Giuseppe Morici

Circulating haemopoietic and endothelial progenitor cells are decreased in COPD

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD). Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean±sd 68±8 yrs; forced expiratory volume in one second: 48±12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8) were measured. Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3±2.5 versus 10.3±4.2 cells·µL−1), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30–50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-α levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies. In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.

Increased airway inflammatory cells in endurance athletes: what do they mean?

Background Inflammatory cells are increased in the airways of endurance athletes, but their role in causing exercise‐induced respiratory symptoms and bronchoconstriction, or their possible long‐term consequences, are uncertain.

Ventilation and entrainment of breathing during cycling and running in triathletes.

PURPOSE To assess whether entrainment of breathing (E) during exercise: 1) differed according to the test protocol in well-trained triathletes, and 2) improved ventilatory efficiency during exercise. METHODS Eight triathletes performed three incremental tests until exhaustion: while cycling (CE), while running at increasing grade and constant speed (increasing GRADE) and while running at increasing speed and constant grade (increasing SPEED), respectively. E was evaluated as the percentage of breaths occurring at respiratory rates (F) corresponding to integer ratios of the exercise cycle rate. To assess whether E improved ventilatory efficiency, deltaVE/VO2 between nonentrained and entrained breaths was measured at each load. RESULTS Mean E was higher in CE (57.2+/-21.9%) than in increasing GRADE (46.9+/-18.7%) and increasing SPEED (41.4+/-17.2%). E decreased at high loads in CE and increasing SPEED but not in increasing GRADE. In the group of subjects, E correlated with the degree of fitness (evaluated as VO2Tvent/VO2peak%) only during increasing GRADE. By multiple regression analysis on all data, minute ventilation correlated with CO2 production but not with the exercise cycle rate; however, either F or tidal volume correlated significantly with both these variables. VE/VO2 was lower in entrained than nonentrained breaths at each load in CE and increasing GRADE experiments, but the difference was small. CONCLUSIONS In spite of some differences among protocols, triathletes showed significant E during incremental exercise tests. Spontaneous E appeared to slightly improve ventilatory efficiency during CE and increasing GRADE protocols.

Airway cells after swimming outdoors or in the sea in nonasthmatic athletes.

BACKGROUND Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasthmatic swimmers [mean age (SD): 23.3 +/- 7.7 yr, training: 32 +/- 15 km.wk-1] habitually training in an outdoor pool (OP), i.e., a low-chlorine environment. METHODS Spirometry, exhaled nitric oxide (NO), induced sputum, and peripheral blood samples were obtained at baseline, after a 5-km trial in OP, and after a 5-km race in the sea (S), i.e., hypertonic airway exposure. RESULTS Airway neutrophil differential counts at baseline were higher in swimmers than in sedentary controls (N = 10), but cell counts, neutrophil elastase, and eosinophil cationic protein were unaffected by 5-km swimming. After swimming, L-selectin expression on airway cells decreased, suggesting exercise-induced cell mobilization into the airways and/or direct effects of hyperventilation on airway cells. After S, airway eosinophil differential counts increased slightly. Exhaled NO concentration was 19 +/- 6 ppb at baseline, 8 +/- 4 ppb after OP, and 21 +/- 7 ppb after S (P < 0.005 for OP vs baseline and S). CONCLUSIONS In swimmers not chronically exposed to high chlorine concentrations, data obtained at baseline suggest a direct relationship between airway neutrophilia and endurance training. The low L-selectin expression by airway cells postexercise suggests hyperventilation-induced cell recruitment or modulation of cell function. Hypertonic exposure of airways during exercise may slightly increase airway eosinophils and exhaled NO. Overall, 5-km swimming exerted smaller effects on airway cells than running a marathon.

Effects of Exercise Training and Montelukast in Children with Mild Asthma

PURPOSE Data from the general population suggest that habitual exercise decreases bronchial responsiveness, but the possible role of exercise in asthmatics is undefined. The leukotriene receptor antagonist montelukast decreases bronchial responsiveness and exercise-induced symptoms in asthmatic children. This randomized study in children with mild asthma evaluated the combined effects of aerobic training for 12 wk and montelukast or placebo on bronchial responsiveness (BHR) to methacholine, exercise-induced bronchoconstriction (EIB), inflammatory markers in exhaled breath condensate (EBC), and asthma exacerbations. METHODS Fifty children (mean age +/- SD: 10.2 +/- 2.4 yr) with mild stable asthma were randomly assigned to placebo (N = 25) or montelukast (N = 25). Before and after training, we assessed BHR and EIB and markers of airway inflammation-that is, exhaled nitric oxide (eNO), pH, and cysteinyl-leukotriene concentration-in EBC. RESULTS Training increased maximal workload and peak minute ventilation. After training, the methacholine dose causing a 20% fall in FEV1 (PD20) increased in both groups. A decreased slope of FEV1 decline at increasing methacholine dose was found only in montelukast-treated children. EIB prevalence halved after training in both groups (EIB + children, placebo group: 10 pretraining, 4 posttraining; EIB + children, montelukast group: 8 pretraining, 5 posttraining; P < 0.05 by chi on all children). Resting eNO was unaffected, whereas the pH of EBC decreased after training in both groups. Cysteinyl-leukotriene concentrations were low in most children at both times. During training, montelukast-treated children showed fewer asthma exacerbations compared with the same period of the previous year. CONCLUSIONS In children with mild stable asthma, exercise training decreased bronchial responsiveness to methacholine. Montelukast also decreased bronchial reactivity (FEV1 slope) and protected against exacerbations, suggesting a beneficial synergistic action of these two interventions in mild asthma.

Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise

The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In 10 healthy amateur runners, we collected venous blood before, at the end of, and the day after a marathon race (n = 9), and before and at the end of a 1.5-km field test (n = 8), and measured hemopoietic and angiogenetic progenitors by flow cytometry and culture assays, as well as plasma or serum concentrations of several cytokines/growth factors. After the marathon, CD34(+) cells were unchanged, whereas clonogenetic assays showed decreased number of colonies for both erythropoietic (BFU-E) and granulocyte-monocyte (CFU-GM) series, returning to baseline the morning post-race. Conversely, CD34(+) cells, BFU-E, and CFU-GM increased after the field test. Angiogenetic progenitors, assessed as CD34(+)KDR(+) and CD133(+)VE-cadherin(+) cells or as adherent cells in culture expressing endothelial markers, increased after both endurance and maximal exercise but showed a different pattern between protocols. Interleukin-6 increased more after the marathon than after the field test, whereas hepatocyte growth factor and stem cell factor increased similarly in both protocols. Plasma levels of angiopoietin (Ang) 1 and 2 increased after both types of exercise, whereas the Ang-1-to-Ang-2 ratio or vascular endothelial growth factor-A were little affected. These data suggest that circulating hemopoietic progenitors may be utilized in peripheral tissues during prolonged endurance exercise. Endothelial progenitor mobilization after exercise in healthy trained subjects appears modulated by the type of exercise. Exercise-induced increase in growth factors suggests a physiological trophic effect of exercise on the bone marrow.

Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners.

High neutrophil counts in induced sputum have been found in nonasthmatic amateur runners at rest and after a marathon, but the pathogenesis of airway neutrophilia in athletes is still poorly understood. Bronchial epithelial damage may occur during intense exercise, as suggested by investigations conducted in endurance-trained mice and competitive human athletes studied under resting conditions. To gain further information on airway changes acutely induced by exercise, airway cell composition, apoptosis, IL-8 concentration in induced sputum, and serum CC-16 level were measured in 15 male amateur runners at rest (baseline) and shortly after a half-marathon. Different from results obtained after a marathon, neutrophil absolute counts were unchanged, whereas bronchial epithelial cell absolute counts and their apoptosis increased significantly (P < 0.01). IL-8 in induced sputum supernatants almost doubled postrace compared with baseline (P < 0.01) and correlated positively with bronchial epithelial cell absolute counts (R(2) = 0.373, P < 0.01). Serum CC-16 significantly increased after all races (P < 0.01). These data show mild bronchial epithelial cell injury acutely induced by intense endurance exercise in humans, extending to large airways the data obtained in peripheral airways of endurance-trained mice. Therefore, neutrophil influx into the airways of athletes may be secondary to bronchial epithelial damage associated with intense exercise.

Comparison of the effects of salmeterol and salbutamol on clinical activity and eosinophil cationic protein serum levels during the pollen season in atopic asthmatics

Background In atopic asthma there is strong evidence of eosinophils playing an active role in pathogencsis. Some investigations demonstrated that eosinophil cationic protein (ECP) serum levels increased in atopic patients with asthma during pollen season.

Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

Environmental conditions, air pollutants, and airway cells in runners: a longitudinal field study.

Abstract Runners have increased numbers of neutrophils in the airways at rest and after exercise compared with sedentary individuals. The aim of this study was to determine whether Mediterranean seasonal changes in temperature, humidity or airborne pollutants affect the airway cells of runners training outdoors in an urban environment. In nine male amateur runners, cell composition, apoptosis, and inflammatory mediators were measured in induced sputum collected at rest (baseline) and the morning after races held in the fall (21 km), winter (12 km), and summer (10 km). Concentrations of air pollutants were below the alert threshold at all times. Neutrophil differential counts tended to increase after all races (P = 0.055). Apoptosis of neutrophils increased with ozone (P < 0.005) and particulate matter <10 μm (PM10) (P < 0.05) exposure. Bronchial epithelial cell counts were low at all times and weakly correlated with ozone and PM10 concentrations. Apoptotic bronchial epithelial cells increased after all races (P < 0.05). Inflammatory mediators in induced sputum were low at baseline and after the races, and correlated with neutrophil differential counts only at rest. In conclusion, apoptosis of airway cells in runners appears to be affected by both exercise and environmental conditions. Apoptosis of neutrophils increased with exposure to environmental pollutants while apoptosis of bronchial epithelial cells increased after intense exercise. Since no relationship was observed between neutrophil counts and inflammatory mediators 20 h after races, airways inflammation at this time point appears blunted in healthy runners and little affected by exposure to mild seasonal changes and airborne pollutants.