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Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

ABSTRACT: Background:Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. Patients and methods:Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. Results:The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11. Conclusion:Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11.

SUBMITTER: Tanaka R

PROVIDER: S-EPMC5927187 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

Tanaka Rie R Sugiura Hisatoshi H Yamada Mitsuhiro M Ichikawa Tomohiro T Koarai Akira A Fujino Naoya N Yanagisawa Satoru S Onodera Katsuhiro K Numakura Tadahisa T Sato Kei K Kyogoku Yorihiko Y Sano Hirohito H Yamanaka Shun S Okazaki Tatsuma T Tamada Tsutomu T Miura Motohiko M Takahashi Tsuneyuki T Ichinose Masakazu M

International journal of chronic obstructive pulmonary disease 20180424

<h4>Background</h4>Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in ...[more]

PMID: 29731621

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Project description:BackgroundAlthough T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain.MethodsWe recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants.ResultsOf 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased.ConclusionsThe decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute.Trial registrationNCT00281216 , ClinicalTrials.gov.

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.

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Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

Publications

Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

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