Biofeedback Training to Increase P co2 in Asthma With Elevated Anxiety: A One-Stop Treatment of Both Conditions?

OBJECTIVE: Anxiety is highly prevalent in individuals with asthma. Asthma symptoms and medication can exacerbate anxiety, and vice versa. Unfortunately, treatments of comorbid anxiety and asthma are largely lacking. A problematic feature common to both conditions is hyperventilation. It adversely affects lung function and symptoms in asthma and anxiety. We examined whether a treatment to reduce hyperventilation, shown to improve asthma symptoms, also improves anxiety in asthma patients with high anxiety. METHOD: One hundred twenty English- or Spanish-speaking adult patients with asthma were randomly assigned to either Capnometry-Assisted Respiratory Training (CART) to raise P co2 or feedback to slow respiratory rate (SLOW). Although anxiety was not an inclusion criterion, 21.7% met clinically relevant anxiety levels on the Hospital Anxiety and Depression Scale (HADS). Anxiety (HADS-A) and depression (HADS-D) scales, anxiety sensitivity (Anxiety Sensitivity Index [ASI]), and negative affect (Negative Affect Scale of the Positive Affect Negative Affect Schedule) were assessed at baseline, posttreatment, 1-month follow-up, and 6-month follow-up. RESULTS: In this secondary analysis, asthma patients with high baseline anxiety showed greater reductions in ASI and PANAS-N in CART than in SLOW ( p values ≤ .005, Cohen d values ≥ 0.58). Furthermore, at 6-month follow-up, these patients also had lower ASI, PANAS-N, and HADS-D in CART than in SLOW ( p values ≤ .012, Cohen d values ≥ 0.54). Patients with low baseline anxiety did not have differential outcomes in CART than in SLOW. CONCLUSIONS: For asthma patients with high anxiety, our brief training designed to raise P co2 resulted in significant and sustained reductions in anxiety sensitivity and negative affect compared with slow-breathing training. The findings lend support for P co2 as a potential physiological target for anxiety reduction in asthma. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00975273 .

Extrapulmonary symptoms of patients with asthma treated in specialist pulmonary care.

OBJECTIVE: Patients seeking treatment for their asthma are most likely motivated by a change in their experience of symptoms, but primary complaints are not always related to the pulmonary system. This study aimed to determine the frequency of such extrapulmonary symptoms in asthma outpatients and their association with psychopathology and asthma outcomes. METHODS: This cross-sectional study utilized data collected as part of a nationwide, clinical-epidemiological study. The final sample of 572 asthma patients represented all levels of asthma control and severity. Information on demographics and respiratory function was obtained from physicians' documentation. Symptoms were explored using a standardized checklist. RESULTS: Primary symptoms reported by asthma patients were not necessarily airway-related. Patients reported feeling at least occasionally "tired" (72.1%) and "exhausted" (66.8%) more than any other asthma symptom. Hyperventilation and mood symptoms were experienced by 34.4-42.6% of patients. Anxiety or depression diagnoses indicated higher scores in all symptom domains. Controlling for asthma-related factors and psychopathology, fatigue had a small but significant effect on both asthma-related quality of life (AQLQ) (rsp2 = 0.02, P < .001) and asthma control (rsp2 = 0.01, P = .003). Mood symptoms also showed a small but significant effect on AQLQ (rsp2 = 0.02, P < .001). CONCLUSION: Findings suggest that extrapulmonary symptoms are endorsed more frequently than previously reported. Symptoms nonspecific to asthma can play a substantial role in clinical presentation and exclusive focus on airway symptoms may miss important information related to patients' well-being. Surveillance of extrapulmonary symptoms alongside pulmonary function is warranted for an integrated medicine approach to asthma management.

Beetroot juice supplementation for the prevention of cold symptoms associated with stress: A proof-of-concept study.

OBJECTIVES: Psychological stress has been linked to common cold symptoms. Nitric oxide (NO) is part of the first line of epithelial defense against pathogens, and beetroot juice is a source of dietary nitrate that increases NO availability. We therefore tested whether beetroot juice protects against cold symptoms in a period of sustained acute stress. DESIGN: Seventy-six students, 16 of these with asthma, were randomly assigned to seven daily doses of beetroot juice or no supplementation control during their final exams. METHODS: Participants completed stress ratings, a cold symptom questionnaire, and exhaled NO measurements at a low-stress period and two periods during their final exams, with one questionnaire follow-up assessment seven days after finals. RESULTS: Beetroot juice was associated with reduced symptoms of cold and sickness during and following finals. Those with asthma showed the greatest benefits. Higher exhaled NO was concurrently and prospectively associated with reduced symptomatology. CONCLUSION: Beetroot juice during periods of psychological stress protects against cold symptoms. Preliminary evidence suggests particular benefits in asthma, which could translate into reduced asthma exacerbations due to respiratory infections. Clinical Trial ID: NCT03159273.

Respiration and applied tension strategies to reduce vasovagal reactions to blood donation: A randomized controlled trial.

BACKGROUND: Whether produced by breathing too fast or too deeply, hyperventilation is common in stressful situations and may contribute to blood donation-related vasovagal symptoms. The effects of some previously tested interventions for vasovagal symptoms, for example, applied tension (AT), may be related to reduction of hyperventilation. More targeted breathing techniques might be useful. STUDY DESIGN AND METHODS: This was a randomized controlled trial comparing the effects of AT, a slow, shallow "anti-hyperventilation" breathing technique previously tested in phobic individuals (respiration control [RESP]), the combination of AT and RESP, and no intervention on blood donors participating in university clinics. A total of 547 eligible donors were assigned randomly to one of these four groups. Observational, self-report, and physiologic measures (primarily via respiratory capnometry) were obtained. RESULTS: Although both RESP and AT had some positive impact on blood donation outcome, the effects of RESP were more numerous, albeit limited primarily to donors who had less general fear of medical procedures. For example, lower-fear donors assigned to practice RESP had significantly lower Blood Donation Reaction Inventory scores and were significantly less likely to require treatment for symptoms than no-treatment individuals. In general, RESP led to a significant decrease in respiration rate, though it did not influence end-tidal CO2 , a more precise measure of hyperventilation. CONCLUSION: While the mechanisms remain somewhat unclear and the interventions did not benefit more fearful, higher-risk donors, respiration control is a promising additional approach to reducing vasovagal symptoms.

Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals.

BACKGROUND AND OBJECTIVE: Nitric oxide (NO) plays an important role in the airways' innate immune response, and the fraction of exhaled NO at a flow rate of 50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are linked to loss of bronchoprotective effects in airway challenges and predict symptoms of respiratory infection. While beetroot juice supplements have been proposed to enhance exercise performance by increasing dietary nitrate consumption, few studies have examined the impact of beetroot juice or nitrate supplementation on airway NO in contexts beyond an exercise challenge, which we know influences FENO50. METHODS: We therefore examined the influence of a beetroot juice supplement on FENO50 in healthy males and females (n = 38) during periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure, and state affect were measured at baseline, 45 minutes, and 90 minutes following ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were followed with ingestion of 70ml of water on a control day. RESULTS: After beetroot consumption, average values of the natural log of FENO50 (lnFENO50) increased by 21.3% (Cohen's d = 1.54, p < .001) 45 minutes after consumption and by 20.3% (Cohen's d = 1.45, p < .001) 90 min after consumption. On the other hand, only very small increases in FENO50 were observed after consumption of the control liquid (less than 1% increase). A small subset (n = 4) of participants completed an extended protocol lasting over 3 hours, where elevated levels of FENO50 persisted. No significant changes in cardiovascular measures were observed with this small single dose of beetroot juice. CONCLUSION: As NO serves a key role in innate immunity, future research is needed to explore the potential clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent respiratory infection.

Asthma Trigger Reports Are Associated with Low Quality of Life, Exacerbations, and Emergency Treatments.

RATIONALE: Despite the importance of trigger perceptions for asthma diagnosis and management, associations among asthma triggers, affective disorders, and asthma outcome have received little attention. OBJECTIVES: Because anxiety and depression are known to influence patients' health reports, we measured and controlled for these affective disorders in analyzing associations among patient perceptions of asthma triggers and asthma treatment outcomes. METHODS: Patients from a nationally representative sample of respiratory specialist practices (N = 459) were assessed for clinically significant anxiety and depression and completed questionnaires on asthma triggers, quality of life, and asthma control. Physicians recorded exacerbation and emergency treatment frequencies in the prior year, spirometric lung function, and allergy test results. Hierarchical multiple regressions examined associations among reported trigger factors, anxiety, depression, and asthma outcomes, including quality of life, asthma control, exacerbations, emergencies, and spirometry. MEASUREMENTS AND MAIN RESULTS: Patients across asthma severity levels were well represented. Anxiety and depression were associated with more frequent nonallergic, in particular psychological, triggers. Controlling for demographics, asthma severity, anxiety, and depression, nonallergic asthma triggers (including psychological triggers) explained substantial portions of variance in asthma control (total of 19.5%, odds ratios [ORs] = 2.07-1.37 for individual triggers), asthma-related quality of life (total of 27.5%, ORs = 3.21-1.49), and general quality of life (total of 11.3%, ORs = 1.93-1.55). Psychological triggers were consistently associated with exacerbations and emergency treatments (ORs = 1.96-2.04) over and above other triggers and affective disorders. Spirometric lung function was largely unrelated to perceived asthma triggers. CONCLUSIONS: Patients' perceptions of asthma triggers are important determinants of asthma outcomes, which can help identify individuals at risk for suboptimal asthma management.

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.

Hypoventilation training for asthma: a case illustration.

Hyperventilation-induced hypocapnia is common among asthma patients. This case study illustrates both methodology and results from a patient undergoing training in capnometry-assisted respiratory training (CART). CART is a 4-week training aimed at normalizing basal and acute levels of end-tidal carbon dioxide (PCO(2)) using a portable capnometer. In the presented case, basal levels of PCO(2) increased from hypocapnic to normocapnic range over the course of treatment. Improvements were accompanied by improvements in lung function and reductions in diurnal lung function variability. Improvements remained stable throughout follow-up.

Changes in pCO2, symptoms, and lung function of asthma patients during capnometry-assisted breathing training.

In a recent pilot study with asthma patients we demonstrated beneficial outcomes of a breathing training using capnometry biofeedback and paced breathing assistance to increase pCO(2) levels and reduce hyperventilation. Here we explored the time course changes in pCO(2), respiration rate, symptoms and lung function across treatment weeks, in order to determine how long training needs to continue. We analyzed in eight asthma patients whether gains in pCO(2) and reductions in respiration rate achieved in home exercises with paced breathing tapes followed a linear trend across the 4-week treatment period. We also explored the extent to which gains at home were manifest in weekly training sessions in the clinic, in terms of improvement in symptoms and spirometric lung function. The increases in pCO(2) and respiration rate were linear across treatment weeks for home exercises. Similar increases were seen for in-session measurements, together with gradual decreases in symptoms from week to week. Basal lung function remained stable throughout treatment. With our current protocol of paced breathing and capnometry-assisted biofeedback at least 4 weeks are needed to achieve a normalization of pCO(2) levels and reduction in symptoms in asthma patients.

Stress effects on lung function in asthma are mediated by changes in airway inflammation.

OBJECTIVE: To examine the association of changes in current negative mood and long-term daily hassles with changes in lung function and airway inflammation in patients suffering from asthma and in healthy controls. Associations between psychological factors and asthma symptoms have been documented, but the relationship between airway inflammation and psychological factors has been largely unexplored. METHOD: Data were analyzed from 46 asthma patients and 25 controls who completed questionnaires on current mood and daily hassles at two assessments 3 months apart. Lung function was measured by spirometry (forced expiratory volume in the first second (FEV(1))) and airway inflammation by the fraction of nitric oxide in exhaled air (FeNO). Regression analyses controlling for allergen load and air pollution (ozone) were calculated to study the association between changes in psychological factors and changes in lung function and airway inflammation, and to examine the mediational role of airway inflammation in the stress-lung function association. RESULTS: In patients with asthma, increases in negative affect were associated with decreases in FEV(1) and increases in FeNO. For daily hassles, a reverse pattern of associations was found, with decreases in daily hassles linked to decreases in FEV(1) and increases in FeNO. Mediation analyses showed that FeNO was a significant mediator of the association of both negative affect and daily hassles with lung function changes. No significant associations were found for healthy controls. CONCLUSION: Psychological variables are consistently associated with spirometric lung function and airway inflammation in asthma patients. For asthma patients, effects of acute negative affect must be distinguished from more chronic distress due to daily hassles.

Feedback of end-tidal pCO2 as a therapeutic approach for panic disorder.

BACKGROUND: Given growing evidence that respiratory dysregulation is a central feature of panic disorder (PD) interventions for panic that specifically target respiratory functions could prove clinically useful and scientifically informative. We tested the effectiveness of a new, brief, capnometry-assisted breathing therapy (BRT) on clinical and respiratory measures in PD. METHODS: Thirty-seven participants with PD with or without agoraphobia were randomly assigned to BRT or to a delayed-treatment control group. Clinical status, respiration rate, and end-tidal pCO(2) were assessed at baseline, post-treatment, 2-month and 12-month follow-up. Respiratory measures were also assessed during homework exercises using a portable capnometer as a feedback device. RESULTS: Significant improvements (in PD severity, agoraphobic avoidance, anxiety sensitivity, disability, and respiratory measures) were seen in treated, but not untreated patients, with moderate to large effect sizes. Improvements were maintained at follow-up. Treatment compliance was high for session attendance and homework exercises; dropouts were few. CONCLUSIONS: The data provide preliminary evidence that raising end-tidal pCO(2) by means of capnometry feedback is therapeutically beneficial for panic patients. Replication and extension will be needed to verify this new treatment's efficacy and determine its mechanisms.

Targeting pCO(2) in asthma: pilot evaluation of a capnometry-assisted breathing training.

OBJECTIVES: This pilot study aimed to evaluate the feasibility and potential benefits of a novel biofeedback breathing training for achieving sustained increases in pCO(2) levels. METHODS: Twelve asthma patients were randomly assigned to an immediate 4-week treatment group or waiting list control. Patients were instructed to modify their respiration in order to change levels of end-tidal pCO(2) using a hand-held capnometer. Treatment outcome was assessed in frequency and distress of symptoms, asthma control, lung function, and variability of peak expiratory flow (PEF). RESULTS: We found stable increases in pCO(2) and reductions in respiration rate during treatment and 2-month follow-up. Mean pCO(2) levels rose from a hypocapnic to a normocapnic range at follow-up. Frequency and distress of symptoms was reduced and reported asthma control increased. In addition, mean PEF variability decreased significantly in the treatment group. CONCLUSIONS: Our pilot intervention provided evidence for the feasibility of pCO(2)-biofeedback training in asthma patients.

Evaluation of a respiratory muscle biofeedback procedure-effects on heart rate and dyspnea.

Patients with respiratory diseases or anxiety frequently complain about dyspnea, which may be partly related to chronic tension of respiratory muscles and/or dynamic hyperinflation. In two experiments we tested a biofeedback technique that recorded electromyographic (EMG) activity from a bipolar surface electrode placement over the right external intercostal muscles with visual signal feedback. Healthy participants were tested in their ability to alter the signal. Heart rate was measured continuously throughout training trials. In the second experiment, dyspnea was rated on a modified Borg scale after each trial. Participants were able to increase their EMG activity considerably while heart rate and dyspnea increased substantially. Changes in EMG activity were achieved mostly by manipulating accessory muscle tension and/or altering breathing pattern. Thus, the technique is capable of altering respiratory muscle tension and associated dyspnea. Further studies may test the procedure as a relaxation technique in patients with respiratory disease or anxiety.

Implementation and interpretation of respiratory sinus arrhythmia measures in psychosomatic medicine: practice against better evidence?

Respiratory sinus arrhythmia (RSA) or high-frequency heart rate variability has been widely used as a noninvasive measure of cardiac vagal tone. However, their dependency on both respiration rate and tidal volume is largely ignored. Only a minority of studies published in Psychosomatic Medicine in recent years has implemented precautions for controlling respiration rate in RSA measures, and tidal volume effects were only rarely addressed. We discuss methodologic issues related to respiratory control methods and present data that demonstrate that both respiration rate and tidal volume contribute substantially to the within-individual RSA variance under conditions of variable breathing, with tidal volume contributing up to one third beyond respiration rate. Finally, we outline a respiratory control method for the time-domain index of RSA and review research pertaining to its reliability, validity, and experimental application.

Voluntary hyperventilation in the treatment of panic disorder--functions of hyperventilation, their implications for breathing training, and recommendations for standardization.

Hyperventilation has numerous theoretical and empirical links to anxiety and panic. Voluntary hyperventilation (VH) tests have been applied experimentally to understand psychological and physiological mechanisms that produce and maintain anxiety, and therapeutically in the treatment of anxiety disorders. From the theoretical perspective of hyperventilation theories of anxiety, VH is useful diagnostically to the clinician and educationally to the patient. From the theoretical perspective of cognitive-behavior therapy, VH is a way to expose patients with panic disorder to sensations associated with panic and to activate catastrophic cognitions that need restructuring. Here we review panic disorder treatment studies using breathing training that have included VH. We differentiate the roles of VH in diagnosis, education about symptoms, training of breathing strategies, interoceptive exposure, and outcome measurement--discussing methodological issues specific to these roles and VH test reliability and validity. We propose how VH procedures might be standardized in future studies.

Behavioral interventions in asthma: biofeedback techniques.

OBJECTIVES: Biofeedback techniques have long been recommended as an adjunctive treatment for bronchial asthma. Techniques that target lung function directly, or indirectly by altering facial muscle tension, heart rate, heart rate variability (HRV) or inspiratory volume together with accessory muscle tension, have been proposed. We review evidence for the effectiveness of these biofeedback interventions and discuss the psychophysiological rationale behind individual techniques. METHOD: Controlled studies of biofeedback in asthma were retrieved using relevant search engines and reference lists of published articles. Effect sizes comparing intervention with control groups were calculated where appropriate. RESULTS: Most of the studies suffer from methodological inadequacies or poor reporting of methods and results. Interventions targeting respiratory resistance directly have yielded only small and inconsistent changes in lung function and are difficult to implement without producing dynamic hyperinflation. Biofeedback-assisted facial muscle relaxation as an indirect intervention has yielded mixed results across studies, with only half of the studies showing significant albeit very small and clinically irrelevant improvements in lung function. The underlying physiological assumptions of the technique are questionable in the light of current knowledge of respiratory physiology. For other indirect techniques, only preliminary evidence of small effects is available. CONCLUSION: Currently, there is little good evidence that biofeedback techniques can contribute substantially to the treatment of asthma.

Behavioral interventions in asthma. Breathing training.

Breathing exercises are frequently recommended as an adjunctive treatment for asthma. A review of the current literature found little that is systematic documenting the benefits of these techniques in asthma patients. The physiological rationale of abdominal breathing in asthma is not clear, and adverse effects have been reported in chronic obstructive states. Theoretical analysis and empirical observations suggest positive effects of pursed-lip breathing and nasal breathing but clinical evidence is lacking. Modification of breathing patterns alone does not yield any significant benefit. There is limited evidence that inspiratory muscle training and hypoventilation training can help reduce medication consumption, in particular beta-adrenergic inhaler use. Breathing exercises do not seem to have any substantial effect on parameters of basal lung function. Additional research is needed on the psychological and physiological mechanisms of individual breathing techniques in asthma, differential effects in subgroups of asthma patients, and the generalization of training effects on daily life.

Breathing training for treating panic disorder. Useful intervention or impediment?

Breathing training (BT) is commonly used for treatment of panic disorder. We identified nine studies that reported the outcome of BT. Overall, the published studies of BT are not sufficiently compelling to allow an unequivocal judgment of whether such techniques are beneficial. This article discusses problems with the underlying rationale, study design, and techniques used in BT, and it identifies factors that may have determined therapy outcomes. The idea that hypocapnia and respiratory irregularities are underlying factors in the development of panic implies that these factors should be monitored physiologically throughout therapy. Techniques taught in BT must take account of respiration rate and tidal volume in the regulation of blood gases (pCO2). More studies are needed that are designed to measure the efficacy of BT using an adequate rationale and methodology. Claims that BT should be rejected in favor of cognitive or other forms of intervention are premature.