Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine.

The purpose of this placebo-controlled, double-blind, randomized study was to assess the effect of nebulized morphine on dyspnoea perceived at rest by patients with advanced disease. Seventeen hospital in-patients with disabling dyspnoea received isotonic saline or morphine via nebulization for 10 min through a mouthpiece, combined with oxygen via nasal prongs. On four consecutive days, they were given one of the four following treatments in random order: saline with 2 L x min(-1) oxygen; 10 mg morphine with 2 L x min(-1) oxygen; 20 mg morphine with 2 L x min(-1) oxygen; and 10 mg morphine without oxygen (prongs fixed, no flow). Dyspnoea was assessed on a bipolar visual analogue scale (VAS) (-100% much more short of breath, +100% much less short of breath), and arterial oxygen saturation (Sa,O2) and respiratory frequency (fR) were recorded at the end of nebulization and 10 min later. In 14 subjects who completed the study, mean VAS ratings 10 min after the end of nebulization ranged +30 to +43%, with no significant difference between the four study days (VAS 20 mg morphine minus VAS saline, 95% confidence interval (95% CI) -6 to +8%). Sa,O2 significantly increased on the 3 days with supplemental oxygen, and remained stable on the zero flow day. Respiratory frequency significantly decreased on the 4 days, with a trend to correlation between VAS rating and parallel change in respiratory frequency (Spearman's rank correlation coefficient (r(s))=0.46; p=0.09). We conclude that the subjects benefited from saline or morphine via a placebo effect and/or a nonspecific effect, and that nebulized morphine had no specific effect on dyspnoea.

Dyspnoea and flow-volume curve during exercise in COPD patients.

The purpose of this study, in patients with chronic obstructive pulmonary disease (COPD), was to examine the relationship of dyspnoea, rated on a visual analogue scale (VAS), to 1) tidal ventilatory variables measured on exercise and 2) pre-exercise lung function. Twenty one patients (forced expiratory volume in one second (FEV1) mean (SD) 1.19 (0.32) l) were studied. During a preliminary test, the maximal workload was assessed and the upper end of the VAS was anchored. On the study day, the tidal flow-volume curve on exercise was monitored and dyspnoea was assessed serially every minute. In each individual, the relationship of dyspnoea to various tidal ventilatory variables was studied using linear regression analysis; results were reported squared correlation coefficients, slopes and dyspnoea thresholds. Subsequently, the relationship of slopes and thresholds to pre-exercise lung function was examined. In all patients, dyspnoea showed a close correlation with ventilation, tidal volume, breathing frequency and tidal flow. The tidal peak inspiratory flow was the best individual predictor of dyspnoea with a median r2 of 0.91. Patients with the poorest pre-exercise lung function exhibited the highest rates of increase in dyspnoea and the lowest thresholds, the strongest correlation being observed between the dyspnoea/ventilation slope and pre-exercise maximal peak inspiratory flow (r2 = 0.54). In conclusion, for individual COPD patients dyspnoea on exercise is closely related to inspiratory flow. The degree of pre-exercise ventilatory impairment accounts, at most, for only half of the variation in dyspnoea perception between subjects.

[Dyspnea and inspiratory effort capacity in COPD]. / Dyspnée et capacité inspiratoire à l'effort dans la BPCO.

The aim of this work was to study the relationship between dynamic hyperinflation and dyspnoea perception on exercise in patients with chronic obstructive pulmonary disease (COPD). Seven men and three women with COPD (mean FEV1 45.9 +/- 9.8% predicted) were studied. The upper end of the visual analogue scale was anchored on a preliminary test on a cycle ergometer (day 1). On the study day (day 2) the relationship between dyspnoea and ventilatory indices during high intensity exercise was evaluated, using within-subject linear regression analysis. On a repeat study (day 3), the addition of inspiratory capacity (IC) manoeuvres allowed to monitor the end expiratory lung volume. The highest degree of within-subject correlation was observed between dyspnoea and the tidal peak inspiratory flow (PIFT), as well without (median r2 = 0.920, day 2) as with (median r2 = 0.880, day 3) IC manoeuvres. At maximal exercise, IC decreased in 8 out of 10 subjects (delta IC range -150 to -900 ml). A negative relationship was found between delta IC and the rate of increase in dyspnoea on exercise, measured as the dyspnoea/PIFT slope (r = 0.844, p < 0.01). Our results suggest that dynamic hyperinflation on exercise observed in most patients with COPD allows these subjects to minimize the rate of increase in dyspnoea on exercise.

Dyspnoea assessed by visual analogue scale in patients with chronic obstructive lung disease during progressive and high intensity exercise.

BACKGROUND: A study was carried out to determine whether rating of dyspnoea by means of a visual analogue scale during a progressive exercise test is affected by the subject's awareness of the progressive nature of the protocol. METHODS: Nineteen patients with chronic obstructive lung disease (FEV1 mean (SE) 1.06 (0.07) 1) were studied. A preliminary incremental test was carried out with a work rate increasing by 10 watts every minute until the subject could no longer exercise, to determine the maximum work load (Wmax) and to anchor the upper end of the visual analogue scale. This was followed by two exercise tests performed one day apart in randomised sequence, with two different protocols. One was a 12 minute protocol that included two sudden bursts of three minute high intensity exercise, up to the subject's Wmax, each preceded by three minutes of low level exercise. The other test was a conventional three minute incremental test lasting 12 minutes. On both study days the only information given to the subject about the temporal profile of load was that a change would be made every three minutes. The relation between dyspnoea, as assessed by the visual analogue scale, and ventilation, measured during high intensity or progressive exercise, was studied. RESULTS: The mean (SE) rates of increase of dyspnoea with increasing ventilation (% of line length 1(-1) min) obtained by linear regression analysis were similar for the two tests (2.86 (0.20) for progressive exercise and 2.87 (0.25) for high intensity exercise); it was 2.59 (0.25) for the initial burst of high intensity exercise when the data on this were analysed separately. In six subjects with stable disease studied again two months later the reproducibility of the rating of dyspnoea was reasonably good for both protocols. CONCLUSION: The results suggest that in most patients with chronic obstructive lung disease the assessment of exercise induced dyspnoea by means of a visual analogue scale during a progressive exercise test is not affected by the subject's awareness of the progressive increase in work intensity.

Lung function, maximum and submaximum exercise testing in COPD patients: reproducibility over a long interval.

This study was designed to investigate the reproducibility and clinical relevance of several lung function and exercise test indices in a sample of patients with stable severe chronic obstructive pulmonary disease (COPD). Twenty subjects (ages 67.8 +/- 2.0 years, forced expiratory volume in 1s, [FEV1] 39.7 +/- 2.8% predicted) receiving conventional medical therapy and pulmonary rehabilitation were tested 4 times at 1 month intervals. Testing procedures included lung function (inspiratory vital capacity [IVC], FEV1, plethysmographic functional residual capacity [FRC], specific conductance of the airways (sGaw), single breath transfer factor divided by the alveolar volume [TL/VA]); incremental, progressive, symptom-limited, cycle exercise (maximum work load [Wmax], maximum heart rate [HRmax], maximum ventilation [VEmax], maximum oxygen uptake [VO2max]); and 2 modes of submaximum exercise (12 min walking test [12 MWD] and endurance cycle test). The mean of the absolute value of the individual patient, session-to-session, variation was found to be 0.131 for FEV1, 102 ml/min for VO2max. The within-subject variability was the smallest for HRmax and IVC (mean intrasubject coefficient of variation, [CV intra] 5.0 and 6.5%) and the greatest for TL/VA, the work performed during the endurance cycle test (EW) and sGaw (CV intra 16.5, 19.4, and 22.7%), while it was reasonably low (8.1-10.2%) for all the other variables studied. Calculation of the F ratio of the intersubject variance to the residual (total minus intersubject) variance, interpreted as a signal-to-noise, ratio, yielded the following, in decreasing order: TL/VA, EW, VEmax, VO2max, IVC, FEV1, HRmax, Wmax, sGaw, 12 MWD, FRC. If we assume that a useful variable should combine a low within-subject variability (CV intra less than or equal to 10%) with a high signal-to-noise ratio, we conclude that, among all the variables studied, IVC, FEV1, VEmax, and VO2max are those with the greatest clinical potential for functional assessment in patients with COPD.

Enoxacin in acute exacerbations of chronic bronchitis: a comparison with amoxycillin.

A total of 43 hospitalized adult patients with acute exacerbations of chronic bronchitis or bronchiectasis due to Gram-negative bacteria were randomized to receive either enoxacin (400 mg bd) or amoxycillin (1,000 mg tid) for 7-12 days. Micro-organisms isolated included 24 Haemophilus influenzae (three beta-lactamases positive), 11 Branhamella catarrhalis (six beta-lactamase positive), two Pseudomonas aeruginosa and two Neisseria meningitidis in 37 evaluable patients. In the enoxacin group (23 patients) 82.6% of the patients were clinically cured or improved against 93% of patients in the amoxycillin group (14 patients). In the enoxacin group 76% of the pathogens were eradicated with two failures (P. aeruginosa), one relapse (H. influenzae) and three superinfections (Streptococcus pneumoniae). In the amoxycillin group, 71% of the pathogens were eradicated with 29% relapses. The differences between the two groups were not statistically significant. An increase in theophylline concentration occurred in 15 of 16 patients receiving simultaneous administration of theophylline, without clinical evidence of toxicity when theophylline dosage was reduced and enoxacin continued. Enoxacin appears to be as effective as amoxycillin in the treatment of acute exacerbations of chronic bronchitis due to susceptible Gram-negative bacteria.

Resistive inspiratory muscle training and exercise performance in COPD patients. A comparative study with conventional breathing retraining.

Twenty patients with stable COPD (mean age 67.8 yr; mean FEV1 1.08 1), all limited by ventilation at maximum exercise, were randomly allocated after a four week control period, to an eight week programme of either inspiratory resistive training (IRT), with a P Flex device, or conventional breathing retraining (BR). Exercise performance was evaluated every four weeks, using a 12-min walking test, an incremental progressive exercise on a cycle ergometer and a cycle endurance test. Inspiratory muscle endurance was measured as the highest tolerated resistance for 10 min on a P Flex device. IRT produced a significant (p less than 0.05) increase in the highest tolerated resistance, but IRT and BR failed to improve lung function or exercise performance. The present study shows that in COPD patients with ventilatory limitation on exercise an IRT programme may fail to improve exercise performance, in spite of an efficient training effect on the endurance of the inspiratory muscles.