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Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis.

ABSTRACT: BACKGROUND:Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-?)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects. METHODS:CXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-?-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function. RESULTS:In a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p?

SUBMITTER: Arger NK

PROVIDER: S-EPMC6594698 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis.

Arger Nicholas K NK Ho Melissa M Woodruff Prescott G PG Koth Laura L LL

Respiratory medicine 20190417

<h4>Background</h4>Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been ...[more]

PMID: 31128616

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Project description:RationaleCurrent practice guidelines recommend pulmonary rehabilitation as an adjunct to standard pharmacologic therapy for individuals with moderate to severe chronic obstructive pulmonary disease (COPD). Whether pulmonary rehabilitation benefits all subjects with COPD independent of baseline disease burden is not known.ObjectivesTo test whether pulmonary rehabilitation benefits patients with COPD independent of baseline exercise capacity, dyspnea, and lung function.MethodsData from a prospectively maintained database of participants with COPD enrolled in pulmonary rehabilitation at the University of Alabama at Birmingham from 1996 to 2013 were retrospectively analyzed. Subjects were divided into four quartiles based on their baseline level of dyspnea as assessed by the San Diego Shortness of Breath Questionnaire at the initial visit. Similar quartiles were assessed for FEV1 percent predicted as well as the 6-minute-walk distance (6MWD). The primary outcome was the change in quality of life as measured by the 36-item Short Form Health Survey (SF-36). Secondary outcomes were change in dyspnea, 6MWD, and depression scores assessed using the Beck Depression Inventory-II. Differences between baseline and final scores were compared using paired t tests and across quartiles using analysis of variance.Measurements and main resultsA total of 229 subjects were included. Their mean age was 66.5 (SD, 9) years. Ninety-one (40%) were female, and 42 (18%) were African American. The mean FEV1 percent predicted was 46.3% (20.0%). On completion of pulmonary rehabilitation, clinically significant improvements were seen in most components of SF-36: physical function, 11.5 (95% confidence interval [CI], 7.4-15.5; P < 0.001); health perception, 2.1 (95% CI, -0.7 to 4.8; P = 0.12); physical role, 16.7 (95% CI, 10.3-23.1; P < 0.001); emotional role, 14.7 (95% CI, 7.1-22.3; P < 0.001); social function, 16.4 (95% CI, 11.3-21.5; P < 0.001); mental health, 5.4 (95% CI, 2.6-8.3; P < 0.001); pain, 5 (95% CI, 1-9.1; P = 0.02); vitality, 12.4 (95% CI, 8.8-16.1; P < 0.001); and depression, 0.01 (95% CI, -0.11 to 0.07; P = 0.54). There was no difference in improvement in SF-36 across quartiles of San Diego Shortness of Breath Questionnaire, 6MWD, and FEV1 percent predicted.ConclusionsPulmonary rehabilitation results in significant improvement in quality of life, dyspnea, and functional capacity independent of baseline disease burden.

Project description:PurposeReduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status.MethodsPhysical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King's Sarcoidosis Questionnaire (KSQ).ResultsPatients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p?<?0.01) and a trend towards fewer sit-to-stand transitions each day (p?=?0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p?<?0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r?=?0.634, p?=?0.01), but not with forced vital capacity (r?=?0.290), fatigue (r?=?0.041), dyspnoea (r?=?-0.466) or KSQ health status (r?=?0.099-0.484). Time spent upright was associated with fatigue (r?=?-0.630, p?=?0.012) and health status (KSQ Lung scores r?=?0.524, p?=?0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r?=?-0.527, p?=?0.044).ConclusionPhysical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

Dataset Information

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis.

Publications

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis.

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