Neuromodulatory Effect of Endogenous Opioids on the Intensity and Unpleasantness of Breathlessness during Resistive Load Breathing in COPD

Figures & data

Figure 1.  Diagram of enrollment, allocation, follow-up and analysis of patients.

Table 1.  Descriptive characteristics of the 14 patients

Variable	Values	% predicted
Age (years)	64 ± 9
Height (centimeters)	165.1 ± 6.0
Weight (kg)	76.1 ± 12.2
Baseline Dyspnea Index^*	6.1 ± 1.1
FEV1 (liters)	1.15 ± 0.39	44 ± 16
FEV1 post-BD (liters)	1.27 ± 0.41	49 ± 16
FVC (liters) (liters)	2.99 ± 0.70	85 ± 17
FVC post-BD	3.28 ± 0.83	93 ± 17
FEV1/FVC post-BD (%)	39 ± 12
IC (liters)	2.06 ± 0.35	86 ± 16
IC post-BD (liters)	2.26 ± 0.37	94 ± 17
PImax (cm H2O)	−64 ± 19	71 ± 16
Diffusing capacity(ml/min/mm Hg)	11.9 ± 2.7	57 ± 16

Data obtained at visit 1.

^*Self-administered and computerized version (43).

FEV₁ = forced expiratory volume in 1 second;

BD = bronchodilator; FVC = forced vital capacity; IC = inspiratory capacity;

PImax = maximal inspiratory mouth pressure measured at functional residual capacity

Six patients had stage II disease, and eight patients had stage III disease.

Table 2.  Physiological responses before and at the end of resistive load breathing

	Naloxone	Normal saline	p-value (95% CI)
Heart rate (beats/min)
Rest, post-intervention	74 ± 14	72 ± 12	0.31 (−1.84, 5.41)
End-RLB	77 ± 15	75 ± 14	0.37 (−1.96, 4.96)
VO2 (ml/min)
Rest, post-intervention	259 ± 44	257 ± 42	0.79 (−15.20, 19.48)
End-RLB	273 ± 47	286 ± 59	0.20 (−36.70, 8.27)
VE (liters/min)
Rest, post-intervention	9.8 ± 1.7	9.8 ± 1.9	0.98 (−0.66, 0.65)
End-RLB	9.7 ± 1.8	10.2 ± 2.3	0.12 (−1.06, 0.13)
Frequency respiration(breaths/min)
Rest, post-intervention	14.5 ± 4.2	13.5 ± 4.0	0.09 (−0.18, 2.31)
End-RLB	13.2 ± 4.5	13.0 ± 4.7	0.77 (−1.09, 1.440)
Tidal volume (ml)
Rest, post-intervention	714 ± 196	766 ± 216	0.12 (−121.63, 16.21)
End-RLB	792 ± 220	847 ± 251	0.13 (−128.30, 17.59)
Total time per breath (sec)
Rest, post-intervention	4.5 ± 1.4	4.8 ± 1.5	0.11 (−0.86, 0.10)
End-RL B	5.1 ± 1.8^†	5.3 ± 2.1^†	0.45 (−0.72, 0.33)
Inspiratory time (sec)
Rest, post-intervention	1.1 ± 0.2	1.2 ± 0.3	0.15 (−0.17, 0.03)
End-RLB	1.6 ± 0.6^†	1.7 ± 0.8^†	0.33 (−0.29, 0.11)
Expiratory time (sec)
Rest, post-intervention	3.4 ± 1.2	3.6 ± 1.3	0.13 (−0.72, 0.10)
End-RLB	3.5 ± 1.4	3.6 ± 1.5	0.57 (−0.46, 0.26)
VCO2 (ml/min)
Rest, post-intervention	222 ± 42	224 ± 41	0.82 (−22.46, 18.18)
End-RLB	228 ± 40	244 ± 55	0.09 (−35.46, 3.17)
SpO2 (%)
Rest, post-intervention	94.6 ± 2.1	94.8 ± 2.1	0.51 (−0.90, 0.47)
End-RLB	94.2 ± 1.9	94.7 ± 1.7	0.15 (−1.21, 0.21)
End-tidal PCO2(mm Hg)
Rest, post-intervention	34.1 ± 3.6	33.9 ± 4.3	0.64 (−1.00, 1.58)
End-RLB	35.1 ± 4.8	34.9 ± 5.0	0.83 (−1.27, 1.55)
Inspiratory capacity (liters)
Rest	2.40 ± 0.53	2.36 ± 0.40	0.47 (−0.08, 0.17)
End-RLB	2.14 ± 0.42	2.14 ± 0.46	0.98 (−0.14,0.14)

Physiological data were obtained during the last minute at rest, at rest post-intervention, and end-resistive load breathing (RLB) at visits 2 and 3.

^†p = 0.0004 comparing rest, rest post-intervention, and end-RLB with naloxone;

VO₂ = oxygen consumption; V_E = minute ventilation;

VCO₂ = carbon dioxide production; SpO2 = oxygen saturation by pulse oximeter;

PCO₂ = partial pressure for carbon dioxide.

Figure 2.  Mean and standard error values for ratings of the intensity (Figure 2A) and unpleasantness (Figure 2B) of breathlessness during 7 minutes of resistive load breathing following administration of naloxone (open circles) and normal saline (closed circles). For both conditions, n = 14 for minutes 1 – 4, n = 13 for minutes 5 – 7.Ratings of the intensity and unpleasantness of breathlessness were significantly correlated for naloxone (r = 0.95; p < 0.001) and for normal saline (r = 0.88; p < 0.001) conditions.

Table 3.  Levels of ß-endorphin immunoreactivity

	Naloxone	Normal saline	p-value (95% CI)
Baseline	6.0 ± 1.5	6.7 ± 1.4	0.08 (−1.42, 0.10)
End-RLB	18.5 ± 3.4^†	13.4 ± 2.5^†	<0.001 (6.68, 4.98)
30 min end-RLB	18.1 ± 4.0^†	13.3 ± 2.6^†	0.001 (6.90, 4.15)

N = 13; in 1 patient, blood could not be withdrawn from the intravenous catheter.

Values are in pmol/L. CI = confidence interval.

^†p < 0.001 compared to baseline values.

Mahler DA, Ward J, Fierro-Carrion G, Waterman L, Lentine TF, Mejia-Alfaro R, Baird JC. Development of self-administered versions of the modified baseline and transition dyspnea indexes in COPD. J COPD 2004; 1:165–172.

 PubMedGoogle Scholar