomarkers for chronic obstructive pulmonary disease (COPD) has been challenging. Most previous studies have utilized individual proteins or pre-selected protein panels measured in blood samples. To identify COPD protein biomarkers by applying comprehensive mass spectrometry proteomics in lung tissue samples. We utilized mass spectrometry proteomic approaches to identify protein biomarkers from 152 lung tissue samples representing COPD cases and controls.

2022-01-07 | PXD024124 | Pride

Chronic obstructive pulmonary disease

Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other

2003-07-16 | GSE475 | GEO

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| S-EPMC3949087 | biostudies-literature

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