Parasympathetic airway response and heart rate variability before and at the end of methacholine challenge

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. 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) FEV1 of 467 +/- 351 mug (range, 70 to 1,426 mug). 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 ms(2) 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(2) = -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.