Voluntary Inspiration Research Articles

Clinical implementation and evaluation of stereotactic liver radiotherapy in inspiration breath-hold using nasal high flow therapy and surface guidance.

To evaluate two years of clinical experience with markerless breath-hold liver stereotactic radiotherapy (SBRT) using non-invasive nasal high flow therapy (NHFT) for breath-hold prolonging and surface guidance (SGRT) for monitoring. Heated and humidified air was administered via a nasal cannula (40 L/min, 80% oxygen, 34 °C). Patients performed voluntary inspiration breath-holds with visual feedback. After a training session, 4-5 breath-hold CT scans were acquired to delineate an internal target volume (ITV) accounting for inter- and intra-breath-hold variations. Patients were treated in 3-8 fractions (7.5-20 Gy/fraction) using SGRT-controlled beam-hold. Patient setup was performed using SGRT and CBCT imaging. A post-treatment CBCT was acquired for evaluation purposes. Fifteen patients started the training session and received treatment, of whom 10 completed treatment in breath-hold. Half of all 60-second CBCT scans were acquired during a single breath-hold. The average maximum breath-hold duration during treatment ranged from 47-108 s. Breath-hold ITV was on average 6.5 cm³/30% larger (range: 1.1-23.9 cm³/5-95%) than the largest GTV. Free-breathing ITV based on 4DCT scans was on average 16.9 cm³/47% larger (range: -2.3-58.7 cm3/-16-157%) than the breath-hold ITV. The average 3D displacement vector of the area around PTV for the post-treatment CBCT scans was 5.0 mm (range: 0.7-12.9 mm). Liver SBRT in breath-hold using NHFT and SGRT is feasible for the majority of patients. An ITV reduction was observed compared to free-breathing treatments. To further decrease the PTV, internal anatomy-based breath-hold monitoring is desired. Non-invasive NHFT allows for prolonged breath-holding during surface-guided liver SBRT.

Low‐cost Kinect Version 2 imaging system for breath hold monitoring and gating: Proof of concept study for breast cancer VMAT radiotherapy

Voluntary inspiration breath hold (VIBH) for left breast cancer patients has been shown to be a safe and effective method of reducing radiation dose to the heart. Currently, VIBH protocol compliance is monitored visually. In this work, we establish whether it is possible to gate the delivery of radiation from an Elekta linac using the Microsoft Kinect version 2 (Kinect v2) depth sensor to measure a patient breathing signal. This would allow contactless monitoring during VMAT treatment, as an alternative to equipment–assisted methods such as active breathing control (ABC). Breathing traces were acquired from six left breast radiotherapy patients during VIBH. We developed a gating interface to an Elekta linac, using the depth signal from a Kinect v2 to control radiation delivery to a programmable motion platform following patient breathing patterns. Radiation dose to a moving phantom with gating was verified using point dose measurements and a Delta4 verification phantom. 60 breathing traces were obtained with an acquisition success rate of 100%. Point dose measurements for gated deliveries to a moving phantom agreed to within 0.5% of ungated delivery to a static phantom using both a conventional and VMAT treatment plan. Dose measurements with the verification phantom showed that there was a median dose difference of better than 0.5% and a mean (3% 3 mm) gamma index of 92.6% for gated deliveries when using static phantom data as a reference. It is possible to use a Kinect v2 device to monitor voluntary breath hold protocol compliance in a cohort of left breast radiotherapy patients. Furthermore, it is possible to use the signal from a Kinect v2 to gate an Elekta linac to deliver radiation only during the peak inhale VIBH phase.

Cortical Drive to Breathe during Wakefulness in Patients with Obstructive Sleep Apnea Syndrome.

The obstructive sleep apnea syndrome (OSAS) involves recurrent sleep-related upper airways (UA) collapse. UA mechanical properties and neural control are altered, imposing a mechanical load on inspiration. UA collapse does not occur during wakefulness, hence arousal-dependent compensation. Experimental inspiratory loading in normal subjects elicits respiratory-related cortical activity. The objective of this study was to test whether awake OSAS patients would exhibit a similar cortical activity. Descriptive physiology study. Sleep laboratory in a large university affiliated tertiary hospital. 26 patients with moderate OSAS according to polysomnography (5 < apnea-hypopnea index [AHI] ≤ 30, n = 14) or severe OSAS (AHI > 30, n = 12); 13 non-OSAS patients for comparison. None. Respiratory time-locked electroencephalographic segments ensemble averaged and analyzed for slow premotor potentials preceding inspiration ("pre-inspiratory potentials" [PIPs]). PIPs were present in 1/13 controls and 11/26 patients (P = 0.0336; 4/14 "moderate" and 7/12 "severe" patients). Awake OSAS patients therefore exhibit respiratory-related cortical activity during quiet breathing significantly more frequently than non-OSAS individuals. The corresponding PIPs resemble those observed during prepared voluntary inspirations and in response to experimental inspiratory loads in normal subjects, which involve a cortical network comprising the supplementary motor area. A respiratory-related cortical activity could contribute to the increased neural drive to upper airway and to inspiratory muscles that has previously been described in obstructive sleep apnea, and could therefore contribute to the arousal-dependent compensation of upper airway abnormalities. Whether or not such cortical compensatory mechanisms have cognitive consequences remains to be determined.

Electroencephalographic evidence for a respiratory-related cortical activity specific of the preparation of prephonatory breaths

Speech is a major disturbance to automatic breathing control. Speech occurs during exhalation, involving controlled inhibition of automatic inspiration. Additionally, utterances are preceded by prephonatory inspirations that must be prepared to account for prosody and loudness. We hypothesized that the speech-related breathing control activities shaping prephonatory breaths originate in cortical pre-motor areas and should be associated with corresponding EEG evidence. We studied 10 normal subjects (4 men, age 23–27) during spontaneous breathing, sniff manoeuvres, and while reading out loud. Fronto-median inspiratory potentials (Cz EEG derivation) were consistently present before voluntary inspirations and large prephonatory breaths, while these potentials were generally absent during resting breathing or small prephonatory breaths. We conclude that the preparation of prephonatory breaths during speech has a cortical substrate, involving the cortical sources of premotor potentials. These results have important implications to validate whether co-modulation of the pre-motor cortex and breathing during speech are incidental or whether these cortical modulations are necessary for initiation of “speech breathing”.

Effect of inspiration on airway dimensions measured in maximal inspiration CT images of subjects without airflow limitation.

To study the effect of inspiration on airway dimensions measured in voluntary inspiration breath-hold examinations. 961 subjects with normal spirometry were selected from the Danish Lung Cancer Screening Trial. Subjects were examined annually for five years with low-dose CT. Automated software was utilized to segment lungs and airways, identify segmental bronchi, and match airway branches in all images of the same subject. Inspiration level was defined as segmented total lung volume (TLV) divided by predicted total lung capacity (pTLC). Mixed-effects models were used to predict relative change in lumen diameter (ALD) and wall thickness (AWT) in airways of generation 0 (trachea) to 7 and segmental bronchi (R1-R10 and L1-L10) from relative changes in inspiration level. Relative changes in ALD were related to relative changes in TLV/pTLC, and this distensibility increased with generation (p < 0.001). Relative changes in AWT were inversely related to relative changes in TLV/pTLC in generation 3--7 (p < 0.001). Segmental bronchi were widely dispersed in terms of ALD (5.7 ± 0.7 mm), AWT (0.86 ± 0.07 mm), and distensibility (23.5 ± 7.7%). Subjects who inspire more deeply prior to imaging have larger ALD and smaller AWT. This effect is more pronounced in higher-generation airways. Therefore, adjustment of inspiration level is necessary to accurately assess airway dimensions. Airway lumen diameter increases and wall thickness decreases with inspiration. The effect of inspiration is greater in higher-generation (more peripheral) airways. Airways of generation 5 and beyond are as distensible as lung parenchyma. Airway dimensions measured from CT should be adjusted for inspiration level.

STUDY OF EFFECT OF YOGA ON BREATH HOLDING TIME IN MEDICAL STUDENTS

Yoga is the science of right living which includes postures, breathing exercises and cleansing practices. Yoga consists of five principles which include pr oper exercise, proper relaxation, proper breathing, proper diet, positive thinking and meditation. Pranayama is a controlled breathing exercise improves lung functions. This study was conducted to show the positive effect of pranayama on lung functions. S ixty first year M.B.B.S students of Sri Ramachandra University served as subjects. Age group of subjects was around 17 20 years of both genders participated in our study. Of these 60 subjects, 30 motivated students were selected to receive yoga training pr anayama group I and remaining 30 students will serve as controls group II. Breath holding time was analyzed before and after pranayama around the time of ten weeks. Results were analyzed accordingly. There is significant difference in breath holding time i n normal inspiration, maximum voluntary inspiration and after forceful expiration between group I and group II with p < 0.001 statically significant. Our results showed significant increase in breath holding time after regular practice of pranayama the sig nificance is more in breath holding time after normal inspiration.

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Respiratory and Cardiovascular Response during Electronic Control Device Exposure in Law Enforcement Trainees

Objective: Law enforcement represents a large population of workers who may be exposed to electronic control devices (ECDs). Little is known about the potential effect of exposure to these devices on respiration or cardiovascular response during current discharge.Methods: Participants (N = 23) were trainees exposed to 5 s of an ECD (Taser X26®) as a component of training. Trainees were asked to volitionally inhale during exposure. Respiratory recordings involved a continuous waveform recorded throughout the session including during the exposure period. Heart rate was calculated from a continuous pulse oximetry recording.Results: The exposure period resulted in the cessation of normal breathing patterns in all participants and in particular a decrease in inspiratory activity. No significant changes in heart rate during ECD exposure were found.Conclusion: This is the first study to examine breathing patterns during ECD exposure with the resolution to detect changes over this discrete period of time. In contrast to reports suggesting respiration is unaffected by ECDs, present evidence suggests that voluntary inspiration is severely compromised. There is no evidence of cardiac disruption during ECD exposure.

Phase-Dependent Respiratory-Motor Interactions in Reaction Time Tasks During Rhythmic Voluntary Breathing

The study investigated squeezing reaction time (RT) in response to a visual cue during rhythmic voluntary breathing at 0.6 Hz paced by a metronome, breath holding, or at rest in 13 healthy subjects. Rhythmic voluntary breathing slowed down RT, only in the expiratory phase with accompanied changes in the length of respiratory phases, while breath-holding reduced RT. The prolonged RT during voluntary expiratory phases and the absence of changes in RT during voluntary inspiratory phases are most likely related to disproportionally increased cognitive demands during the expiratory phase of voluntary breathing. The absence of changes in RT during voluntary inspiration is likely to be compensated by respiratory-motor facilitation mechanisms in this phase. Shortened RT during breath holding is possibly associated with increased attention.

Initiating inspiration outside the medulla does produce eupneic breathing

ARTERIAL PCO2 IS DICTATED by the ratio between the level of pulmonary gas exchange and alveolar ventilation (VA), not minute ventilation. If so, how could isocapnia be maintained if only the magnitude (tidal volume, VT) and duration (TI and TTOT) of the neural output produced by the central pattern generator of breathing (CPG) can be altered? In other words, what is the strategy used by the respiratory control system to match its output to the level of pulmonary gas exchange to keep arterial blood gas homeostasis if this neural output con- tributes to dead space ventilation? In this Viewpoint, we will show that when the spontaneous breathing is replaced by a cortically triggered breathing pattern at various breathing frequencies (we will name this new rhythm an "ecto-rhythm"), the relationship between TTOT and VT has a positive intercept that averages the pulmonary dead space. As a result, the coupling between ventilation and the pulmonary gas exchange becomes possible (17). We will present the idea that whenever isocapnia is maintained during spontaneous or automatic breathing, the magnitude and dura- tion of breath cycles must display the same relationship as during an ecto-rhythm (15). Conversely, we will discuss the implications of the observation that breathing can display the same essential regulatory properties whether generated outside or within the pontomedullary CPG area (7). Ecto-rhythm, breathing pattern, and gas exchange: the re-

Imaging the brain during sniffing: A pilot fMRI study

Whilst the act of sniffing can provide us with an indirect method to study the central mechanisms of respiratory control, functional neuroimaging now provides us with a tool to directly visualise the activity of the human brain during this voluntary action using functional magnetic resonance imaging (fMRI). We performed fMRI during sniffing in 11 healthy volunteers where all subjects executed single, brisk sniffs of around 60% of their maximum sniff pressure at intervals of approximately every 20 s. Simultaneous nasal pressure and chest movements were also measured during the task and a statistical parametric map of activation correlating with the sniff manoeuvre was calculated. A bilateral cortical and subcortical sensorimotor network was activated. The activations were localised within the primary sensorimotor cortex, lateral premotor cortex, supplementary motor area, anterior cingulate, insula, basal ganglia, thalami, mesencephalon, upper pons, cerebellar vermis, piriform cortex, entorhinal cortex and parahippocampal gyrus. The activated brain areas identified, i.e. the cortical and subcortical respiratory network, are similar to those described in other neuroimaging studies of voluntary inspiration. Sniffing is a component of olfactory processing and activations of the olfaction-related cortical areas were also observed in our study. The results of our study show that event-related fMRI can be successfully used to study sniffing. This provides a novel approach to our study of the central neural control of respiration.

How do respiratory state and measurement method affect bra size calculations?

Objectives: To investigate the effects of respiratory state and measurement method on bra size calculation. Methods: The bra sizes of 16 large-breasted women were measured during two respiratory states, end...

Interactions between volitional and automatic breathing during respiratory apraxia

The sites and forms of interactions between voluntary breathing acts and automatic respiratory rhythm generation are the subject of considerable research interest. We report here observations of the control of breathing in a patient suffering from an advanced form of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). This patient demonstrated a severely compromised ability to perform volitional respiratory acts upon command, despite exacerbated behavioural and automatic control of respiration. The presence of residual volitional control of breathing in this patient provided interesting insights concerning the interaction between the automatic and the voluntary control of respiration. We observed that (1) when the subjects was asked to inspire voluntarily he could at best mobilize a volume similar to spontaneous VT and only very slowly; (2) automatic breathing movements persisted, superimposed onto the active voluntary movements, with an amplitude that decreased when the inspiratory activity, albeit weak, reached its maximal level; (3) during breath holding both the amplitude and the frequency of the basal spontaneous rhythmic activity were depressed. This observation therefore supports the idea of a strong interaction between volitional and automatic breathing in the form of an inhibition of automatic activity during voluntary breathing. Although, the site of interaction (spinal versus supraspinal) could not be determined during volitional inspiration, the effect of breath holding on the frequency of the spontaneous breathing activity supports the view that a volitional breathing arrest has some inhibitory effects on the respiratory oscillator at the medullary level. Finally, in an attempt to reconcile the persistence of a rhythmic activity during voluntary inspiration and expiration with previous data from the literature, it is proposed that the normal suppression of the automatic activity during voluntary inspiration relies on cortical and sub-cortical structures involved in the planning, i.e. the praxic component, of a respiratory task rather than on projections originating from the primary motor cortex.

Measurement of neural respiratory drive in patients with COPD

Assessment of neural respiratory drive may be useful in patients with chronic obstructive pulmonary disease (COPD) for diverse clinical and academic reasons. We hypothesised that the oesophageal diaphragm EMG during CO2 rebreathing and treadmill exercise could be used for this purpose. The oesophageal catheter consisted of nine consecutive recording electrode coils, which formed five pairs of electrodes with an inter-electrode distance 3.2 cm within a recording pair. Each coil was 1cm in length and the gap between adjacent coils was 0.5 mm. Maximal isometric contractions at functional residual capacity (FRC) and maximal voluntary inspirations from FRC to total lung capacity (TLC) were performed. All subjects performed CO2 rebreathing until end-tidal CO2 was approximately 9% or they became intolerably breathless. There was a good linear relationship between peak of root mean square (RMS) of the diaphragm EMG and end-tidal CO2 (r = 0.92 +/- 0.06) during CO2 rebreathing. The method was also shown to be feasible during exercise. It is concluded that the diaphragm EMG recorded from an oesophageal electrode is a useful technique to assess neural respiratory drive in patients with COPD.

Breathing adapted radiotherapy of breast cancer: reduction of cardiac and pulmonary doses using voluntary inspiration breath-hold

Background and purposeAdjuvant radiotherapy of breast cancer using wide tangential photon fields implies a risk of late cardiac and pulmonary toxicity. This CT-study evaluates the detailed potential dosimetric consequences of applying breathing adapted radiotherapy (BART), and the feasibility of a monitored voluntary breath-hold technique for right-sided as well as for left-sided tumours. Patients and methodsAfter breast-conserving surgery, 16 patients were CT-scanned in distinct respiratory phases using the varian real-time position management system™ for the monitoring of respiratory anterioposterior chest wall excursion. Each patient underwent three scans: during free breathing (FB), voluntary expiration breath-hold (EBH) and voluntary deep inspiration breath-hold (DIBH). For each scan, an optimised treatment plan was designed with conformal tangential fields encompassing the clinical target volume (CTV) of the breast and ipsilateral internal mammary nodes, and an anterior supraclavicular field. ResultsBreath-hold was well accepted by the patients, with a median duration of 24 s for both EBH and DIBH. The mean anterioposterior chest wall excursions were 2.5, 2.6 and 4.1 mm during FB, EBH and DIBH, respectively. During EBH, the mean front chest wall position was 2.7 mm posterior to its mid-FB position, and during DIBH 12.6 mm anterior to its mid-FB position. For right-sided tumours, the median ipsilateral relative lung volume receiving >50% of the prescribed CTV dose was 39, 49 and 32% for FB, EBH and DIBH, respectively. For left-sided tumours, the corresponding percentages were 37, 46 and 31%. The median heart volume receiving >50% of the prescription dose was reduced from 8% for FB to 1% for DIBH, and the median left anterior descending coronary artery volume was reduced from 54 to 5%. ConclusionsIrradiated cardiac volumes can consistently be reduced for left-sided breast cancers using DIBH for wide tangential treatment fields. Additionally, substantial dose reductions in the lung are observed for both right- and left-sided tumours.

Distribution and course of cortico-respiratory projections for voluntary activation in man. A transcranial magnetic stimulation study in healthy subjects and patients with cerebral ischemia.

The function and course of the cortico-respiratory projections in man are not yet well established. In 30 normal volunteers respiratory muscles were activated by magnetic stimulation of the motor cortex and the cervical and thoracic spinal roots with bilateral recordings from the respiratory muscles. Following cortical stimulation contralateral responses were obtained in all subjects during voluntary inspiration showing a mean latency and amplitude of 13.4+/-1.4ms/1.6+/-1.2 mV (stimulation of the left hemisphere) and 13.2+/-1.3ms/2.5+/-2.5 mV (stimulation of the right hemisphere). Ipsilateral responses were obtained in only 18 (right side) and 21 (left side) subjects and had a significantly (p < 0.001) longer mean latency and lower mean amplitude than the contralateral responses. In 31 patients with impairment of the cortico-respiratory projections due to cerebral infarction demonstrated by magnetic resonance imaging studies, the responsible lesion topography was analysed. We found that, 1. the voluntary activation of respiratory muscles is mediated predominantly by the contralateral motor cortex, 2. the descending cortico-respiratory projections are located within the pyramidal tract, and 3. the cortico-respiratory projections to the respiratory muscles are frequently affected in patients with hemiparesis due to acute stroke. These findings might explain the increased incidence of pneumonia at the hemiparetic side in patients with cerebral ischemia as shown in previous studies.

Movement related cortical source for elbow flexion in patients with brachial plexus injury after intercostal-musculocutaneous nerve crossing

Nine patients with brachial plexus injury whose transected musculo-cutaneous nerves had been sutured with intercostal nerves were examined and the relationship between flexion of the operated elbow and the respiratory movement were shown. Three out of nine patients showed independent control of movement from respiration after regeneration. The primary motor cortex for either flexion of the elbow to the operated side or brisk voluntary inspiration was estimated in the medial vertex region of the frontal cortex by the dipole-tracing method in these three patients. The present results suggest that patients contract the biceps muscle reinnervated by the intercostal nerve independently from respiratory movements using the same primary motor cortex with trunk movements. Functional plasticity may occur in the patients using the primary trunk motor cortex for elbow flexion.

Does the motor cortical control of the diaphragm ‘bypass’ the brain stem respiratory centres in man?

In humans, cortico-motor excitation of the diaphragm may act directly on the phrenic motor nucleus via the cortico-spinal tract ‘bypassing’ brain stem respiratory centres (RC); alternatively, or in addition, this control may be indirect via the RC and bulbo-spinal paths. To investigate this, we stimulated the motor cortex using transcranial magnetic stimulation (TMS) in six subjects at end-expiration (diaphragm relaxed) and during voluntary inspiration. The sizes of the evoked compound action potentials in the diaphragm and also, as a control, in the thumb were no different whether TMS was delivered during normocapnia or during hypocapnia (P et CO 2 =25 mmHg) when, presumably, the respiratory ‘oscillator’ was silent. In a further six subjects, TMS was performed during relaxed spontaneous breathing at three different points in the respiratory cycle. No perturbations in respiratory pattern (either tidal volume or respiratory timing) were seen. Thus we have been unable to demonstrate that the cortico-motor excitation of the diaphragm acts via the brain stem RC.

Preservation of sustainable inspiratory muscle pressure at increased end-expiratory lung volume.

Previous studies in isolated muscles have shown that decreases in muscle length reduce the loss of force resulting from fatigue in response to repeated maximal stimulations. However, increases in end-expiratory lung volume (EEV), which presumably decrease the length of the inspiratory muscles, appear to make the inspiratory muscles more susceptible to fatigue. To address this paradox, we studied the influence of changes in EEV on inspiratory muscle fatigue resulting from repeated maximal voluntary inspirations for 15 min in normal humans. Tidal volume and breath timing were constant between runs. Fatigue runs were compared with atmospheric, positive or negative pressures applied to the mouth, sufficient to change EEV by approximately +30% or -20% of inspiratory capacity. Although the maximal initial pressure-time product for the inspiratory muscles (PTmus) was reduced by increased EEV, sustainable PTmus was not significantly affected. In contrast, both initial and sustainable pressure-time products for the diaphragm were reduced at elevated EEV. The rate at which the fatigue process developed was also reduced at increased EEV. There were no significant effects of decreased EEV on any measured pressures. We conclude that when EEV is elevated, within a moderate range, sustainable inspiratory muscle pressure is preserved. However, the contribution of the diaphragm to inspiratory pressure development during fatigue may be uniquely compromised by increased EEV.