Paced Respiration Research Articles

A randomised controlled trial of a cognitive behavioural intervention for men who have hot flushes following prostate cancer treatment (MANCAN): trial protocol.

BackgroundThis randomised controlled trial (RCT) aims to evaluate the effectiveness of a guided self-help cognitive behavioural intervention to alleviate problematic hot flushes (HF) and night sweats (NS) in men who are undergoing prostate cancer treatment. The trial and the self-help materials have been adapted from a previous RCT, which showed that a cognitive behavioural intervention reduced the self-reported problem-rating of hot flushes in women with menopausal symptoms, and in women undergoing breast cancer treatment. We hypothesize that guided self-help will be more effective than usual care in reducing HF/NS problem-rating at post treatment assessment.Methods/DesignSeventy men who are undergoing treatment for prostate cancer and who have been experiencing more than ten HF/NS weekly for over a month are recruited into the trial from urology clinics in London. They are randomly allocated to either a four-week self-help cognitive behavioural therapy (CBT) treatment or to their usual care (control group). The treatment includes information and discussion about hot flushes and night sweats in the context of prostate cancer, monitoring and modifying precipitants, relaxation and paced respiration, stress management, cognitive therapy for unhelpful thoughts and beliefs, managing sleep and night sweats, and advice on maintaining these changes.Prior to randomisation, men attend a clinical interview, undergo 24-48-hour sternal skin conductance monitoring, and complete pre-treatment questionnaires (e.g., problem-rating and frequency of hot flushes and night sweats; quality of life; mood; hot flush beliefs and behaviours). Post-treatment measures (sternal skin conductance and the above questionnaires) are collected four-six weeks later, and again at a six-month follow-up.DiscussionMANCAN is the first randomised controlled trial of cognitive behavioural therapy for HF/NS for men that measures both self-reported and physiologically indexed symptoms. The results will inform future clinical practice by evaluating an evidence-based, non-medical treatment, which can be delivered by trained health professionals.Trial registrationUK Clinical Research Network UKCRN10904.

Device-Guided Paced Respiration as an Adjunctive Therapy for Hypertension in Obstructive Sleep Apnea: A Pilot Feasibility Study

Data suggest that device-guided paced respiration (<10 breaths/min) may reduce blood pressure in hypertensive patients. We hypothesized that daily device-guided slow breathing may lower blood pressure in patients with hypertension and obstructive sleep apnea (OSA). In this one-arm pilot study, we enrolled 25 subjects with hypertension and OSA. Subjects were asked to perform device-guided paced respiration 30min a day for 8weeks. Our primary outcome was change in office systolic and diastolic blood pressures from baseline to 8weeks. Twenty-four subjects completed the study. Mean baseline blood pressure was 140.0±10.2mmHg systolic and 82.7±8.9mmHg diastolic. Complete device data were available for 17 subjects. Mean device adherence was 81±24% and 51% achieved a mean breath rate ≤10 breaths/min over 8weeks. Three subjects had changes in their anti-hypertensive medications during the study. Among the remaining 21 subjects, mean difference in office blood pressure from baseline to 8weeks was -9.6±11.8mmHg systolic (p≤0.01) and -2.52±8.9mmHg diastolic (p=0.21). Device-guided paced respiration may lower systolic blood pressure in patients with hypertension and OSA; however, our findings need to be confirmed with larger randomized controlled trials.

A randomised controlled trial of a cognitive behavioural intervention for women who have menopausal symptoms following breast cancer treatment (MENOS 1): Trial protocol

BackgroundThis trial aims to evaluate the effectiveness of a group cognitive behavioural intervention to alleviate menopausal symptoms (hot flushes and night sweats) in women who have had breast cancer treatment. Hot flushes and night sweats are highly prevalent but challenging to treat in this population. Cognitive behaviour therapy has been found to reduce these symptoms in well women and results of an exploratory trial suggest that it might be effective for breast cancer patients. Two hypotheses are tested:Compared to usual care, group cognitive behavioural therapy will:1. Significantly reduce the problem rating and frequency of hot flushes and nights sweats after six weeks of treatment and at six months post-randomisation.2. Improve mood and quality of life after six weeks of treatment and at six months post-randomisation.Methods/DesignNinety-six women who have completed their main treatment for breast cancer and who have been experiencing problematic hot flushes and night sweats for over two months are recruited into the trial from oncology and breast clinics in South East London. They are randomised to either six weekly group cognitive behavioural therapy (Group CBT) sessions or to usual care. Group CBT includes information and discussion about hot flushes and night sweats in the context of breast cancer, monitoring and modifying precipitants, relaxation and paced respiration, stress management, cognitive therapy for unhelpful thoughts and beliefs, managing sleep and night sweats and maintaining changes.Prior to randomisation women attend a clinical interview, undergo 24-hour sternal skin conductance monitoring, and complete questionnaire measures of hot flushes and night sweats, mood, quality of life, hot flush beliefs and behaviours, optimism and somatic amplification. Post-treatment measures (sternal skin conductance and questionnaires) are collected six to eight weeks later and follow-up measures (questionnaires and a use of medical services measure) at six months post-randomisation.DiscussionMENOS 1 is the first randomised controlled trial of cognitive behavioural therapy for hot flushes and night sweats that measures both self-reported and physiologically indexed symptoms. The results will inform future clinical practice by developing an evidence-based, non-medical treatment, which can be delivered by trained health professionals.Trial RegistrationCurrent Controlled Trials ISRCTN13771934

Advances in the Treatment of Menopausal Symptoms

Vasomotor symptoms and vaginal atrophy are both common menopausal symptoms. Hormone therapy is currently the only FDA-approved treatment for hot flashes. Current recommendations are to use the lowest dose of hormone therapy for the shortest period that will allow treatment goals to be met. Although the reanalysis of the WHI in 2007 by Roussow et al. provided evidence of coronary heart safety for users of hormone therapy under the age of 60 years and within 10 years of the onset of menopause, not all women desire or are candidates for hormone therapy. In this review we present an evidence-based discussion considering the effectiveness of hormonal and nonhormonal therapies for the relief of vasomotor symptoms and vaginal atrophy. Concern exists regarding systemic absorption of vaginal estrogen and possible adverse effects on the breast and uterus. Selective estrogen receptor modulators and estrogen agonists offer benefits through targeted estrogen agonist/antagonistic effects and are being evaluated with and without estrogen for symptomatic menopausal women. Centrally acting nonhormonal therapies that are effective for the relief of vasomotor symptoms include various antidepressants, gabapentin and clonidine. A limited number of clinical trials have been conducted with nonprescription remedies, including paced respiration, yoga, acupuncture, exercise, homeopathy and magnet therapy, and some, but not all of these, have been found to be more effective than placebo. Dietary herbal supplements, such as soy and black cohosh, have demonstrated mixed and inconclusive results in placebo-controlled trials. Potential therapies for vasomotor symptoms and vaginal atrophy require randomized, placebo-controlled trials of sufficient duration to establish efficacy and safety. Agents under investigation for vasomotor symptoms relief include neuroactive agents, such as gabapentin and desvenlafaxine; an estrogen receptor-beta-targeted herbal therapy, MF-101; and the selective estrogen receptor modulator, bazedoxifene, paired with estrogen.

Influence of respiratory rate on the variability of blood volume pulse characteristics

Photoplethysmogram (PPG) measures have been proven useful for the quantification of sympathetic reactivity and continuous monitoring of vascular reactivity. This study was designed to delineate the influence of respiratory rate on the variability of various PPG characteristics in time and frequency domains. PPG, electrocardiogram (ECG) and respiration were simultaneously recorded for 2 min from eight healthy volunteers during paced respiration of 6, 12 and 18 cycles min−1. The PPG characteristics such as peak-to-peak interval (PPI), systolic peak amplitude, slope, Tcrest, Tdecay and pulse transit time (PTT) were computed for every pulse. In time domain, the mean of amplitude, slope and Tcrest were not significantly different amongst three different respiratory rates. However, the mean of Tdecay, PPI and PTT were significantly increased (p < 0.05, p < 0.05 and p < 0.01, respectively) during respiration of 6 cycles min−1 compared to 12 cycles min−1. The maximal spectral powers of the variability of all PPG measures were centred on the respiratory frequency in frequency domain. In conclusion, the results that the amplitude and slope in time domain are not altered by the respiratory frequency suggest their application in faithful assessment of cardiovascular reactivity. As the variability of PPI, Tdecay and PTT are altered by the slow respiration, the influence of respiration on these time derivatives should not be ignored during interpretation of vascular reactivity.

Breast Cancer Survivors and Hot Flashes: The Search for Nonhormonal Treatments

Breast Cancer Survivors and Hot Flashes: The Search for Nonhormonal Treatments

Point:Counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is

Trait Negative Affect: Toward an Integrated Model of Understanding Psychological Risk for Impairment in Cardiac Autonomic Function

To assess depression, anxiety, and anger as well as the variance that these emotions share (conceptualized as negative affect) in relationship to high-frequency heart rate variability (HF-HRV), a specific indicator of parasympathetic cardiac autonomic function related to premature cardiovascular morbidity and mortality. Although individual trait negative emotions have been studied in relation to risk for coronary heart disease (CHD) as well as biological mechanisms leading to CHD end points (e.g., autonomic nervous system [ANS] dysfunction), the degree to which a general tendency to experience negative emotions may account for these relations is not known. The sample included 653 community volunteers (51.0% female; 15.8% Black) aged 30 to 54 years (mean +/- standard deviation = 43.8 +/- 7.1 years). Latent constructs of depression, anxiety, and anger were each measured by three scales from well-validated self-report questionnaires. Resting HF-HRV was derived from 5-minute segments of continuous electrocadiographs recorded during both unpaced and paced respiration conditions. Structural equation models (SEM) of the individual trait emotions showed depression and anxiety related inversely to HF-HRV and anger unrelated to HF-HRV. SEM also showed negative affect related inversely to HF-HRV. All associations were present after covariate adjustment for traditional cardiovascular risk factors, including age, sex, race, education, body mass index, smoking status, and blood pressure. Negative affect as a common pathway between depression, anxiety, and anger and impairments in cardiac autonomic function was supported, suggesting negative affect may be the unifying and potentially toxic element linking individual trait negative emotions to ANS dysregulation.

Stimulated Production of Proinflammatory Cytokines Covaries Inversely With Heart Rate Variability

To examine whether high-frequency heart rate variability, an indirect measure of parasympathetic (vagal) control over variations in heart rate, is associated with immune reactivity to an in vitro inflammatory challenge. Convergent evidence from the animal literature shows that the autonomic nervous system plays a key role in regulating the magnitude of immune responses to inflammatory stimuli. Signaling by the parasympathetic system inhibits the production of proinflammatory cytokines by activated monocytes/macrophages and thus decreases local and systemic inflammation. As yet, no direct human evidence links parasympathetic activity to inflammatory competence. We examined the relationship of variations in heart rate, recorded during paced respiration, to lipopolysaccharide-induced production of the inflammatory cytokines interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10 among a community sample of 183 healthy adults (mean age = 45 years; 59% male; 92% White, 7% African-American). Consistent with animal findings, higher derived estimates of vagal activity measured during paced respiration were associated with lower production of the proinflammatory cytokines TNF-alpha and IL-6 (r = -.18 to -.30), but were not related to production of the anti-inflammatory cytokine IL-10. These associations persisted after controlling for demographic and health characteristics, including age, gender, race, years of education, smoking, hypertension, and white blood cell count. These data provide initial human evidence that vagal activity is inversely related to inflammatory competence, raising the possibility that vagal regulation of immune reactivity may represent a pathway linking psychosocial factors to risk for inflammatory disease.

Hot flashes: behavioral treatments, mechanisms, and relation to sleep

Hot flashes are the most common symptom of the climacteric and occur in about 75% of perimenopausal and postmenopausal women in Western societies. Although hot flashes accompany the withdrawal of estrogen at menopause, the decline in estrogen levels is not sufficient to explain their occurrence. Elevated sympathetic activation acting through central alpha(2)-adrenergic receptors contributes to the initiation of hot flashes, possibly by narrowing the thermoneutral zone in symptomatic women. Hot flashes are then triggered by small elevations in core body temperature acting within this narrowed zone. A relaxation-based method, paced respiration, has been shown in 3 controlled investigations to significantly reduce objectively measured hot flash occurrence by about 50% with no adverse effects. In 6 studies of physical exercise, however, investigators did not find positive effects on hot flashes, possibly because exercise raises core body temperature, thereby triggering hot flashes. Although many epidemiologic studies have found increased reports of sleep disturbance during the menopausal transition, recent laboratory investigations have not found this effect, nor have they found that hot flashes produce disturbed sleep. Therefore, sleep complaints in women at midlife should not routinely be attributed to hot flashes or to menopause.

Leave-one-out prediction error of systolic arterial pressure time series under paced breathing

In this paper, we consider systolic arterial pressure time series from healthy subjects and chronic heart failure patients, undergoing paced respiration, and show that different physiological states and pathological conditions may be characterized in terms of predictability of time series signals from the underlying biological system. We model time series by the regularized least-squares approach and quantify predictability by the leave-one-out error. We find that the entrainment mechanism connected to paced breath, that renders the arterial blood pressure signal more regular and thus more predictable, is less effective in patients, and this effect correlates with the seriousness of the heart failure. Using a Gaussian kernel, so that all orders of nonlinearity are taken into account, the leave-one-out error separates controls from patients (probability less than 10−7), and alive patients from patients for whom cardiac death occurred (probability less than 0.01).

Deriving main rhythms of the human cardiovascular system from the heartbeat time series and detecting their synchronization

We demonstrate a possibility of determining the instantaneous phases and instantaneous frequencies of the main rhythmic processes governing the cardiovascular dynamics in humans from heart rate variability data with the methods using bandpass filtration, empirical mode decomposition and wavelet transform. For the cases of spontaneous respiration and paced respiration with a fixed frequency we investigate synchronization between the rhythms of the cardiovascular system analyzing univariate data in the form of the heartbeat time series. It is shown that the main heart rhythm and the rhythm of slow regulation of blood pressure with fundamental frequency close to 0.1 Hz can be synchronized with respiration.

Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis

Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25–27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of spontaneous respiration (either two or three recordings with a constant frequency in the interval between 0.09 and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was confirmed that the dynamics of blood flow can usefully be considered in terms of coupled oscillators, and demonstrated that interactions between the cardiac and respiratory processes are weak and time-varying, and that they can be nonlinear. Nonlinear coupling was revealed to exist during both spontaneous and paced respiration. When present, it was detected in all four blood flow signals and in the cross-bispectrum between the ECG and respiratory signal. The episodes with nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19 s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency paced respiration (0.11 Hz).

Deriving main rhythms of the human cardiovascular system from the heartbeat time series and detecting their synchronization

We demonstrate a possibility of determining the instantaneous phases and instantaneous frequencies of the main rhythmic processes governing the cardiovascular dynamics in humans from heart rate variability data with the methods using bandpass filtration, empirical mode decomposition and wavelet transform. For the cases of spontaneous respiration and paced respiration with a fixed frequency we investigate synchronization between the rhythms of the cardiovascular system analyzing univariate data in the form of the heartbeat time series. It is shown that the main heart rhythm and the rhythm of slow regulation of blood pressure with fundamental frequency close to 0.1 Hz can be synchronized with respiration.

Causality Between the Amplitude and Frequency of Cardiac Oscillations

Using an information-theoretic approach, causality between the systolic amplitude in blood pressure and the frequency of the heart beat was analyzed. Blood pressure and ECG were noninvasively recorded in young, healthy subjects. Three successive measurements were performed: during spontaneous breathing and during paced respiration—at frequencies both higher and lower than that of spontaneous respiration. We demonstrate that the amplitude and frequency of the cardiac rhythm are synchronized for most of the time. The synchronization is stronger during paced respiration at a frequency lower than that of spontaneous breathing. Episodes where the cardiac frequency was driven by the systolic pressure were also detected during slow, paced respiration.

Influence of controlled breathing patterns on cerebrovascular autoregulation and cardiac baroreceptor sensitivity

Transfer function analysis has become one of the main techniques to study the dynamic relationship between cerebral blood flow and arterial blood pressure, but the influence of different respiratory rates on cerebral blood flow has not been fully investigated. In 14 healthy volunteers, middle cerebral artery blood flow velocity, recorded using transcranial Doppler ultrasound, non-invasive beat-to-beat Finapres blood pressure, ECG and end-tidal CO(2) ( P ECTO(2)) levels were recorded with subjects resting supine and breathing spontaneously or at controlled rates of 6, 10 and 15 breaths/min. Transfer function analysis and impulse and step responses were computed at each respiratory rate. P ECTO(2) levels tended to fall slightly during paced respiration, especially at 15 breaths/min. Controlled breathing rates did not alter transfer function analysis in the frequency range below 0.08 Hz but, above this frequency, the coherence function contained significant peaks corresponding to the respiratory frequencies. The impulse response was similar at all breathing rates, but the step response was characteristic of more efficient autoregulation with reduced P ECTO(2) levels associated with increasing respiratory rate. The effects of breathing rate and rhythmicity and P ECTO(2) must be considered in studies of cerebral autoregulation.

Menopause: new therapies.

The risk-benefit ratio of traditional postmenopausal hormone therapy is considered by many to be unacceptable. Low-dose oestrogen-progestin therapy (oral or non-oral and continuous or pulsatile) may have a better risk-benefit ratio, but this remains unproven. Steroids with selective tissue activation, such as tibolone, alleviate symptoms and protect against bone loss, but long-term safety data are lacking. Selective oestrogen receptor modulators (SERMs), such as raloxifene, prevent bone loss when used alone, and may soon be combined with oestradiol to treat symptoms and prevent osteoporotic fracture. Effects of SERMs on the cardiovascular system are currently being evaluated.

Regions of cardiorespiratory synchronization in humans under paced respiration.

Cardiorespiratory synchronization under paced respiration is studied systematically as the respiration frequency is changed between 3 and 30 breaths per min. We plot a one-dimensional cut of the classical picture of synchronization regions along the line defining the current breathing amplitude. The existence of n:m synchronization regions of finite width is demonstrated for each of six subjects studied. The statistics of the different types of synchronization and their stability are discussed.

Modulating effect of respiration on atrioventricular conduction time assessed using PR interval variation.

Respiratory sinus arrhythmia (RSA) is the variation of heart rate (or RR interval) in phase with respiration and has been extensively studied. However, the effect of respiration on atrioventricular conduction delay (and hence PR interval length) has not yet received much attention. This work reports on measurements of respiration and associated RR and PR variability, in 11 subjects, assessed through surface electrocardiogram measurements, for both paced and spontaneous respiration in the supine position. A wavelet-based approach was used to extract RR and PR intervals. The accuracy of RR and PR interval measurement was consistent with previously published work. Respiratory atrioventricular conduction delay variability (RCV) was assessed using three techniques: spectral, peak-to-trough and cosinor methods. All measures showed statistically significant variations in PR interval due to respiration during paced respiration at 6 min(-1). Of the three measures, cosinor analysis was most reliable in highlighting RCV. Using this measure, statistically significant RCV was seen in ten out of the 11 subjects during paced respiration. The magnitude of the variability was estimated as +/- 5.9% of the mean PR interval. In spontaneous respiration, statistically significant RCV was seen in approximately half of the subjects, with an estimated variability of +/- 1.5%. As a control, statistically significant values for RSA were also obtained from the same data, which agreed with previously published measurements. It was concluded that respiration does indeed modulate atrioventricular conduction delay, deep breathing in the supine position accentuates this effect, and cosinor analysis provides a reliable means for quantifying this effect.

The effect of stimulus probability on P3 in the respiratory‐related evoked potential

The present study investigated the effect of target stimulus probability on the P3 component of the respiratory‐related evoked potential (RREP). A single respiratory stimulus paradigm was employed where normal breaths served as standard stimuli and occluded breaths presented at various probability levels served as target stimuli. EEG was recorded from 29 channels in young adults in two conditions. In Condition 1, occlusions were presented at target probabilities of 0.5, 0.33, 0.25, 0.2, 0.1, and 0.05, that is, every 2nd, 3rd, 4th, 5th, 10th, and 20th breath. Order of target probability presentation varied randomly. Condition 2 used the same target probabilities, but held breathing rate constant by using a paced respiration task. Results indicated that P3 amplitude was significantly affected by stimulus probability, such that the component showed an inverse relationship with probability. This effect was similar between conditions. However, P3 amplitude reduced and latency increased when the secondary task of paced respiration was introduced. These data suggest that models developed to describe the effect of stimulus probability on the amplitude of visual and auditory P3 components are applicable to the respiratory somatosensory modality.