Robert W. Lansing

The Affective Dimension of Laboratory Dyspnea Air Hunger Is More Unpleasant than Work/Effort

RATIONALE It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea. OBJECTIVES We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea. METHODS Twelve healthy subjects experienced three stimuli: stimulus 1: maximal eucapnic voluntary hyperpnea against inspiratory resistance, requiring 15 times the work of resting breathing; stimulus 2: Pet(CO(2)) 6.1 mm Hg above resting with ventilation restricted to less than spontaneous breathing; stimulus 3: Pet(CO(2)) 7.7 mm Hg above resting with ventilation further restricted. After each trial, subjects rated SI, A(1), and qualities of dyspnea on the Multidimensional Dyspnea Profile (MDP), a comprehensive instrument tested here for the first time. MEASUREMENTS AND MAIN RESULTS Stimulus 1 was always limited by subjects failing to meet a higher ventilation target; none signaled severe discomfort. This evoked work and effort sensations, with relatively low unpleasantness (mean A(1)/SI = 0.64). Stimulus 2, titrated to produce dyspnea ratings similar to those subjects gave during stimulus 1, evoked air hunger and produced significantly greater unpleasantness (mean A(1)/SI = 0.95). Stimulus 3, increased until air hunger was intolerable, evoked the highest intensity and unpleasantness ratings and high unpleasantness ratio (mean A(1)/SI = 1.09). When asked which they would prefer to repeat, all subjects chose stimulus 1. CONCLUSIONS (1) Maximal respiratory work is less unpleasant than moderately intense air hunger in this brief test; (2) unpleasantness of dyspnea can vary independently from perceived intensity, consistent with the prevailing model of pain; (3) separate dimensions of dyspnea can be measured with the MDP.

Electroencephalographic Correlates of Binocular Rivalry in Man

Under conditions of ocular rivalry, changes in the rhythmic brain response to flicker stimulation of one eye correspond closely to the subjects report of changes in the perceptual dominance of that eye.

Cardiorespiratory variables and sensation during stimulation of the left vagus in patients with epilepsy.

We studied physiological and sensory effects of left cervical vagal stimulation in six adult patients receiving this stimulation as adjunctive therapy for intractable epilepsy. Stimulus strength varied among subjects from 0.1 to 2.1 microCoulomb (microC) per pulse, delivered in trains of 30-45 s at frequencies from 20 to 30 Hz; these stimulation parameters were standard in a North American study. The stimulation produced no systematic changes in ECG, arterial pressure, breathing frequency tidal volume or end-expiratory volume. Five subjects experienced hoarseness during stimulation. Three subjects with high stimulus strength (0.9-2.1 microC) recalled shortness of breath during stimulation when exercising; these sensations were seldom present during stimulation at rest. No subjects reported the thoracic burning sensation or cough previously reported with chemical stimulation of pulmonary C fibers. Four of six subjects (all those receiving stimuli at or above 0.6 microC) experienced a substantial reduction in monthly seizure occurrence at the settings used in our studies. Although animal models of epilepsy suggest that C fibers are the most important fibers mediating the anti-seizure effect of vagal stimulation, our present findings suggest that the therapeutic stimulus activated A fibers (evidenced by laryngeal effects) but was not strong enough to activate B or C fibers.

Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test–retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions. The Multidimensional Dyspnea Profile provides a unified, reliable instrument for both clinical and laboratory research http://ow.ly/Ix8ic

Entrainment of respiration to repetitive finger tapping

Subjects were instructed to synchronize finger tapping with visual signals of various frequencies. It was found that breathing rate became entrained to tapping rate if the latter fell within a range of two breaths per minute of the subject’s previous breathing rate. Entrainment did not occur when the subject merely monitored the visual stimuli but only during performance of tapping. The effect occurred without subjects’ awareness and was observed only in the absence of deliberate adjustments in respiratory frequency on the part of the subject. Temporal restrictions on the neural events responsible for motor output appear to be responsible for the phenomenon.

Reliability and Validity of the Multidimensional Dyspnea Profile

BACKGROUND Most measures of dyspnea assess a single aspect (intensity or distress) of the symptom. We developed the Multidimensional Dyspnea Profile (MDP) to measure qualities and intensities of the sensory dimension and components of the affective dimension. The MDP is not indexed to a particular activity and can be applied at rest, during exertion, or during clinical care. We report on the development and testing of the MDP in patients with a variety of acute and chronic cardiopulmonary conditions. METHODS One hundred fifty-one adults admitted to the ED with breathing symptoms completed the MDP three times in the ED, twice at least 1 h apart (T1, T2), and near discharge from the ED (T3). Measures were repeated in 68 patients twice in a follow-up session 4 to 6 weeks later (T4-T5). The ED sample was 56% men with a mean age of 53 ± 15 years; the follow-up sample was similar. RESULTS Factor analysis resulted in a two-factor solution with a total explained variance of 63%, 74%, and 72% at T1, T2, and T3, respectively. One domain related to primary sensory qualities and immediate unpleasantness, and the second encompassed emotional response. For the two domains, Cronbach α ranged from 0.82 to 0.95, and the intraclass correlation coefficient ranged from 0.91 to 0.98. Repeated-measures analysis was significant for change (T1, T3, T4), showing responsiveness to change in MDP domains with treatment (F([2,66]) = 19.67, P > .001). CONCLUSIONS These analyses support the reliability, validity, and responsiveness to clinical change of the MDP with two domains in an acute care and follow-up setting.

Effect of inhaled furosemide on air hunger induced in healthy humans

Recent evidence suggests that inhaled furosemide relieves dyspnoea in patients and in normal subjects made dyspnoeic by external resistive loads combined with added dead-space. Furosemide sensitizes lung inflation receptors in rats, and lung inflation reduces air hunger in humans. We therefore hypothesised that inhaled furosemide acts on the air hunger component of dyspnoea. Ten subjects inhaled aerosolized furosemide (40 mg) or placebo in randomised, double blind, crossover experiments. Air hunger was induced by hypercapnia (50+/-2 mmHg) during constrained ventilation (8+/-0.9 L/min) before and after treatment, and rated by subjects using a 100 mm visual analogue scale. Subjects described a sensation of air hunger with little or no work/effort of breathing. Hypercapnia generated less air hunger in the first trial at 23+/-3 min after start of furosemide treatment (58+/-11% to 39+/-14% full scale); the effect varied substantially among subjects. The mean treatment effect, accounting for placebo, was 13% of full scale (P=0.052). We conclude that 40 mg of inhaled furosemide partially relieves air hunger within 1h and is accompanied by substantial diuresis.

Variations in the motor potential with force exerted during voluntary arm movements in man

Abstract Human subjects were trained to perform a simple forearm extension in a uniform way against two different conditions of force opposing movement. The subjects always knew before-hand how much force they had to exert to execute the movement precisely. The EEG was computer-averaged to identify any differences which could be attributed to the force of movement. The findings were: (1) No voltage change before the beginning of EMG activity could be detected in the averaged record except a slowly increasing negativity. (2) A surface negative-to-positive deflection which appeared after movement began had a greater amplitude in the greater force condition for all subjects. (3) The point of maximum negativity which began this deflection occurred with a constant latency with respect to the beginning of EMG activity for a given subject, but was not constantly related to movement itself. (4) The motor potential was of slightly greater amplitude on the side opposite to the moving limb. It appears that certain components of the motor potential are not associated with events directly concerned with initiating movement. They are possibly reflections of the feedback of movement-related information to the motor cortex from elsewhere in the brain.

Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness

Breathlessness that persists despite treatment for the underlying conditions is debilitating. Identifying this discrete entity as a clinical syndrome should raise awareness amongst patients, clinicians, service providers, researchers and research funders. Using the Delphi method, questions and statements were generated via expert group consultations and one-to-one interviews (n=17). These were subsequently circulated in three survey rounds (n=34, n=25, n=31) to an extended international group from various settings (clinical and laboratory; hospital, hospice and community) and working within the basic sciences and clinical specialties. The a priori target agreement for each question was 70%. Findings were discussed at a multinational workshop. The agreed term, chronic breathlessness syndrome, was defined as breathlessness that persists despite optimal treatment of the underlying pathophysiology and that results in disability. A stated duration was not needed for “chronic”. Key terms for French and German translation were also discussed and the need for further consensus recognised, especially with regard to cultural and linguistic interpretation. We propose criteria for chronic breathlessness syndrome. Recognition is an important first step to address the therapeutic nihilism that has pervaded this neglected symptom and could empower patients and caregivers, improve clinical care, focus research, and encourage wider uptake of available and emerging evidence-based interventions. Chronic breathlessness syndrome: breathlessness and disability despite an optimally treated underlying pathophysiology http://ow.ly/V0g2309z4tF

Acute partial paralysis alters perceptions of air, hunger, work and effort at constant PCO2 and Ve.

Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.