Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease

Abstract

Background: Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS).

Methods: Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity.

Results: SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV1/FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups: reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions.

Conclusion: SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04062409.

Keywords: asthma; heart rate variability; salbutamol; sickle cell disease; sympathetic activity; vagal activity; vaso-occlusive event.

Copyright © 2020 Bokov, El Jurdi, Denjoy, Peiffer, Medjahdi, Holvoet, Benkerrou and Delclaux.

Figures

FIGURE 1

Response to paced ventilation (respiratory sinus arrhythmia evaluation). The upper panel is the HFa (raw values of HF), the middle panel is the normalized HF (Hfnu), and the lower panel is the ΔHFnu (stimulated minus baseline condition). p values are those of the Kruskal–Wallis test between the three groups. The Mann–Whitney U test further demonstrated that the two SCD groups differed from the asthmatic non-SCD group in the middle and lower panels (data not shown). Box and whisker plots show median, 25 and 75th percentiles, and 10 and 90th percentiles.

FIGURE 2

Relationship between the effect of paced ventilation and VC/VA. A significant correlation was evidenced between VC/VA and ΔHFnu: R = 0.406, p = 0.0002. Black circles are SDC children while open circles are asthmatic non-SCD children.

FIGURE 3

Response to salbutamol stimulation. Sympathetic stimulation was obtained after 400 μg of salbutamol administration (10 min after inhalation). The six SCD patients with typical asthma are individualized in the SCD asthma group as circles on the left side of the group with the black contour line. The p value is that of the Kruskal–Wallis test between the three groups. The Mann–Whitney U tests further demonstrated that the two SCD groups differed from the asthmatic non-SCD group (data not shown). The box and whisker plots show median, 25 and 75th percentiles, and 10 and 90th percentiles.