Airway Occlusion Research Articles

Macrophage Impairment Underlies Airway Occlusion in Primary Respiratory Syncytial Virus Bronchiolitis

Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis.

The neurophysiology of dyspnea

AbstractObjective – To review the human and veterinary literature regarding the neurophysiology of dyspnea and to provide evidence for the beneficial effects of several novel therapies aimed at the alleviation of dyspneic sensations.Data Sources – Data sources included scientific reviews, case reports, original research publications, and recent research conference proceedings.Human Data Synthesis – The use of blood oxygenation level‐dependent functional magnetic resonance imaging technology has revealed that the brain regions activated by air hunger in humans are also those activated by fear, pain, and thirst perception. In human subjects, it has been found that agents known to enhance the firing of pulmonary slowly adapting receptors (SARs) can alleviate the sensation of dyspnea without altering central respiratory drive. Several small studies have also shown that nebulized opioids can reduce the sensation of dyspnea apparently via activation of peripheral opioid receptors in the lung.Veterinary Data Synthesis – There are several animal models relevant to both small and large animal clinical patient populations. Treatment of rats with a nebulized SAR sensitizing agent (furosemide) enhances SAR firing in response to lung inflation. Behavioral escape responses to airway occlusion are reduced in lightly anesthetized cats when treated with nebulized furosemide. Opioid agonists have been shown to inhibit the release of acetylcholine and other mediators from the airways of dogs and guinea pigs. Studies using a goat model with bilateral destruction of the pre‐Bötzinger Complex do not support current paradigms of air hunger origination.Conclusions – Veterinary patients may benefit from an approach to dyspnea that incorporates an understanding of the origins of the unpleasant sensations associated with the condition. Several novel therapies have shown promise in alleviating dyspneic sensations without altering respiratory drive. Further study is needed to determine the safety and efficacy of these therapies in veterinary patients.

Pathophysiology of dyspnea evaluated by breath-holding test: Studies of furosemide treatment

Breath-holding is one of the most powerful methods to induce the dyspneic sensation, and the breath-holding test gives us much information on the onset and endurance of dyspnea. In conscious subjects, immediately after the start of breath-holding at functional residual capacity (FRC), there is a certain period of no particular respiratory sensation lasting for 20-30s, which is designated "no respiratory sensation period". This period is terminated by the onset of dyspnea and followed by a progressive increase in the intensity of dyspnea until the breaking point of breath-holding. The measurement of the period of no respiratory sensation provides us with information about the threshold of dyspneic sensation whereas the measurement of the total breath-holding time is a behavioral measure of the tolerable limit of dyspneic sensation. The behavioral measure of tolerable limit of dyspnea can permit the study of dyspnea even in anesthetized animals while observing escape behavior in response to airway occlusion. Inhaled furosemide causes prolongation of both the period of no respiratory sensation and total breath-holding time in conscious subjects, indicating that inhaled furosemide alleviates experimentally induced dyspnea. Alleviation of dyspnea with inhaled furosemide in conscious subjects is also consistent with the result of animal studies in which inhaled furosemide suppresses the escape behavior in the lightly anesthetized condition. The purpose of this article is to emphasize the usefulness of breath-holding test as a tool for evaluation of dyspnea. Furthermore, the possible mechanisms of alleviation of dyspnea with inhaled furosemide are highlighted.

Abstract P28: Early Antioxidant Treatment Does Not Provide Additive Neuroprotection with Delayed Hypothermia after Asphyxic Cardiac Arrest in Newborn Pigs

Clinical efficacy of hypothermia in neonatal hypoxic-ischemic (HI) encephalopathy is limited, in part, by the delay in instituting hypothermia. In a piglet model of HI, half of the neurons in putamen already show ischemic cytopathology by 6 h of recovery. We tested the hypothesis that treatment with the SOD-catalase mimetic EUK-134 at 30 min of recovery provides additive neuronal protection with a clinically relevant delay of 4 h in the onset of whole body hypothermia. Anesthetized piglets were subjected to 40 min of hypoxia (10% inspired O 2 ) followed by 7 min of airway occlusion and resuscitation with epinephrine and chest compressions. Body temperature was maintained at 38.5 °C in normothermic groups and at 34 °C in hypothermic groups from 4 h through 24 h of recovery. All groups were mechanically ventilated and sedated with continuous fentanyl and pancuronium infusion during the 4 –24 h period to reduce the stress of hypothermia and shivering. At 10 days of recovery, viable neurons remaining in putamen in a normothermic control group was reduced to 20±13% (±SD; n=8) of the value in a sham-operated control group (100±19%; n=8). Infusion of EUK-134 (2.5 mg/kg at 30 min recovery + 1.25 mg/kg/h until 4 h recovery) with normothermic recovery resulted in 36±18% (n=8) viable neurons in putamen. Treatment with saline vehicle followed by delayed hypothermia resulted in partial protection (58±25%; n=8). Combining early treatment with EUK-134 and delayed hypothermia did not produce additional protection in putamen (47±29%; n=8). We conclude that early treatment with this antioxidant does not extend the therapeutic window of hypothermia in protecting highly vulnerable neurons of putamen in newborn brain subjected to HI, possibly because a subpopulation of neurons are already undergoing irreversible cell death signaling by the 30 min treatment time with EUK-134.

Measurement of maximal inspiratory pressure in ventilated children

Maximal inspiratory pressure (PIMAX), the maximum negative pressure generated during temporary occlusion of the airway, is commonly used to measure inspiratory muscle strength in mechanically ventilated infants and children. There are, however, no guidelines as to how the PIMAX measurement should be made. We compared the maximum inspiratory pressure generated during airway occlusion (PIMAX(OCC)) to that when a unidirectional valve (PIMAX(UNI)), which allowed expiration, but not inspiration was used. Twenty-two mechanically ventilated children (mean (SD) age 4.8 (4.5) years) were studied. Three sets of end expiratory occlusions were performed for each method in random order. The expired volume during PIMAX(UNI) was assessed and related to the functional residual capacity (FRC) measured using a helium dilution technique.The mean (SD) PIMAX(UNI) (45.5 (15.2) cmH(2)O) was significantly greater than mean (SD) PIMAX(OCC) (30.9 (9.0) cmH(2)O) (P < 0.0001). The mean (SD) expired volume during PIMAX(UNI), was 98 ml (62.3), a mean reduction in FRC of 33.1% (SD 13.9). There were no significant differences between techniques in the baseline respiratory drive, the number of efforts required and the time to reach PIMAX. Regardless of technique, PIMAX was reached in 10 inspiratory efforts or 15 sec of airway occlusion.A unidirectional valve allowing expiration, but not inspiration yields greater PIMAX values in children. Occlusions should be maintained for 12 sec or eight breaths (99% CI of mean).

Going to the movies can make all the difference

The upper airway is a complex structure (see Fig. 1). It is a conduit to life, facilitating the basic requirements of breathing and swallowing, as well as higher functions such as speech. Understanding the factors which control the muscles of the upper airway is therefore of major importance, especially so since collapse of the upper airway during sleep is relatively common. Obstructive sleep apnoea (OSA) is the third most common respiratory disorder, after asthma and chronic obstructive airway disease. Moreover the long-term consequences of severe OSA syndrome are considerable. Daytime sleepiness impairs social function and increases accident risk. The cardiovascular risks are also increased with a 10-years predicted occurrence of stroke of 14%, and 23% for myocardial infarction (Kiely & McNicholas, 2000). T1-weighted, magnetic resonance image in a healthy subject The sagittal view shows the tongue and the complexity of the structures surrounding the upper airway. Thirty years ago Remmers et al. published their seminal paper on the ‘pathogenesis of upper airway occlusion during sleep’ (Remmers et al. 1978). The study examined the relationship between the genioglossal electomyogram (EMG) and pharyngeal pressure, and concluded that airway occlusion occurred when the negative pharyngeal pressure exceeded the genioglossus force; the so called ‘balance of forces’. This theory led to a multitude of studies measuring upper airway muscle activation, specifically the muscles of the soft palate and the genioglossus EMG, with the assumption that these are the key muscles for controlling upper airway patency, and that EMG activation is related to muscle stiffening. In this issue of The Journal of Physiology (Cheng et al. 2008) point out that, ‘EMG does not necessarily translate into muscle motion, and the exact mechanism by which the airway is kept patent by the genioglossus is unknown’. Accordingly the EMG may not be the best methodology to capture the functional significance of genioglossal activation, not least because it is a complex structure with multiple fibre directions; indeed few studies have attempted to map the activity of the whole muscle (Eastwood et al. 2003). Cheng et al. (2008) report a technique that provides a method of quantifying the activity of the entire genioglossus muscle. The methodology also allows visualization within the muscle, while providing a high temporal resolution to capture within-breath movements. The technique also advances other imaging modalities, such as endoscopic imaging, which provide information on changes in the size of the airway lumen rather than the surrounding tissues. Cheng et al. have employed fast spoiled gradient echo imaging techniques to reveal how MRI tagging is deformed with tissue motion. Application of this technique to the measurement of genioglossus activity in humans required the ability to monitor breathing with MRI compatible techniques, the development of non-cardiac gated tagging techniques, and the capacity to obtain multiple within breath scans per subject, while analysis of the images involved adaptation of harmonic phase methodology. By combining all these elements the authors have produced a series of great movies illustrating the complexity of the genioglossus activity throughout the respiratory cycle. Watching these movies it is easy to see how a picture is worth a thousand words. However, the value of the images would be limited if there was no way of quantifying the muscle movement seen. It is therefore important to note that authors have also been able to measure the lateral and anterior–posterior displacement of the tongue throughout the respiratory cycle; allowing within- and between-subject comparisons. These data demonstrate that the tongue retains a constant volume throughout the respiratory cycle, albeit redistributed during contraction or compression. To say that the methodology used influences the answers obtained may be an obvious statement when referring to this paper. By developing new methods of visualizing and quantifying genioglossus activity, the authors have opened up the possibility of further understanding the physiological principles of how the upper airway remains patent during the respiratory cycle; how the activity may change under pathological conditions such as those which occur in OSA. Above all the paper illustrates the value of an interdisciplinary approach to produce technological advances that allow new ways of investigating physiology.

Stimulation of the Expiratory Muscles Using Microstimulators

Respiratory complications constitute a major cause of morbidity and mortality in patients with spinal cord injury. These complications arise in part due to the loss of supraspinal control over the expiratory muscles and the resultant difficulties in clearing airway secretions effectively. The purpose of the present study is to evaluate the efficacy of lower thoracic spinal nerve stimulation using wireless microstimulators in activating the expiratory muscles. Studies were performed on nine anesthetized dogs. A thoracic laminectomy was performed on each dog,and was followed by spinal cord transection at T2. A total of 16 microstimulators (supplied by the Alfred Mann Foundation, Santa Clarita, CA) were inserted percutaneously into the bilateral intercostal nerves approximately 1 to approximately 3 cm distal to the neuroforamen from T7 to L1 in each dog. The stimulation parameters were: frequency of 20 Hz, pulse width of 200 micros, and stimulation burst of 2 s. The stimulation intensities were 3.78, 5.4, 8.1, and 10.8 mA. The pressure-generating capacity of the expiratory muscles was evaluated by the change in airway pressure (Paw) at functional residual capacity, which was produced by the microstimulators during airway occlusion. As a general trend, the expiratory pressure generated using the microstimulators increased with increasing intensity and the number of spinal nerves recruited. The maximal expiratory pressures generated from one, two, three, four, five, six, seven, and eight pairs of spinal nerves were 8.4 +/- 0.8, 12.2 +/- 1.0, 14.6 +/- 1.4, 17.8 +/- 1.8, 23.0 +/- 1.8, 27.7 +/- 2.2, 35.2 +/- 2.7, and 40.4 +/- 2.9 cmH2O, respectively. Bilateral stimulation of seven (from T8 to L1) and eight spinal nerve levels (from T7 to L1) produced the highest changes in(Paw). Stimulation of six or less spinal nerve levels resulted in significantly lower (Paw). We conclude: 1) lower thoracic spinal nerve stimulation near the neuroforamen using microstimulators produces significant expiratory pressure, 2) percutaneous placement of the microstimulators near the neuroforamen is effective in producing expiratory pressure, and 3) percutaneous placement of the microstimulators for restoring cough may potentially be used as a relatively noninvasive clinical tool for patients with spinal cord injury, or other neurological or respiratory disorders. Further studies will be needed.

Successful Transtracheal Lung Ventilation Using a Manual Respiration Valve

Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or "cannot intubate, cannot ventilate" situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation. The effectiveness of such a valve was tested in vitro using mechanical lungs in combination with two different cannula sizes and various gas flows. The valve was then tested in five pigs using a transtracheal 16-gauge cannula with three different combinations of inspiratory/expiratory times and gas flows and an occluded upper airway. In the mechanical lungs, the valve permitted higher minute volumes compared with spontaneous lung emptying. In vivo, the arterial oxygen and carbon dioxide partial pressures increased initially and then remained stable over 1 h (arterial oxygen tension, 470.8 +/- 86.8; arterial carbon dioxide tension, 63.0 +/- 7.2 mmHg). The inspiratory pressures measured in the trachea remained below 10 cm H2O and did not substantially influence central venous and pulmonary artery pressures. Mean arterial pressure and cardiac output were unaffected by the ventilation maneuvers. This study demonstrated in vitro and in vivo in adult pigs that satisfactory lung ventilation can be assured with transtracheal ventilation through a 16-gauge cannula for a prolonged period of time if combined with a bidirectional manual respiration valve.

Alterações da função pulmonar após tratamento cirúrgico de cardiopatias congênitas com hiperfluxo pulmonar

Analysis of pulmonary status of pediatric patients in the postoperative phase of cardiac surgery. To assess pulmonary compliance and airway resistance in patients with congenital heart disease and pulmonary hyperflow submitted to surgical treatment with the use of extracorporeal circulation. Thirty-five patients were evaluated during surgery with measurements of static compliance and airway resistance at four different timepoints. Pulmonary measurements were performed non-invasively using end-inspiratory airway occlusion and specific mathematical formulas. The variables examined and related to pulmonary changes were: preoperative - age, weight, and relationship between systemic and pulmonary blood flow; intraoperative - perfusion times, anoxia times and minimum temperature; postoperative - time on mechanical ventilation and length of stay in the intensive care unit. Pulmonary compliance in all patients had an immediate and significant increase (P<0.001) at the end of surgery. Patients older than 30 months experienced a greater increase (P=0.0004). Those with more than 10 kg also had a greater increase (P=0.0006). In patients on extracorporeal circulation for more than 50 minutes, the increase in pulmonary compliance took longer to occur (P=0.04). Airway resistance was not significantly changed at the end of surgery (P=0.393). All patients experienced improved pulmonary compliance at the end of surgery, and this was significantly influenced by age, weight and time on extracorporeal circulation. Airway resistance, however, was not changed.

Cortical Processing of Respiratory Occlusion Stimuli in Children with Central Hypoventilation Syndrome

The ability of patients with central hypoventilation syndrome (CHS) to produce and process mechanoreceptor signals is unknown. Children with CHS hypoventilate during sleep, although they generally breathe adequately during wakefulness. Previous studies suggest that they have compromised central integration of afferent stimuli, rather than abnormal sensors or receptors. Cortical integration of afferent mechanical stimuli caused by respiratory loading or upper airway occlusion can be tested by measuring respiratory-related evoked potentials (RREPs). We hypothesized that patients with CHS would have blunted RREP during both wakefulness and sleep. RREPs were produced with multiple upper airway occlusions and were obtained during wakefulness, stage 2, slow-wave, and REM sleep. Ten patients with CHS and 20 control subjects participated in the study, which took place at the Children's Hospital of Philadelphia. Each patient was age- and sex-matched to two control subjects. Wakefulness data were collected from 9 patients and 18 control subjects. During wakefulness, patients demonstrated reduced Nf and P300 responses compared with control subjects. During non-REM sleep, patients demonstrated a reduced N350 response. In REM sleep, patients had a later P2 response. CHS patients are able to produce cortical responses to mechanical load stimulation during both wakefulness and sleep; however, central integration of the afferent signal is disrupted during wakefulness, and responses during non-REM are damped relative to control subjects. The finding of differences between patients and control subjects during REM may be due to increased intrinsic excitatory inputs to the respiratory system in this state.

Neuromechanical control of the isolated upper airway of mice

We characterized the passive structural and active neuromuscular control of pharyngeal collapsibility in mice and hypothesized that pharyngeal collapsibility, which is elevated by anatomic loads, is reduced by active neuromuscular responses to airflow obstruction. To address this hypothesis, we examined the dynamic control of upper airway function in the isolated upper airway of anesthetized C57BL/6J mice. Pressures were lowered downstream and upstream to the upper airway to induce inspiratory airflow limitation and critical closure of the upper airway, respectively. After hyperventilating the mice to central apnea, we demonstrated a critical closing pressure (Pcrit) of -6.2 +/- 1.1 cmH(2)O under passive conditions that was unaltered by the state of lung inflation. After a period of central apnea, lower airway occlusion led to progressive increases in phasic genioglossal electromyographic activity (EMG(GG)), and in maximal inspiratory airflow (Vi(max)) through the isolated upper airway, particularly as the nasal pressure was lowered toward the passive Pcrit level. Moreover, the active Pcrit fell during inspiration by 8.2 +/- 1.4 cmH(2)O relative to the passive condition (P < 0.0005). We conclude that upper airway collapsibility (passive Pcrit) in the C57BL/6J mouse is similar to that in the anesthetized canine, feline, and sleeping human upper airway, and that collapsibility falls markedly under active conditions. Active EMG(GG) and Vi(max) responses dissociated at higher upstream pressure levels, suggesting a decrease in the mechanical efficiency of upper airway dilators. Our findings in mice imply that anatomic and neuromuscular factors interact dynamically to modulate upper airway function, and provide a novel approach to modeling the impact of genetic and environmental factors in inbred murine strains.

Reproducibility of the short-latency reflex inhibition to loading of human inspiratory muscles

Loading of inspiratory muscles produces a profound short-latency inhibitory response (IR) of the electromyogram (EMG), followed by an excitatory response (ER). Duration of IR correlates positively with the apnoea hypopnoea index in obstructive sleep apnoea (OSA) patients, for whom measurement of this reflex may allow the assessment of a physiological response to therapy. To test the reliability of reflex measurement, we studied 11 human subjects on 4 separate days. Inspiration was transiently occluded during 2 sets of 30 trials on each day. Scalene muscle EMG was rectified and averaged. Ten parameters (4 latencies and 6 EMG sizes) were measured. Reproducibility was analysed by ANOVA, intraclass correlation coefficient (ICC) and coefficient of variation (CV). The mean ICC was 0.56 (range 0.30-0.76) and the mean CV was 25% (range 6.7-48%). These results show good measurement reliability. The abnormalities seen in disease are significantly larger than these CVs. The reflex response to airway occlusion may be assessed reliably using our method.

Response to hypercapnic challenge is associated with successful weaning from prolonged mechanical ventilation due to brain stem lesions

We propose that higher airway occlusion pressure (P0.1) responses to hypercapnic challenge (HC) indicate less severe injury. The study aim was to determine whether P0.1 responses to HC were associated with successful weaning after prolonged mechanical ventilation (PMV) in patients with brainstem lesions and to determine a reference value for clinical use. Forty-two patients with brainstem lesions on PMV were recruited. Breathing parameters and P0.1 were measured before HC. Three-minute HC challenges with increasing CO(2) concentrations were initiated and P0.1, respiratory rate, minute ventilation (V (e)), tidal volume (V (t)) and end tidal CO(2) were measured. Patients were classified into high (group I) and low (group II) response groups on the basis of P0.1 responses to HC. Increases in V (e) and V (t) after HC were significantly greater in group I patients (12.22 +/- 8.22 vs. 3.08 +/- 4.84 L/min, P < 0.001 and 399.11 +/- 278.18 vs. 110.54 +/- 18.275 ml, P < 0.001). P0.1 levels were significantly higher in group I compared to group II before HC (2.69 +/- 1.81 vs. 1.28 +/- 1.04 cmH(2)O, P = 0.003). The increase in P0.1 following HC was significantly greater in group I compared to group II patients (11.05 +/- 4.06 vs. 2.90 +/- 2.53 cmH(2)O, P < 0.001). Weaning success was significantly higher in group I compared to group II patients (72.2% vs. 33.3%, P = 0.02). A P0.1 increase of >6 cmH(2)O following HC was significantly associated with successful weaning. Assessing the P.01 response to serial increases in the level of HC may be a safe means to ascertain whether patients with brainstem lesions are ready for ventilator weaning.

A drop in gas temperature in the external part of the endotracheal tube is problematic during neonatal respiratory support

During neonatal respiratory support, maintaining optimal humidity minimizes the risk of airway occlusion and chronic lung disease. With neonatal respiratory support using a heated humidifier,condensation following decreases in temperature within the unheated part of the inspiratory circuit represents a serious problem, due to the resulting drop in absolute humidity. Several reports describing the temperature/humidity gradient in the unheated inspiratory limb have excluded the endotracheal tube (ETT). The present study investigated the extent to which the temperature gradient in the ETT affects breathing gas conditioning in premature infants, who display tiny minute volumes. By measuring temperature/dew point at various sites along the inspiratory circuit, including inside the ETT, we evaluated the effects of temperature change in the ETT using an in vitro model of a micropremie on mechanical respirator care in an incubator. We confirmed significant moisture loss (absolute humidity loss; 7.5-10.1 mg/L) with decreasing gas temperature in the ETT external to the body, with subsequent drying of the gas (relative humidity drop, 10.7-22.3%) as temperature increased in the ETT inside the body. The present results suggest that temperature decreases in the ETT represent an important issue in the respiratory care of very premature infants.

Obstructive sleep apnoea and CMT1A: answers and more questions

Dziewas and colleagues1 report that patients with Charcot–Marie–Tooth disease type 1A (CMT1A) have an increased prevalence of obstructive sleep apnoea (see page 829) . Sleep apnoea can be caused by...

Homicidal smothering: vital histological confirmation of orofacial injury despite a prolonged post-mortem interval

Homicidal smothering is the deliberate occlusion of the external airways, usually using the hands, pillows, or bedding. Victims are often those who are unable to resist, such as the young or the old. The limited resistance offered by these individuals may result in a comparative lack of injury. We present a case of a 72-year-old female, found deceased on her bed. The case was initially not considered suspicious and a coronial autopsy was performed. Concerns were subsequently raised and the body remained refrigerated. Six months after the initial examination, an opinion was requested as to whether further examination would be worthwhile to consider allegations of deliberate smothering. Review of the scene photographs showed deviation of the nose, eversion of the upper lip, and suspected intra-oral bruising. A bloodstained pillow was adjacent to the face. At the later autopsy, the body was found to show significant post-mortem deterioration and the facial tissues were mummified. The upper lip was excised and routinely processed for histology, sections showing remarkably good tissue preservation and extensive recent bruising, allowing the suspicious lip injuries in the scene photographs to be safely interpreted. This report illustrates the subtle pathological findings apparent in many of these cases and reinforces the need for thorough external examination and correlation with forensic scene investigation. Histological sampling of suspected injuries can be rewarding, even in the presence of severe post-mortem deterioration.

The role of arousal related brainstem reflexes in causing recovery from upper airway occlusion in infants.

During obstructive sleep apnea (OSA) in adults upper airway reopening coincides with a sudden burst in activity of pharyngeal dilating muscles. This has been attributed to arousal from sleep as indicated by increased EEG activity. Recovery from OSA in infants often occurs in the absence of cortical arousal. To investigate mechanisms involved in recovery, we performed experimental airway occlusions in sleeping infants. Based on past work, our hypothesis was that a sleep startle combined with an augmented breath and heart rate acceleration would occur during the occlusion, and that such brainstem mediated reflexes might provide an explanation for recovery from OSA in the absence of cortical arousal. However, this is contrary to expectations, since lung inflation is believed to be necessary for occurrence of an augmented breath. We studied 16 healthy infants during sleep. We recorded EEG, EOG, ECG, oxygen saturation, diaphragmatic, nuchal and limb electromyograms, face mask pressure, and airflow. A startle, accompanied by neck extension, limb and nuchal EMG activation, as well as heart rate acceleration occurred during all airway occlusions. The startle occurred simultaneously with a large biphasic inspiratory effort, having characteristics of an augmented breath (sigh). In more than a third of cases, this occurred without any evidence of cortical arousal activity. The magnitude of startles as well as the increase in heart rate correlated positively with peak airway negative pressure, indicating that arousal processes are graded in intensity. We conclude that the neck extension and pharyngeal dilating muscle activity associated with the startle and augmented breath may account for recovery of airway patency in infants as they do adults. Lung inflation is not a prerequisite for the reflex to occur.

Effect of intrapulmonary percussive ventilation on expiratory flow limitation in chronic obstructive pulmonary disease patients

PurposeThe aims of this prospective study were (1) to select, after weaning and extubation, chronic obstructive pulmonary disease (COPD) patients with expiratory flow limitation (EFL) measured by the negative expiratory pressure method and (2) to assess, in these patients, the short-term (30 minutes) physiologic effect of a session of intrapulmonary percussive ventilation (IPV). Materials and MethodsAll COPD patients who were intubated and needed weaning from mechanical ventilation were screened after extubation. The patients were placed in half-sitting position and breathed spontaneously. The EFL and the airway occlusion pressure after 0.1 second (P0.1) were measured at the first hour after extubation. In COPD patients with EFL, an IPV session of 30 minutes was promptly performed by a physiotherapist accustomed to the technique. Expiratory flow limitation, gas exchange, and P0.1 were recorded at the end of the IPV session. ResultsAmong 35 patients studied after extubation, 25 patients presented an EFL and were included in the study. Intrapulmonary percussive ventilation led to a significant improvement in EFL, respectively, before and 30 minutes after IPV (65.4 ± 18.2 vs 35.6 ± 22.8; P < .05). Three patients were not expiratory flow limited after IPV. Intrapulmonary percussive ventilation led to a significant decrease in P0.1 (3.9 ± 1.6 vs 2.8 ± 1.1; P < .05). Thirty minutes of IPV led to a significant increase in Pao2 and pH and a decrease in Paco2 and respiratory rate (P < .05). ConclusionIn COPD patients, a session of IPV allowed a significant reduction of EFL and of P01 and a significant improvement of gas exchange.

Upper airway pressure-flow relationships and pharyngeal constrictor EMG activity during prolonged expiration in awake goats

We undertook the present investigation to establish whether narrowing/closure of the upper airway occurs during spontaneous and provoked respiratory rhythm disturbances and whether pharyngeal constrictor muscle recruitment occurs coincident with upper airway occlusion during prolonged expiratory periods. Upper airway pressure-flow relationships and middle pharyngeal constrictor (mPC) EMG activities were recorded in 11 adult female goats during spontaneous and provoked prolongations in expiratory time (Te). A total of 213 spontaneous prolongations of expiration were recorded. Additionally, 169 prolonged expiratory events preceded by an augmented breath were included in the analyses. In separate trials on different days, Te was prolonged by systemic administration of dopamine, by raising the inspired fraction of O(2) from 0.10 to 1.00 during poikilocapnic conditions or by systemic administration of clonidine. Continuous tonic activation of the mPC EMG was observed during each prolonged Te period regardless of the duration or initiating cause. However, significant increases in subglottic tracheal pressure, with expiratory airflow braking indicative of upper airway narrowing or closure, was only observed during spontaneous events without a preceding augmented breath and during clonidine-induced events. Tonic mPC activation proved an unreliable indicator of airway occlusion. Furthermore, mPC muscle activation alone is not sufficient to induce pharyngeal occlusion during prolonged expiration. Our data suggest that airway closure is not a common occurrence during provoked respiratory disturbances in awake goats. We propose that airway closure, when present during prolonged Te, is more likely dependent on activation of laryngeal adductor muscles with glottic braking independent of pharyngeal narrowing.

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest