Induction of dyspnea evokes increased anxiety and maladaptive breathing in individuals with high anxiety sensitivity and suffocation fear

Although respiratory symptoms are relevant for diagnosis and etiology of panic disorder, anxiety responses and breathing behavior evoked by induction of dyspnea have rarely been studied. Therefore, dyspnea sensations and affective evaluations evoked by inspiratory resistive loads of different intensities were first assessed in 23 individuals with high versus 24 participants with low anxiety sensitivity (AS). High AS participants with high fear of suffocation rated loads of the same physical intensity as more unpleasant and reported more intense feelings of dyspnea and more respiratory and panic symptoms than low AS individuals. In the second experiment assessing physiological responses to physically comparable loads, high suffocation fear participants showed an increase in minute ventilation to compensate for fear‐induced air hunger. This ventilation behavior results in increased frequency of dyspnea sensations, thus increasing fear of suffocation.     

Effects of naloxone on respiratory sensation before and after a removal of severe respiratory stress

Severe respiratory stress causes dyspnea, and a sudden release of this stress frequently accompanies a euphoric sensation. We hypothesized that acute severe respiratory stress may result in an elaboration of endogenous opioids within the central nervous system, and that these opioids may play significant roles in relieving dyspnea and generating euphoric sensation after a sudden removal of the stress. To test this hypothesis, we examined the effects of naloxone (0.04 mg/kg, I.V.) and the placebo (normal saline) on changes in respiratory sensation before and after the release of severe respiratory stress in a double-blind, randomized, crossover study in 14 healthy adults. Acute severe respiratory stress was induced by loaded breathing with a combination of resistive loading and hypercapnia. The subjects rated their changes in sensation by using a bidirectional visual analogue scale. Naloxone pretreatment affected neither the ventilation nor the development of dyspneic sensation during loaded breathing. Naloxone pretreatment only slightly attentuated the euphoric sensation developed after the release of severe respiratory stress. These findings suggest a small role of opioids in relieving dyspnea and in generating euphoria before and after a sudden removal of stress.     

Dyspnea

Dyspnea is the medical term for the patient's or subject's complaint of shortness of breath. It encompasses the respiratory discomfort experienced in many different diease states as well as the shortness of breath felt by a normal subject during or after strenuous exercise. Several parameters which have been shown to correlate with the onset or severity of dyspnea are described, including reduced vital capacity, the ratio of minute ventilation to vital capacity, reduced breathing reserve, the work of breathing, and the oxygen cost of breathing. Attempts at quantitation of dyspnea have usually consisted of measuring physiological parameters associated with the sensation, such as the "dyspneic index". The direct measurement of respiratory sensations using modern psycho-physical methods is at an early stage of development. Since the observation that the existence of dyspnea is often unrelated to any disturbance of arterial blood gas composition, it has been generally held that the mechanism of dyspnea is primarily neurophysiological. The neural pathways may conceptually be divided into those which transmit the "dyspnea message" from the respiratory apparatus to integrating centers in the brain, and those concerned with subsequently bringing the sensation to the level of consciousness. It seems likely that there is no single sensing mechanism and neural pathway which will be able to explain dyspnea in the diverse populations of patients and subjects who experience unpleasant respiratory sensations. Three theories concerning mechanisms of dyspnea are briefly described: "length-tension inappropriateness", vagal afferent activity especially from the J-receptors, and the recent concept of diaphragmatic fatigue. Some specific characteristics of the shortness of breath experienced in certain disease states are described, including chronic bronchitis and emphysema, bronchial asthma, pulmonary fibrosis and congestive heart disease.     

Defensiveness and Perception of External Inspiratory Resistive Loads in Asthma

This study examined the relationship between defensiveness, as measured by the Marlowe–Crowne Social Desirability Scale (MCSDS), and the perception of an externally applied respiratory resistance among people with asthma. Thirty asthmatic adults breathed through nine levels of inspiratory resistive load. Participants higher on the MCSDS were less accurate than others in psychophysical magnitude estimates of resistive load, and showed a reduced relationship between the physical load and the quality of respiratory sensations associated with exposure to the resistors. Defensive subjects also showed a differentially high increase in correlation between unpleasantness of respiratory sensations and resistance levels after receiving parenteral naloxone. These findings are consistent with the hypothesis that defensiveness may increase risk of asthma morbidity, due to inaccuracy in detecting sensations of dyspnea during asthma exacerbations. The inaccuracy may be caused by elevated endogenous opioids among defensive individuals.     

When dyspnea gets worse: Suffocation fear and the dynamics of defensive respiratory responses to increasing interoceptive threat

In patients with anxiety and/or respiratory diseases, body sensations, particularly from the respiratory system, may increase in intensity and aversiveness and thus lead into defensive action (e.g., escape) or panic. The processes, however, that might contribute to the culmination of symptoms and the switch into defensive action have not been well understood yet. The current study aimed at evaluating an experimental paradigm to characterize the dynamics of defensive mobilization to body sensations increasing in intensity and aversiveness. Persons reporting low and high suffocation fear (SF; N = 69) were exposed to increasingly unpleasant feelings of dyspnea induced by inspiratory resistive loads and a breathing occlusion requiring voluntary breath holding. Respiratory responses were assessed along with subjective reports of anxiety and panic symptoms. Presentation of respiratory loads with increasing physical resistance led to increasingly unpleasant feelings of dyspnea. Twenty‐eight participants terminated the exposure prematurely at least once. When dyspnea was severe, high compared to low SF persons exhibited an increased respiratory rate that was accompanied by reports of more intense panic symptoms. Premature terminations of exposure were preceded by a surge in anxiety, breathing frequency, and mouth pressure, and a decrease in tidal volume. We successfully established an experimental paradigm to assess changes in defensive responding with increasing intensity of an interoceptive threat. The current data foster our understanding of behavioral expression patterns observed in patients with anxiety and/or respiratory diseases and the processes involved in the culmination of bodily sensations and anxiety into panic.     

Urge-to-cough and dyspnea conceal perception of pain in healthy adults

Although dyspnea has been shown to attenuate pain, whether urge-to-cough, a respiratory sensation preceding cough, exerts a similar inhibitory effect on pain has not been clarified. We examined the effects of both urge-to-cough and dyspnea on pain induced by thermal noxious stimuli. Urge-to-cough was induced by citric acid challenge and dyspnea was induced by external inspiratory resistive loads. During inductions of two respiratory sensations, perception of pain was assessed by thermal pain threshold (TPTh) and tolerance (TPTo). TPTh and TPTo were significantly increased accompanied by increases in perception of both urge-to-cough and dyspnea. Fractional change in TPTh during dyspnea was significantly correlated with that during urge-to-cough. Fractional change in TPTo during dyspnea was significantly correlated with that during urge-to-cough. The study suggests that both two distinct respiratory sensations, i.e., urge-to-cough and dyspnea may harbor perception of pain. Further studies investigating interactions among these sensations in clinical settings are warranted.     

Perceptual contributions to optimization of breathing

Besides regulating the energetic cost of breathing, optimization of breathing may involve the alleviation of an uncomfortable breathing sensation. In this article, we consider perceptual contributions to the optimization of breathing. Just as the cost function proposed by Poon depends on ventilation and arterial so does the sense of dyspnea. Consequently, we examined the relationship between breathing discomfort and Poon's cost function. Based on our model and psychophysical studies, it appears that braathing discomfort, which can integrate chemical and mechanical inputs to the respiratory controller, may not operate simply as an estimate of a cost function. We explain how our reflex control model can dynamically minimize a cost function such as Poon's. Also, we consider the influence of willful adjustments of ventilation on breathing discomfort. From this we infer that ventilatory optimization may emerge from automatic reflexes and behavioral responses that involve excitatory chemical and inhibitory neuromechanical feedbacks.     

Geriatric dyspnea: Doing worse,feeling better

Older age is associated with a decline in physical fitness and reduced efficiency of the respiratory system. Paradoxically, it is also related to reduced report of dyspnea, that is, the experience of difficult and uncomfortable breathing. Reduced symptom reporting contributes to misdiagnosis or late diagnosis of underlying disease, suboptimal treatment, faster disease progression, shorter life expectancy, lower quality of life for patients, and considerably increased costs for the health care system in an aging society. However, pathways in the complex relationship between dyspnea and age are not well explored yet.We propose a model on geriatric dyspnea that integrates physiological, neurological, psychological and social pathways which link older age with dyspnea perception and expression. We suggest that the seemingly paradox of reduction of dyspnea in older age, despite physiological decline, can be solved by taking age-related changes on these multiple levels into account. In identifying these variables, the Geriatric Dyspnea Model highlights risk factors for reduced dyspnea perception and report in older age and pathways for intervention.     

Mechanical chest-wall vibration does not relieve air hunger

Mechanical vibration of the chest wall can reduce dyspnea. It is unclear which sensations of respiratory discomfort are modulated by vibration (work/effort, air hunger, tightness). We performed two experiments to test whether vibration modifies air hunger: Experiment 1-eight adults performed six breath holds and rated their uncomfortable 'urge to breathe.' Vibration was applied separately at four chest-wall and two control sites, using two amplitudes. Breath-hold duration and ratings were unchanged by vibration at any site or amplitude. Experiment 2-nine adults were mechanically ventilated (mean 8.73 L/min) at constant hypercapnia (mean 48 mmHg) to produce mild to moderate ratings of air hunger (mean 37% of scale) with minimal respiratory muscle work. Vibration at 2nd or 3rd intercostal spaces during either inspiration or expiration did not change air hunger compared to triceps vibration. These experiments demonstrated that vibration does not relieve air hunger; we postulate that the effect of vibration is specific to the form of dyspnea.     

Associations between the perception of dyspnea, pain, and negative affect

The perception of dyspnea shares many characteristics with the perception of pain, and both sensations might be linked to affective states. Therefore, the present study investigated the associations between perceived dyspnea, pain, and negative affect during resistive load breathing, the cold-pressor test, and affective picture viewing in healthy volunteers. Physiological and psychological measures confirmed successful experimental manipulation. There was a positive correlation between perceived dyspnea and pain in the unpleasantness dimension, but not in the intensity dimension, and this was further related to negative affect. These associations might be explained by similarities in the cortical processing of dyspnea, pain, and negative affect. The present findings extend the knowledge on similarities between dyspnea and pain and provide support for theories focusing on the perception of physiologic sensations in the development of affective states.     

Training to yoga respiration selectively increases respiratory sensation in healthy man

Because yoga practitioners think they are benefiting from their breath training we hypothesized that yoga respiration training (YRT) could modify the respiratory sensation. Yoga respiration (YR) ("ujjai") consisted of very slow, deep breaths (2-3 min(-1)) with sustained breath-hold after each inspiration and expiration. At inclusion in the study and after a 2-month YRT program, we determined in healthy subjects their eupneic ventilatory pattern and their capacity to discriminate external inspiratory resistive loads (respiratory sensation), digital tactile mechanical pressures (somesthetic sensation) and sound-pressure stimulations (auditory sensation). Data were compared to a gender-, age-, and weight-matched control group of healthy subjects who did not undergo the YRT program but were explored at the same epochs. After the 2-month YRT program, the respiratory sensation increased. Thus, both the exponent of the Steven's power law (Psi=kPhin) and the slope of the linear-linear plot between Psi and mouth pressure (Pm) were significantly higher, and the intercept with ordinate axis of the Psi versus Pm relationship was lower. After YRT, the peak Pm developed against inspiratory loads was significantly lower, reducing the load-induced activation of respiratory afferents. YRT induced long-lasting modifications of the ventilatory pattern with a significant lengthening of expiratory duration and a modest tidal volume increase. No significant changes in somesthetic and auditory sensations were noted. In the control group, the respiratory sensation was not modified during a 15-min period of yoga respiration, despite the peak Pm changes in response to added loads were then significantly reduced. These data suggest that training to yoga respiration selectively increases the respiratory sensation, perhaps through its persistent conditioning of the breathing pattern.     

Positive emotion reduces dyspnea during slow paced breathing

Slow breathing is used to induce cardiovascular resonance, a state associated with health benefits, but it can also increase tidal volume and associated dyspnea (respiratory discomfort). Dyspnea may be decreased by induced positive affect. In this study, 71 subjects (36 men, M = 20 years) breathed at 6 breaths per min. In condition one, subjects paced their breathing by inhaling and exhaling as a vertical bar moved up and down. In condition two, breathing was paced by a timed slideshow of positive images; subjects inhaled during a black screen and exhaled as the image appeared. Cardiac, respiratory, and self‐reported dyspnea and emotional indices were recorded. Tidal volume and the intensity and unpleasantness of dyspnea were reduced when paced breathing was combined with pleasant images. These results show that positive affect can reduce dyspnea during slow paced breathing, and may have applications for induced cardiovascular resonance.     

Dyspnea on exertion in obese men

Recently, we reported that dyspnea on exertion is strongly associated with an increased oxygen cost of breathing in otherwise healthy obese women; the mechanism of dyspnea on exertion in obese men is unknown. Obese men underwent measurements of body composition, fat distribution, pulmonary function, steady state and maximal graded cycle ergometry, and oxygen cost of breathing. Nine men (34 ± 8 years, 35 ± 4 BMI) with ratings of perceived breathlessness of ≤2 during cycling, and ten men (36 ± 9 years, 38 ± 5 BMI) with ratings of perceived breathlessness ≥4 were studied (ratings of perceived breathlessness: 1.8 ± 0.4 vs. 4.7 ± 0.8, respectively; p < 0.0001). Groups had only minor differences in fat distribution, pulmonary function, and steady state exercise. There was no association between ratings of perceived breathlessness and oxygen cost of breathing; but ratings of perceived breathlessness was strongly correlated with ratings of perceived exertion (RPE, rho = 0.87, p < 0.0001). The differences in exercise intensity, ventilatory demand, cardiovascular conditioning and/or the quality of respiratory sensation did not appear to play a role in the development of dyspnea on exertion. The mechanism of dyspnea on exertion in obese men seems unrelated to the oxygen cost of breathing.     

Sensation and control of breathing: A dynamic model

A dynamic model of the CO₂ respiratory control system is proposed, which can provide a qualitative basis for predicting breathing sensations. The discomfort index, which represents breathing sensations, is assumed to be composed of two sources: the arterial CO₂ level and the respiratory motor command. The respiratory controller receives inhibitory neuromechanical and excitatory CO₂ signals from the plant. The CO₂ signal is enhanced by exercise stimuli. This dynamic multiplicative-type controller is used in simulations of key experiments: exercise and CO₂ rebreathing with and without resistive loading. The dynamics of the discomfor index, the respiratory motor command, ventilation, and arterial CO₂ concentration conform to the experimental data. The perceptual sensitivity to CO₂ relative to respiratory effort is significantly correlated with the slope of hypercapnic ventilatory response. This result shows a clear linkage between ventilatory response and breathing sensations. Although it is shown that the automatic controller effectively minimizes the discomfort index for perturbations about an operating point under certain conditions, the discomfort index itself does not seem to be an underlying control principle of the proposed automatic controller model. Rather, breathing sensations may influence ventilatory responses by modifying the output of the automatic controller.     

Cancer stereotypes: A multidimensional scaling analysis

The body of empirical research investigating the structure of stereotypes held by the physically healthy population toward individuals with medically related problems is remarkably small. This is particularly true for stereotypes related to cancer. This study adopted a multidimensional scaling (MDS) strategy in order to identify medically related stereotype dimensions for cancer and other illnesses. Sixty-eight subjects judged the similarity of cancer and eleven other medical conditions and rated each on 7-point attribute scales. A two-dimensional solution of respondents' similarity judgments was found and four distinct clusters of related conditions were perceived: (1) cancer and other illnesses with controllable risk factors, (2) conditions affecting motor function, (3) psychological/functional disorders and (4) communication/sensory functional disorders. Regression of mean attribute ratings onto the MDS disability coordinates labeled the two dimensions Normality and Physical Health. Implications of these dimensions for planning effective programs to change stereotypes and improve attitudes toward individuals with cancer and other medical conditions are discussed.     

The role of fearful beliefs in the relationship between situational self‐awareness and report of breathing‐related sensations

Background and aims. Gating models of sensory perception suggest that increased attention towards the self leads to more on‐line processing of sensory information and less report bias. However, little is known about the interaction of self‐awareness with fearful beliefs about bodily sensations. In the present study, we explored report bias of breathing‐related sensation under increased self‐awareness compared to increased focus on external cues related to breathlessness. We expected report bias under internal focus to be lower than under external focus. However, we expected this effect of internal focus to be moderated by fearful beliefs about bodily sensations. Methods. Thirty participants completed two appointments in which attention was directed either towards the self or towards the surroundings. On both sessions, participants' detection threshold for inspiratory loads, negative mood, and fear of bodily sensations was assessed. Changes in threshold were tested using repeated measures ANOVA. The role of fear of bodily sensations was tested in a within‐subject moderation analysis. Results and conclusion. Relative over report of sensations was lower under internal focus compared to external focus. However, this effect was moderated by fear of bodily sensations: the greater fear of bodily sensations was, the lower the effect of self‐awareness. Results encourage research on the interaction of self‐awareness and fearful beliefs in the top‐down modulation of perception.     

Multidimensional scaling of ferrous sulfate and basic tastes

The status of metallic sensations as a primary or basic taste category is controversial. Ferrous sulfate (FeSO4) has been suggested as a prototypical metallic chemosensory stimulus. At least part of the metallic sensation from FeSO4 arises from a metallic retronasal smell. The quality of this sensation was studied via multidimensional scaling (MDS) of taste similarities, with and without nasal closure to eliminate retronasal olfactory sensations. The metallic stimulus was embedded in a series containing classical "basic taste" stimuli, alum and monosodium glutamate. With olfaction available, the metallic stimulus plotted away from basic tastes and taste mixtures. Scaled ratings of sensory properties related to metallic taste (iron-nail, copper-penny-like, aftertaste) of FeSO4 decreased with nasal closure. Results are consistent with the idea that ferrous sulfate produces a distinctly different sensation from the traditional basic tastes, which includes both olfactory and oral sensations.     

Coupling of dyspnea perception and tachypneic breathing during hypercapnia

Respiratory rhythm is susceptible to behavioral influences including emotions. Since laboratory dyspnea induces negative emotions, we examined whether tachypneic breathing occurs in relation to perception of dyspnea during CO(2) rebreathing (n=21). Dyspnea intensity scored by a visual analog scale and respiratory frequency started to increase rapidly once the intensity of the stimuli exceeded a threshold for the end-tidal CO(2) fraction. The thresholds for dyspnea and respiratory frequency were similar (7.5±0.1% and 7.6±0.2% of the end-tidal CO(2) fraction, respectively), while the threshold for tidal volume (8.0±0.2%), when the tidal volume had stabilized, was significantly higher than the thresholds for dyspnea (p<0.01) and respiratory frequency (p<0.05). A positive correlation was found between the thresholds for dyspnea and respiratory frequency (r=0.81, p<0.001), and these thresholds showed good agreement on a Bland-Altman plot. These findings suggest that the start of tachypneic breathing is coupled with the threshold for dyspnea.     

Respiratory sensations evoked by activation of bronchopulmonary C-fibers

C-fibers represent the majority of vagal afferents innervating the airways and lung, and can be activated by inhaled chemical irritants and certain endogenous substances. Stimulation of bronchopulmonary C-fibers with selective chemical activators by either inhalation or intravenous injection evokes irritation, burning and choking sensations in the throat, neck and upper chest (mid-sternum region) in healthy human subjects. These irritating sensations are often accompanied by bouts of coughs either during inhalation challenge or when a higher dose of the chemical activator is administered by intravenous injection. Dyspnea and breathless sensation are not always evoked when these afferents are activated by different types of chemical stimulants. This variability probably reflects the chemical nature of the stimulants, as well as the possibility that different subtypes of C-fibers encoded by different receptor proteins are activated. These respiratory sensations and reflex responses (e.g., cough) are believed to play an important role in protecting the lung against inhaled irritants and preventing overexertion under unusual physiological stresses (e.g., during strenuous exercise) in healthy individuals. More importantly, recent studies have revealed that the sensitivity of bronchopulmonary C-fibers can be markedly elevated in acute and chronic airway inflammatory diseases, probably caused by a sensitizing effect of certain endogenously released inflammatory mediators (e.g., prostaglandin E(2)) that act directly or indirectly on specific ion channels expressed on the sensory terminals. Normal physiological actions such as an increase in tidal volume (e.g., during mild exercise) can then activate these C-fiber afferents, and consequently may contribute, in part, to the lingering respiratory discomforts and other debilitating symptoms in patients with lung diseases.