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Chest computed tomography-derived low fat-free mass index and mortality in COPD.

ABSTRACT: Low fat-free mass index (FFMI) is an independent risk factor for mortality in chronic obstructive pulmonary disease (COPD) not typically measured during routine care. In the present study, we aimed to derive fat-free mass from the pectoralis muscle area (FFMPMA) and assess whether low FFMIPMA is associated with all-cause mortality in COPD cases. We used data from two independent COPD cohorts, ECLIPSE and COPDGene.Two equal sized groups of COPD cases (n=759) from the ECLIPSE study were used to derive and validate an equation to calculate the FFMPMA measured using bioelectrical impedance from PMA. We then applied the equation in COPD cases (n=3121) from the COPDGene cohort, and assessed survival. Low FFMIPMA was defined, using the Schols classification (FFMI <16 in men, FFMI <15 in women) and the fifth percentile normative values of FFMI from the UK Biobank.The final regression model included PMA, weight, sex and height, and had an adjusted R2 of 0.92 with fat-free mass (FFM) as the outcome. In the test group, the correlation between FFMPMA and FFM remained high (Pearson correlation=0.97). In COPDGene, COPD cases with a low FFMIPMA had an increased risk of death (HR 1.6, p<0.001).We demonstrated COPD cases with a low FFMIPMA have an increased risk of death.

SUBMITTER: McDonald MN

PROVIDER: S-EPMC5890424 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Chest computed tomography-derived low fat-free mass index and mortality in COPD.

McDonald Merry-Lynn N MN Diaz Alejandro A AA Rutten Erica E Lutz Sharon M SM Harmouche Rola R San Jose Estepar Raul R Kinney Greg G Hokanson John E JE Gower Barbara A BA Wouters Emiel F M EFM Rennard Stephen I SI Hersh Craig P CP Casaburi Richard R Dransfield Mark T MT Silverman Edwin K EK Washko George R GR

The European respiratory journal 20171214 6

Low fat-free mass index (FFMI) is an independent risk factor for mortality in chronic obstructive pulmonary disease (COPD) not typically measured during routine care. In the present study, we aimed to derive fat-free mass from the pectoralis muscle area (FFM<sub>PMA</sub>) and assess whether low FFMI<sub>PMA</sub> is associated with all-cause mortality in COPD cases. We used data from two independent COPD cohorts, ECLIPSE and COPDGene.Two equal sized groups of COPD cases (n=759) from the ECLIPSE ...[more]

PMID: 29242259

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Project description:BackgroundLoss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men.MethodsWe identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence.ResultsImprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR-675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR-675 represses regeneration.ConclusionsThe data suggest that increased expression of miR-675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.

Project description:ObjectiveChest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization.MethodsWe conducted a retrospective cohort study of all adult donation after brain death donors managed through our local organ procurement organization from June 2011 to November 2016. An experienced thoracic radiologist independently reviewed donor chest CT and chest x-ray images in a blinded, standardized manner to determine the presence of structural lung disease (eg, emphysema, interstitial lung disease [ILD]) and acute abnormalities (eg, traumatic lung injury [TLI]). Distinct models of lung utilization were fit to groups with initial partial pressure of oxygen (iPaO2) ≤300 mm Hg (suboptimal) and iPaO2 >300 mm Hg (optimal).ResultsThe organ procurement organization managed 753 donors during the study period, with a lung utilization rate ([lung donors/all organ donors] × 100) of 36.5% (275 of 753). Four hundred forty-five (59.1%) donors received chest CT imaging, revealing emphysema (13.7%), ILD (2.5%), and TLI (7.2%). In univariate analysis, findings of TLI (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61) were positively associated with lung utilization, whereas findings of emphysema (OR, 0.18; CI, 0.08-0.40) were negatively associated with utilization. In multivariate analysis, CT findings of emphysema (OR, 0.21; CI 0.08-0.54) remained negatively associated with utilization. No potential donors with CT findings of ILD became lung donors. After controlling for chest x-ray findings, chest CT imaging findings of structural lung disease remained negatively associated with utilization (P = .0001). Lung utilization rate in the suboptimal and optimal iPaO2 populations was 35.1% and 41.4%, respectively, and CT findings of emphysema had a significant association with nonutilization in both groups.ConclusionsIn the evaluation of potential lung donors, chest CT imaging findings of structural lung disease, such as emphysema and ILD, have a significant negative association with lung utilization. Our findings suggest that chest CT imaging might be an important adjunct to conventional lung donor assessment criteria.

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Chest computed tomography-derived low fat-free mass index and mortality in COPD.

Publications

Chest computed tomography-derived low fat-free mass index and mortality in COPD.

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