Effects of clorazepate on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Non-pharmacological intervention for breathlessness in lung cancer. Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers. Efficacy of benztropine therapy for drooling. Breathlessness and psychiatric morbidity in chronic bronchitis and emphysema: a study of psychotherapeutic management. Randomized trial of paroxetine in end-stage COPD. Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS). Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler. Physiologic effects of oral bronchodilators during rest and exercise in chronic obstructive pulmonary disease.
Five patients with severe chronic lung disease were given placebo or 7.5 mg of clorazepate, a benzodiazepine, at bedtime for two weeks using a double-blind cross-over study design. Exercise tolerance, arterial blood gases, pulmonary function tests, self-rated breathlessness, and self-administered depression and anxiety scores were similar during drug treatment, placebo treatment, and washout periods. Higher doses of clorazepate were not tolerated by three of five patients. Nonanxious patients with chronic lung disease seem not to benefit subjectively or objectively from a low-dose benzodiazepine regimen. To evaluate the effect of non-pharmacological intervention for breathlessness in lung cancer on breathlessness ratings and patient functioning.
                Randomised controlled pilot study.
                A nurse led clinic in a specialist cancer centre.
                20 patients with advanced small cell and non-small cell lung cancer.
                Weekly sessions with a nurse research practitioner over 3-6 weeks using counselling, breathing re-training, relaxation and teaching coping and adaptation strategies.
                Visual analogue scale ratings of breathlessness, distress caused by breathlessness, functional capacity, ability to perform activities of daily living and the Hospital Anxiety and Depression Scale.
                Improvements in median scores on all measures were observed in the intervention group with the exception of depression, compared with the control group where median scores were static or worsened. Distress from breathlessness was improved by a median of 53%, breathlessness at worst by 35% and functional capacity by 21%. In contrast, distress in the control group worsened by a median of 10%. Significant improvements compared with the control group were observed in breathlessness at best (p < 0.02), breathlessness at worst (p < 0.05), distress caused by breathlessness (p < 0.01), functional capacity (p < 0.02) and ability to perform activities of daily living (p < 0.03) but were not observed for anxiety or depression.
                Lung cancer patients suffering from breathlessness benefited from this rehabilitative approach to breathlessness management and strategies employed in this pilot study warrant further multicentre research. Macmillan nurses and palliative care teams are recommended to explore the potential of adopting similar approaches. Fifteen out of 18 "pink and puffing" patients completed a double-blind, placebo-controlled cross-over trial of diazepam and promethazine for breathlessness and reduced exercise tolerance. Dosages were 25 mg and 125 mg daily, respectively, and each course lasted two weeks. Patients with psychiatric or other major medical histories were excluded. Of the three patients who did not complete the trial, one died during an exacerbation of breathlessness while taking diazepam, one was withdrawn because of mild hypercapnia while taking placebo, and one suffered intolerable drowsiness while taking diazepam. Of the remaining 15 patients, six needed a reduction in dosage because of drowsiness: one of these was taking promethazine and five diazepam. Diazepam had no effect on breathlessness and noticeably reduced exercise tolerance. Promethazine reduced breathlessness and improved exercise tolerance without altering lung function. From these results diazepam is contraindicated for breathlessness and reduced exercise tolerance in fixed airways obstruction, but promethazine may be beneficial. This study assessed the efficacy of synthetic anticholinergic benztropine and incidence of side-effects in 20 developmentally-disabled patients with severe drooling. The double-blind, placebo-controlled, crossover protocol included one-week baseline, two-week placebo and two-week benztropine conditions (mean dose 3.8 mg). A significant decrease in drooling during the benztropine condition relative to placebo was demonstrated and conservative response rates (calculated by deleting placebo responders), ranged up to 65 to 70 per cent. For patients completing the protocol the incidence of side-effects did not differ across conditions and minor problems such as a dry mouth were eliminated by small dose adjustments. More serious cholinergic side-effects, which resolved within 24 to 48 hours, necessitated discontinuation of the drug in three patients. This study demonstrates that synthetic anticholinergics can provide an important therapeutic alternative to surgical and behavioral therapies for drooling. This paper describes a study of the outcome of psychotherapy with patients disabled by chronic obstructive airways disease giving rise to dyspnoea. Forty-three men and 22 women with severe COAD were randomly allocated for 8 weeks to one of three types of psychotherapy or to an untreated control group, and were followed up six months later. The group treated by a medical nurse without training in psychotherapy experienced sustained relief of dyspnoea but tended to undergo less psychodynamic change; psychiatric symptoms were reduced in those receiving supportive, but not analytical, psychotherapy. The psychosomatic mechanisms involved and the implications for medical and nursing practice and for liaison psychotherapy are discussed. Although the underlying pathology is initially confined to the lungs, the associated emotional responses to chronic obstructive pulmonary disease (COPD) contribute greatly to the resulting morbidity. The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms.
                We conducted a 12-week, randomized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Questionnaire (CRQ), an evaluative COPD-specific quality-of-life questionnaire, was the primary outcome.
                23 patients were randomized and 15 completed the trial (8 on Paroxetine; 7 on placebo). In the per-protocol analysis, we observed statistically and clinically significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ: emotional function (adjusted mean difference: 1.1; 95% confidence interval [CI]: 0.0 - 2.2) and mastery (difference: 1.1; CI: 0.4 - 1.8). Dyspnea and fatigue improved, but to an extent that did not reach statistical significance. In the intention-to-treat analysis, none of the differences in CRQ scores was significant. Paroxetine was not associated to any worsening of respiratory symptoms.
                The results of this small randomized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present. This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD. The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD. Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy. At rest and during exercise, noninvasive studies of cardiopulmonary physiology in patients with chronic obstructive pulmonary disease (COPD) were carried out to determine the objective benefits of commonly used oral bronchodilator drugs in 15 stable patients without cardiovascular disease or reversible obstruction of airflow. Theophylline, terbutaline, a combination of theophylline and terbutaline, and placebo were given for ten days each in a randomly sequenced double-blind protocol for outpatients. Spirometric values, the ratio of physiologic dead space to tidal volume (VDp/VT), and the alveolar-arterial oxygen pressure difference (P[A-a]O2) were studied at rest on each regimen. During steady-state exercise the changes in VDp/VT and P(A-a)O2, as well as the ventilatory equivalent for oxygen and oxygen pulse, were measured. When compared with placebo, no significant change was noted in the previously mentioned measurements with any regimen, with the exception of a small improvement in the forced expiratory volume in one second, which was significant for all regimens. These findings suggest that commonly used oral bronchodilator drugs in usual doses may have small effects on airflow even in "irreversible" COPD but that the objective effect of these agents on gas exchange during rest and exercise is not significant.
There is no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in patients with advanced cancer and COPD. There is a slight but non-significant trend towards a beneficial effect but the overall effect size is small. Benzodiazepines caused more drowsiness as an adverse effect compared to placebo, but less compared to morphine. These results justify considering benzodiazepines as a second or third-line treatment within an individual therapeutic trial, when opioids and non-pharmacological measures have failed to control breathlessness. Although a few good quality studies were included in this review, there is still a further need for well-conducted and adequately powered studies.