These are the first observations comparing multiple aspects of the dyspnea experience of HV and COPD patients following exposure to a laboratory dyspnea challenge that is physiologically equivalent in the two groups. Exercise has different physiologic implications for respiratory function in COPD, especially tidal volume limitation because of dynamic elevation of FRC [24, 25], resulting in different qualities of dyspnea sensation and affective response . Consequently, we selected a stimulus that evoked dyspnea without increased ventilation in an attempt to provoke the same sensation in both groups.
Our results are consistent with the three null hypotheses proposed: 1) COPD patients and HV report similar unpleasantness for a given intensity of sensation (AH and WE) in laboratory experiments; 2) COPD patients and HV reported similar emotional responses during laboratory dyspnea; 3) COPD patients reported similar frustration and anxiety with ADL as they did with laboratory dyspnea. Given the modest sample size, we consider below whether any important differences are likely to have gone undetected by this study (‘Type II error’).
Do patients with chronic lung disease have a different affective response to dyspnea?
We showed that COPD patients and HV undergoing the same laboratory dyspnea experience report the same quality of sensation and the same immediate unpleasantness. This implies that long experience to clinical dyspnea has not greatly altered the immediate processing of respiratory discomfort. This is consistent with findings in competitive breath-hold divers whose perception of laboratory air hunger is not different from normal subjects .
We observed that the emotional component of dyspnea differed widely among individuals at both moderate and high strength laboratory stimulus levels (see graph in Additional file 7, interindividual variability of anxiety ratings (A2) following moderate and high level stimulus exposure). This type of individual difference in the emotional response to unpleasant stimuli has been termed affective style, and is likely an individual characteristic . This affective style, captured by the MDP, may contribute to differences in clinical expression of symptoms and, ultimately, influence whether a particular individual seeks medical care for her symptom .
In COPD patients, does the affective response to laboratory dyspnea challenge differ from the affective response to dyspnea in daily life?
COPD patients reported episodes of dyspnea during ADL that were similar in intensity and unpleasantness to our moderate strength laboratory dyspnea challenge. Ratings of anxiety, frustration and fear were in the lower third of the scale. Patients frequently reported that they limit physical activity in daily life to avoid high dyspnea levels, probably to avoid discomfort and adverse emotions. The relatively low A2 ratings may reflect a sense of control during daily activity. At higher levels of laboratory stimulus, ratings often exceeded 50%FS, but, probably because subjects were also in control of the maximal stimulus, anxiety ratings seldom reached 100%. This contrasts with emotional responses to dyspnea in acutely ill patients with inescapable dyspnea. For example, as noted by one patient after rating A1 at 75% FS and anxiety at 50%FS, “if I was alone and breathing like this I would be scared, would definitely feel more afraid [at home] not knowing how long it will last”. This is consistent with reports from patients seeking treatment in an emergency room .
Limitations of this study
We studied a relatively small number of subjects, thus the lack of statistically significant differences may reflect Type II errors. What is the likelihood that Type II errors could have obscured functionally important differences? The mean differences we report between affective responses by subject type (healthy vs. COPD) is virtually nil at moderate stimulus, and at most 14% FS at high stimulus for anxious (see Figure 3). Based on current data our best estimate is that anxiety in COPD patients during laboratory stimuli is very similar to healthy controls. However, because variance was large (coefficient of variation >60% for both HV and COPD patients), we can not state with confidence that anxiety in COPD is less than 20% FS different from controls following exposure to high intensity laboratory stimulus. Even this worst-case estimate would not be large enough to invalidate the use of the air hunger laboratory model for investigation of dyspnea. As described above, the large SD was mainly attributable to inter-, rather than intra-, individual variation of emotional responses in both subject groups. Repeat assessment in the laboratory (see Additional file 4) and clinical  setting demonstrate intraindividual consistency of affective ratings using the MDP. Thus, the effect of individual psychological characteristics seems to overwhelm the effect of chronic respiratory disease on the emotional response to dyspnea.
COPD patients (67.5 ± 7.8) were older than healthy volunteers (54.8 ± 4.8). We found no reports of age associated differences in dyspnea perception during well-controlled stimulus exposure among adult subjects who differ in age by 10 to 15 years. Indirect evidence of age associated differences comes from studies of resistive load threshold detection among older asthmatics [28, 29]. As we selected a stimulus not directly affected by mechanical load, we don’t think this evidence is relevant to interpretation of our results. To affirm this conclusion, we selected the 6 (50%) healthy volunteers (ages 56–61) and 8 (66%) COPD patients (ages 56–67) with overlapping age ranges. As in the larger groups, results for this subset were similar between subject types.
Ability of MDP to discriminate sensory quality
There was a clear favorite choice of descriptor that best characterized the sensation during laboratory dyspnea, yet there was considerable overlap in the ratings of descriptors on a scale from 0–10. Our interpretation of this is that when subjects are presented with several parallel rating scales, many tend not to greatly separate ratings. On the other hand, when forced to make a choice about the most prominent sensation, the subject makes a judgment. As expected from results in earlier studies that exposed subjects to a similar dyspnea stimulus , air hunger was the best descriptor. In addition, high ratings of ‘work effort’ may reflect a combination of respiratory muscle effort and mental effort. Subjects presented with the supplementary descriptor “my breathing required concentration or mental effort” rated this item 62%FS and rated muscle work 56%FS.
The average changes from resting (∆PETCO2) associated with the BDVAS ratings differed somewhat between COPD patients and HV, although the difference was not statistically significant. In COPD, PETCO2 is not a reliable indicator of arterial blood gasses due to heterogeneous ventilation/perfusion ratio, the effect of which causes PETCO2-PaCO2 difference to vary with tidal volume, TE, and PICO2-PaCO2 difference. Furthermore, ratings of SI for a given ∆PCO2 is known to vary widely among individuals . For these reasons we chose to match stimulus strength based on on-line ratings, not on ∆PCO2. Because the range of ∆PCO2 was modest, approximately 2–10 mmHg, symptoms and signs attributable to elevated PaCO2, such as headache, elevated blood pressure and flushing, did not appear to affect discomfort ratings.