Physical activity in asthma control and its immune modulatory effect in asthmatic preschoolers

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% 1-3 h daily and only 25.7% vs. 47.2% ≤1 h 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 readiness of circulating immune cells for type 1, 2, and 17 cytokine release compared to subjects with low PA and high TV attendance. This may also represent a proinflammatory state in high PA asthmatic children. Low physical activity and high TV attendance were associated with a decrease in proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in vitro immune responses of asthmatic children, but not healthy controls, this correlation was more pronounced in children with sedentary behavior.

Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control is associated with a substantial decrease in physical activity. Our results suggest that asthmatic children may 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. However, it has to be considered that a hyperinflammatory state in high PA may not be beneficial in asthmatic children.

Keywords: PreDicta; asthma; cytokines; immune modulation; physical activity.

FIGURE 1

Impact of asthma control on weekly physical activity (A) and TV attendance (B). (A) Fraction of total (%) analysis of subjects with vigorous PA ≥ 3 times a week, 1–2 times a week or never/occasionally physically active, grouped according to asthma control. (B) Fraction of total (%) analysis of subjects with daily TV attendance >1 h per day or ≤1 h per day, grouped according to asthma control. *p < .05 intergroup difference

FIGURE 2

Increased (A) and decreased (B) cytokines under different stimulations in asthmatic preschoolers. Violin plots with median and quartiles visualizing cytokine levels. Asthma n = 140, healthy n = 53. PBMCs were cultured with different stimulants for 48 h. Cytokine levels were determined using a multiplex immunoassay. *p < .05, **p < .01, and ****p < .0001 intergroup difference, respectively

FIGURE 3

Impact of physical activity and TV attendance on unstimulated cytokines in asthmatic (A, B) and healthy (C, D) preschoolers. Violin plots with median and quartiles visualizing cytokine levels. Red and blue arrows indicate increase or decrease of cytokine levels with higher PA or TVA. (A) Asthma, physical activity: n/o (n = 42), 1–2/w (n = 24), ≥3/w (n = 75). (B) Asthma, TV attendance: ≤1 h/d (n = 36), 1–3 h/d (n = 82), ≥3 h/day (n = 22). (C) Healthy, physical activity: n/o (n = 13), 1–2/w (n = 10), ≥3/w (n = 30). (D) Healthy, TV attendance: ≤1 h/d (n = 25), 1–3 h/d (n = 22), ≥3 h/day (n = 6). *p < .05, **p < .01, ***p < .001 and ****p < .0001 intergroup difference, respectively. n/o (never or occasionally), 1–2/w (once or twice per week), ≥3/w (3 or more times per week), ≤1 h/d (less than one hour per day), 1–3 h/d (one to three hours per day), ≥3 h/day (3 or more hours per day)

FIGURE 4

Impact of physical activity on PBMC cytokine response in asthmatic (A) and healthy (B) preschoolers. Violin plots with median and quartiles visualizing cytokine levels. Red and blue arrows indicate increase or decrease of cytokine levels with higher PA. (A) Asthma, physical activity: n/o (n = 42), 1–2/w (n = 24), ≥3/w (n = 75). (B) Healthy, physical activity: n/o (n = 13), 1–2/w (n = 10), ≥3/w (n = 30). *p < .05, **p < .01, ***p < .001, and ****p < .0001 intergroup difference, respectively. n/o (never or occasionally), 1–2/w (once or twice per week), ≥3/w (3 or more times per week)

FIGURE 5

Impact of TV attendance on PBMC cytokine response in asthmatic (A) and healthy (B) preschoolers. Violin plots with median and quartiles visualizing cytokine levels. Red and blue arrows indicate increase or decrease of cytokine levels with higher TVA. (A) Asthma, TV attendance: ≤1 h/d (n = 36), 1–3 h/d (n = 82), ≥3 h/day (n = 22). (B) Healthy, TV attendance: ≤1 h/d (n = 25), 1–3 h/d (n = 22), ≥3 h/day (n = 6). *p < .05, **p < .01, ***p < .001 and ****p < .0001 intergroup difference, respectively. ≤1 h/d (less than one hour per day), 1–3 h/d (one to three hours per day), ≥3 h/day (3 or more hours per day)

FIGURE 6

Correlations between cytokines in asthmatic and healthy preschoolers with low weekly physical activity (A, C) and high daily TV attendance (B, D). Spearman correlation heat maps visualizing correlations between measured cytokines in both asthmatic (A, B) and healthy (C, D) preschoolers. Red and blue squares indicate positive (0 to +1) and negative (0 to −1) correlations, respectively. (E) Spearman correlation scatter plots showing significant correlations between cytokines