Compliance and outcomes in patients with asthma.

The severity of asthma varies within and between individuals, and the disease has a variable impact on quality of life. Disease severity can be modified but not cured by long term anti-inflammatory therapy. Compliance with, or adherence to, such therapeutic regimens is difficult, and it is affected by a number of factors. Patterns of compliance are variable; some patients take only half the prescribed drug all the time, while others take all their prescribed medication for a while and then "take a break'. Understandably, there is no single factor that would account for such a variety of human behaviour, but generally the frequency and ease of drug administration, as well as adverse effects (real or imagined), can affect compliance. Poor communication regarding the precise regimen will also impair compliance. Psychosocial factors such as depression, poor interpersonal skills and coping strategies, and rejection of the diagnosis will lead to lower levels of compliance. Interventional programmes using a combination of education, skills training and methods to modify behaviour are needed to improve the quality of life in asthmatics. The role of the newer generations of once-/twice-daily oral anti-inflammatory preparations in improving compliance requires further investigation.

Home nebulized therapy for patients with COPD: patient compliance with treatment and its relation to quality of life.

STUDY OBJECTIVES: To assess compliance with home nebulized therapy in patients with COPD. DESIGN: Patients' home nebulizers were replaced with nebulizers that recorded the date and time of each treatment over a period of 4 weeks. Poor compliance was defined as taking <70% of the prescribed dose (or <60% for those prescribed treatments five or more times daily). SETTING: Patients were seen at the hospital COPD outpatient clinic. The compliance data obtained were recorded while they were at home. PATIENTS: Ninety-three patients aged 44 to 76 years (mean, 64.9 years) were recruited from the hospital nebulizer database. MEASUREMENTS: Patients completed a self-reported quality of life scale, the St. George's Respiratory Questionnaire (SGRQ), both before (SGRQ1) and after (SGRQ2) the 4-week study period to look at whether quality of life was either predictive of or subsequent to level of compliance. RESULTS: Data were obtained from 82 patients. Mean compliance was 57% (range, 0 to 124%). Thirty-six (44%) patients were compliant and 46 (56%) were poorly compliant. There was no difference between the two groups in age or sex distribution. Compliance was negatively correlated with the total score on the SGRQ2 (p=0.03). CONCLUSION: The study shows that levels of compliance with nebulized therapy are low in a large proportion of patients with COPD and that patients with low levels of compliance report greater impairment in their quality of life.

Ventilatory changes during exercise and arterial PCO2 oscillations in chronic airway obstruction patients.

Ventilatory kinetics during exercise (30 W for 6 min) were studied in 3 asthmatics, 14 patients with chronic airway obstruction (11 with bronchial or type B disease, 3 with emphysematous or type A disease), and in 5 normal age-matched controls. The measure of ventilatory increase during early exercise, alpha 1-3%, was calculated as (avg minute ventilation over 1st-3rd min of exercise--resting minute ventilation)/(avg minute ventilation over 4th-6th min of exercise--resting minute ventilation) X 100. Arterial pH, PO2, and PCO2 (PaCO2) were measured in vitro at rest and within 20 s of termination of exercise. Respiratory PaCO2 oscillations had previously been monitored at rest in the patients (indirectly as in vivo arterial pH, using a fast-response pH electrode) and quantified by upslope (delta PaCO2/delta t). alpha 1-3% was normal in asthmatics (whose respiratory oscillations as a group showed least attenuation) and in type A patients (whose respiratory oscillations as a group were most attenuated). In type B patients reduction in alpha 1-3% correlated with attenuation of delta PaCO2/delta t (r = 0.75; P less than 0.01). There was no significant correlation between delta PaCO2/delta t and change of in vitro PaCO2 from rest to the immediate postexercise period. These findings are consistent with the hypothesis that attenuation of delta PaCO2/delta t slows ventilatory kinetics during exercise in type B but not type A patients. Intact respiratory oscillations are not necessary for CO2 homeostasis after the first few minutes of exercise.

A double-blind comparison of naproxen with indomethacin in osteoarthrosis.

Twenty-two patients with osteoarthrosis of one or both knee joints and 28 patients with osteoarthrosis of one or both hips completed a double-blind trial of 500 mg naproxen daily versus 100 mg indomethacin daily. All patients had been on other active medication up to the start of the trial. Identical trial designs were followed with both classes of patients, namely, a crossover pattern of four weeks on each drug with patients being assessed at -2, 0, 2, 4, 6, and 8 weeks. Assessments made included objective measurement of joint range, stair climbing and walking times, and subjective grading of pain present during normal activity, of which the patient kept a daily record. Patients were also questioned at each clinic visit regarding possible side effects. Study groups were comparable for both drugs. In the majority of subjective and objective parameters, there were significant improvements from baseline on both drugs of statistically comparable magnitude. Significantly fewer side effects were noted during the period on naproxen compared with those on indomethacin. There were no abnormalities discovered in hematologic or biochemical tests performed during the course of the trial.

Psychological disorder in asthma is associated with poor control and poor adherence to inhaled steroids.

Previous studies have linked psychological morbidity to poor control of asthma, but have not objectively measured adherence to treatment, and have linked poor adherence to depression, but have not measured asthma severity. This study assessed asthma and psychological morbidity and objectively measured adherence to medication and showed that psychological morbidity in those with asthma is significantly increased when control of asthma is poor, especially when control is poor and adherence to inhaled steroid regimen is low.

Management of asthma in general practice.

An audit of the management of asthma in two large general practices has been undertaken. The overall level of therapy prescribed was, in general, related to both the objective severity of the patients' asthma and the extent of symptoms. However, many individual patients received sub-optimal therapy. Prophylactic inhaled beta agonists were used infrequently. Inhaled steroids were prescribed to only one third of the patients and to less than half of severely affected patients. The results suggest that this group of adult asthmatics were relatively under treated in general practice, but a prospective study with proven compliance is necessary to confirm this.

An audit of morbidity associated with chronic asthma in general practice.

A survey of 312 adult asthmatic subjects has been undertaken. Only 3.5% of the total adult list were known to have asthma and this may represent underdiagnosis. Spirometry was normal in under half the patients and below 50% predicted in one fifth. Forced expired volume in 1s had declined more rapidly than expected with increasing age, particularly amongst smokers. Morbidity from asthma was extensive, patients reporting substantial breathlessness and restrictions of their life style; nearly half had lost time from work in the preceding twelve months. Morbidity was correlated with spirometry.

Compliance in asthma.

Low rates of compliance with medication pose a major challenge to the effective management of most chronic diseases, including asthma. The high medical and social costs of non-compliance, and the apparent lack of effective methods for dealing with it, has stimulated renewed interest in this complex issue. Two broad categories of non-compliance have been identified, namely unintentional (or 'accidental') and intentional (or 'deliberate'). Unintentional non-compliance may result from poor doctor-patient communication or a lack of ability to follow advice. Intentional non-compliance occurs when the patient knows what is required but decides not to follow this to some degree. Healthcare professionals need to be aware of the various issues affecting compliance in all patients. The reasons for non-compliance are many and varied, and include factors such as complexity of the treatment regimen, administration route, patient beliefs about therapy and other psychological factors. Improvement in patient compliance with therapy will require better doctor-patient communication, improved patient education, the tailoring of therapy to the individual and possible novel strategies such as offering feedback to the patients on their level of compliance.

Single centre open study to compare patient recording of PRN salbutamol use on a daily diary card with actual use as recorded by the MDI compliance monitor.

The aim of this study was to assess the patients' use of inhaled short acting bronchodilators as rescue therapy during a 4-week study period. In this study an electronic metered-dose inhaler compliance monitor (MDI-CM) was used to measure the time and date of actuations of the device and this information was then compared with the patients' self reporting diary card (DC). Salbutamol canisters were used in the compliance monitor. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. Patients aged 18 years and over who were either receiving, or in the investigators opinion required, inhaled salbutamol on a PRN basis were enrolled for a 4-week monitoring phase during which all rescue salbutamol used was obtained from the MDI-CM. Patients were recording their use of salbutamol in the DC each morning and evening. There was a 2-week follow-up period following completion of the monitoring phase or withdrawal from the study. Forty-four patients were enrolled and 35 patients completed the study. The mean age (range) was 43 (20-76) years and mean FEV1 2.32 (0.7-4.0) 1, with male:female ratio of 19:25. Comparison of MDI-CM and DC recordings showed patients fell into three categories: (1) patients who used rescue salbutamol appropriately and whose MDI-CM and DC recordings matched closely; (2) patients who used rescue salbutamol for acute relief but whose MDI-CM and DC recordings did not correlate and (3) patients whose use of rescue salbutamol was inappropriate or erratic according to the MDI-CM but whose DC indicated good compliance. This category of patients include those who 'dumped' all their salbutamol before attending clinic appointments. There was no significant difference in the demographic details or the severity of disease in the three groups. Recorded use of 'rescue' bronchodilator is frequently used as an indicator of efficacy for new anti-asthma therapies. This study comparing electronic data monitoring and remembered rescue salbutamol highlights the potential errors that can occur without accurate recording systems.

Can the morbidity of asthma be reduced by high dose inhaled therapy? A prospective study.

A community based, prospective study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken. One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol. Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a 'partially double-blind' manner. The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1. All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority. Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone, particularly when inhaled steroids were started in relatively high dosage.

Compliance with inhaled therapy and morbidity from asthma.

Patient compliance with a standardized incremental regimen of inhaled anti-asthma therapy has been assessed in a large, prospective study in general practice. Urine salbutamol estimations were made in 30 patients who had the largest improvement with therapy (mean increase in FEV1 0.45 l above baseline: Responsive) and in 30 patients whose airflow obstruction failed to improve (FEV1-0.14 l: Nonresponsive). The urine salbutamol concentrations rose over the 9 month period in the responsive patients as expected with the incremental doses prescribed, and were significantly higher than urine levels in nonresponsive patients at two dose levels. Poor compliance with prescribed inhaled therapy is an important cause of persistent morbidity from asthma.

Does urinary salbutamol reflect compliance with the aerosol regimen in patients with asthma?

Compliance with inhaled beta agonist therapy in a group of asthmatic patients in general practice has been monitored using a high performance thin layer chromatographic assay of salbutamol in urine. Urine salbutamol levels were lower than expected in five of 51 patients and much higher than expected in a further 11 patients. These results suggest the assay may be clinically useful for monitoring compliance of asthmatic patients with inhaled salbutamol.

Compliance with prescribed drug therapy in asthma.

Morbidity and mortality from asthma in the Western world is increasing despite effective prophylactic drugs. Beta agonists are increasingly considered causal; while under-prescribing of inhaled steroids or other anti-inflammatories are accepted as causes for the problems, but the role of non-compliance with inhaled asthma therapy is rarely mentioned. Using a novel electromechanical counter MDI actuations have been recorded in three small (9-11 patients), short (2-3 weeks) studies. When aware compliance with prescribed inhaled steroids was under scrutiny, six patients were fully compliant, two took just 70% of the prescribed regimen, but two did not follow the prescribed regimen at all. When unaware of scrutiny, six out of 11 were compliant but five patients were estimated as taking less than 30-51% of the prescribed dose of inhaled steroid. When asked to monitor rescue bronchodilator usage patients consistently under-recorded. Under-use as well as under prescription of inhaled steroids and under-estimation (8) of beta 2-agonists use may be contributory factors to the present increase in asthma mortality and morbidity. These potential problems of poor compliance need larger scale studies to show how and if behaviour can be altered to improve compliance.

Evaluation of an electronic hand-held spirometer in patients with asthma.

In this pilot study we assessed patient compliance and acceptability of data recorded in the home environment by asthmatics using a Vitalograph 2110 spirometer which measures peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1). This meter automatically time and date stamps all measurements and can also assess the technical acceptability of results. Data are uploaded to a personal computer for review and analysis. We recruited 30 patients (10 male and 20 female, age range 21-72 years) from the chest clinic at Guy's Hospital (n = 20) and from a GP clinic (n = 10). Patients were asked to record spirometry data using the meter at set times (8.00 a.m. and 8.00 p.m.) for 2 weeks. The spirometer incorporated an alarm to remind patients to take measurements. All patients completed the study. Mean (SD) compliance with spirometer use was 100.8% (49.9%). Nineteen patients had a compliance rate of between 80% and 120% of expected use. Timing of recordings was compared with the scheduled times of 8.00 a.m. and 8.00 p.m. Values recorded with +/- 2 h were judged as acceptable. For morning recordings 67.4% of all values and for evening recordings 71.7% of all values met this criterion. Technical acceptability of spirometry data was also assessed by using quality assurance criteria recorded by the spirometer. Valid tests were performed for 75.2% of all recordings. Twenty-two patients performed valid tests for 80-100% of the time. We suggest that the use of an electronic meter in the home environment is practical and is likely to generate more accurate and reliable data.

A study of self poisoning with oral salbutamol--laboratory and clinical features.

1. The recent increase in asthma mortality coupled with reports of fatal asthma associated with beta-2-agonist therapy, has stimulated interest in the plasma concentrations of beta-2-agonists that produce systemic toxicity. 2. We prospectively studied 17 patients (9 male), mean age 23 years (range 2-72), who attended the emergency departments of hospitals throughout the United Kingdom having recently ingested an overdose of salbutamol. 3. Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasma was assayed for salbutamol concentration using a high performance TLC-photodensitometric method. 4. The mean (+/- s.d.) salbutamol dose reported to have been ingested was 89(+83)mg and the mean plasma salbutamol concentration was 166 (range 18-449) ng ml-1. The mean plasma potassium was 2.9 (s.d. +/- 0.6) mM (n = 16). None of the patients in this study developed serious cardiac dysrrhythmias. 5. There were significant correlations between the plasma salbutamol concentration and plasma potassium concentration (r = -0.85; P < 0.00005) and between plasma salbutamol concentration and pulse rate (r = 0.66; P < 0.005). 6. We conclude that in these patients, without respiratory decompensation, suprapharmacological plasma concentrations of salbutamol were tolerated without serious cardiac arrhythmias or any fatalities.

Controlled release salbutamol tablets versus sustained release theophylline tablets in the control of reversible obstructive airways disease.

A crossover pilot study was undertaken to compare the acceptability of controlled release salbutamol tablets (8 mg twice daily) with a sustained release theophylline preparation (400-800 mg given once each night) in patients with reversible obstructive airways disease. A 2-week run-in period was used to titrate the theophylline dosage. Patients were then allocated at random to one of the treatments before being immediately crossed over to the other for a further 4 weeks. Thirty-two patients, aged 17-66 years, entered the trial. Seventeen patients (53%) were withdrawn. The majority of the 13 withdrawals due to side-effects of theophylline occurred during the run-in period. There were no statistically significant differences between treatments for either lung function tests performed at the clinic or for peak expiratory flow rate recorded by the patients. The non-asthma symptom score was significantly higher with theophylline than with the salbutamol preparation. A preference for treatment with the controlled release salbutamol tablets was expressed by 11/15 patients.

Home-monitoring of peak expiratory flow rate using mini-Wright peak flow meter in diagnosis of asthma.

Home-monitoring of peak expiratory flow rate using the mini-Wright peak flow meter is a useful technique for determining whether or not unexplained respiratory symptoms are caused by asthma. It is of particular value when airflow obstruction cannot be demonstrated at the time of consultation.

Effect of inhaled alpha-blocker on airflow obstruction in asthma.

A controlled study of the effect on airflow obstruction of 30 mg of the alpha-blocker thymoxamine given by inhalation is reported in 10 patients with chronic stable asthma. No significant change in peak expiratory flow rate was seen with either thymoxamine or placebo in any patient. Alpha-adrenergic receptors are therefore unlikely to contribute significantly to resting bronchomotor tone in chronic stable asthma.

Swallowing in motor neurone disease.

Ninety-two patients with motor neurone disease have been assessed clinically and radiologically for evidence of swallowing problems. At the time of examination, moderate or severe swallowing difficulty was present in 89% of those whose disease had presented as bulbar palsy, in 45% of those in whom the disease began many months before as progressive muscular atrophy and in 29% of those with amyotrophic lateral sclerosis. Patients with more severe swallowing symptoms appeared more likely to have abnormal findings on videofluoroscopy overall. However, not all patients with an abnormal radiological picture had swallowing difficulties. It is suggested that radiological signs should only be used within the context of clinical symptoms and signs in the selection of patients for palliative surgery. Thirteen patients with pseudobulbar symptoms and signs had a cricopharyngeal myotomy performed: two suffered major post-operative complications. However, the satisfaction rate was 89% and we recommend cricopharyngeal myotomy for such patients. Pharyngostomy was performed for seven patients unable to initiate swallowing, six had post-operative complications.

Sleep apnoea in diabetic patients with autonomic neuropathy.

Breathing during sleep was monitored in 8 diabetic patients with objective evidence of autonomic neuropathy and in 8 diabetic patients without neuropathy. Thirty or more periods of apnoea lasting 10 seconds or longer during one night's sleep were demonstrated in 3 of the diabetic patients with autonomic neuropathy. Such apnoeic periods may be related to the high incidence of cardiorespiratory arrests reported in such patients, particularly in association with anaesthesia or pneumonia.