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 FEV 1 /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.

Deterioration of lung diffusion capacity during childhood in sickle cell disease

“…Sixty children/adolescents of Sub-Saharan African or Caribbean ethnicity were prospectively included in the DrepaSympa trial. 5 Among them, 43 had subsequent PFTs as part of their routine follow-up (without DLNO measurement). These 43 participants are described in this retrospective study and the 17 non-included children are described in the online supplement.…”

“…First visit: Children underwent spirometry and DLCO/DLNO measurement (Medisoft, Hyp'Air Compact, Belgium) to calculate the membrane diffusion (Dm) and capillary blood volume (Vc), as recommended (a finite specific conductance in the blood for NO (θNO) was assumed), as previously described. 5 The breathhold time of this DLCO/DLNO measurement was 4 seconds.…”

“…To this end, we retrospectively recorded the routine follow-up PFTs of children with SCD who were included in a prospective cross-sectional study that included the measurement of both DLCO and DLNO with the calculation of Dm and Vc. 5…”

Hidden Comorbidities in Asthma: A Perspective for a Personalized Approach

“…This mediates abnormal gas exchange leading to bronchoconstriction-induced ventilation–perfusion mismatch and tissue hypoxia associated with increased small airway “compression” and resistance. The presence of high pulmonary ET-1 expression combined with reduced NO bioavailability and autonomic dysfunction has been proposed to play a key role in increased airway hyper-reactivity observed in patients with SCD [ 71 ]. Some of these features are shared by asthma as well as endothelial disfunction, which is also a key element in the pathogenesis of obstructive pulmonary diseases [ 72 ].…”