Dyspnea: Psychologic and physiologic observations☆

Anxiety and depression can increase the intensity of dyspnea out of proportion to the impairment in cardiorespiratory function and may contribute to the degree of disability associated with dyspnea. The effect of anxiety/depression on the sensory and affective components of reported dyspnea in patients with respiratory disorders might be of particular importance in improving the accuracy of the diagnostic process. However, the exact cause-relationship between dyspnea and anxiety/depression are unclear. A multidimensional model of dyspnea subsuming sensory components (i.e. intensity and quality) and affective components has recently been proposed. Affective responses drive patients to seek treatment which can cause them to alter their lifestyle to avoid dyspnea. Brain imaging techniques help identify distinct cortical structures involved in processing the discrete components of dyspnea.

The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested δ-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of δ-opioid receptors in a mouse model affects respiratory response to elevated CO₂, and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO₂ were compared between δ-opioid receptor knockout mice and wild-type mice after saline, diazepam (1 mg/kg), and alprazolam (0.3 mg/kg) injections. The results show that lack of δ-opioid receptors does not affect normal response to elevated CO₂, but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO₂ were enhanced in δ-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and δ-opioid receptors in regulating the respiratory effects of elevated CO₂, which might be related to CO₂ induced panic.

We investigated the effects of anxiety on the intensity of air hunger during gradually increasing levels of CO₂ until the end-tidal fractional concentration of CO₂ was 7.9% or air hunger was intolerable. Normal high and low (trait) anxious participants (N = 23) went through three rebreathing trials (15 min interval). Breathing behaviour was continuously monitored and air hunger was rated every 12 s. The threshold for responding to the increased CO₂ was always lower for the subjective rating than for the ventilatory response. Habituation across trials was observed for both the ventilatory response and the air hunger rating regardless of anxiety. However, beyond the threshold, the slope in air hunger ratings decreased across trials in low anxious persons and tended to increase in high anxious persons (interaction P < 0.05). No differences occurred in the slopes of the breathing responses. The findings documented uncoupling of the physiological and subjective responses during CO₂-induced air hunger.

The purpose of this study was to examine the psychological functioning and quality of life (QOL) of lung transplant candidates and recipients.

The following measures were completed by 36 lung transplant candidates (the pretransplant group [PRE]) and 73 recipients (the posttransplant group [POST]): the Rand-36 Item Health Survey 1.0 (RAND-36), visual analog scale of overall QOL (OQOL), Brief Symptoms Inventory (BSI), Derogatis Sexual Functioning Inventory (DSFI), Hospital Anxiety and Depression Scale (HAD), Rosenberg Self-Esteem Scale (RSES), and Body Cathexis Scale (BC).

Compared to the PRE, POST patients had significantly better scores on the following measures: RAND-36 total, physical health, role limitations due to physical health, general health, vitality, and social functioning subscales (all p < 0.0001); visual analog scale of OQOL (p < 0.0001); BSI (p < 0.05); BC (p < 0.05); HAD anxiety (p < 0.05) and depression (p < 0.0001); and RSES (p < 0.05). Despite better scores, some areas did not differ between the PRE and the POST, and many patients continued to experience impairments in psychological functioning. Specifically, the RAND-36 emotional health and role limitations due to emotional health subscale scores did not differ between the PRE and the POST and they remained lower than published norms. A significant proportion of patients in both groups (44% of PRE patients and 28% of POST patients) had borderline or clinical levels of anxiety (ie, the HAD). Finally, PRE and POST mean scores were significantly lower than published norms on the RSES (p < 0.05) and the body image scale of the DSFI (p < 0.05).

Although lung transplant recipients have better general, physical, and psychological health than their pretransplant counterparts, the present research suggests that both groups experience impairment in several areas of psychological functioning. Future research into the QOL of the lung transplant population should be aimed at recognizing, intervening, and improving patients’ psychological and emotional well-being.

We wished to identify the physiologic abnormalities that distinguish severely breathless (SB) patients with chronic airflow limitation (CAL) from mildly breathless (MB) patients. Thirty-seven patients with stable, advanced CAL (FEV₁ = 38 ± 10 percent predicted, mean ± SD) were separated into two distinct groups, SB and MB, solely on the basis of their baseline dyspnea index (BDI). BDI ratings in SB (n = 17) and MB (n = 20) patients were 2.5 ± 1.5 and 8.5 ± 1.5 (mean ± SD), respectively (p<0.001). Groups were compared with respect to pulmonary function, breathing pattern parameters, arterial blood gases (ABCs), and responses to progressive exercise. Steady-state gas-exchange parameters were measured in a subgroup of 16 patients during exercise. There were no significant intergroup differences in dynamic flows, plethysmographic lung volumes, ABGs, resting ventilation, or breathing pattern parameters. However, the SB group had significantly lower single-breath diffusing capacities for carbon monoxide (Dco) (by an average of 50 percent, p<0.001), together with significantly higher resting ventilatory equivalents for carbon dioxide ( ${\dot{\text{V}}}_{\text{E}}/{\dot{\text{V}}}_{{\text{CO}}_2}$) (by 17 percent, p<0.01) and dead space to tidal volume ratios (by 11 percent, p<0.05). Ventilatory responses for a given metabolic load were, on average, 33 percent higher (p<0.05) in the SB group reflecting greater ventilation-perfusion inhomogeneity and wasted ventilation. The SB subgroup (n = 7), in contrast to the MB subgroup (n = 9), demonstrated significantly (p<0.01) greater O₂ desaturation during exercise; PaO₂ decreased in SB and MB at peak exercise by –13 ± 7 mm Hg and –4 ± 2 mm Hg (mean ± SD), respectively. Stepwise regression analysis selected Dco and ${\dot{\text{V}}}_{\text{E}}/{\dot{\text{V}}}_{{\text{CO}}_2}$ as the only predictors of breathlessness in this group, accounting for 52 percent of the variance in BDI (F-ratio = 18.49, p<0.001). Although the origin of breathlessness is multifactorial, variation in its intensity among patients with comparable levels of airflow limitation can be accounted for, in part, by underlying pathophysiologic differences. Severely breathless patients were characterized by lower resting diffusing capacities and accelerated ventilatory responses to exercise.

In order to examine the relationship of dyspnea to anxiety and depression, the authors rated dyspnea using several methods in 50 patients with chronic respiratory impairment. Anxiety and depression were measured by the Symptom Checklist-90 and the Symptom Questionnaire. Results varied with the method of assessing dyspnea. Physician-rated dyspnea was significantly associated with patients' self-ratings of breathlessness as well as with pulmonary function tests, but not with any of the self-rating scales of emotions. Self-rated breathlessness was significantly associated with self-rated depression. In multiple regression analyses, depression was predictive of breathlessness. When the sample was limited to patients with chronic obstructive pulminary disease, the results remained the same. The patients were significantly more depressed and anxious than matched family practice patients. In the study of the complex relationship of dyspnea to physical and emotional factors, it is desirable to use more than one measure of dyspnea because the results depend in part on the method of assessment.