Autonomic nervous system dysfunction and their relationship with disease severity in children with atopic asthma

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Abstract

The involvement of autonomic imbalance has been reported in the pathogenesis of allergic diseases. The aim of this study was to investigate the association between the clinical severity of childhood asthma with autonomic nervous system (ANS) dysfunction and to define whether the severity of asthma correlates with ANS activity. In this case–control study, we evaluated the ANS activity by testing heart rate variability (HRV) and sympathetic skin response (SRR) in 77 asthmatic children, age 7–12 yrs, who had no co-morbidity and compared them with 40 gender- and age-matched control subjects. According to the severity of their asthma, study subjects were further divided into three groups: I (mild asthmatics), II (moderate asthmatics), and III (severe asthmatics). Inter-group ANS scale scores differed significantly (p < 0.01) between Groups I and III and between Groups II and III. Combined use of HRV and SSR provides a higher degree of sensitivity for assessing disease severity in cases of pediatric asthma.

Highlights

► The involvement of autonomic imbalance has been reported in the pathogenesis of allergic diseases. ► A comparison of the autonomic nervous system (ANS) testing scores of the control subjects with those of children with asthma revealed significant differences. ► Combined use of HRV and SSR provides a higher degree of sensitivity for assessing disease severity in cases of pediatric asthma.

Introduction

In recent years, asthma has become the most common chronic childhood disease (Asher, 2008). An important feature of asthma is an exaggerated broncho-constrictor response to a wide variety of stimuli. This airway hyper-responsiveness can be attributed in part to an airway inflammatory response as markers for airway inflammation correlate with bronchial hyper-responsiveness. However, anti-inflammatory therapy merely reduces airway hyper-responsiveness, but does not abolish it; therefore, factors other than inflammation may contribute to airway hyper-responsiveness (Lundgren et al., 1988). Asthma is also associated with autonomic nervous system (ANS) imbalance, increased bronchial sensitivity to cholinergic constrictors, and possibly decreased sensitivity to β2-adrenergic dilators (Jartti, 2001). According to Meessen et al. (1996), several mechanisms may contribute to exaggerated cholinergic bronchospasm in asthmatics and the release of inflammatory mediators, such as airway epithelium damage due to viral infections, allergen stimuli, or various chemical and mechanical irritants (cold air and tobacco smoke) when in close contact with sensory vagal nerve endings (Meessen et al., 1996). From a physiological perspective, parasympathetic innervation mediates both cholinergic contractions and non-cholinergic relaxation of the airway (Chesrown et al., 1980). Asthma presents either as a hyperfunction of the parasympathetic nervous system (PNS) in the airways or as an imbalance between the PNS and the sympathetic nervous system (SNS) (van der Velden and Hulsmann, 1999). The hypothesis that PNS dysfunction is the cause of asthma is based on both clinical observation (Morrison and Pearson, 1991, Lin et al., 1998, Ducharme and Davis, 1998) and experimental research (Ollerenshaw et al., 1991). No studies have objectively investigated the relationship between the severity of asthma as an autonomic nervous system (ANS) dysfunction in childhood. With the introduction and use of modern-day laboratory testing for dysautonomia, we examined a series of children with asthma in an attempt to further elucidate the relationship between disease severity and ANS dysfunction.

Section snippets

Ethical approval

The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice and was approved by the local Ethics Committee. Informed consent was obtained from the parents of all study participants.

Subjects

This study was conducted from December 2010 through June 2011 in the Pediatric Allergy-Pulmonology outpatient clinic at Bezmialem Vakif University Hospital. The sample population was comprised of 77 children (46 boys, 31 girls; aged 7–12 years) who had been recently diagnosed and

Subjects

The sample for this study consisted of a total of 36 (56%) boys and 28 (44%) girls. According to the severity of their asthma, each subject was assigned to one of three groups: Group I (Mild Intermittent Asthma), Group II (Moderate Asthma), or Group III (Severe Asthma). The mean ages of Groups I, II, and III were 8.73 ± 3.7, 8.2 ± 4.2, and 8.92 ± 3.9, respectively. Gender distribution in the study groups were as follows: Group I: 14 (61%) boys and 9 (39%) girls; Group II: 19 (58%) boys and 14 (42%)

Discussion

To our knowledge this is the first study to assess HRV and SSR, parameters of ANS functions, for evaluation of disease severity in selected outpatient children with asthma. This study showed that in asthmatic children, ANS parameters correlated positively with severity of their atopic asthma. HRV and HRDB, two easily performed parameters related to the primary PNS dysfunctions correlate to the level of severity of asthma symptoms. We also observed that SSR, which primarily indicates SNS

Acknowledgement

The authors have no financial or personal relationships with other people or organization that could pose a conflict of interest in connection with the present work.

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