Heart rate variability as a marker of autonomic nervous system activity in young people with eosinophilic and non-eosinophilic asthma

Abstract

Objective

An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma.

Methods

HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14–21 years) with (n = 96) and without (n = 72) generally well-controlled asthma. HRV parameters associated with sympathetic and parasympathetic ANS branches were analyzed. EA and NEA were defined using a 2.5% sputum eosinophil cut-point. Airway hyperreactivity (AHR) was defined as ≥15% reduction in FEV₁ following saline challenge.

Results

HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LFµs²; representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used β-agonist medication compared to those who did not (median: 1611, IQR 892–3036 vs 754, 565–1592; p < 0.05) and increased normalized low frequency (LF nu) was found in those with AHR compared to without AHR (64, 48–71 vs 53, 43–66; p < 0.05).

Conclusion

ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use β-agonist medication.

Keywords:

• asthma
• autonomic nervous system
• heart rate variability
• airway inflammation
• inflammatory phenotypes

Acknowledgements

We are grateful to the study participants. We also thank Elizabeth Harding, Angela Thurston, Christoph Martens, Stephanie Hobbs and Mary Tohill for conducting the clinical assessments, Prachee Gokhale and Jeroen Burmanje for their involvement with sample processing, and Soo Cheng for her involvement in data analysis. We would also like to thank colleagues at the Centre for Translational Physiology, Otago University, Wellington, for allowing us to use their facility for the clinical assessments. The Research Centre for Hauora and Health (formerly the Centre for Public Health Research) is funded by a Programme Grant from the Health Research Council (HRC) of New Zealand, and this research was funded by an HRC Project Grant.

Declaration of interest

R.B. reports research funding from Health Research Council of New Zealand, AstraZeneca, GlaxoSmithKline and Genentech; and personal fees from AstraZeneca, Theravance, GlaxoSmithKline, Cipla and Avillion, outside the submitted work. P.G.G. reports research grants and personal fees from AstraZeneca, GlaxoSmithKline, Novartis outside the submitted work.