Abstract
Background : The impact of physical activity on immune response is a hot topic in exercise immunology, but studies involving asthmatic children are scarce. Our aims were to examine whether there were any differences in the level of physical activity and daily TV attendance, to assess its role on asthma control and immune responses to various immune stimulants.
Methods: Weekly physical activity and daily television attendance were obtained from questionnaires at inclusion of the PreDicta study. PBMC cultures were stimulated with phytohemagglutinin (PHA), R848, poly I:C and zymosan. A panel of cytokines was measured and quantified in cell culture supernatants using luminometric multiplex immunofluorescence beads-based assay.
Results: Asthmatic preschoolers showed significantly more TV attendance than their healthy peers (58.6% vs. 41.5% 1-3h daily and only 25.7% vs. 47.2% ≤ 1h daily) and poor asthma control was associated with less frequent physical activity (PA) (75% no or occasional activity in uncontrolled vs. 20% in controlled asthma; 25% ≥ 3 times weekly vs. 62%). Asthmatics with increased PA exhibited elevated cytokine levels in response to polyclonal stimulants, suggesting a fitness and readiness of circulating immune cells for type 1, 2 and 17 cytokine release compared to subjects with low PA and high TV attendance. Low physical activity and high TV attendance were associated with an increase in proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in vitro immune responses of asthmatic children, but not healthy controls.
Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control leads to a substantial decrease in physical activity. Our results suggest that asthmatic children profit from regular exercise, as elevated cytokine levels in stimulated conditions indicate an immune system prepared for responding strongly in case of different types of infections.
Keywords: asthma; cytokines; immune modulation; physical activity; PreDicta
Introduction
Asthma affects more than 300 million people worldwide, and it is estimated that this number will increase to over one billion by 2050.1 It is more prevalent in children, where it lies among the top 20 chronic diseases for the global ranking of disability-adjusted life years1,2 with up to 25% of children affected in Western urban areas.3 The global burden of asthma in children and adolescents increased significantly over the last decades, while previously countries affected at lesser extent in Africa, South America and Asia started to catch up on these numbers.1,4 Multiple factors are thought to play a role in this world-wide increase in asthma prevalence including allergen exposure and sensitization, environmental influences, viral infections, urbanization, diet and sedentary lifestyle with physical inactivity.5,6 Asthma attacks often appear during physical activity (PA),7 termed “exercise-induced asthma” (EIA) affecting 70-90% of asthmatic children.3
PA is beneficial both for growth and the psychological development of children.8-10 Whereas the World Health Organization (WHO) recommends for children and adolescents aged 5 to 17 years to be moderately to vigorously active for a minimum of 60 minutes daily,10,11 specific guidelines for children suffering from asthma are lacking.12 Although it is agreed that it is essential for asthmatic children to participate in sports,7 fear of EIA might prevent the practice of regular PA in children, particularly the ones with severe and/or uncontrolled asthma.3,13 This self-limiting cycle of inactivity has led to the common perception that asthmatics are more physically inactive in comparison to healthy individuals.3
Asthma pathogenesis is a consequence of epithelial barrier dysfunction,14 and research has shown that there are several underlying pathophysiological mechanisms (endotypes) that can lead to variable clinical presentations (phenotypes).15-17 An imbalance of both Th1/Th2 cells and Th17/Treg cells can play a crucial role in its development.18-20 Type 2 inflammation is considered to be the major driver in the most common phenotype, allergic asthma,21 and seems to be the result of a complex cross-talk between airway epithelium, innate and adaptive immunity.19 PA is known to impact both the innate and adaptive immune responses in various ways: For example, moderate exercise was found to lead to an acute increase in the absolute numbers of natural killer (NK) cells and NK cell cytotoxicity.22,23 As for the adaptive immune response, increased and intensified training loads were shown to lead to a reduction of T cell functionality in well-trained individuals, with lower numbers of circulating type 1 T cells, reduced T cell proliferation responses and B cell immunoglobulin synthesis.22 While Walsh et al. describe in their position statement on immune function and exercise a resulting temporary inhibition of Th1 cytokine production in trained individuals without asthma, studies examining the impact of aerobic exercise in murine asthma models reported an enhancement of Th-1 and Treg responses and lower levels of Th-2 cytokines.22,24,25
The “Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases” (PreDicta) study, was designed to prospectively evaluate asthma persistence in preschoolers in association with microbial exposures and immunological responses.26 PreDicta has demonstrated differential immune responses to viruses in asthma,27,28 as well as evolution of airway inflammation at that age.29 The objective of the present study was i) to evaluate whether there were any differences in the level of PA and sedentary behavior between asthmatic and non-asthmatic children, ii) to assess the impact of asthma control on PA and iii) to examine the influence of PA and long time TV attendance on the immune system in asthmatic children. We have investigated multiple cytokine levels in response to four different immune stimuli: by phytohemagglutinin (PHA) that mimics polyclonal innate immune activation, by polyinosinic-polycytidylic acid (poly I:C) and R848 (resiquimod) that both mimic respiratory virus stimulation and by zymosan (zymo) that mimics fungal stimulation in PBMC cultures. R848 is an imidazoquinoline compound with potent antiviral activity that functions through the Toll-like receptor (TLR)7/TLR8 myeloid differentiation primary response protein (MyD88)-dependent signaling pathway.30 Poly I:C is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3.31Zymosan is a glucan binding to TLR2 and dectin1 found on the surface of yeasts.32
Methods