G.M. Cochrane

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.

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.

Attenuation of nocturnal asthma by cromakalim

In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.

INHALED THERAPY REDUCES MORNING DIPS IN ASTHMA

14 asthmatic patients with nocturnal symptoms and morning dips in peak expiratory flow rate (PEFR) were treated with regular inhaled salbutamol for 1 or 2 weeks, followed by regular inhaled beclomethasone dipropionate, in addition to salbutamol, for a further 2 weeks. Mean PEFR rose to normal values in all but 1 patient. Morning dips in PEFR were substantially reduced in 8 patients. There was an equivalent rise in mean PEFR in the other 6 patients, but their morning dips did not improve. Inhaled salbutamol reduced the dips in the responsive patients, but addition of inhaled steroid produced further improvement. Inhaled beta agonist alone improved mean PEFR in these patients, but inhaled steroids produced most of the improvement in the other subgroup. No patient experienced side-effects. Thus mean PEFR can be improved and morning dips in PEFR reduced in a high proportion of asthmatic patients by the use of regular inhaled therapy without resorting to less-well-tolerated oral agents.

Long term treatment of severe asthma with subcutaneous terbutaline

We have investigated the use of subcutaneous terbutaline in 17 patients with brittle asthma and five patients with chronic severe asthma. Twelve of the 17 patients with brittle asthma improved both subjectively and objectively (mean lowest daily PEF rising from 142 litres/min to 297 litres/min), with reduction in oral steroid dose, nebulized beta-agonist dose and number of hospital admissions. Both continuous infusion and 6-hourly divided dose regimens were equally effective. Only one of the five with chronic severe asthma showed any lasting response. Eighteen patients have continued to use subcutaneous terbutaline over long periods (2-40 months). Overall 11 patients suffered side-effects of usually minor degree, although one patient had to withdraw because of the development of painful subcutaneous nodules. We conclude that subcutaneous terbutaline delivered by infusion or by intermittent injections is a useful addition to the therapy of some patients with brittle asthma.

Is there a circadian variation in respiratory morbidity

In a retrospective study of the time of presentation to an accident and emergency department patients with acute respiratory symptoms presented more commonly at night compared to a control group with abdominal pain. In a subsequent prospective study doctors from a GP deputizing service were called much more frequently at night by patients with asthma than by those with other symptoms. These findings refute the suggestion that the observed increased mortality from respiratory diseases at night results from reduced medical care as a consequence of a reluctance of patients to present during the night.

An unusual local reaction to continuous subcutaneous infused terbutaline in unstable asthmatics

Three out of nine unstable asthmatics whose asthma is subjectively and objectively better controlled on continuous subcutaneous terbutaline infusions (6-12 mg/24 hours) developed tender indurated subcutaneous swellings at the infusion site. In the two cases reported here in detail, histologically the lesions were areas of panniculitis and deep dermal collagen necrosis. Further investigation of the possible causative mechanism for these lesions--drug solution pH, osmolality, or impurities--suggests that impurities in the solution are the most likely cause.