Breathlessness and dysfunctional breathing in patients with postural orthostatic tachycardia syndrome (POTS): The impact of a physiotherapy intervention.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, multifactorial syndrome with complex symptoms of orthostatic intolerance. Breathlessness is a prevalent symptom, however little is known about the aetiology. Anecdotal evidence suggests that breathless POTS patients commonly demonstrate dysfunctional breathing/hyperventilation syndrome (DB/HVS). There are, however, no published data regarding DB/HVS in POTS, and whether physiotherapy/breathing retraining may improve patients' breathing pattern and symptoms. The aim of this study was to explore the potential impact of a physiotherapy intervention involving education and breathing control on DB/HVS in POTS. A retrospective observational cohort study of all patients with POTS referred to respiratory physiotherapy for treatment of DB/HVS over a 20-month period was undertaken. 100 patients (99 female, mean (standard deviation) age 31 (12) years) with a clinical diagnosis of DB/HV were referred, of which data was available for 66 patients pre - post intervention. Significant improvements in Nijmegen score, respiratory rate and breath hold time (seconds) were observed following treatment. These data provide a testable hypothesis that breathing retraining may provide breathless POTS patients with some symptomatic relief, thus improving their health-related quality of life. The intervention can be easily protocolised to ensure treatment fidelity. Our preliminary findings provide a platform for a subsequent randomised controlled trial of breathing retraining in POTS.

Assessing and responding to anxiety and panic in the Emergency Department.

Anxiety and panic symptoms are widespread in the general population. The physical manifestations of anxiety and panic commonly account for people presenting to Emergency Departments (EDs). It is therefore important for ED clinicians to be informed of the numerous causes of anxiety and panic and equipped to respond effectively. This paper describes the underlying pathophysiology of the physical symptoms of anxiety and panic and differential diagnoses to consider. Organic conditions that are associated with symptoms of anxiety and panic are highlighted. Brief interventions are tabled for ED clinicians to use when explaining symptoms, and to promote individual self-management.

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.

Purinergic and adenosine receptors contribute to hypoxic hyperventilation in zebrafish (Danio rerio).

The chemoreceptors involved in oxygen sensing in teleost fish are neuroepithelial cells (NECs) in the gills, and are analogous to glomus cells in the mammalian carotid body. Purinergic signalling mechanisms involving the neurotransmitters, ATP and adenosine, have been identified in mediating hypoxic signalling in the carotid body, but these pathways are not well understood in the fish gill. The present study used a behavioural assay to screen for the effects of drugs, that target purinergic and adenosine receptors, on the hyperventilatory response to hypoxia in larval zebrafish (Danio rerio) in order to determine if the receptors on which these drugs act may be involved in hypoxic signalling. The purinergic receptor antagonist, PPADS, targets purinergic P2X2/3 receptors and inhibited the hyperventilatory response to hypoxia (IC50=18.9µM). The broad-spectrum purinergic agonist, ATPγS, elicited a hyperventilatory response (EC50=168µM). The non-specific adenosine receptor antagonist, caffeine, inhibited the hyperventilatory response to hypoxia, as did the specific A2a receptor antagonist, SCH58261 (IC50=220nM). These results suggest that P2X2/3 and A2a receptors are candidates for mediating hypoxic hyperventilation in zebrafish. This study highlights the potential of applying chemical screening to ventilatory behaviour in zebrafish to further our understanding of the pathways involved in signalling by gill NECs and oxygen sensing in vertebrates.

Effects of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients: A randomized controlled trial.

INTRODUCTION: HIV infection is often preceded or accompanied by psychiatric comorbidities. These disorders improve with complementary therapies. The aim of this study was to measure the effect of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients. METHOD: Adult HIV-infected patients were randomized (n=29) in massage therapy group (one hour a week during four weeks) and control group. Anxiety and depression (HADS-A and HADS-D), hyperventilation (Nijmegen questionnaire) and quality of life (WHOQOL-HIV) were evaluated at inclusion and after 4 weeks. RESULTS: At inclusion, 51% and 17% of the patients had a positive HADS-A and HADS-D score respectively. Two facets from WHOQOL-HIV ("Home environment" and "Death and dying" (p=0.04)) were different between groups. After the four week massage therapy, a significant improvement was observed only for Nijmegen questionnaire (p=0.01) and HADS-A (p=0.04) contrarily to WHOQOL-HIV and HADS-D. Domains of the WHOQOL-HIV did not improve following the massage therapy. Only "Pain and discomfort" facet improved after massage therapy (p=0.04). CONCLUSION: This study highlights the positive impact of a four week massage therapy on anxiety and hyperventilation in HIV infected patients. However, neither benefit of this program was observed on depression and quality of life.

Physiological and behavioral indices of emotion dysregulation as predictors of outcome from cognitive behavioral therapy and acceptance and commitment therapy for anxiety.

BACKGROUND AND OBJECTIVES: Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. METHODS: Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. RESULTS: Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. LIMITATIONS: Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. CONCLUSIONS: Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts.

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.

Breathing and temporomandibular joint disease.

Temporomandibular joint disease (TMD) refers to a collection of pain related conditions in the masticatory muscles and temporomandibular joint. Occlusal factors have been implicated in TMD pathogenesis, yet despite decades of research no causal relationship between occlusion and TMD has been found. The significance of psychosocial factors in both the assessment and the long-term management of patients with TMD is receiving increased recognition. The teaching of relaxation skills and coping strategies are effective, proven TMD therapies. The role of breathing re-education in temporomandibular joint (TMJ) disorders is rarely mentioned. A focus on breathing patterns and their disorders potentially explains how biomechanical factors associated with psychosocial influences might lead to pathophysiological changes within the TMJ as well as in the associated muscles. Attention to factors such as breathing and postural rehabilitation provides health professionals valuable, additional tools to help care for patients with TMD.

Bronchoconstriction induced by hyperventilation with humidified hot air: role of TRPV1-expressing airway afferents.

A recent study by our laboratory has shown that an increase in intrathoracic temperature activates vagal pulmonary C-fibers. Because these afferents are known to elicit reflex bronchoconstriction upon stimulation, this study was carried out to investigate if an increase in airway temperature within the physiological range alters bronchomotor tone. Adult guinea pigs were anesthetized and mechanically ventilated via a tracheal tube. After the lung had been hyperventilated with humidified hot air (HHA) for 4 min, the tracheal temperature was elevated from 36.4 to 40.5 degrees C, which induced an immediate bronchoconstriction, increasing total pulmonary resistance (R(L)) to 177 +/- 10% and decreasing dynamic lung compliance to 81 +/- 6% of their respective baselines. The increase in R(L) returned spontaneously toward the baseline in <10 min and was reproducible in the same animals. There were no difference in the responses whether the humidity was generated from distilled water or isotonic saline. In contrast, hyperventilation with humidified air at room temperature did not cause any increase in R(L). The increase in R(L) caused by HHA was attenuated by 65.9% after a pretreatment with atropine alone and by 72.0% after a pretreatment with a combination of atropine and neurokinin receptor type 1 and 2 antagonists. In addition, capsazepine, a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, reduced the HHA-induced increase in R(L) by 64.1% but did not abolish it. However, pretreatment with formoterol, a beta(2)-agonist, completely prevented the HHA-induced bronchoconstriction. These results indicate that the increase in airway temperature induced transient airway constriction in guinea pigs. Approximately two-thirds of the increase in bronchomotor tone was mediated through the cholinergic reflex, which was probably elicited by the activation of TRPV1-expressing airway afferents. The remaining bronchoconstriction was caused by other, yet unidentified factors.

Breathing exercises for asthma: a randomised controlled trial.

BACKGROUND: The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain. METHODS: A prospective, parallel group, single-blind, randomised controlled trial comparing breathing training with asthma education (to control for non-specific effects of clinician attention) was performed. Subjects with asthma with impaired health status managed in primary care were randomised to receive three sessions of either physiotherapist-supervised breathing training (n = 94) or asthma nurse-delivered asthma education (n = 89). The main outcome was Asthma Quality of Life Questionnaire (AQLQ) score, with secondary outcomes including spirometry, bronchial hyper-responsiveness, exhaled nitric oxide, induced sputum eosinophil count and Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression (HAD) and hyperventilation (Nijmegen) questionnaire scores. RESULTS: One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training (0.38 units, 95% CI 0.08 to 0.68). At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety (1.1, 95% CI 0.2 to 1.9), HAD depression (0.8, 95% CI 0.1 to 1.4) and Nijmegen (3.2, 95% CI 1.0 to 5.4) scores, with trends to improved ACQ (0.2, 95% CI 0.0 to 0.4). No significant between-group differences were seen at 1 month. Breathing training was not associated with significant changes in airways physiology, inflammation or hyper-responsiveness. CONCLUSION: Breathing training resulted in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology. Such exercises may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication.

Autonomic nervous system abnormalities in spinocerebellar ataxia type 2: a cardiovascular neurophysiologic study.

Autonomic nervous system dysfunction is part of the spinocerebellar ataxia (SCA) clinical picture, but few data are available on this topic. The present study is aimed to report a detailed investigation of autonomic nervous system in patients with molecular diagnosis of SCA type 2, one of the most frequent forms and the commonest in Italy. Nine patients with a mild to moderate form of SCA2 underwent a questionnaire about dysautonomic symptoms and a complete cardiovascular neurophysiologic evaluation of both sympathetic and parasympathetic system, comprising head-up tilt, standing, isometric hand grip, cold pressure, mental arithmetic, Valsalva manoeuvre, deep breathing, and hyperventilation tests. An echocardiographic study and Holter-ECG recording were also performed. All patients complained dysautonomic problems regarding urinary tract, cardiovascular system, or gastrointestinal dysfunction. The neurophysiologic study showed both sympathetic and parasympathetic involvement, with highly variable degree and pattern of dysautonomia. The present study results show that the autonomic dysfunction is common in SCA2 representing a significant component of the complex picture of the disease. We found a wide spectrum of cardiovascular autonomic abnormalities, without a typical pattern of dysfunction and without correlation with clinical variables.

Fearful imagery induces hyperventilation and dyspnea in medically unexplained dyspnea.

BACKGROUND: Medically unexplained dyspnea refers to a condition characterized by a sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without underlying cardiopulmonary pathology. We were interested to know how anxiety triggers hyperventilation and elicits subjective symptoms in those patients. Using an imagery paradigm, we investigated the role of fearful imagery in provoking hyperventilation and in eliciting symptoms, specifically dyspnea. METHODS: Forty patients with medically unexplained dyspnea and 40 normal subjects matched for age and gender were exposed to scripts and asked to imagine both fearful and restful scenarios, while end-tidal PCO(2) (PetCO(2)) and breathing frequency were recorded and subjective symptoms evaluated. The subject who had PetCO(2) falling more than 5 mmHg from baseline and persisting at this low level for more than 15 seconds in the imagination was regarded as a hyperventilation responder. RESULTS: In patients with medically unexplained dyspnea, imagination of fearful scenarios, being blocked in an elevator in particular, induced anxious feelings, and provoked a significant fall in PetCO(2) (P < 0.05). Breathing frequency tended to increase. Eighteen out of 40 patients were identified as hyperventilation responders compared to 5 out of 40 normal subjects (P < 0.01). The patients reported symptoms of dyspnea, palpitation or fast heart beat in the same fearful script imagery. Additionally, PetCO(2) fall was significantly correlated with the intensity of dyspnea and palpitation experienced during the mental imagery on one hand, and with anxiety symptoms on the other. CONCLUSIONS: Fearful imagery provokes hyperventilation and induces subjective symptoms of dyspnea and palpitation in patients with medically unexplained dyspnea.

Disproportionate breathlessness associated with deep sighing breathing in a patient presenting with difficult-to-treat asthma.

Disproportionate breathlessness is a term that is used synonymously with dysfunctional breathing and idiopathic hyperventilation in the absence of chest disease. In the presence of chest disease, it may not be possible to use these three terms interchangeably. We report a case of a patient with documented asthma but breathlessness that was out of proportion to the measured lung function or exercise tolerance. The breathing pattern was abnormal and was characterized by the need to take frequent deep sighs, which increased in frequency during incremental exercise, despite increasing respiratory rate and tidal volume. Treatment with physiotherapist-led breathing retraining resulted in an improvement in the sigh rate and breathlessness scores. Disproportionate breathlessness and deep sighing breathing are part of the spectrum of conditions that comprise dysfunctional breathing and can cause symptoms that may be wrongly attributed to asthma.

Acute cardio-respiratory changes induced by hyperpnoea using a respiratory muscle trainer.

The aim of this study was to examine the cardio-respiratory effects of voluntary hyperpnoea using a respiratory muscle trainer (RMT) with three different sized rebreathing bags. In particular, the effects of hyperpnoea on inspired and end-tidal gas concentrations were determined. Seven adult males completed three 30 min bouts of hyperpnoea using optimal, oversized and undersized rebreathing bags. Inspired (F(I)) and expired end-tidal (F(ET)) O2 and CO2 concentrations, arterial O2 saturation (S(AO2)) and heart rate were measured during hyperpnoea. Before and after a bout of hyperpnoea, pulmonary function and blood pressure (BP) were assessed. Data were analysed using a two-way repeated-measures ANOVA, with p < 0.05 considered significant. Three subjects experienced discomfort during hyperpnoea and stopped after 20 min. During hyperpnoea, the F(ETCO2) was maintained at 4.6 +/- 0.7% irrespective of bag size. The increase in F(ICO2) over time reached 0.5 +/- 0.5% at 20 min. The F(IO2) fell to 19.4 +/- 0.8% at 20 min, and S(AO2) decreased to 97%. Heart rate and systolic BP increased slightly, but independently of rebreathing bag volume. No changes in pulmonary function or diastolic BP were found. It is concluded that the RMT maintained a constant F(ETCO2) at the expense of a mild hypoxia. The acute effects of hyperpnoea on the cardio-respiratory system are generally mild, but not always tolerable for 30 min.

Induced arousal and reexperiencing in acute stress disorder.

This study investigated the relationship of hyperarousal and intrusive symptoms in acute stress disorder (ASD). Civilian trauma survivors with ASD (n = 18) and without ASD (n = 14) completed a hyperventilation provocation test (HVPT) and then completed the Physical Reactions Scale. All participants provided a narrative describing their hyperventilation experience that was audiotaped and independently coded. Individuals with ASD reported greater numbers of intrusive memories and reported greater distress than non-ASD participants. More ASD than non-ASD participants experienced a flashback-type reaction during the hyperventilation. Intrusive symptoms were significantly correlated with elevated arousal following the HVPT. The findings provide evidence that reexperiencing is directly associated with elevated states of arousal.

['Hyperventilation syndrome': often an easy to treat panic disorder]. / 'Hyperventilatiesyndroom': veelal goed behandelbare paniekstoornis.

Three patients, 2 men aged 35 and 26 years and 1 woman aged 41 years, had acutely occurring attacks, accompanied by diverse somatic complaints, and were diagnosed with hyperventilation syndrome. They recovered only when the complaints were recognised and treated as a panic disorder. Hyperventilation and the decrease of CO2 in the blood do not explain the symptoms and complaints in patients with panic disorder, a psychiatric disorder with a good prognosis. Treatment consists of cognitive behavioural therapy or a selective serotonin re-uptake inhibitor in the case of panic disorder and of a combination of those two treatments in the case of panic disorder with agoraphobia. Breathing exercises can form part of the behavioural therapy but not because the disorder is due to faulty breathing habits.

Respiratory feedback for treating panic disorder.

Panic disorder patients often complain of shortness of breath or other respiratory complaints, which has been used as evidence for both hyperventilation and false suffocation alarm theories of panic. Training patients to change their breathing patterns is a common intervention, but breathing rarely has been measured objectively in assessing the patient or monitoring therapy results. We report a new breathing training method that makes use of respiratory biofeedback to teach individuals to modify four respiratory characteristics: increased ventilation (Respiratory Rate x Tidal Volume), breath-to-breath irregularity in rate and depth, and chest breathing. As illustrated by a composite case, feedback of respiratory rate and end-tidal pCO2 can facilitate voluntary control of respiration and reduce symptoms. Respiratory monitoring may provide relevant diagnostic, prognostic, and outcome information.

Chronic dyspnea and hyperventilation in an awake patient with small subcortical infarcts.

A 79-year-old woman presented with chronic dyspnea and hyperventilation. There was no evidence of pulmonary disease. Hyperventilation persisted during sleep and after high-dose administration of a narcotic. A head MRI revealed bilateral medial thalamic infarctions. Central neurogenic hyperventilation was diagnosed in this alert patient. The case may illustrate a role for the thalamus in regulating ventilation, but another small infarct not visible on MRI also could be responsible.