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

Rie Tanaka,1 Hisatoshi Sugiura,1 Mitsuhiro Yamada,1 Tomohiro Ichikawa,1 Akira Koarai,1 Naoya Fujino,1 Satoru Yanagisawa,1 Katsuhiro Onodera,1 Tadahisa Numakura,1 Kei Sato,1 Yorihiko Kyogoku,1 Hirohito Sano,1 Shun Yamanaka,1 Tatsuma Okazaki,1 Tsutomu Tamada,1 Motohiko Miura,2 Tsuneyuki Takahashi,3 Masakazu Ichinose1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan; 2Department of Respiratory Medicine, Tohoku Rosai Hospital, Aoba-ku, Sendai, Japan; 3Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Wakabayashi-ku, Sendai, Japan 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. Keywords: physical activity, muscle strength, rejuvenating factor, COP

Association between socioeconomic status and physical inactivity in a general Japanese population: NIPPON DATA2010.

Background:Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan.Methods:The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity.Results:In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity.Conclusions:The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle

Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro

Human airway smooth muscle possesses an inhibitory nonad-renergic noncholinergic neural bronchodilator response me-diated by nitric oxide (NO). In guinea pig trachea both endoge-nous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase a-chymo-trypsin on contractile responses evoked by electrical field stimu-lation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in tra-chea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism ofthis mod-ulation we then studied the effects ofendogenous NO on acetyl-choline (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism ofACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways. (J. Clin. Invest. 1993.92:736-743.) Key words: acetylcholine release * functional antagonism * bronchodilation * parasympathetic innervation * inhibitory nonadrenergic non-cholinergic (i-NANC