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Parasympathetic Airway Response and Heart Rate Variability Before and at the End of Methacholine Challenge^*

^* From the Laboratoire des Adaptations Physiologiques aux Activités Physiques (Drs. Pichon and de Bisschop), Faculté des Sciences du Sport, UPRES EA 3813; and Service d’Explorations Fonctionnelles (Drs. Diaz and Denjean), Physiologie Respiratoire et de l’Exercice, Pôle Cur-Poumons, CHU de Poitiers, Poitiers, France.

Correspondence to: Aurélien Pichon, PhD, Laboratoire ‘Réponses cellulaires et fonctionnelles à l’hypoxie,’ UFR Santé Médecine Biologie Humaine, 74 rue Marcel Cachin, 93017 Bobigny, France; e-mail: aurelien.pichon{at}orange.fr

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 µg (range, 70 to 1,426 µg). 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 (r² = – 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.

Key Words: bronchial challenge test • bronchial hyperreactivity • heart rate variability • parasympathetic nervous system • spectral analysis