Brittle asthma: Management
Patients with brittle asthma pose difficult and complex management problems. Jon Ayres identifies possible management strategies for these patients.
Jon Ayres, BSc, MD, FRCP, is Professor of Respiratory Medicine (University of Warwick) in the Department of Respiratory Medicine, Birmingham Heartlands Hospital, Birmingham.
The term 'brittle asthma' was first used by Turner-Warwick (1977) to describe patients with asthma whose peak expiratory flow (PEF) varied 'chaotically'; a pattern which could lead to death from an acute severe, attack (Bateman and Clarke, 1979; Westerman et al, 1979). Morbidity from brittle asthma is considerable, and this review aims to identify possible causes and management strategies for this group of patients.
It is crucial that peak flow readings are corrected for non-linearity (Miller et al, 1992) when calculating diurnal variation in type 1 brittle asthma. These patients are typically female (4:1 in our clinic) and aged between 15 and 55 years.
The patient may not have been mechanically ventilated as a result of the attack but is very likely to exhibit a severe respiratory acidosis in an attack and, if ventilated, needs support for relatively short time periods (Wasserfallen et al, 1990). Type 2 brittle asthma seems to be equally prevalent in men and women.
Type 1 brittle asthma is a cause of significant morbidity associated with frequent accident and emergency attendances and hospital admissions and the resultant use of considerable amounts of medication. Consequently, side effects of therapy, particularly oral corticosteroids, are common, e.g. osteoporosis, weight gain and oesophageal reflux (Miles et al, 1993). In addition, this can result in the development of obstructive sleep apnoea which may remain unsuspected because poor sleep quality tends to be attributed to asthma, even though the symptom pattern is exactly the same in these patients compared to isolated sleep apnoea. Within our clinic 12% of subjects suffer from sleep apnoea and are treated with nasal continuous positive airway pressure.
Table 1: Positive Food Challenges in Brittle Asthma
Management: Type I brittle asthma
These patients are, by definition, extremely difficult to manage. Many of them have fallen out with their doctor, who perhaps understandably. has run out of ideas and, often, patience. Management should be holistic, trying to approach all areas which impact on an individual's symptoms. This involves identifying causal factors and dealing where possible with psychosocial factors, before attempting to wrestle with polypharmacy. Trying to identify psychosocial factors and dealing with them (including help with Disability Living Allowance, for instance) can help significantly, and group therapy has been of some use in patients who are able to meet on a regular basis, by providing an auto-support network.
Where foods are identified as allergic triggers they should be avoided. In some cases such avoidance can be remarkably effective while in others the benefit is limited, but compliance with what is often a difficult diet may not always be good. Good dietary advice and support is crucial as Baker and colleagues (1995) have shown that the diets of these patients are very often deficient in minerals such as selenium and magnesium and in the anti-oxidant vitamins A, C and B. This is probably because their diet lacks food that they are avoiding because of intolerance and a desperate need to lose weight with consequent reduction in calorie intake.
Subcutaneous §2 agonists
Figure 1: Peak flow readings (before and after bronchodilator) in a patient with type 1 brittle asthma
Before Subcutaneous Terbutaline
On Continuous Subcutaneous Terbutaline
On Terbutaline subcutaneously in 4 daily divided doses.
The infusions are given through a battery-powered syringe driver (such as the Graseby MS26, Graseby Ltd, UK) which need to be provided in successful cases on a long-term basis. If provision of a pump is not possible then the daily dose can be delivered by divided doses, albeit with slightly less effective control (Figure 1). The best tolerated subcutaneous needles are the Sof-Set and the Disetronics needles (Applied Medical Technology, Cambridge, UK), which although more expensive than the standard butterfly, last much longer; one needle often remains in situ for a week or more compared to 48 hours or less for the butterfly needle.
The usual dose needed ranges between 6 and 15mg a day, mean blood levels of terbutaline achieved by this technique are around 150 nmol/litre, the normal therapeutic range for oral terbutaline treatment (7.5 mg twice daily) being 10-20 nmol/litre but despite this, significant changes in serum potassium or glucose concentrations are rare as, surprisingly, is tremor which may suggest the development of tolerance to the side effects of this form of treatment. Muscle cramps are common and may sometimes be severe, with elevation of plasma creatinine phosphokinase (Sykes et al, 1991) although levels of the myocardial fraction are normal. Some patients complain of an effect on memory and ability to concentrate and occasionally menorrhagia is seen but this is not usually severe.
The main problem is the development of subcutaneous inflammatory nodules. When biopsied these show an eosinophilic infiltrate (Lewis et al, 1987). These usually settle down once that area of skin is avoided, but often leave a fibrotic nodule. More recently a more aggressive type of lesion has been demonstrated which sometimes leads on to frank abscess formation, the pus from which is usually sterile. The formulation of the drug has not changed nor have the preservatives, so the reason for these reactions remains elusive. Although using nebulizer solution rather than the injectable form of terbutaline may help, in some the skin changes are so severe that administration has to be changed to continuous intravenous infusion via an indwelling line such as a Portacath or Hickman line, although in those patients who have had many hospital admissions, such vascular access may also be needed because of lack of useable veins.
Long-acting inhaled §2 agonists
Management: Type 2 brittle asthma
Management of type 2 patients is less difficult. In view of the rapid onset of attacks each patient should be provided with a medic alert bracelet or equivalent. Again identification of inhaled or ingested triggers, e.g. peanuts (Loza and Brostoff, 1995), is crucial, but the mainstay of self treatment for these attacks is adrenaline. Although these patients often appear to be relatively symptom free between attacks in some cases significant peak flow variability is seen which is not matched by perceived symptoms, which may explain the appearance of sudden attacks occurring on the background of significant but undetected airway narrowing.
Patients with brittle asthma, whether type 1 or type 2, pose difficult and complex management problems. Trying to classify these severe patients will help to determine the differing factors involved and, while this classification will not embrace all patients with severe asthma, it will provide a framework for beginning to unravel aetiology and treatment of this high morbidity group. Once identified, dealing with individual factors may in themselves have only a small impact on their condition but these can be cumulative, and even if these result in only modest improvements in control, the patient will believe that some improvement can after all be achieved.
Ayres JG (1992)
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Baker JC, Tunnicliffe WS, Duncanson RC, Ayres JG (1996)
Barnes PJ, Adcock IM (1995)
Bateman JRM, Clarke SW (1979)
British Thoracic Society, British Paediatric Association, Royal College of Physicians of London et al (1996)
Garden GMF, Ayres JG (1993)
Lewis LD, O'Driscoll BRC, Hartley RB, Cochrane GM (1987)
Loza C, Brostoff J (1995)
Miles JF, Noble K, Matthews BR, Cayson RM, Ayres JG (1993)
Miles JF, Cayton RM, Tunnicliffe WS, Ayres JG (1995)
Miles IF, Garden GM, Tunnicliffe W, Cayton RM, Ayres JG (1997)
Miller MR, Dickinson SA, Hitchings DJ (1992)
O'Driscoll BRC, Ruffles SP, Ayres JG, Cochrane GM (1988)
Sykes AP, Lawson N, Finnegan JA, Ayres JG (1991)
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Wasserfallen JB, Schaller MD, Feihl F, Perret CH (1990)
Westerman DE. Benatar SR. Porigieter PD. Ferguson AD (1979)
The following article is taken from Practice Nursing, Vol 9, No 12 14 July 1998 with the permission of Mark Allen publishing. Other articles which may be of interest are published on their website.