A decreased inspiratory capacity (IC)/total lung capacity (TLC) ratio is associated with dynamic hyperinflation and decreased exercise capacity. The present authors hypothesised that static (low IC/TLC) and dynamic hyperinflation impair cardiac function as assessed by oxygen pulse at rest and during cardiopulmonary exercise testing (CPET). Lung function, body mass index, hand grip strength and CPET parameters were measured (oxygen uptake (mL x kg(-1) x min(-1)) and oxygen pulse (mL x beat(-1))) in 87 chronic obstructive pulmonary disease (COPD) patients (American Thoracic Society/European Respiratory Society/Global Initiative for Chronic Obstructive Lung Disease stage 3-4) and 46 controls. The patients were divided into those with IC/TLC > 25% or < or = 25%. The IC/TLC ratio at rest and at peak exercise was associated significantly with oxygen pulse. Patients with IC/TLC < or = 25% (n = 45) had significantly lower exercise capacity, peak oxygen pulse, peak minus baseline oxygen pulse, peak IC, peak IC/TLC ratio and % change from baseline to peak IC/TLC ratio compared with patients with IC/TLC > 25% and controls. During CPET, the oxygen pulse was lower at iso-work in patients with IC/TLC < or = 25% than in those with IC/TLC > 25%. Resting hyperinflation (inspiratory capacity/total lung capacity) is associated with lower oxygen pulse, peak exercise inspiratory capacity/total lung capacity and exercise capacity in patients with severe chronic obstructive pulmonary disease. The present results support an interaction between hyperinflation and decreased cardiac function that may contribute to exercise limitation in these patients.
BACKGROUND:The impulse oscillometry system (IOS) is increasingly used to evaluate lung function, but individual results must be compared with appropriate reference values. We aimed to obtain such reference values in Mexican children and adolescents. METHODS: Healthy subjects were recruited from kindergartens and schools after their parents signed a consent letter. Respiratory system impedances (Zrs), resistances (Rrs), and reactances (Xrs) were measured at 5, 10, 15, and 20 Hz, and the resonant frequency, reactance area, and difference between Rrs5 minus Rrs20 were also calculated. RESULTS: After exclusion of 4 children who were unable to perform an acceptable IOS recording, the final population comprised 283 children (153 females) 2.7-15.4 y of age. As a group, girls tended to have lower Xrs5 and higher Zrs20 and Rrs20 values. In bivariate analyses, all IOS variables had good correlation with age, height, and weight, and a better straightline fitting was obtained through data transformation to the log 10 (age) or reciprocal (height and weight) values. Comparison of regression lines revealed small differences between males and females, especially in Xrs. Multiple linear regression analysis identified height as the most influential variable in the majority of IOS variables, but age also accounted for a moderate-to-large influence in the regression models in many IOS variables. CONCLUSIONS: In this study, we generated reference equations for each IOS variable in healthy children and adolescents. Although these equations were generated in a Mexican population, they are probably also applicable in other Latin American populations with the same ethnic background.
The transmembrane protein TIM-3 is a type I protein expressed by sub-types of lymphoid cells, such as lymphocytes Th1, Th17, Tc1, NK, as well as in myeloid cells. Scientific evidence indicates that this molecule acts as a negative regulator of T lymphocyte activation and that its expression is modified in viral infections or autoimmune diseases. In addition to evidence from lymphoid cells, the function of TIM-3 has been investigated in myeloid cells, such as monocytes, macrophages, and dendritic cells (DC), where studies have demonstrated that it can regulate cytokine production, cell activation, and the capture of apoptotic bodies. Despite these advances, the function of TIM-3 in myeloid cells and the molecular mechanisms that this protein regulates are not yet fully understood. This review examines the most recent evidence concerning the function of TIM-3 when expressed in myeloid cells, primarily macrophages, and the potential impact of that function on the field of basic immunology.
T cell immunoglobulin and mucin-(Tim)-3 domain is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion. However, we recently demonstrated that Tim3 and Galectin-9 (Gal9) interaction induces a program of macrophage activation that results in killing of Mycobacterium tuberculosis (M.tb) in the mouse model of infection. In this study we sought to determine whether Tim3-Gal9 pathway plays a similar role in human pulmonary tuberculosis. We identified that pulmonary tuberculosis (PTB) patients have reduced expression of Tim3 on CD14+ monocytes in vivo. By blocking Tim3 and Gal9 interaction in vitro, we show that these molecules contribute to the control of intracellular bacterial replication in human macrophages. The antimicrobial effect was partially dependent on the production of IL-1β. Our results establish that Tim3/Gal9 interaction activates human M.tb-infected macrophages and leads to the control of bacterial growth through the production of the pro-inflammatory cytokine IL-1β. Data presented here suggest that one of the potential pathways activated by Tim3/Gal9 is the secretion of IL-1β, which plays a crucial role in antimicrobial immunity by modulating innate inflammatory networks.
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