Background: The autonomic nervous system plays a primary role in regulating airway caliber, and its dysfunction is likely to contribute to the pathogenesis of airways diseases. Moreover, some findings support the hypothesis that autonomic dysfunction and/or dysregulation contributes to the pathogenesis of airway hyperresponsiveness (AHR). Heart rate variability (HRV) spectral analysis allows identifying noninvasively perturbations of the autonomic system.

Purpose: We tested the relationship between AHR and cardiac parasympathetic tone assessed by HRV spectral analysis in patients submitted to a diagnostic methacholine bronchial challenge (MBC).

Methods: Fifteen women and 38 men (age range, 18 to 56 years) participated in the study. The principal indications for MBC were suspected asthma, chronic cough, unexplained exercise-induced dyspnea, or cough. The R-R intervals were continuously recorded during the MBC. Autoregressive method was performed on two series of 256 R-R intervals extracted before and after the MBC to obtain low-frequency (LF) and high-frequency (HF) components discount generic medications.

Results: The MBC distinguished 29 subjects without airway responsiveness (R—) and 24 responder or hyperresponsive subjects (R+): mean provocative dose of methacholine causing a 20% reduction in mean (± SD) FEV_X of 467 ± 351 p,g (range, 70 to 1,426 p,g). The HF component expressed in normalized units (n.u.) [the index of parasympathetic modulation] was significantly higher in R+ than in R— at baseline, before MBC (21 ± 21 n.u. vs 11 ± 9 n.u., p < 0.05). Interestingly, R+ showed a significant increase of HF component after MBC (243 ± 30 to 567 ± 620 ms² and 21 ± 21 to 34 ± 30 n.u., p < 0.01). For all subjects, HF (n.u.) calculated at baseline and after MBC were significantly influenced by the bronchial responsiveness (r = — 0.28 and – 0.51, respectively; p < 0.001).

Conclusion: In summary, we found that R+ had a significantly higher parasympathetic tone than R— at baseline, and that R+ showed a significant increase in cardiac reactivity after bronchial challenge. These findings demonstrate that the autonomic nervous system, which contributes to the pathogenesis of AHR, is closely linked to cardiac modulation.

Abbreviations: AHR = airway hyperresponsiveness; HF = high frequency; HR = heart rate; HRV = heart rate variability; LF = low frequency; MBC = methacholine bronchial challenge; n.u. = normalized units; PD₂₀ = provocative dose of methacholine causing a 20% fall in FEV₁; R+ = responder or hyperresponsive subjects; R— = subjects without airway responsiveness; SD₁ = short-term R-R interval variability; SD₂ = long-term R-R interval variability; SDNN = SD of all normal-to-normal intervals; STFT = short-time Fourier transform ympathetic, parasympathetic and nonadrenergic noncholinergic pathways innervate airway smooth muscle and can produce either broncho-constriction or bronchodilation when they are activated or inhibited.