A randomised 2 x 2 trial of community versus hospital pulmonary rehabilitation, followed by telephone or conventional follow-up.

OBJECTIVES: To determine whether pulmonary rehabilitation carried out in a community setting is more effective than that carried out in a standard hospital setting and which is more cost-effective; also whether telephone follow-up is both cost-effective and useful in prolonging the beneficial effects of a pulmonary rehabilitation programme. DESIGN: A randomised trial. Participants were randomised in 2 x 2 factorial fashion to hospital or community rehabilitation and telephone or standard follow-up with review. SETTING: Hospitals or community sites in Sheffield. The community venues were selected to be close to public transport routes and have good parking and level access. The two hospital venues were the physiotherapy gym and a staff gym within the grounds of the hospital. PARTICIPANTS: Patients with chronic obstructive pulmonary disease diagnosed by respiratory physicians according to Global Initiative for Chronic Obstructive Lung Disease guidelines. INTERVENTIONS: Participants were randomised to one of four groups: hospital rehabilitation with no telephone follow-up; hospital rehabilitation with telephone follow-up; community rehabilitation with no telephone follow-up; or community rehabilitation with telephone follow-up. All were blinded to the telephone intervention arm until 1 month post rehabilitation, when only the assessment team and research participants were unblinded. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in improvement in endurance shuttle walking test (ESWT) between hospital and community pulmonary rehabilitation groups post rehabilitation, and the difference in ESWT during 18 months' follow-up between those receiving telephone encouragement and those receiving standard care. A secondary measure was health-related quality of life. RESULTS: A total of 240 participants had evaluable data. Of these, 129 were randomised to hospital rehabilitation (64 with telephone follow-up and 65 with no telephone follow-up) and 111 to community rehabilitation (55 with telephone follow-up and 56 with no telephone follow-up). For the primary outcome measure, there were 162 patients with data for analysis: hospital rehabilitation with no telephone follow-up (n = 38); hospital rehabilitation with telephone follow-up (n = 48); community rehabilitation with no telephone follow-up (n = 43); and community rehabilitation with telephone follow-up (n = 33). For the acute phase post-rehabilitation outcomes, before patients had the opportunity for telephone follow-up, we compared outcomes between the 76 patients in the community rehabilitation group and the 86 patients in the hospital rehabilitation group. Patients in the hospital rehabilitation group increased the distance they could walk at the post-rehabilitation follow-up by 283 m (SD 360 m), an increase relative to baseline of 109% (SD 137%). Patients in the community rehabilitation group increased the distance they could walk at the post-rehabilitation follow-up by 216 m (SD 340 m), an increase relative to baseline of 91% (SD 133%). There was no statistically significant difference between the groups [17.8% (95% CI -24.3 to 59.9, p = 0.405)]. For longer term outcomes at 6, 12 and 18 months post rehabilitation there was no evidence of a rehabilitation group effect. After allowing for the initial post-rehabilitation baseline distance walked, time (follow-up visit) and the factorial design (telephone follow-up group), the average difference in the post-rehabilitation follow-up distance walked on the ESWT between the hospital and community rehabilitation groups was 1.5 m (95% CI -82.1 to 97.2, p = 0.971), and between the telephone and no-telephone groups it was 56.9 m (95% CI -25.2 to 139, p = 0.174). There was no difference between hospital or community groups in terms of acute effect or persistence of effect. Health economic analysis favoured neither hospital nor community settings, nor did it clearly favour telephone follow-up or routine care. CONCLUSIONS: Pulmonary rehabilitation delivered in a community setting has similar efficacy to that produced in a more traditional hospital-based setting, both settings producing significant improvements in terms of exercise capacity and quality of life acutely and after long-term follow-up. Health economic analysis showed that neither hospital nor community programmes were greatly favoured. The choice of model will depend on local factors of convenience, existing availability of resources and incremental costs. Staff characteristics may be important in gaining optimal outcome, and care should be taken in staff recruitment and training. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86821773.

Comparative genome hybridization of Streptococcus mutans strains.

The basis for genotypic and phenotypic variation within Streptococcus mutans is poorly understood but the availability of the genome sequence of strain UA159 provides an opportunity for comparative studies. Genomic DNA prepared from nine strains of S. mutans was used to probe a microarray consisting of oligonucleotides representing 1948 open reading frames of S. mutans UA159. A total of 385 (20%) of the UA159 open reading frames were found to be absent from one or more of the test strains. Absent open reading frames frequently occurred in blocks of adjacent open reading frames and represented regions previously experimentally detected by polymerase chain reaction, predicted genomic islands and insertion sequence elements as well as novel open reading frames. Approximately half appear to involve foreign DNA acquired by horizontal transmission. The results indicate the existence of distinct core and dispensable genomes and may help explain the phenotypic and genotypic variation within S. mutans.

Use of whole-body plethysmography to compare bronchodilator inhaler efficacy.

Whole-body plethysmography is not included in guidelines from regulatory authorities for the development of treatments or delivery devices for lung disease, despite its potential advantages compared to spirometry. Two separate studies were undertaken to assess the use of specific airway conductance (sGaw) as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery systems (a novel dry powder inhaler and a standard metered dose inhaler). The first pilot study involved delivery of a single dose of salbutamol (200 micrograms) to 12 healthy volunteers and determination of sGaw up to 120 min after treatment. The second study involved delivery of cumulative doses of salbutamol (100, 200 and 400 micrograms) to 19 healthy volunteers with demonstrated reversibility of sGaw to the bronchodilator and measurement of sGaw up to 240 min after treatment. In both studies, increases in sGaw after treatment were significant compared to placebo and larger than the recorded increases in FEV1. Increases in sGaw were similar for both delivery devices and support the therapeutic equivalence of the two products. Power calculations indicated that the second study had appropriate statistical power to discriminate between treatments. It is concluded that the assessment of sGaw in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.

Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting.

BACKGROUND: To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients' perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George's Respiratory Questionnaire (SGRQ) and Guyatt's Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients' scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.

Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate.

The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity.

Hormonal, renal, and autonomic nerve factors involved in the excretion of sodium and water during dynamic salt and water loading in hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop sodium and water retention and a subclinical autonomic neuropathy. The possibility that these might be associated has been investigated. METHODS: The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels, osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium content, glomerular filtration rate, renal blood flow, and cardiovascular autonomic nerve function were measured. Patients were divided into groups of eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no oedema, patients in group B were more hypoxaemic but had never been oedematous, whilst those in group C were hypoxaemic and mildly oedematous at the time of the study. RESULTS: Patients in groups B and C excreted less sodium and water during saline loading and a lesser proportion of the water load. Patients in group C had a reduction in renal blood flow and glomerular filtration rate and all had a subclinical autonomic neuropathy, which was also found in three patients in group B. Their plasma aldosterone level was raised but did suppress appropriately on saline loading. Vasopressin levels were abnormally raised for the osmolality in patients in group C and in those with autonomic dysfunction throughout the water load and at 240 minutes after the salt load. Sodium and urine excretion was highly correlated with autonomic dysfunction, aldosterone levels at time zero, and renal blood flow. The 11 patients with autonomic dysfunction were more likely to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower glomerular filtration rate and renal blood flow, and higher aldosterone and vasopressin levels than the remaining patients. CONCLUSIONS: In patients with COPD the inability to excrete sodium and water is multifactorial. This is the first study to show that autonomic dysfunction is at least associated and might play an important part in the impaired sodium and water homeostasis seen in patients with severe COPD.

The QTc interval, autonomic neuropathy and mortality in hypoxaemic COPD.

Patients with hypoxaemic chronic obstructive pulmonary disease (COPD) have a subclinical autonomic neuropathy. Autonomic neuropathy has been associated with a prolonged electrocardiograph QTc interval and risk of ventricular arrhythmias and death. We studied cardiovascular autonomic nerve function and QTc interval at rest and during stress (a valsalva manoeuvre) in 34 patients with hypoxaemic COPD who were followed up after 2 yr. Seventeen patients had a subclinical autonomic neuropathy (group AN) and the remaining 17 were normal (group C). Group AN were significantly more hypoxaemic (PaO2 7.3 +/- 0.3 compared to 9.2 +/- 1.8, P < 0.05), had a lower FEV1 and had a longer QTc at rest (0.43 +/- 0.01 compared to 0.40 +/- 0.01, P < 0.01) and at peak valsalva (0.44 +/- 0.01 compared to 0.41 +/- 0.01, P < 0.05). When analysed after 2 yr, there were two deaths in group C and seven deaths in group AN. The QTc was abnormal > 0.44s at rest and at peak valsalva stress in five of group AN, three of these five patients died. QTc was normal at rest but abnormal at peak valsalva stress in eight further patients. This included three further patients from group AN of whom two had died and five group C patients which included both the group C deaths. The presence of autonomic neuropathy and QTc prolongation (> 0.44s) at rest was significantly associated (P < 0.05). Likewise QTc prolongation at the peak of a valsalva stress was significantly associated with death at 2 yr follow-up (P < 0.01) with an odds ratio of 11.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Survey on domiciliary oxygen by concentrator in England and Wales.

Long-term oxygen therapy is initiated in England and Wales by the patient's family doctor, sometimes at the request of a hospital consultant. Guidelines for therapy exist but are not mandatory. We wish to investigate the numbers and types of patients being treated under this regimen, the method of treatment and how they responded to their oxygen dose. We therefore interviewed and tested patients at the inception of therapy in six of the nine prescribing areas of the whole country, during August 1990 and February 1991. Main outcome measures were diagnoses, daily duration and flow prescribed, arterial oxygen saturation (SaO2) breathing air and improvement in arterial oxygen saturation on prescribed oxygen. Most patients both in summer and winter reported diagnoses of chronic bronchitis (45%) or emphysema (50%), in addition to other conditions. Most were male (58%), and most (72%) were over retirement age. Roughly half (45%) were house-bound, but only 28 (6%) were totally bedridden. Three quarters (77%) reported that a hospital consultant had told them how much oxygen to use, and in all diagnostic groups mean prescriptions exceeded 15 h.day-1 and 2 l.min-1. However, only half (54%) of the patients with complete measurements had basal arterial oxygen saturation of 90% or less at the start of treatment, together with a satisfactory improvement in arterial oxygen saturation on the prescribed flow of oxygen. In conclusion, patients are usually prescribed adequate regimens but little attempt is made to ensure that prescription is appropriate or response satisfactory. Resources continue to be used for treating patients without ensuring that they benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of angiotensin converting enzyme inhibition on sodium excretion in patients with hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop cor pulmonale with sodium and water retention. The sodium retention has been explained as a result of increased plasma levels of aldosterone. If this was true angiotensin converting enzyme (ACE) inhibition would be expected to lower plasma levels of aldosterone and improve the renal excretion of sodium. METHODS: Six patients with stable hypoxaemic COPD (PaO2 < 8.0 kPa) and a history of an oedematous exacerbation received an intravenous hypertonic saline load (6 ml/kg body weight of 2.7% saline over one hour) before and while taking 4 mg/day perindopril, an ACE inhibitor, for one month. Aldosterone, antidiuretic hormone (ADH), plasma and urine electrolyte levels, osmolality, and volume were measured over four hours. The repeatability of the saline load test was assessed in six patients with a similar severity of hypoxaemic COPD. For comparison the saline load test was also performed in six patients with mild COPD. RESULTS: The hypertonic saline load test results were repeatable. Perindopril reduced the mean (SD) plasma level of aldosterone from 142 (88) pg/ml to 54 (24) pg/ml at 0 minutes before the saline infusion, and from 64 (35) pg/ml to 30 (17) pg/ml after the infusion without improving the urinary volume or sodium excretion. Before starting treatment with perindopril 43.7 (6.9) mmol (20%) of the sodium load was excreted compared with 49.6 (7.9) mmol (22% of load) when taking perindopril. Patients with mild COPD excreted more sodium (77.6 (21.4) mmol (38.7% of load)) despite having similar plasma aldosterone levels to those in the patients receiving perindopril. CONCLUSIONS: Patients with stable hypoxaemic COPD have an impaired ability to excrete sodium which is not improved by the administration of an ACE inhibitor. ACE inhibition lowered the plasma level of aldosterone without improving sodium excretion. This suggests that the inability of patients with hypoxaemic COPD to excrete sodium is not caused by their increased plasma levels of aldosterone.

Autonomic nerve dysfunction in COPD as assessed by the acetylcholine sweat-spot test.

Patients with hypoxic chronic obstructive pulmonary disease (COPD) have evidence of a subclinical parasympathetic autonomic neuropathy, with apparent preservation of sympathetic function. However, these cardiovascular-respiratory tests might have been biased by concomitant chest disease, the acetylcholine sweat-spot test avoids this bias. This sweat-spot test assesses sympathetic nerve function, it relies upon the fact that denervated sweat glands do not produce sweat. 35 patients with hypoxaemic COPD and seven age matched normal subjects were studied. Following intradermal injection of 0.1 of 1% acetylcholine into the dorsum of the feet, the number of sweatglands able to respond in a given surface area was recorded. Cardiovascular autonomic nerve function, arterial oxygen and carbon dioxide tensions, lung function and cigarette consumption were also recorded. The acetylcholine sweat-spot test was highly repeatable in eight COPD patients, no person with normal or frankly abnormal function being wrongly assigned. The age matched control subjects had normal acetylcholine sweat-spot scores and cardiovascular autonomic tests. The acetylcholine sweat-spot test was abnormal in 24 patients, borderline in 8 and normal in 3 patients. The abnormal sweat-spot test group had significant worse FEV1, arterial blood gases and autonomic function. The acetylcholine sweat-spot score correlated with the severity of arterial hypoxaemia (r = 0.78, p < 0.001) and with the parasympathetic cardiovascular tests (r = 0.80, p < 0.001). In conclusion, patients with hypoxaemic COPD have a parasympathetic cardiovascular and a peripheral sympathetic autonomic neuropathy. The acetylcholine sweat-spot test is repeatable, easy to perform and a sensitive indicator for autonomic dysfunction in breathless individuals with COPD.

Hyperinflation, trapped gas and theophylline in chronic obstructive pulmonary disease.

Assessment of patients with chronic airflow limitation traditionally involves the measurement of airway obstruction by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as well as hyperinflation by residual volume (RV). Patients often claim reduction of breathlessness during theophylline therapy, without change of spirometry. In severe airflow limitation there is often a difference in lung volumes measured by helium dilution and plethysmography. The latter is thought to measure the absolute amount of gas in the lungs at functional residual capacity (FRC), whereas helium dilution measures only air in rapid communication with the mouth. The difference between the two is considered to represent poorly-ventilated areas of the lung, and is termed trapped gas volume. Twenty two patients with "irreversible" airflow limitation, mean (SD) FEV1 1.15 (0.52) l, FVC 2.57 (0.88) l, were studied. Uniphyllin Continus tablets (Napp Laboratories) were given at a dose to provide a mean steady-state plasma level of 14 mg.l-1, in a placebo-controlled, double-blind, cross-over study. The measurements made were FEV1, FVC, static lung volumes, 6 min walking distance (6WD), breathlessness after exercise assessed by visual analogue scales (VAB), and arterial blood gases. No significant correlation was found between changes in VAB and changes in RV measured by the helium dilution technique (RV (He)), FEV1 or FVC, but there were good correlations with trapped gas volume (r = 0.61, p < 0.01). The plethysmographic element of the calculated trapped gas volume reflects change in the sensation of breathlessness, and is affected by treatment with theophylline.

Comparative assessment of a new breath-actuated inhaler in patients with reversible airways obstruction.

Twenty-five patients with reversible airways obstruction inhaled salbutamol (200 micrograms) from the standard press and breathe-metered dose inhaler or a new breath-actuated metered dose inhaler (Aerolin in the Autohaler inhalation device; 3M Health Care Ltd.) in a single dose, double-blind, double-dummy, 2-period, cross-over study. Forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate were measured in the 4-hour period after inhalation. The equivalence of the two inhaler devices was determined by analysis of the peak change and time to peak, with reference to the initial recorded baselines of the measured parameters. The efficacy of the two devices was very similar. The breath-actuated device is likely to benefit inhaler users who suffer from poor co-ordination of actuation and inhalation with a standard inhaler.

Cardiovascular autonomic nerve function in patients with hypoxaemic chronic obstructive pulmonary disease.

Intraneural hypoxaemia is recognized as a pathogenic mechanism in diabetic neuropathy. A similar pathophysiological process may occur in chronic obstructive pulmonary disease (COPD). Autonomic neuropathy is not recognized in COPD. We compared 96 patients with hypoxaemic COPD to 22 age-matched control subjects to see whether autonomic dysfunction occurs in COPD and whether there was any correlation with the severity of hypoxaemia. The cardiovascular autonomic tests consisted of heart rate responses (mainly parasympathetic function) to a Valsalva manoeuvre, deep breathing and postural change and blood pressure responses (mainly of sympathetic origin) to postural change and sustained handgrip. Early autonomic neuropathy is defined as one abnormal test and definite autonomic neuropathy as two abnormal tests according to the normal range. These autonomic tests were reproducible in our study population. Although the symptoms and signs of autonomic neuropathy were rare, definite autonomic dysfunction was found in 35%, and early autonomic neuropathy in a further 47%, of patients whose arterial oxygen tension (PaO2) was less than 8 kPa (60 mmHg). Only 18% of the control group had evidence of an age-related early autonomic dysfunction. Parasympathetic autonomic dysfunction was significantly correlated with PaO2 whilst the sympathetic tests were relatively normal. Correction of hypoxaemia for one hour or administration of ipratropium bromide or terbutaline had no effect on autonomic function. Subclinical autonomic neuropathy is a feature of hypoxaemic COPD. Its importance in the disease process and its role in prognosis needs evaluation.

Changes in atrial natriuretic peptide concentrations during intravenous saline infusion in hypoxic cor pulmonale.

BACKGROUND: The pathogenesis of oedema in hypoxic cor pulmonale is poorly understood. One possibility is a failure of atrial natriuretic peptide release, leading to salt and water retention. This hypothesis was tested by observing the response to an intravenous saline challenge in patients with and without cor pulmonale. METHODS: Plasma atrial natriuretic peptide concentrations were measured before and for three hours after an intravenous saline load (0.1 ml 2.7% saline/kg/min for 60 minutes) in 20 patients with chronic obstructive airways disease. Ten patients with cor pulmonale, as judged clinically by the presence of peripheral oedema with a previously documented increase in the jugular venous pressure or pleural effusions during an acute exacerbation of airway obstruction (mean (SE) age 67 (3) years, FEV1 0.73 (0.08) 1, arterial oxygen tension (PaO2) 6.4 (0.4) kPa, and arterial carbon dioxide tension (PaCO2) 6.7 (0.3) kPa), were compared with 10 patients with hypoxic chronic obstructive airways disease who had never had oedema (mean age 63 (1) years, FEV1 1.07 (0.09) 1, PaO2 8.6 (0.4) kPa, and PaCO2 5.3 (0.2) kPa). All patients were studied fasting and after diuretics had been stopped for three days. No supplemental oxygen was given. RESULTS: The mean four hourly urine sodium excretion was less in the patients who had oedema (27 (4.6) mmol, 13% of the intravenous load) than in those without oedema (82 (15.5) mmol, 43% of the load). Initial mean plasma atrial natriuretic peptide values were significantly higher in the patients with cor pulmonale (19.1 (1.6) compared with 10.2 (0.7) pmol/l) and the mean peak rise in atrial natriuretic peptide after the intravenous saline load had been given was 13 (8.0) pmol/l in the patients with cor pulmonale and 5.5 (2.3) pmol/l in the controls. There were no significant differences in plasma and urinary osmolality, blood pressure, or creatinine clearance between the groups. CONCLUSION: Patients with chronic obstructive airways disease and cor pulmonale have an impaired ability to excrete a hypertonic intravenous saline load despite a normal physiological release of plasma atrial natriuretic peptide.

Long term domiciliary oxygen treatment for chronic respiratory failure reviewed.

The use of long term domiciliary oxygen therapy in the Sheffield area from June to August 1987 has been surveyed. Of the 74 patients prescribed long term domiciliary oxygen therapy, 64 were visited at home. These had arterial blood gas tensions or oxygen saturation measured (while breathing oxygen and air), and the indications for long term domiciliary oxygen therapy were examined retrospectively. Fifty two patients had chronic bronchitis and emphysema, the remainder having pneumoconiosis, bronchiectasis, fibrosing alveolitis, and congestive cardiac failure. Of the 54 cases where indications for treatment could be compared with the Department of Health and Social Security (DHSS) guidelines, only 23 (43%) met the full DHSS criteria before the start of treatment. The median length of treatment was 16 months. At follow up 51 patients had an arterial oxygen tension (PaO2) greater than 8.0 kPa when breathing oxygen. They had a significantly higher PaO2 when breathing air than before long term oxygen therapy (6.7 (SD 1.2) kPa before oxygen treatment, 7.6 (1.4) kPa on reassessment). A similar change was seen in the 23 patients assessed as recommended by the DHSS (6.1 (0.8) kPa; 7.2 (1.2]. PaO2 during the breathing of air was less than 7.3 kPa at reassessment in only 21 (33%) patients. Thirteen patients had carboxyhaemoglobin concentrations above 2.5%, the 95th centile of the distribution in nonsmokers in the laboratory.

Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.

The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.

A conservation device for oxygen therapy in COPD.

Patients with hypoxaemia secondary to chronic obstructive pulmonary disease (COPD) are frequently prescribed oxygen therapy for short- and long-term domiciliary use. Oxygen administered via nasal cannulae incorporating a small collapsible reservoir ("Oxymizer", Chad Therapeutics Inc., CA, USA) improves transcutaneous oxygen tensions in the short-term when compared to standard nasal cannulae. The effects of this device on arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions was assessed over 60 min in twelve patients with severe hypoxaemia (6.2 +/- 0.9 kPa, mean +/- SD) and hypercapnia (7.5 +/- 1.2 kPa). Following baseline measurements, oxygen was administered using standard nasal cannulae, and further measurements were made at 15 min intervals for at least 45 min. Patients were then changed to the "Oxymizer" and measurements continued at 15 min intervals for a further 60 min. Mean PaO2 increased by 1.1 +/- 0.78 kPa (p less than 0.001), using the "Oxymizer", but PaO2 was significantly greater after 15 min on the device than after 60 min (p less than 0.05). There was no change in PaCO2 (p greater than 0.05). The "Oxymizer" increases PaO2 compared with standard cannulae, but the effect may not be sustained.