Acute thoracoabdominal and hemodynamic responses to tapered flow resistive loading in healthy adults.

We investigated the acute physiological responses of tapered flow resistive loading (TFRL) at 30, 50 and 70 % maximal inspiratory pressure (PImax) in 12 healthy adults to determine an optimal resistive load. Increased end-inspiratory rib cage and decreased end-expiratory abdominal volumes equally contributed to the expansion of thoracoabdominal tidal volume (captured by optoelectronic plethysmography). A significant decrease in end-expiratory thoracoabdominal volume was observed from 30 to 50 % PImax, from 30 to 70 % PImax, and from 50 to 70 % PImax. Cardiac output (recorded by cardio-impedance) increased from rest by 30 % across the three loading trials. Borg dyspnoea increased from 2.36 ±â€¯0.20 at 30 % PImax, to 3.45 ±â€¯0.21 at 50 % PImax, and 4.91 ±â€¯0.25 at 70 % PImax. End-tidal CO2 decreased from rest during 30, 50 and 70 %PImax (26.23 ±â€¯0.59, 25.87 ±â€¯1.02 and 24.30 ±â€¯0.82 mmHg, respectively). Optimal intensity for TFRL is at 50 % PImax to maximise global respiratory muscle and cardiovascular loading whilst minimising hyperventilation and breathlessness.

Voluntary hypocapnic hyperventilation lasting 5†min and 20†min similarly reduce aerobic metabolism without affecting power outputs during Wingate anaerobic test.

AbstractTwenty minutes of voluntary hypocapnic hyperventilation prior to exercise reduces the aerobic metabolic rate with a compensatory increase in the anaerobic metabolic rate without affecting exercise performance during the Wingate anaerobic test (WAnT). Thus, pre-exercise hypocapnic hyperventilation may be a useful means of stressing the anaerobic energy system during training, ultimately improving anaerobic exercise performance. However, it remains unclear whether a shorter (e.g., 5 min) pre-exercise hypocapnic hyperventilation is sufficient to reduce the aerobic metabolic rate during high-intensity exercise. We therefore compared the effects of 5-min and 20-min pre-exercise hypocapnic hyperventilation on aerobic metabolism during the 30-s WAnT. Ten healthy young males and one female performed the WAnT following 20 min of spontaneous breathing (control trial) or 5 or 20 min of voluntary hypocapnic hyperventilation. Both the 5-min and 20-min hyperventilation reduced end-tidal CO2 partial pressure (an index of arterial CO2 partial pressure) to ∼23 mmHg, whereas it remained unchanged during the spontaneous breathing. The peak, mean and minimum power outputs during the WAnT did not differ among the three trials. Oxygen uptake during the WAnT was lower in both the 5-min (1493 ± 257 mL min-1) and 20-min (1397 ± 447 mL min-1) hyperventilation trials than during the control trial (1847 ± 286 mL min-1), and was similar in the two hyperventilation trials. These results suggest that 5 min of pre-exercise hypocapnic hyperventilation reduces aerobic metabolism during the 30-s WAnT to a level similar to that seen with the 20-min hyperventilation. Moreover, exercise performance was unaffected, which implies anaerobic metabolism was enhanced.

Effects of GB34 acupuncture on hyperventilation-induced carbon dioxide reactivity and cerebral blood flow velocity in the anterior and middle cerebral arteries of normal subjects.

OBJECTIVES: To determine whether acupuncture at GB34 affects cerebral blood flow (CBF) via the anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs). METHODS: This study included 10 healthy young male volunteers. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified blood flow velocity at 40 mm Hg (CV40) were observed for both ACAs and MCAs before and after GB34 acupuncture treatment. Blood pressure and heart rate were also measured before and after GB34 acupuncture treatment. RESULTS: The CO2 reactivity of the ipsilateral MCA significantly increased after GB34 acupuncture treatment, compared with that at baseline (P=0.007). In contrast, the CO2 reactivity of both ACAs and the contralateral MCA remained unchanged. The CV40 of both ACAs and MCAs did not change after GB34 acupuncture treatment and neither did the mean arterial blood pressure and heart rate. CONCLUSIONS: GB34 acupuncture treatment increased CO2 reactivity specifically in the ipsilateral MCA, but had no effect on either the ACAs or the contralateral MCA. These data suggest that GB34 acupuncture treatment improves the vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions and could potentially be useful for the treatment of disorders of the ipsilateral MCA circulation.

Dysfunctional breathing: what do we know?

Dysfunctional breathing (DB) is a respiratory condition characterized by irregular breathing patterns that occur either in the absence of concurrent diseases or secondary to cardiopulmonary diseases. Although the primary symptom is often dyspnea or "air hunger", DB is also associated with nonrespiratory symptoms such as dizziness and palpitations. DB has been identified across all ages. Its prevalence among adults in primary care in the United Kingdom is approximately 9.5%. In addition, among individuals with asthma, a positive diagnosis of DB is found in a third of women and a fifth of men. Although DB has been investigated for decades, it remains poorly understood because of a paucity of high-quality clinical trials and validated outcome measures specific to this population. Accordingly, DB is often underdiagnosed or misdiagnosed, given the similarity of its associated symptoms (dyspnea, tachycardia, and dizziness) to those of other common cardiopulmonary diseases such as COPD and asthma. The high rates of misdiagnosis of DB suggest that health care professionals do not fully understand this condition and may therefore fail to provide patients with an appropriate treatment. Given the multifarious, psychophysiological nature of DB, a holistic, multidimensional assessment would seem the most appropriate way to enhance understanding and diagnostic accuracy. The present narrative review was developed as a means of summarizing the available evidence about DB, as well as improving understanding of the condition by researchers and practitioners.

Respiratory mechanics and cerebral blood flow during heat-induced hyperventilation and its voluntary suppression in passively heated humans.

We investigated whether heat-induced hyperventilation can be voluntarily prevented, and, if so, how this modulates respiratory mechanics and cerebral blood flow in resting heated humans. In two separate trials, 10 healthy men were passively heated using lower body hot-water immersion and a water-perfused garment covering their upper body (both 41°C) until esophageal temperature (Tes ) reached 39°C or volitional termination. In each trial, participants breathed normally (normal-breathing) or voluntarily controlled minute ventilation (VE ) at a level equivalent to that observed after 5 min of heating (controlled-breathing). Respiratory gases, middle cerebral artery blood velocity (MCAV), work of breathing, and end-expiratory and inspiratory lung volumes were measured. During normal-breathing, VE increased as Tes rose above 38.0 ± 0.3°C, whereas controlled-breathing diminished the increase in VE (VE at Tes  = 38.6°C: 25.6 ± 5.9 and 11.9 ± 1.3 L min-1 during normal- and controlled-breathing, respectively, P < 0.001). During normal-breathing, end-tidal CO2 pressure and MCAV decreased with rising Tes , but controlled-breathing diminished these reductions (at Tes  = 38.6°C, 24.7 ± 5.0 vs. 39.5 ± 2.8 mmHg; 44.9 ± 5.9 vs. 60.2 ± 6.3 cm sec-1 , both P < 0.001). The work of breathing correlated positively with changes in VE (P < 0.001) and was lower during controlled- than normal-breathing (16.1 ± 12.6 and 59.4 ± 49.5 J min-1 , respectively, at heating termination, P = 0.013). End-expiratory and inspiratory lung volumes did not differ between trials (P = 0.25 and 0.71, respectively). These results suggest that during passive heating at rest, heat-induced hyperventilation increases the work of breathing without affecting end-expiratory lung volume, and that voluntary control of breathing can nearly abolish this hyperventilation, thereby diminishing hypocapnia, cerebral hypoperfusion, and increased work of breathing.

Carotid chemoreceptors have a limited role in mediating the hyperthermia-induced hyperventilation in exercising humans.

Hyperthermia causes hyperventilation at rest and during exercise. We previously reported that carotid chemoreceptors partly contribute to the hyperthermia-induced hyperventilation at rest. However, given that a hyperthermia-induced hyperventilation markedly differs between rest and exercise, the results obtained at rest may not be representative of the response in exercise. Therefore, we evaluated whether carotid chemoreceptors contribute to hyperthermia-induced hyperventilation in exercising humans. Eleven healthy young men (23 ± 2 yr) cycled in the heat (37°C) at a fixed submaximal workload equal to ~55% of the individual's predetermined peak oxygen uptake (moderate intensity). To suppress carotid chemoreceptor activity, 30-s hyperoxia breathing (100% O2) was performed at rest (before exercise) and during exercise at increasing levels of hyperthermia as defined by an increase in esophageal temperature of 0.5°C (low), 1.0°C (moderate), 1.5°C (high), and 2.0°C (severe) above resting levels. Ventilation during exercise gradually increased as esophageal temperature increased (all P ≤ 0.05), indicating that hyperthermia-induced hyperventilation occurred. Hyperoxia breathing suppressed ventilation in a greater manner during exercise (-9 to -13 l/min) than at rest (-2 ± 1 l/min); however, the magnitude of reduction during exercise did not differ at low (0.5°C) to severe (2.0°C) increases in esophageal temperature (all P > 0.05). Similarly, hyperoxia-induced changes in ventilation during exercise as assessed by percent change from prehyperoxic levels were not different at all levels of hyperthermia (~15-20%, all P > 0.05). We show that in young men carotid chemoreceptor contribution to hyperthermia-induced hyperventilation is relatively small at low-to-severe increases in body core temperature induced by moderate-intensity exercise in the heat. NEW & NOTEWORTHY Exercise-induced increases in hyperthermia cause a progressive increase in ventilation in humans. However, the mechanisms underpinning this response remain unresolved. We showed that in young men hyperventilation associated with exercise-induced hyperthermia is not predominantly mediated by carotid chemoreceptors. This study provides important new insights into the mechanism(s) underpinning the regulation of hyperthermia-induced hyperventilation in humans and suggests that factor(s) other than carotid chemoreceptors play a more important role in mediating this response.

Dysfunctional breathing: what do we know? / Disfunção respiratória: o que sabemos?

ABSTRACT Dysfunctional breathing (DB) is a respiratory condition characterized by irregular breathing patterns that occur either in the absence of concurrent diseases or secondary to cardiopulmonary diseases. Although the primary symptom is often dyspnea or "air hunger", DB is also associated with nonrespiratory symptoms such as dizziness and palpitations. DB has been identified across all ages. Its prevalence among adults in primary care in the United Kingdom is approximately 9.5%. In addition, among individuals with asthma, a positive diagnosis of DB is found in a third of women and a fifth of men. Although DB has been investigated for decades, it remains poorly understood because of a paucity of high-quality clinical trials and validated outcome measures specific to this population. Accordingly, DB is often underdiagnosed or misdiagnosed, given the similarity of its associated symptoms (dyspnea, tachycardia, and dizziness) to those of other common cardiopulmonary diseases such as COPD and asthma. The high rates of misdiagnosis of DB suggest that health care professionals do not fully understand this condition and may therefore fail to provide patients with an appropriate treatment. Given the multifarious, psychophysiological nature of DB, a holistic, multidimensional assessment would seem the most appropriate way to enhance understanding and diagnostic accuracy. The present narrative review was developed as a means of summarizing the available evidence about DB, as well as improving understanding of the condition by researchers and practitioners.

RESUMO A disfunção respiratória (DR) é um quadro respiratório caracterizado por padrões respiratórios irregulares que ocorrem na ausência de doenças concomitantes ou secundariamente a doenças cardiopulmonares. Embora o principal sintoma seja frequentemente dispneia ou "fome por ar", a DR também está associada a sintomas não respiratórios, como vertigem e palpitações. A DR pode ser identificada em todas as idades. Sua prevalência entre adultos na atenção primária no Reino Unido é de aproximadamente 9,5%. Além disso, entre indivíduos com asma, um diagnóstico positivo de DR é encontrado em um terço das mulheres e um quinto dos homens. Embora a DR tenha sido investigada por décadas, ela permanece pouco compreendida devido a uma escassez de ensaios clínicos de alta qualidade e de variáveis de desfecho validadas especificamente para essa população. Assim, a DR é frequentemente subdiagnosticada ou diagnosticada incorretamente, devido à similaridade de seus sintomas associados (dispneia, taquicardia e vertigem) aos de outras doenças cardiopulmonares comuns, como DPOC e asma. As altas taxas de diagnóstico incorreto de DR sugerem que os profissionais de saúde não entendam completamente esse quadro e possam, portanto, não fornecer aos pacientes um tratamento adequado. Dada à natureza multifatorial e psicofisiológica da DR, uma avaliação holística e multidimensional parece ser a maneira mais apropriada de melhorar a compreensão e a precisão do diagnóstico. A presente revisão foi desenvolvida como um meio de resumir as evidências disponíveis sobre DB, bem como de melhorar a compreensão do quadro por pesquisadores e profissionais.

Respiratory muscle training positively affects vasomotor response in young healthy women.

Vasomotor response is related to the capacity of the vessel to maintain vascular tone within a narrow range. Two main control mechanisms are involved: the autonomic control of the sympathetic neural drive (global control) and the endothelial smooth cells capacity to respond to mechanical stress by releasing vasoactive factors (peripheral control). The aim of this study was to evaluate the effects of respiratory muscle training (RMT) on vasomotor response, assessed by flow-mediated dilation (FMD) and heart rate variability, in young healthy females. The hypothesis was that RMT could enhance the balance between sympathetic and parasympathetic neural drive and reduce vessel shear stress. Thus, twenty-four women were randomly assigned to either RMT or SHAM group. Maximal inspiratory mouth pressure and maximum voluntary ventilation were utilized to assess the effectiveness of the RMT program, which consisted of three sessions of isocapnic hyperventilation/ week for eight weeks, (twenty-four training sessions). Heart rate variability assessed autonomic balance, a global factor regulating the vasomotor response. Endothelial function was determined by measuring brachial artery vasodilation normalized by shear rate (%FMD/SR). After RMT, but not SHAM, maximal inspiratory mouth pressure and maximum voluntary ventilation increased significantly (+31% and +16%, respectively). Changes in heart rate variability were negligible in both groups. Only RMT exhibited a significant increase in %FMD/SR (+45%; p<0.05). These data suggest a positive effect of RMT on vasomotor response that may be due to a reduction in arterial shear stress, and not through modulation of sympatho-vagal balance.

Eucapnic voluntary hyperventilation test in children.

BACKGROUND: In children, exercise-induced dyspnea is a common symptom that can be due to dysfunctional breathing. EVH test has bee used especially in elite athletes as bronchoprovocation test. Currently, there are only few studies on the EVH test. New research methods are required alongside the traditionally used tests especially due to dysfunctional breathing disorder. PURPOSE: The purpose of the "pilot study" was to study the usability of the EVH test with real time biofeedback in children of 10-16 years of age in the diagnostics of exercise-induced dyspnea. METHODS: Six 10-16-year-old teenagers with history of exercise-induced dyspnea and three healthy control subjects were selected for the study. A 6-minute EVH test with realtime biofeedback was performed on the patients and the diagnosis was confirmed on the basis of clinical findings and spirometry follow-up either as normal, asthma or dysfunctional breathing. RESULTS: The study was successful in the patients. In the spirometry follow-up, three patients had bronchoconstriction (FEV1 decline over 10%), dysfunctional breathing condition was observed in three patients and three control patients experienced no symptoms. Only two DFB-patients didn't reach the target level of minute ventilation due to a clinical symptom (inspiratory stridor). CONCLUSION: The EVH test was successful in the 10-16-year-old children having participated in the study and the test was well tolerated. Through the study, it was possible to provoke both dysfunctional breathing disorder and bronchoconstriction in the symptomatic patients. Based on the pilot study, EVH test seems to be usable in the diagnostics of pediatric exercise-induced dyspnea but larger studies are warranted to confirm our preliminary findings.

Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans.

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) ( P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating ( P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes - V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min-1·°C-1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating ( P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia. NEW & NOTEWORTHY Hyperthermia causes hyperventilation and concomitant hypocapnia and cerebral hypoperfusion. The last may underlie central fatigue. We are the first to demonstrate that hyperthermia-induced hyperventilation is not suppressed by the resultant hypocapnia and that hypocapnia explains only 36% of cerebral hypoperfusion elicited by hyperthermia. These new findings advance our understanding of the mechanisms controlling ventilation and cerebral blood flow during heat stress, which may be useful for developing interventions aimed at preventing central fatigue during hyperthermia.

Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia - An Experimental Cardiovascular Magnetic Resonance Study.

BACKGROUND: Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR). METHODS AND FINDINGS: In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point. CONCLUSION: In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This maneuver may allow for detecting severe coronary artery stenosis and have a significant clinical potential as a non-pharmacological method for diagnostic testing in patients with suspected coronary artery disease.

Respiratory Muscle Training and Exercise Endurance at Altitude.

BACKGROUND: Climbing and trekking at altitude are common recreational and military activities. Physiological effects of altitude are hypoxia and hyperventilation. The hyperventilatory response to altitude may cause respiratory muscle fatigue and reduce sustained submaximal exercise. Voluntary isocapnic hyperpnea respiratory muscle training (VIHT) improves exercise endurance at sea level and at depth. The purpose of this study was to test the hypothesis that VIHT would improve exercise time at altitude [3600 m (11,811 ft)] compared to control and placebo groups. METHODS: Subjects pedaled an ergometer until exhaustion at simulated altitude in a hypobaric chamber while noninvasive arterial saturation (Sao2), ventilation (VE), and oxygen consumption (Vo2) were measured. RESULTS: As expected, Sao2 decreased to 88 ± 4% saturation at rest and to 81 ± 2% during exercise, and was not affected by VIHT. VIHT resulted in a 40% increase in maximal training VE compared to pre-VIHT. Exercise endurance significantly increased 44% after VIHT (P = <0.001). Vo2 (30 ± 3 ml · kg(-1) · min(-1)) and heart rate (177 ± 10 bpm) did not change during exercise and were not affected by VIHT (P = 0.531). Pre-VIHT VE increased 21-27% during the initial 12 min of exercise, after which it decreased 17% at 17.7 ± 6.0 min. VE at altitude post-VIHT increased more (49%) for longer (21 min) and decreased less (11% at 25.4 ± 6.7 min). DISCUSSION: VIHT improved exercise time at altitude and sustained VE. This suggests that VIHT reduced respiratory muscle fatigue and would be useful to trekkers and military personnel working at altitude. Helfer S, Quackenbush J, Fletcher M, Pendergast DR. Respiratory muscle training and exercise endurance at altitutde. Aerosp Med Hum Perform. 2016; 87(8):704-711.

Mechanisms and clinical consequences of untreated central sleep apnea in heart failure.

Central sleep apnea (CSA) is a highly prevalent, though often unrecognized, comorbidity in patients with heart failure (HF). Data from HF population studies suggest that it may present in 30% to 50% of HF patients. CSA is recognized as an important contributor to the progression of HF and to HF-related morbidity and mortality. Over the past 2 decades, an expanding body of research has begun to shed light on the pathophysiologic mechanisms of CSA. Armed with this growing knowledge base, the sleep, respiratory, and cardiovascular research communities have been working to identify ways to treat CSA in HF with the ultimate goal of improving patient quality of life and clinical outcomes. In this paper, we examine the current state of knowledge about the mechanisms of CSA in HF and review emerging therapies for this disorder.

Extra-cerebral oxygenation influence on near-infrared-spectroscopy-determined frontal lobe oxygenation in healthy volunteers: a comparison between INVOS-4100 and NIRO-200NX.

INTRODUCTION: Frontal lobe oxygenation (Sc O2 ) is assessed by spatially resolved near-infrared spectroscopy (SR-NIRS) although it seems influenced by extra-cerebral oxygenation. We aimed to quantify the impact of extra-cerebral oxygenation on two SR-NIRS derived Sc O2 . METHODS: Multiple regression analysis estimated the influence of extra-cerebral oxygenation as exemplified by skin oxygenation (Sskin O2 ) on Sc O2 in 21 healthy subjects exposed to whole-body exercise in hypoxia (Fi O2  = 12%; n = 10) and normoxia (n = 12), whole-body heating, hyperventilation (n = 21), administration of norepinephrine with and without petCO2 -correction (n = 15), phenylephrine and head-up tilt (n = 7). Sc O2 was assessed simultaneously by NIRO-200NX (Sniro O2 ) and INVOS-4100 (Sinvos O2 ). Arterial (Sa O2 ) and jugular bulb oxygen saturations (Sj O2 ) were obtained. RESULTS: The regression analysis indicated that Sinvos O2 reflects 46% arterial, 14% jugular, 35% skin and 4% oxygenation of tissues not interrogated. Sinvos O2 follows a calculated estimate of cerebral capillary oxygenation (r = 0·67; P<0·0001). In contrast, the NIRO-200NX-determined Sc O2 did not correlate with the estimate of cerebral oxygenation (r = 0·026; P = 0·71). CONCLUSION: For all interventions, 35% of the INVOS-4100 signal reflected extra-cerebral oxygenation while, on the other hand, NIRO-200NX did not follow changes in a calculated estimate of cerebral capillary oxygenation. Thus, the NIRO-200NX and INVOS-4100 do not provide for unbiased evaluation of the cerebral signal.

Inspiratory high frequency airway oscillation attenuates resistive loaded dyspnea and modulates respiratory function in young healthy individuals.

Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT). We tested whether high-frequency airway oscillation (HFAO), a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20) compared to a SHAM-RMT (conventional flow-resistive RMT) device (n = 15) in healthy volunteers (13 males; aged 20-36 yrs). HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2 × 30 breaths at 70% peak flow, 5 days a week). Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003) and SHAM-RMT (p = 0.005) groups. Maximum inspiratory static pressure (cm H2O) was significantly increased by HFAO training (vs. PRE; p<0.001). Maximum inspiratory dynamic pressure was increased by training in both the HFAO (vs. PRE; p<0.001) and SHAM-RMT (vs. PRE; p = 0.021) groups. Peak inspiratory flow rate (L.s(-1)) achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001) in the HFAO group only. HFAO reduced inspiratory resistive loading-induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT) in healthy individuals without the respiratory discomfort associated with RMT.

Marine lipid fraction PCSO-524 (lyprinol/omega XL) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma.

PURPOSE: Evaluate the effect of the marine lipid fraction of the New Zealand green-lipped mussel (Perna canaliculus) PCSO-524 (Lyprinol/Omega XL), rich in omega-3 fatty acids, on airway inflammation and the bronchoconstrictor response to eucapnic voluntary hyperpnea (EVH) in asthmatics. METHODS: Twenty asthmatic subjects, with documented HIB, participated in a placebo controlled double-blind randomized crossover trial. Subjects entered the study on their usual diet and were then placed on 3 weeks of PCSO-524 or placebo supplementation, followed by a 2 week washout period, before crossing over to the alternative diet. Pre- and post-eucapnic voluntary hyperpnea (EVH) pulmonary function, fraction of exhaled nitric oxide (FENO), asthma symptom scores, medication use, exhaled breath condensate (EBC) pH, cysteinyl leukotrienes (cyst-LT), 8-isoprostane and urinary 9α, 11ß-prostaglandin (PG)F2 and Clara (CC16) protein concentrations were assessed at the beginning of the trial and at the end of each treatment period. RESULTS: The PCSO-524 diet significantly reduced (p < 0.05) the maximum fall in post-EVH FEV1 (-8.4 ± 3.2%) compared to usual (-19.3 ± 5.4%) and placebo diet (-22.5 ± 13.7%). Pre- and post- EVH EBC cyst-LT and 8-isoprostane, and urinary 9α, 11ß-PGF2 and CC16 concentrations were significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. EBC pH and asthma symptom scores were significantly improved (p < 0.05) and rescue medication use significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. CONCLUSION: PCSO-524 (Lyprinol)/Omega XL) may have beneficial effects in HIB and asthma by serving as a pro-resolving agonist and/or inflammatory antagonist.

Respiratory muscle tension as symptom generator in individuals with high anxiety sensitivity.

OBJECTIVE: Anxiety and panic are associated with the experience of a range of bodily symptoms, in particular unpleasant breathing sensations (dyspnea). Respiratory theories of panic disorder have focused on disturbances in blood gas regulation, but respiratory muscle tension as a source of dyspnea has not been considered. We therefore examined the potential of intercostal muscle tension to elicit dyspnea in individuals with high anxiety sensitivity, a risk factor for developing panic disorder. METHODS: Individuals high and low in anxiety sensitivity (total N=62) completed four tasks: electromyogram biofeedback for tensing intercostal muscle, electromyogram biofeedback for tensing leg muscles, paced breathing at three different speeds, and a fine motor task. Global dyspnea, individual respiratory sensations, nonrespiratory sensations, and discomfort were assessed after each task, whereas respiratory pattern (respiratory inductance plethysmography) and end-tidal carbon dioxide (capnography) were measured continuously. RESULTS: In individuals with high compared to low anxiety sensitivity, intercostal muscle tension elicited a particularly strong report of obstruction (M=5.1, SD=3.6 versus M=2.5, SD=3.0), air hunger (M=1.9, SD=2.1 versus M=0.4, SD=0.8), hyperventilation symptoms (M=0.6, SD=0.6 versus M=0.1, SD=0.1), and discomfort (M=5.1, SD=3.2 versus M=2.2, SD=2.1) (all p values<.05). This effect was not explained by site-unspecific muscle tension, voluntary manipulation of respiration, or sustained task-related attention. Nonrespiratory control sensations were not significantly affected by tasks (F<1), and respiratory variables did not reflect any specific responding of high-Anxiety Sensitivity Index participants to intercostal muscle tension. CONCLUSIONS: Respiratory muscle tension may contribute to the respiratory sensations experienced by panic-prone individuals. Theories and treatments for panic disorder should consider this potential source of symptoms.

Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation.

It remains unclear if diminished high frequency heart rate variability (HF-HRV) can be found across anxiety disorders. HF-HRV and heart rate (HR) were examined in panic (PD), generalized anxiety (GAD), social anxiety (SAD), and obsessive-compulsive disorder (OCD) relative to healthy controls at baseline and during anxiety stressors. All disorders evidenced diminished baseline HF-HRV relative to controls. Baseline HRV differences were maintained throughout relaxation. For hyperventilation, PD and GAD demonstrated greater HR than controls. Psychotropic medication did not account for HF-HRV differences except in OCD. Age and sex evidenced multiple main effects. Findings suggest that low baseline HF-HRV represents a common index for inhibitory deficits across PD, GAD, and SAD, which is consistent with the notion of autonomic inflexibility in anxiety disorders. Elevated HR responses to hyperventilation, however, are specific to PD and GAD.

Opposing breathing therapies for panic disorder: a randomized controlled trial of lowering vs raising end-tidal P(CO2).

BACKGROUND: Teaching anxious clients to stop hyperventilating is a popular therapeutic intervention for panic. However, evidence for the theory behind this approach is tenuous, and this theory is contradicted by an opposing theory of panic, the false-suffocation alarm theory, which can be interpreted to imply that the opposite would be helpful. OBJECTIVE: To test these opposing approaches by investigating whether either, both, or neither of the 2 breathing therapies is effective in treating patients with panic disorder. METHOD: We randomly assigned 74 consecutive patients with DSM-IV-diagnosed panic disorder (mean age at onset = 33.0 years) to 1 of 3 groups in the setting of an academic research clinic. One group was trained to raise its end-tidal P(CO2) (partial pressure of carbon dioxide, mm Hg) to counteract hyperventilation by using feedback from a hand-held capnometer, a second group was trained to lower its end-tidal P(CO2) in the same way, and a third group received 1 of these treatments after a delay (wait-list). We assessed patients physiologically and psychologically before treatment began and at 1 and 6 months after treatment. The study was conducted from September 2005 through November 2009. RESULTS: Using the Panic Disorder Severity Scale as a primary outcome measure, we found that both breathing training methods effectively reduced the severity of panic disorder 1 month after treatment and that treatment effects were maintained at 6-month follow-up (effect sizes at 1-month follow-up were 1.34 for the raise-CO(2) group and 1.53 for the lower-CO(2) group; P < .01). Physiologic measurements of respiration at follow-up showed that patients had learned to alter their P(CO2) levels and respiration rates as they had been taught in therapy. CONCLUSIONS: Clinical improvement must have depended on elements common to both breathing therapies rather than on the effect of the therapies themselves on CO(2) levels. These elements may have been changed beliefs and expectancies, exposure to ominous bodily sensations, and attention to regular and slow breathing. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00183521.

Inspiratory-resistive loading increases the ventilatory response to arousal but does not reduce genioglossus muscle activity on the return to sleep.

Arousals from sleep are thought to predispose to obstructive sleep apnea by causing hyperventilation and hypocapnia, which reduce airway dilator muscle activity on the return to sleep. However, prior studies of auditory arousals have not resulted in reduced genioglossus muscle activity [GG-electromyogram (EMG)], potentially because airway resistance prior to arousal was low, leading to a small ventilatory response to arousal and minimal hypocapnia. Thus we aimed to increase the ventilatory response to arousal by resistive loading prior to auditory arousal and determine whether reduced GG-EMG occurred on the return to sleep. Eighteen healthy young men and women were recruited. Subjects were instrumented with a nasal mask with a pneumotachograph, an epiglottic pressure catheter, and intramuscular GG-EMG electrodes. Mask CO(2) levels were monitored. Three- to 15-s arousals from sleep were induced with auditory tones after resting breathing (No-Load) or inspiratory-resistive loading (Load; average 8.4 cmH(2)O·l(-1)·s(-1)). Peak minute ventilation following arousal was greater after Load than No-Load (mean ± SE; 8.0 ± 0.6 vs. 7.4 ± 0.6 l/min, respectively). However, the nadir end tidal partial pressure of CO(2) did not differ between Load conditions (43.1 ± 0.6 and 42.8 ± 0.5 mmHg, respectively), and no period of reduced GG activity occurred following the return to sleep (GG-EMG baseline, minimum after Load and No-Load = 2.9 ± 1.2%, 3.1 ± 1.3%, and 3.0 ± 1.3% max, respectively). These findings indicate that the hyperventilation, which occurs following tone-induced arousal, is appropriate for the prevailing level of respiratory drive, because loading did not induce marked hypocapnia or lower GG muscle activity on the return to sleep. Whether similar findings occur following obstructive events in patients remains to be determined.