Relatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs), but whether exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30 min of constant, heavy ( approximately 80% peak O(2) uptake) cycle ergometer exercise in 12 healthy men (19-29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. With false discovery rate (FDR) <0.05 with 95% confidence, a total of 526 genes were differentially expressed between before and after exercise. Three hundred and sixteen genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, P < 0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL-32, TNFSF8, and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression.

MicroRNAs are increasingly seen as targets of drug discovery because they influence gene function acting both to silence and subtly modulate protein translation. Little is known about effects of dynamic physiological states on microRNA regulation in humans. We hypothesized that microRNA expression in peripheral blood mononuclear cells (PBMCs) would be affected by brief exercise. Twelve young men performed brief bouts of heavy exercise. PBMC microRNA was analyzed before and immediately after exercise using the Agilent Human microRNA V2 Microarray. Exercise altered expression level of 34 microRNAs (FDR < 0.05). Many of them play roles in inflammatory processes (e.g., miR-125b[↓], down-regulated by proinflammatory factor LPS; and miR-132[↑], 125b[↓] and let-7e[↓] involved inTLR4 signaling). Using previous exercise data in PBMCs, we linked the microRNA changes to specific gene pathways. This analysis identified 12 pathways including the TGF-β and MAPK signaling. We also compared exercise-associated microRNA changes in PBMCs with the exercise-associated microRNAs previously identified in neutrophils. Nine microRNAs were affected in both PBMCs and neutrophils, but only six changed in the same direction. A commonly occurring physiologic perturbation, brief heavy exercise, changes microRNA profiles in PBMCs, many of which are related to inflammatory processes. The pattern of change suggests that exercise differentially influences microRNAs in leukocyte subtypes.

The normal-weight, physically active group was fitter and had greater lean body mass, stronger bones, and lower levels of inflammatory markers than did the normal-weight, sedentary group. In adolescent girls, the choice of a lifestyle involving high school sports is characterized by a circulating mediator and body composition pattern that, if sustained, is associated with generally lower long-term risk of cardiovascular disease and osteoporosis.

BackgroundThe exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'awNO (nl/s), maximum airway flux] and distal contributions [CANO (ppb), distal airway/alveolar NO concentration]. We hypothesized that J'awNO and CANO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.MethodsIn 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'awNO and CANO.ResultsJ'awNO was not correlated with CANO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'awNO (≥ 1.5 nl/s) and CANO (≥ 2.3 ppb): Type I (normal J'awNO and CANO), Type II (elevated J'awNO and normal CANO), Type III (elevated J'awNO and CANO) and Type IV (normal J'awNO and elevated CANO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'awNO, but was not related to CANO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CANO (III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.ConclusionsJ'awNO and CANO reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CANO were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.

Purpose Cardiopulmonary exercise testing (CPET) is increasingly used as a biomarker of fitness in children. Maximal or peak values remain the most common variables obtained in CPET, but these physiologically challenging high-intensity work rates are often not achieved. We hypothesized that interactions of gas exchange, heart rate (HR), and work rate (WR) CPET variables (slopes) could yield useful mechanistic and clinical insights that might enhance the clinical utility of CPET in children. We further hypothesized that the dependence of the slope on body mass could be predicted by first-principle analysis of body size and physiological response. Methods One hundred sixty-nine healthy participants (8–18 years old, BMI<95th percentile, 82 females) underwent dual X-ray absorptiometry scan to estimate lean body mass (LBM) and performed a ramp-type progressive cycle ergometry exercise protocol with breath-by-breath measurement of gas exchange. Linear regression was used to calculate the slopes among V•O2,V•normalCO2,normalV•E, HR, and WR. Results ΔWR/ΔHR (r=0.87) and normalΔV•O2/normalΔnormalHnormalRfalse(normalr=0.96false) were strongly correlated with peak V•O2, while normalΔV•O2/normalΔnormalWnormalRfalse(normalr=0.42false) and normalΔnormalV•E/normalΔV•normalCO2false(normalr=−0.51false) were mildly correlated with peak values. LBM was more highly correlated than was total body mass with those slopes predicted to be body size dependent (p<0.0001). Conclusion The data largely supported our original hypotheses. Unlike peak or maximal values, which are derived from no more than a few data points at the end of a progressive exercise test, the CPET slopes were calculated from a much larger data set obtained throughout the test. Analysis of these slopes might ultimately prove useful clinically and in research studies when peak values are not achieved.