Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pichon, A.
Right arrow Articles by Denjean, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pichon, A.
Right arrow Articles by Denjean, A.
(Chest. 2005;127:23-29.)
© 2005 American College of Chest Physicians

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

Aurélien Pichon, PhD; Claire de Bisschop, PhD; Véronique Diaz, MD, PhD and André Denjean, MD, PhD

* 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 Coeur-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


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
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


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Sympathetic, parasympathetic and nonadrenergic noncholinergic pathways innervate airway smooth muscle and can produce either bronchoconstriction or bronchodilation when they are activated or inhibited.1 Therefore, 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.2 Indeed, parasympathetic activity is known to promote bronchoconstriction of the airways,3 and an alteration of muscarinic receptors could lead to an increase of airway hyperresponsiveness (AHR) and then to bronchoconstriction.4 Moreover, Crimi et al5 showed that airway inflammation, which is a characteristic feature of bronchial asthma, might alter both the contractile properties and the autonomic regulation of airway smooth muscle. These findings support the hypothesis that autonomic dysfunction and/or dysregulation contributes to the pathogenesis of AHR.6

Some authors78 have investigated the possible relationship between the modulation of the sympathovagal balance, assessed by heart rate variability (HRV) spectral analysis,91011 and the prevalence of AHR or asthma. Spectral analysis of HRV allows a noninvasive measurement of autonomic modulation of the sinoatrial node by the quantification of low-frequency (LF) and high-frequency (HF) oscillations of R-R intervals (HF, the index of parasympathetic modulation). Some authors used HRV spectral analysis in order to identify perturbations of the autonomic system in some pathologies such as heart failure,12 COPD13 and asthma.7 However, few studies have tested the direct link that may exist between the amount of parasympathetic tone and AHR.

Therefore, we aimed to establish the relationship between AHR and cardiac autonomic tone assessed by HRV spectral analysis during diagnostic methacholine bronchial challenge (MBC). Changes of HRV before and after MBC in subjects with normal airway responsiveness and hyperresponsive subjects have been studied as well as correlating changes in HRV indexes with the magnitude of hyperresponsiveness.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Subjects
Fifty-three subjects (15 women and 38 men) aged 18 to 56 years were studied. They were free of known cardiac, circulatory, or neuromuscular diseases, and were referred to the laboratory for investigation of nonspecific bronchial responsiveness. The principal indications for this bronchial testing were suspected asthma, chronic cough, unexplained exercise-induced dyspnea, or cough. All subjects denied having recently experienced an upper respiratory infection, and none were receiving medications. Our institutional review board approved the study, and all subjects gave their written informed consent.

Study Design
The study required only one visit to the laboratory for the MBC. Each subject underwent baseline spirometry with FVC maneuver, physical examination, and a bronchial provocation test during which R-R periods were continuously recorded using a Polar heart rate (HR) monitor (Polar Vantage NV; Polar Electro Oy; Kempele, Finland). Subjects were asked to rest during 5 min to allow R-R intervals baseline measurement. Then the MBC was performed. When the test was achieved or the maximal dose of methacholine was reached, R-R intervals were recorded during 5 min before inhalation of 200 µg of salbutamol. During physical examination, questions were systematically asked about physical activity (type and weekly duration) and smoking habits.

Lung Function Measurements
The FVC maneuver was performed with the subjects wearing a nose clip and connected directly by a mouthpiece to an automated spirometer (Unit MF-PFT; Erich Jaeger AG; Wurzberg, Germany). The subjects performed an FVC maneuver to obtain the FEV1. The subjects inspired fully, then exhaled forcefully into the mouthpiece for at least 6 s. The FEV1 and FVC were calculated from the best maximal expiratory flow maneuver.

MBC
Bronchial provocation challenge was performed only if baseline lung function was close to normal (FEV1 > 70% predicted). The subjects wore a nose clip and inhaled the aerosol of methacholine through a mouthpiece by slow inspiratory maneuvers from functional residual capacity to total lung capacity, and then maintained a 5-s breathhold. Methacholine inhalation was performed using a metered-dose inhaler (FDC 88; Mediprom; Paris, France). The FEV1 and FVC were measured at baseline and 1 min after inhalation of graded doses of methacholine. Solutions of methacholine were prepared by adding 50 mL saline solution to 1 g dry powder methacholine chloride (Allerbio; Varennes, France) in order to obtain a methacholine concentration of 20 mg/mL. After inhalation of saline solution, as a control, the initial methacholine dose was 50 µg (ie, 2.5 µL methacholine solution), and the inhaled dose was doubled at each increment (50 µg, 100 µg, 200 µg, 400 µg, etc...) until the maximum cumulative dose of 2,400 µg was delivered, or until FEV1 fell by at least 20% from baseline value. The provocative dose of methacholine causing a 20% fall in FEV1 (PD20) was calculated by interpolating the dose-response curve. Subjects were considered to have bronchial hyperresponsiveness when the PD20 was ≤ 1,600 µg. After the final methacholine dose and whatever the FEV1 change, salbutamol was delivered (200 µg) using a metered-dose inhaler and a spacer (Volumatic; Allen & Hanburys; Greenford, UK).

HRV Analysis
Recorded R-R periods were firstly transferred to American Standard Code for Information Interchange files. A visual inspection of the R-R interval sequences obtained at baseline or after MBC was done, and artifactual measures were manually replaced by interpolated and extrapolated data. Then, series of 256 suitable R-R periods of pre-MBC and post-MBC R-R recordings were chosen for analysis.

Time-Domain Analysis:
SD of all normal-to-normal intervals (SDNN) was calculated. Two-dimensional Poincaré plots were also generated by plotting each R-R interval as a function of its previous R-R interval obtained at baseline and after MBC. A two-dimensional vector analysis was then used to quantify the shape of the plots: short-term R-R interval variability (SD1) and long-term RR interval variability (SD2) of the plot were separately quantified.14

Autoregessive Analysis:
Harmonic components of the R-R interval were analyzed by the autoregressive method (HRV Analysis Software 1.1 for Windows; Biomedical Signal Analysis Group, Department of Applied Physics, University of Kuopio; Kuopio, Finland). Autoregressive coefficients were estimated using the forward-backward linear least-squares algorithm with a 16th-order autoregressive model. The R-R interval time series were interpolated at a rate of 2 Hz and detrend prior to the analysis. The power density of LF and HF components was calculated and expressed in absolute units (ms2) and normalized units (n.u.),11 which were obtained as follows: HF n.u. = (HF ms2)/(LF ms2 + HF ms2) x 100). The LF/HF ratio was also calculated to assess sympathetic/parasympathetic modulation.11

Short-Time Fourier Transform:
The short-time Fourier transform (STFT) of R-R intervals corresponds to a sliding fast Fourier transform analysis. The STFT processing yields an analysis in time-frequency domain that can be exemplified with a three-dimensional figure to exhibit the evolution of HRV throughout the observed bouts of exercise. The signal is convolved with some constant-duration time window, and the spectral components are calculated for each windowed segment.15 The STFT analyses were performed using specific software after Hamming windowing (MATLAB 5.3; The MathWorks; Natick, MA). After loading the American Standard Code for Information Interchange file, an R-R periodogram was performed and displayed in order to pick out the more relevant stretch for STFT analysis. This stretch needs to be > 320 values to perform a STFT on a block of 256 values.

Statistical Analysis
Data are expressed as mean ± SD. Statistical analysis was performed using a software package (Statistica 5.1; Statsoft; Tulsa, OK).

The comparison of HRV indexes between the two groups of subjects (nonresponders and responders) at baseline and after MBC were evaluated using analysis of variance for repeated measures. The Newman-Keuls test was used for post hoc test. Influences of some variables were assessed with ascendant multiple regression analyses. The F value for n – 1° of freedom was used to determine significance. Values of p < 0.05 were considered statistically significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Physiologic Characteristics of the Subjects
The MBC distinguished 29 nonresponder subjects (subjects without airway responsiveness [R–]) and 24 responder or hyperresponsive subjects (R+) [PD20 = 467 ± 351 µg; range, 70 to 1,426 µg; Table 1 ]. Twenty-two subjects of the responder group received a diagnosis of asthma, and the two other subjects had chronic cough. Although FEV1 remained in a normal range in both groups, baseline FEV1 (percentage of theoretical value) was significantly lower in R+ group compared to R – (p < 0.05).


View this table:
[in this window]
[in a new window]

  		Table 1. Anthropometric and Spirometric Characteristics of the Subjects*

 
HRV Measurement
Results are displayed in Table 2 . The R-R intervals decreased significantly after MBC compared to baseline in R+ and R– (F[1,51] = 47.0, p < 0.01), and SDNN decreased after MBC compared to baseline only in R+ (F[1,51] = 8.6, p < 0.05). The SD1 index was significantly greater in R+ after MBC compared to baseline (F[1,51] = 6.30, p < 0.05), SD2 increased significantly after MBC compared to baseline in all subjects (F[1,51] = 12.7, p < 0.01).


View this table:
[in this window]
[in a new window]

  		Table 2. Time-Domain and Frequency Analysis of HRV at Baseline and After the MBC for Responder and Nonresponder Subjects*

 
The HF component expressed in absolute units (ms2) increased significantly after MBC as compared to baseline for R+, whereas no change was observed in R– (F[1,51] = 14.4, p < 0.01). This result was confirmed by STFT analysis (Fig 1 ), which displays an increase in the HF power after methacholine inhalation and a suppression of this component after salbutamol inhalation. We did not observe any difference in LF (ms2) component or in LF/HF ratio, neither at baseline nor after MBC in both groups. The HF n.u. were significantly greater in R+ than in R– at baseline (p < 0.01), and increased significantly after MBC only in R+ (F[1,51] = 9.2, p < 0.05).



View larger version (53K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Three-dimensional representation of the evolution of R-R interval variability spectral analysis from short term Fourier transform (STFT) during an MBC for one hyperresponsive subject (PD20 = 115 µg). This figure shows changes in spectral power (y-axis) for each frequency (x-axis) as a function of time (z-axis). The two arrows represent the beginning and the end of the inhalation of methacholine.

 
Multiple Regression Analyses
Multiple regression analyses were performed in all subjects at baseline and after the MBC on the HF component expressed in absolute units and n.u. At baseline, these analyses showed a significant influence of physical activity (r2 = 0.52, p < 0.001) and height (r2 = – 0.27, p < 0.01) on HF ms2 and of bronchial responsiveness on HF n.u. (r2 = – 0.28, p < 0.01). After the bronchial challenge test, multiple regression analyses demonstrated a significant effect of physical activity (r2 = 0.83, p < 0.0001), baseline FVC (r2 = – 0.3, p < 0.005), and smoking habits on HF ms2 (r2 = – 0.19, p < 0.01), whereas the HF n.u. was only influenced by the bronchial responsiveness (r2 = – 0.51, p < 0.0001).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
The main finding of this study is that R+ have a significantly higher parasympathetic tone than R– at baseline. Interestingly, R+ also showed a significant increase of the index of parasympathetic modulation of HR after bronchial challenge, suggesting a significant increase in cardiac reactivity. Moreover, there was a significant relationship between the HF (n.u.) component of HRV and hyperresponsiveness of the subjects.

Basal Parasympathetic Tone at Rest
Several studies161718 have shown that airway parasympathetic nerves are tonically active during tidal breathing, producing a stable, readily reversible baseline tone of the airway smooth muscles that likely reflects the opposing influences of contractile and relaxant airway parasympathetic nerves. Airway smooth muscle is tonically active under resting conditions since its effects can be abolished by atropine1 or ipratropium bromide infusion.17 Moreover, electrophysiologic recordings from both preganglionic parasympathetic nerves fibers and postganglionic parasympathetic ganglion neurones confirm the existence of a persistent outflow of parasympathetic nerves activity to the airways.18 These results support the view that, in humans, airway tone is mainly vagally controlled. Furthermore, parasympathetic airway tone appears to be significantly increased in asthmatic subjects compared with nonasthmatic subjects.19 In this study, spectral analysis of HRV was used to assess sympathetic/parasympathetic modulation in subjects who performed the bronchial challenge test. This method allows identification of LF and HF components. The LF component corresponds mainly to sympathetic modulation and partially to parasympathetic modulation, whereas the HF component represents only parasympathetic modulation that could also be assessed by short-term indices of Poincaré plot (SD1).91011 Indexes of sympathetic modulation did not change during bronchial provocation test (LF and SD2), but those of parasympathetic modulation of HRV (SD1 and HF n.u.) were significantly greater in R+ than in R– at baseline. These results suggest a higher cardiac parasympathetic tone in hyperresponsive subjects. The increase in bronchial parasympathetic tone and in cardiac parasympathetic modulation, observed in AHR subjects, probably reflects a whole-body imbalance between parasympathetic and sympathetic modulation.

Bronchial and Cardiac Parasympathetic Outflows in Nonresponder Subjects
Nonresponder subjects who had been included in the study because of their prescription for a bronchial challenge test were suspected having asthma-like symptoms. Therefore, they could not be strictly considered as normal subjects. However, in these subjects we observed no relationship between parasympathetic tone and bronchial tone. Nonresponder subjects always inhaled the maximal dose of methacholine (2,400 µg), which represents four times the mean dose inhaled by the responders, without any increase of cardiac reactivity or systemic effects of methacholine. These results confirm the observations of Horvath et al20 in healthy subjects after an infusion of full-dose atropine under resting conditions. They did not observe any significant correlation between bronchial and cardiac parasympathetic tone even if after complete cholinergic blockade airway resistance and heart period were significantly reduced. We concluded that even if bronchial and cardiac parasympathetic tones are effective in nonresponder subjects under resting conditions, they are not related one each other.

Bronchial and Cardiac Parasympathetic Outflows in Responder Subjects
Conversely, in asthmatic or responder subjects, the concordance between bronchial and cardiac parasympathetic tone is obvious. Indeed, we have shown a significant increase of parasympathetic modulation of HR after MBC in R+, suggesting a concomitant increase of bronchial and cardiac parasympathetic activity during the challenge (Fig 1). We have also shown that HF n.u. was significantly linked to the bronchial responsiveness at baseline or after MBC. These results are in agreement with a previous study21 showing that asthmatic subjects exhibited a significant increased response to occulocardiac reflex testing. The R-R interval variability was also significantly greater in asthmatic patients than in subjects with normal airway responsiveness as observed by Hashimoto et al,22 who showed a significant correlation between the R-R variability and the increase in respiratory resistance after MBC (r = 0.536, p < 0.05). Other authors723 suggested the presence of a relationship between the magnitude of respiratory sinus arrhythmia and the degree of bronchial hyperreactivity in a group of asthmatic patients. However, other phenomenon could contribute to the increase in HF oscillations in hyperresponsive patients, such as the increase in transpulmonary pressure during bronchoconstriction, which could directly affect intrathoracic baroreceptors and produce a direct parasympathetic stimulation.

Parasympathetic Tone and Disease
AHR associated with asthma, upper respiratory tract infection, rhinitis, or gastroesophageal reflux can often be reversed by anticholinergic agents such as atropine or ipratropium bromide, suggesting a prominent role for the autonomic nervous system in airway dysfunction.3 Indeed, Knopfli and Bar-Or24 observed that the protective effect of ipratropium bromide inhalation was linked to the cardiac parasympathetic activity in six healthy cross-country runners who acquired exercise-induced bronchoconstriction. These results confirm a relationship between cardiac and bronchial parasympathetic tone.25 In this study, a correlation between the increase in airway parasympathetic tone assessed by the decrease of FEV1 and the rise in cardiac parasympathetic tone (HF ms2) was observed after MBC (r = 0.39, p < 0.01). Similar results have been observed in asthma.723 However, some authors have observed a significant decrease of autonomic nervous system activity in patients with COPD1326 that could be related to the worsening of the disease.26 Therefore, it could be of great interest to focus on the reason why changes in autonomic nervous system activity are opposite in asthma and COPD. As proposed by Costello et al,27 the activity of sensory nerves and of vagal nerves center output, and the transmission through cholinergic ganglia would increase with asthma or AHR. Therefore, the modifications or dysregulation of autonomic neural control of airway might produce an extensive parasympathetic/sympathetic imbalance, which can be observed on HR modulation. Indeed, neuronal reflex locally initiated in the airway via methacholine inhalation can deeply influence the physiologic factors of other sites, and produce both local and systemic symptoms. In the CNS, where afferent inputs from throughout the body converge, airway stimulation may be associated with central sensitization, leading to the modulation of the neural reflexes.28 Therefore, it will be of great interest to assess the relationship between changes in autonomic nervous system response and bronchial hyperresponsiveness immediately and few months after lung transplantation in normal and asthmatic recipients and with transplant organ from normal and asthmatic patients.29

Effects of Outcome Variables
Multiple regression analyses have shown that the HF ms2 component was influenced by physical activity habits at baseline and after MBC. Recently, Langdeau et al8 failed to demonstrate any significant link between SDNN, an index of parasympathetic modulation, and AHR, in spite of a greater SDNN in hyperresponsive athletes than in control subjects. However, they observed a significant relationship between the catecholamines/parasympathetic tone balance and the AHR. They have proposed that the decrease in sympathovagal balance toward parasympathetic prevalence might contribute to the increase in AHR in athletes. In this study, there was no correlation between hyperresponsiveness and parasympathetic tone in R+, but we have found a significant relationship between the amount of physical activity and the index of parasympathetic modulation (HF ms2) in all the subjects. Consequently, we only confirm the increase of parasympathetic basal tone with physical activity.30 We have also shown in all subjects a significant influence of smoking habits and baseline FVC on the HF ms2 measured after MBC. These results confirm the effects of baseline respiratory characteristics on changes in parasympathetic modulation after the MBC.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
In summary, this study has established a relationship between bronchial and cardiac parasympathetic tone in subjects with AHR, either at baseline or after an MBC. Moreover, we observed in all subjects that physical activity and hyperresponsiveness significantly influenced parasympathetic modulation of HR. We propose that modification of HR oscillatory pattern or its impaired responsiveness to a given stimulus can reflect an altered autonomic control and thus furnish interesting prognostic markers.


   Acknowledgements
 
We thank the lung physiology laboratory technicians for their help during the experiments and the subjects for their participation.


   Footnotes
 
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

This work was performed at Service d’Explorations Fonctionnelles, Physiologie Respiratoire et de l’Exercice, Pôle Coeur-Poumons, CHU de Poitiers, 86021 Poitiers, France; Number of agreement: 20020S 20020M.

Received for publication March 8, 2004. Accepted for publication August 18, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Jordan, D (2001) Central nervous pathways and control of the airways. Respir Physiol 125,67-81[CrossRef][ISI][Medline]
  2. Canning, BJ, Fischer, A Neural regulation of airway smooth muscle tone. Respir Physiol 2001;125,113-127[CrossRef][ISI][Medline]
  3. Mazzone, SB, Canning, BJ Evidence for differential reflex regulation of cholinergic and noncholinergic parasympathetic nerves innervating the airways. Am J Respir Crit Care Med 2002;165,1076-1083[Abstract/Free Full Text]
  4. Zaagsma, J, Roffel, AF, Meurs, H Muscarinic control of airway function. Life Sci 1997;60,1061-1068[CrossRef][ISI][Medline]
  5. Crimi, E, Milanese, M, Pingfang, S, et al Allergic inflammation and airway smooth muscle function. Sci Total Environ 2001;270,57-61[CrossRef][Medline]
  6. Barnes, PJ Neural control of human airways in health and disease. Am Rev Respir Dis 1986;134,1289-1314[ISI][Medline]
  7. Fujii, H, Fukutomi, O, Inoue, R, et al Autonomic regulation after exercise evidenced by spectral analysis of heart rate variability in asthmatic children. Ann Allergy Asthma Immunol 2000;85,233-237[ISI][Medline]
  8. Langdeau, JB, Turcotte, H, Desagne, P, et al Influence of sympatho-vagal balance on airway responsiveness in athletes. Eur J Appl Physiol 2000;83,370-375[CrossRef][ISI][Medline]
  9. Akselrod, SD, Gordon, FA, Ubel, DC, et al Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981;213,220-222[Abstract/Free Full Text]
  10. Pomeranz, B, Macaulay, RJ, Caudill, MA, et al Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 1985;248,H151-H153
  11. Pagani, M, Lombardi, F, Guzzetti, S, et al Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 1986;59,178-193[Abstract/Free Full Text]
  12. Saul, JP, Arai, Y, Berger, RD, et al Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol 1988;61,1292-1299[CrossRef][ISI][Medline]
  13. Volterrani, M, Scalvini, S, Mazzuero, G, et al Decreased heart rate variability in patients with chronic obstructive pulmonary disease. Chest 1994;106,1432-1437[Abstract/Free Full Text]
  14. Tulppo, MP, Makikallio, TH, Seppanen, T, et al Heart rate dynamics during accentuated sympathovagal interaction. Am J Physiol 1998;274,H810-H816
  15. Keselbrener, L, Akselrod, S Selective discrete Fourier transform algorithm for time-frequency analysis: method and application on simulated and cardiovascular signals. IEEE Trans Biomed Eng 1996;43,789-802[CrossRef][ISI][Medline]
  16. Canning, BJ, Fischer, A Neural regulation of airway smooth muscle tone. Respir Physiol 2000;125,113-127
  17. Douglas, NJ, Sudlow, MF, Flenley, DC Effect of an inhaled atropine-like agent on normal airway function. J Appl Physiol 1979;46,256-262[Abstract/Free Full Text]
  18. Widdicombe, JG Action potentials in parasympathetic and sympathetic efferent fibres to the trachea and lungs of dogs and cats. J Physiol 1966;186,56-88[ISI][Medline]
  19. Molfino, NA, Slutsky, AS, Julia-Serda, G, et al Assessment of airway tone in asthma: comparison between double lung transplant patients and healthy subjects. Am Rev Respir Dis 1993;148,1238-1243[ISI][Medline]
  20. Horvath, I, Argay, K, Herjavecz, I, et al Relation between bronchial and cardiac vagal tone in healthy humans. Chest 1995;108,701-705[Abstract/Free Full Text]
  21. Denjean, A, Renaudin, P, Gaultier, C Increased vagally-mediated response to oculo-cardiac reflex in asthmatic subjects compared to normal subjects [abstract]. Am Rev Respir Dis 1990;141,A755
  22. Hashimoto, A, Maeda, H, Yokoyama, M Augmentation of parasympathetic nerve function in patients with extrinsic bronchial asthma: evaluation by coefficiency of variance of R-R interval with modified long-term ECG monitoring system. Kobe J Med Sci 1996;42,347-359[Medline]
  23. Kallenbach, JM, Webster, T, Dowdeswell, R, et al Reflex heart rate control in asthma: evidence of parasympathetic overactivity. Chest 1985;87,644-648[Abstract/Free Full Text]
  24. Knopfli, BH, Bar-Or, O Vagal activity and airway response to ipratropium bromide before and after exercise in ambient and cold conditions in healthy cross-country runners. Clin J Sport Med 1999;9,170-176[ISI][Medline]
  25. Finnerty, JP, Holgate, ST The contribution of histamine release and vagal reflexes, alone and in combination, to exercise-induced asthma. Eur Respir J 1993;6,1132-1137[ISI][Medline]
  26. Stein, PK, Nelson, P, Rottman, JN, et al Heart rate variability reflects severity of COPD in PiZ {alpha}1-antitrypsin deficiency. Chest 1998;113,327-333[Abstract/Free Full Text]
  27. Costello, RW, Jacoby, DB, Fryer, AD Pulmonary neuronal M2 muscarinic receptor function in asthma and animal models of hyperreactivity. Thorax 1998;53,613-616[Free Full Text]
  28. Undem, BJ, Kajekar, R, Hunter, DD, et al Neural integration and allergic disease. J Allergy Clin Immunol 2000;106(suppl),S213-S220
  29. Corris, PA, Dark, JH Aetiology of asthma: lessons from lung transplantation. Lancet 1993;341,1369-1371[CrossRef][ISI][Medline]
  30. Mandigout, S, Melin, A, Fauchier, L, et al Physical training increases heart rate variability in healthy prepubertal children. Eur J Clin Invest 2002;32,479-487[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pichon, A.
Right arrow Articles by Denjean, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pichon, A.
Right arrow Articles by Denjean, A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS